The Chronicle of Neurology + Psychiatry Aug 30 2011

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by Josh Long, Assistant Editor, The Chronicle I TS TOO SOON to establish causality, but research has shown one thing about obesity and headaches, accord- ing to an assistant professor at Johns Hopkins University School of Medicine. “Obesity and migraine headaches are related,” said Dr. Lee Peterlin. “Specifically, several studies have established that obesity increases the odds of migraine in reproductive aged women and men.” More recently a study published in Headache (April 2011; 51(4):559-569) which she co-authored with Dr. Michelle Williams evaluat- ed the relationship between weight gain, obesity, and migraine in over 3,700 pre- menopausal women. “In this study, women with migraine as children had a 67 per cent increased risk of gain- ing 10 or more kg—that is 20 lbs or more—by adulthood as compared to women who did not have migraine,” she said Furthermore she said, this study demonstrated that the risk of migraine substantially increased with increasing severity of obesity. Those women with class I obesity (BMI 30-34.9) had a 48% increased odds of migraine, Migraine Possible link between headaches and obesity n But specialists are unsure of directionality THE CHRONICLE is commit- ted to environmentally sus- tainable policies, and to encouraging “green aware” practices in healthcare. We are now proud to pro- vide this journal on the highest percentage of recy- cled paper stock currently commercially available. Guest Editorial: Neurosurgical treatment delays ................3 Clinical practices in intimate partner violence ..................15 Canadian Psychiatric Association meeting preview ............16 Canada’s National Newspaper of the CNS Sciences n August 2011 In this month’s Chronicle Vitae profile, we talk to Dr. Steven Cohen, a psychiatrist with Doctors without Borders who has gone on missions to Chad and the Sudan. He talks about his travels, his motivation, and the patients he treated. See page 22 Addiction Smoking while on a low-dose patch n Patients smoke less and experience fewer cravings by Josh Long, Assistant Editor, The Chronicle W HEN SOME OF HIS schizophrenia patients told him that they were contin- uing to smoke while on the nicotine patch, Dr. Peter Selby says he became concerned. “Initially, I got a bit of tachycardia myself,” said the head of the nicotine dependence clinic at the Centre for Addiction and Mental Health in Toronto. Then he asked his patients how it felt, and they told him that when smoked while on the patch, they did not want to smoke as Patient safety Schizophrenia and substance abuse STATISTICALLY SPEAKING the most at risk population of people with schizophrenia are those who have comorbid substance abuse. Dr. Soojin Chun explains the risk factors on page 8. please turn to page 10 please turn to page 6 The photograph above comes from a new radiological scanning method using 123 I-ioflupane, which can visually identify dopamine receptor loss. On the left is a normal brain and on the right is the abnormal brain. please turn to page 12 Diagnosing Parkinson’s Disease Radiologically Now printed on 50% post-consumer recycled paper

description

The Chronicle of Neurology + Psychiatry, Aug. 30 2011 edition of Canadian newspaper for the CNS sciences

Transcript of The Chronicle of Neurology + Psychiatry Aug 30 2011

Page 1: The Chronicle of Neurology + Psychiatry Aug 30 2011

by Josh Long,Assistant Editor, The Chronicle

IT’S TOO SOON to establishcausality, but research hasshown one thing about

obesity and headaches, accord-ing to an assistant professor atJohns Hopkins UniversitySchool of Medicine.

“Obesity and migraineheadaches are related,” saidDr. Lee Peterlin.

“Specifically, several studieshave established that obesityincreases the odds of migrainein reproductive aged womenand men.” More recently astudy published in Headache(April 2011; 51(4):559-569)which she co-authored with

Dr. Michelle Williams evaluat-ed the relationship betweenweight gain, obesity, andmigraine in over 3,700 pre-menopausal women.

“In this study, women withmigraine as children had a 67per cent increased risk of gain-ing 10 or more kg—that is 20lbs or more—by adulthood ascompared to women who didnot have migraine,” she said

Furthermore she said, thisstudy demonstrated that therisk of migraine substantiallyincreased with increasingseverity of obesity. Thosewomen with class I obesity(BMI 30-34.9) had a 48%increased odds of migraine,

M i g r a i n e

Possible link betweenheadaches and obesityn But specialists are unsure of directionality

THE CHRONICLE is commit-ted to environmentally sus-tainable policies, and toencouraging “green aware”practices in healthcare.

We are now proud to pro-vide this journal on thehighest percentage of recy-cled paper stock currentlycommercially available.

Guest Editorial: Neurosurgical treatment delays ................3Clinical practices in intimate partner violence ..................15

Canadian Psychiatric Association meeting preview ............16

Canada’s National Newspaper of the CNS Sciences n August 2011

In this month’s Chronicle Vitae profile, we talk to Dr.Steven Cohen, a psychiatrist with Doctors without Borderswho has gone on missions to Chad and the Sudan. Hetalks about his travels, his motivation, and the patients hetreated. See page 22

A d d i c t i o n

Smoking while on a low-dose patchn Patients smoke less and experience fewer cravingsby Josh Long, Assistant Editor, The Chronicle

WHEN SOME OF HIS schizophrenia patients told him that they were contin-uing to smoke while on the nicotine patch, Dr. Peter Selby says hebecame concerned.

“Initially, I got a bit of tachycardia myself,” said the head of the nicotinedependence clinic at the Centre for Addiction and Mental Health in Toronto.

Then he asked his patients how it felt, and they told him that when smokedwhile on the patch, they did not want to smoke as

P a t i e n t s a f e t y

Schizophrenia and substance abuseSTATISTICALLY SPEAKING the most at risk population of peoplewith schizophrenia are those who have comorbid substanceabuse. Dr. Soojin Chun explains the risk factors on page 8.

—please turn to page 10

—please turn to page 6

The photograph above comes from a new radiological scanning method using123I-ioflupane, which can visually identify dopamine receptor loss. On the left isa normal brain and on the right is the abnormal brain. —please turn to page 12

DiagnosingParkinson’s Disease

Radiologically

Now printed on 50% post-consumer recycled paper

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Page 2: The Chronicle of Neurology + Psychiatry Aug 30 2011

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XEOMIN® scienceNew Revised Indications For the treatment of hypertonicity disorders of the 7th nerve such as blepharospasm including

benign essential blepharospasm and hemifacial spasm in adults

To reduce the subjective symptoms and objective signs of cervical dystonia (spasmodic torticollis)

in adults

For the treatment of upper limb spasticity associated with stroke in adults

XEOMIN ®

UPDATE

(Clostridium Botulinum Neurotoxin Type A [150 kD], free from complexing proteins)

INDICATIONS AND CLINICAL USE: XEOMIN® is indicated for the treatment of hypertonicity disorders of the 7th nerve such as blepharospasm including benign essential blepharospasm and hemifacial spasm, upper limb spasticity associated with stroke, and to reduce the subjective symptoms and objective signs of cervical dystonia (spasmodic torticollis) in adults.

XEOMIN® as a treatment for focal spasticity has been studied in association with usual standard care regimens and is not intended as a replacement for these treatment modalities.

XEOMIN® is not likely to be effective at a joint affected by a fixed contracture.

XEOMIN® may only be used by physicians with suitable qualifications and proven experience in the application of Botulinum toxin type A and in the use of the necessary equipment, e.g. EMG (electromyography).

CONTRAINDICATIONS: Hypersensitivity to Botulinum neurotoxin type A or to any of the excipients. Generalised disorders of muscle activity (e.g. myasthenia gravis, Lambert-Eaton syndrome). Presence of infection at the proposed injection site.

Serious Warnings and Precautions

The term “unit” or “U” upon which dosing is based, is a specific measurement of toxin activity that is unique to XEOMIN®. Therefore, the “unit” or “U” used to describe XEOMIN® activity are different from those used to describe that of other Botulinum toxin preparations and the units representing XEOMIN® activity are not interchangeable with other products.

Follow the recommended dosage and frequency of administration for XEOMIN® (See product monograph for DOSAGE AND ADMINISTRATION).

General: Patients and caregivers should be advised to seek immediate medical consultation if swallowing, speech, or respiratory disorders arise.

In very rare cases severe adverse events like muscle weakness, dysphagia or aspiration pneumonia with a suspected causal relationship to toxin spread have been reported with the use of botulinum toxin. Also very rare cases of adverse events with a fatal outcome have been reported. Patients with a neurological underlying disease or swallowing, speech or respiratory difficulties have an increased risk for these adverse drug reactions and should be treated and supervised very carefully.

An anaphylactic reaction may occur rarely after injection of Botulinum neurotoxin type A (See ADVERSE REACTIONS). Adrenaline and other medical aids for treating anaphylaxis should be available.

Extra caution is required when injecting at sites close to sensitive structures such as the carotid artery and lung apices.

XEOMIN® should be used with caution: in patients suffering from amyotrophic lateral sclerosis or other diseases which result in peripheral neuromuscular dysfunction; in targeted muscles which display pronounced weakness or atrophy. Spasmodic torticollis: Patients should be informed that injections of XEOMIN® for the management of spasmodic torticollis may cause mild to severe dysphagia with the risk of aspiration and dyspnoea. Dysphagia can last for up to two to three weeks after injection. Patients with smaller neck muscle mass, or patients who require bilateral injections into the sternocleidomastoid muscles are at greater risk. The occurrence of dysphagia is attributable to the spread of the pharmacological effect of Botulinum toxin as the result of the neurotoxin spread into the oesophageal musculature.

Please see product monograph for full warnings, precautions, adverse events and patient selection criteria

To report an adverse reaction please notify Health Canada at 1-866-234-2345 or MERZ Canada at 1-866-815-8715.

XEOMIN® is a registered trademark of Merz GmbH. Full product monograph available on request by contacting Merz Pharma Canada Ltd. at 1-877-811-6379.

XEOMIN® is a registered trademark of Merz GmbH.

See Prescribing Summary on page 19

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Dr. Klimek’s letter to the Ontario Minister of Health and Long-Term Care

The consequences of acute neurologic catastrophe aredevastating and ample evidence demonstrates that thebest care for patients is timely care, but given the

scarcity of resources this is not always what we are able toprovide for our patients.

As a neurologist in a community setting, myfirst catastrophe sent out of country for emer-gent care occurred in July 2006. Since myletter to then Ontario Health MinisterGeorge Smitherman, the Ministry ofHealth and Long-term Care recog-nized the reduced surge capacity todeal with catastrophes. In 2008-09,120 patients went out of countryfor neurosurgery. In 2009-10, 202patients went out of country. Themost recent data I heard was 50patients were sent to the U.S. forthis purpose alone this last year.Family members of a patients ofmine said 12 Canadians were alsotreated in the same U.S. facility.

Several studies and interviewsat high levels promised improve-ment. Now we have a 24 hour tele-phone CritiCal network available,complete with preprinted forms, foremergent out-of-country transfer to pre-ferred providers offering prenegotiated dis-count service invoiced to the Ontario government.Health Minister Deborah Matthews admits, “The memberopposite is absolutely right: There has been a dramaticincrease in out-of-country health care provided and coveredthrough OHIP.” (Hansard, Nov. 26, 2011). Maybe this iseffective cost reduction. If so, the cheapest form of care isneglect and comes with an immensely personal cost.

If we don’t inform the public, and the patient, that the

best care may not be available in Ontario, then we are notdefending ourselves or fully informing the person consentingto the care proposed. But should we do so, then we generatemore (CYA) nonmedical activity or risk allegations of unpro-fessionalism in commenting on the availability of others (or

other centres).This is particularly true if treatment else-where is not equivalent or identical to treat-

ment in Ontario and the proposed treat-ment is not available anywhere inOntario. Cases in the public domain

brought before the Health ServicesAppeal and Review Board (HSARB)by educated and persistent patientshave shown the magnitude of theproblem. It is clear in the findingsof the HSARB that patients areobliged to seek care across theborder for which OHIP must pay.(File # 10-HIA-0063 HealthServices Appeal and ReviewBoard, Oct. 27, 2010 Toronto)

Simultaneously health careproviders are considered technical

experts and agents responsible forimplementing a social policy of

rationing and delayed care. Any MD hasdifficulty defending a foreseeable and pre-

ventable adverse outcome. It is compoundedif one is also held to a standard of care which pre-

sumes infrastructural shortage is an inadequate defense, noattempt has been made to correct it and no immunity isgranted for acting as an agent of social policy in rationingcare.

Dr. Edwin Klimek is president of the Association of Ontario Neurologistsand operates a neurology practice in St. Catharines, Ont.

The Chronicle of Neurology & Psychiatry is published six times annually by the proprietor, Chronicle Information Resources Ltd., with offices at555 Burnhamthorpe Rd., Ste. 306, Toronto, Ont. M9C 2Y1 Canada. Telephone: 416.916.2476; Fax. 416.352.6199. E-mail: [email protected].

Contents © Chronicle Information Resources Ltd., 2011, except where noted. All rights reserved worldwide. The Publisher prohibits repro-duction in any form, including print, broadcast, and electronic, without written permissions. Printed in Canada. Mail subscriptions: $72 per year inCanada, $125 per year in all other countries. Single copies: $12 per issue (plus 13% HST)

Canada Post Canadian Publications Mail Sales Product Agreement Number 40016917The Publisher certifies that advertising placed in this publication meets Revenue Canada requirements for tax deductibility.Volume 14, Number 3, published August 2011ISSN 1209-0565

Guest editorial: Treatment delayed is treatment denied

THIS LETTER IS directed to several who maybe in a position of authority to correct aremediable and foreseeable problem, andthe Minister of Health and Long-term Careof Ontario specifically. It is unclear to mewho has the greatest burden for sharedresponsibility (hospital, LHIN, province) inthe neurosurgical infrastructure of Ontario.

Vignette 1On July 5, 2006, Mr. X, a 47-year-old,

arrived 10 a.m. in the office with an overt spastic para-paresis of subacute onset. He used a cane and was bare-ly ambulatory. A symptomatic navel level was noted withsphincter involvement.

The required emergent MRI scan was scheduled fornoon after telephone solicitation. Unable to lie adequate-

ly motionless due to pain, he was sedated in ER. Asecond effort proved diagnostic by 2:30 of a tho-racic spine central posterior disc herniation with alunate crescent of residual spinal cord visible.

After engaging Critical in futile hours of can-vassing the province for emergent neurosurgicalassistance, the case was transferred out-of-coun-try by 8 p.m. for definitive immediate neurosurgicalmanagement. Faxing of paper work for out ofcountry treatment approval occurs at 9 pm.

Homeland Security required documentation of citizenshipwithout a criminal record.

Vignette 2Mr. X, a 39-year-old man, experiences an injury to the

neck and is confirmed to have a fractured spine. Theemergency room seeks advice on management and is

advised that patient needs surgical stabilization at region-al spine centre, but there are no beds. Patient is heldover. He is found on the morning of the 3rd day awaitingtransfer in hospital “not moving legs.”

These vignettes taken from professional practice in St.Catharines demonstrate that patients suffer from neuro-surgical infrastructural inadequacies in Ontario and thisresults in transfer of patients to the United States. By anyestimate, the cost of long term care of the latter unfortu-nate man exceeds the cost of the definitive care he wasdenied. Surely, either individual’s loss of societal contri-bution alone should persuade anyone the current inade-quate neurosurgical infrastructure is not in society’s bestinterest.

—See the Ontario Association of Neurologists’website at http://www.aoneuro.on.ca

Dr. Edwin Klimek

August 2011 n 3

“I spend a lot of my time trying to draw the attention of actors to the minute andsubtle details of human behavior, which was the sort of thing I was looking at when

I was a neurologist.” —Jonathan Miller

I n t h e n e w s

n In the London [Ont.] Free Press, Dr.Klimek talks about the problemshe’s experienced with CritiCall,including what he calls an inabili-ty to keep track of empty beds,and how patients entering theU.S. for surgery must still becleared by Homeland Securityand have a valid passport toenter. —Read this London Free Press

article at http://ow.ly/4WpHg

n If Alzheimer’s disease grows at therate predicted by the Alzheimer’sSociety, that is 40% in 10 years,Dr. Klimek says this single disor-der will take up the time of everyneurologist in Ontario. This waspart of a presentation made onJan. 24, 2011 to the StandingCommittee on Finance andEconomic Affairs. He also saidthat though additional serviceshad been supported, they had notbeen funded.

—Read Dr. Klimek’s Hansardexcerpt in the St. Catharines

Standard at http://ow.ly/4WoNl

n In a CBC interview, Dr. Klimek esti-mates that the cost of sendingpatients to the U.S. costs Canadaover $100 million a year. Though hesays he’s been writing letters aboutthis for years, he’s seen little action.

—Read the CBC article athttp://ow.ly/4WqLB

N ®

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PARALYZED WITH AN INJURY to his spinalcord from C7-T1, Rob Summers is nowable to stand with the help of electricalstimulation to the spinal cord, accordingto The Lancet (May 20, 2011).

“Epidural stimulation enabled theman to achieve full weight-bearingstanding with assistance provided onlyfor balance for 4-25 minutes,” wrote theauthors.

“The patient achieved this standingduring stimulation using parametersidentified as specific for standing whileproviding bilateral load-bearing proprio-ceptive input. We also noted locomotor-like patterns when stimulation parame-ters were optimized for stepping.”

MedPage Today reports that Summers

was struck by a hit-and-run driver andwas unable to walk due to the spinalcord injury he received, and that sincethe device was implanted in Decemberof 2006, he has regained control of hisbladder, sexual functioning, and the abil-ity to regulate his body temperature.

His ability to carry his own weight hasalso improved. Though he was initiallyonly able to carry 65% of his weight, hemay now carry all of it with the assis-tance of balance aids.

Reggie Edgerton, PhD, was one ofthe researchers who worked on this ther-apy. He told National Public Radio thatseeing Summers move his legs was a bigsurprise.

“This demonstrates that you can

regain voluntary control,” Dr. Edgertonsaid, “but the voluntary control is onlyregained in the presence of stimulation.”

So far, the device implanted intoSummers is only active about two hoursa day, but he did say that there are linger-ing effects when the device is not acti-vated, including increased feeling.

“I had a shot in my lower back justthe other day as part of a check-up andI felt the entire thing—the needle go in,the pain, everything,” he said. “So thatwas both good and bad, exciting toexperience that again, but knowing that Icontinue to make progress is very excit-ing.”

—Read this Lancet articleat http://ow.ly/51DCv

4 n August 2011

Neurology EditorRichard Gladstone,

MD, FRCPCPsychiatry Editor

J. J. Warsh, MD, FRCPCEditor, Innovation in the Mind Sciences

Roger S. McIntyre, MD, FRCPC

Editorial DirectorR. Allan Ryan

Senior Associate EditorLynn Bradshaw

Assistant EditorJosh Long

PublisherMitchell Shannon

Sales DirectorPeter M. Stamp

Production and CirculationCathy Dusome

ComptrollerRose Arciero

s Atelier: The artist who created this work is 90 years of age, and has experienced astroke. She can only use her right dominant hand.

She is restricted to a wheelchair, and she takes medication for depression.Esther Zeller, her art therapist, says that this client considers her atwork to be

an outlet for extreme sadness of her personal, physical, and emotional challenges.“There is little conversation between us,” said Zeller, “but she feels enabled,

valued and determined to share her emotions as expressed through her art.”—More information on Esther Zeller and her work in art therapy is available at

www.artdynamics.ca

s Quick-start guide to The Chronicle, August 2011:

Conference IndexOntario Psychiatric Association Smoking while on the patch (p.1),

Substance abuse puts schizophrenia patients at risk (p. 8), Treating sub-stance abuse in schizophrenia (p. 9)

American Academy of Neurology: New adjunct diagnostic tool forParkinson’s examined by Dr. Frederick Weiland (p. 12)

Canadian Psychiatric Association: Conference preview (p. 16)Chronicle Vitae: Overseas psychiatry (p. 22)

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Page 5: The Chronicle of Neurology + Psychiatry Aug 30 2011

Parental Alienation Syndrome and the DSM-5n DSM-5 working group says insufficient evidence to classify condition as a mental disorder

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August 2011 n 5

“Attempts have been made to educate psychiatrists aboutadult ADHD, but many doctors still don’t believe in it.”

—Dr. Umesh Jain, an ADHD researcher at Toronto's Centre forAddiction and Mental Health

I n t h e n e w s . . .

n Questions were raised regarding theethics and efficacy of behaviourmodification in prisons. “Not only isthis treatment unethical and inef-fectual in the real world, not only isits refusal to see the underlyingcauses tantamount to professionalnegligence…this form of treatmentundoubtedly exacerbates certainforms of mental illness, while caus-ing others,” wrote Dave Holmes,PhD, and University ResearchChair in Forensic Nursing at theUniversity of Ottawa in the Journal of Nursing Management(April 2011; 19(3):293–301). Hesays this is because it treats prisoners like children. Forensicpsychiatrist Dr. Adekunle GarbaAhmed disagreed, saying that therepeat offender rates are muchlower at prisons that use this pro-gram, and that Dr. Holmes’ studyplaces too much emphais onsocial scientists rather than psy-chological studies.

—Read this original study athttp://ow.ly/51ILo

n The link between suicide and nativeNorth Americans may be purelyincidental. When controlling formental illness, suicide was foundto be no more prevalent in thisgroup than in the general popula-tion, says Shay-Lee Bolton, PhD,of the University of Manitoba inWinnipeg. This research was pre-sented during an oral session atthe American PsychiatricAssociation meeting in Honolulu,Hawaii.

—Read this article athttp://ow.ly/51Mz6

O n t h e w e b

n Thought-controlled video games arebeing explored as a possible ther-apy for ADHD. “It’s a very innova-tive strategy,” said CAMH psychia-trist Dr. Umesh Jain, who is cur-rently in the process of applying fora grant to fund this research. Theidea is to use technology beingdeveloped by the Toronto-basedcompany, Interaxon. In this sys-tem, a gamer wears a headbandwith sensors that monitor theirbrain waves. Dr. Jain still questionswhether this will enhance attentionskills when not playing the game.

—Read the CBC article athttp://ow.ly/51NtB

ub-

SEVERAL PERSPECTIVES OVER whetherto include alienation syndrome in theDSM-5 were expressed on the CBCradio program, The Current (May 17,2011).

Dr. Rachel Klein, a member of theDSM-5 Child and Adolescent WorkingGroup, said that it was unlikely to beincluded as a mental disorder.

“There are [many] clinical anec-dotes but that’s insufficient for inclu-sion in the [DSM].” said Dr. Klein..

“I want to add that I think it’s real-ly real, that it happens, it’s a big prob-lem. The question is whether it reflectsmental dysfunction.”

Joseph Goldberg, the founder ofthe Canadian Symposium forParental Alienation Syndrome, dis-

agreed that there was no scientificevidence to support the idea thatparental alienation syndrome existsas a mental disorder, and that itshould be considered a mental disor-der in the DSM-5.

“What makes this a mental disorderis that they have a gradual denegationof the parent they were once bondedto,” he said. “That’s different thanwhen a child rejects a parent for legiti-mate reasons.”

Opposed the inclusion of this syn-drome in the DSM-5 is Terry O’Neill,the President of the NationalOrganization for Women.

“The problem with this so-calledsyndrome is that it confuses law andpolicy with medicine,” she said.

Treatment requires cutting off con-tact with the preferred parent and puting the child into the custody of therejected parent, O’Neill said,

Classifying parental alienation syn-drome as a mental disorder could leadto children being misdiagnosed withparental alienation syndrome when theycould have a legitimate reason forrejecting one parent, either due to abuseor neglect.

O’Neill said that frequently indivorce cases where a child rejects aparent, the situation resolves itselfafter two years and the child oftenexpresses remorse for their actions.

—Listen to the show online on the CBC website at

http://ow.ly/5A1l8

n

by Josh Long, Assistant Editor, The Chronicle

UNIVERSITY OF TORONTO students have developed a speechenabling mobile phone application called MyVoice thatwill allow people who are unable to speak to communicate.

Freely available,the program offersusers a more costeffective option tofind out if the prod-uct suits their needs.

“When we metusers and read sto-ries about the com-munities that use theaids that we com-pare with, we’veheard somethingthat we found par-ticularly troubling.That was a phenom-enon where peopletook a leap of faithinto a device, spend-ing $10,000 or$12,000, and findingthree or six monthslater that it wasn’tthe right device forthat person,” saidAlexander Levy, the creator and lead researcher on the proj-ect.

Once the money is spent, either by the purchaser orthrough a possible government subsidy program, he said,they were effectively committed to a product that may nothave been the most suitable.

By contrast, MyVoice is free, though Levy says that there

will be a $30 a month subscription fee later for people whowant premium services added.

In the meantime, the free version of the MyVoice applica-tion allows the user to prepare phrases according to commonsituations and uses the GPS feature now available in many

mobile phones, afeature that theycall locationawareness.

“ L o c a t i o nawareness is afeature whicha u t o m a t i c a l l yprovides wordsand phrasesbased on whereyou are,” saidLevy. “Oneexample, veryCanadian, is ifyou walk intoTim Hortons thewords ‘Timbits’and ‘double-dou-ble’ could auto-matically comeonto the screen ifyou tag them todo so. Thismeans easier,more comfort-

able communication for people with speech and languagechallenges.”

Users can create a customized vocabulary if, for example,they regularly order their coffee as half decaf and half regu-lar. They also have access to specialized vocabulary lists

Giving the voiceless a voice through new technologyn Text-to-speech software allows aphasiacs to speak through their smartphones

—please turn to page 16

Aakash Sahney (left) and Alexander Levy (right) discuss their smartphoneapplication for people unable to speak

42815 N_P Chronicle.qxd:42815 N_P Chronicle.qxd 31/08/11 3:48 PM Page 5

Page 6: The Chronicle of Neurology + Psychiatry Aug 30 2011

by LoCorre

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much, he said at the OntarioPsychiatric Association’s 91st annual meeting in Toronto.

Dr. Selby says it is because with the steady dose of nicotineprovided by the patch, the patient no longer experienced thedopaminergic effect implicated in addictive response to nico-tine they once received when they smoked.

PUTTING NICOTINE ADDICTION IN PERSPECTIVE“Any drug you inhale is more addictive than anything you inject,”he said. “Think about it. It goes straight to your lungs, straight toyour right, left atrium, left ventricle, andthrough your carotids to your brain. Ittakes seven to thirty seconds to hit yourbrain and release dopamine.”

It also bypasses the first pass metab-olism in the liver, so that a higher druglevel is delivered through the respirato-ry route versus the injected route.

That’s with every puff, he says. Andwith an average cigarette taking about 10puffs to finish, Dr. Selby said a personsmoking 20 cigarettes a day would take200 puffs per day. Each puff would be apositive reinforcement to continue smok-ing. It’s part of the reason that he sayssmoking is such an addictive behaviour.

“In essence that behaviour has been rewarded more thaneating, sex, voiding, you name it,” he said.

And so, he said, taking a drag of a cigarette remains astrongly conditioned response.

When the patient can’t have a cigarette because of theirnicotine patch dosage, the patient has a choice. Stay on thepatch and have no way to safely satisfy their cravings, or giveup the patch to give in to the craving.

“Guess what happens? Because they are in a personifiedrelationship with the cigarette, the new kid on the block comesoff,” said Dr. Selby, and patients switch back to cigarettes.

In traditional nicotine therapy, patients start with a highdose patch and titrate until they don’t need a patch at all. Dr.Selby has turned that approach on its head, starting the patienton a low dose patch and gradually increasing the dose until thepatient no longer wants to smoke, and then titrating downafter six weeks over a four week period.

“We’ve got to figure out how to get the dose of nicotine tothe level where if you have a cigarette with it, you’re going tosay, ‘The cigarette doesn’t do anything,’” he said.

In an interview with THE CHRONICLE, Dr. Selby explainedthe role pharmacological interventions can play.

He first said that nicotine replacement therapy makes senseas first-line treatment because the patient has already demon-strated that nicotine is well-tolerated.

Still, other pharmacological interventions may be helpful,he said, if nicotine replacement therapy has not had thedesired effect after four weeks of treatment. However, anylevel of success requires careful analysis, he said, which hecalls “more art than science.”

In the case of a partialresponse to treatment, Dr. Selbysaid that it may be necessary to“tweak” the treatment.

“If they say they’re smokingsteady, like seven cigarettes a day[...] then we may boost their dosage[of nicotine replacement therapy]by seven milligrams,” he said.

ANALYSING EFFECTIVENESSFinding the best approachrequires an assessment of theenvironmental factors that maycause the patient to smoke. These

factors may affect the patient’s success but can be remedied bya change in the environment, or other non-pharmacologicaltechniques, he said, adding that. if the patient says they smokein response to a stress trigger, an inhaler or nicotine gummight be a viable option to consider.

“On the other hand, if they say they have to smoke ten ortwenty cigarettes on top of the patch, then we know the treat-ment isn’t working,” said Dr. Selby.

“And then you make a decision—are you going to up thedose, add a medication or switch?”

Bupropion is effective in tobacco cessation among patientswith comorbid mental illness, is well-tolerated, and compati-ble with nicotine replacement therapy.

“But you have to be careful in people with [mania in bipo-lar disorder] because you may precipitate a manic episode,” hesaid, regarding bupropion.

“So you can use it in people with [bipolar disorder] but you[have to] make sure they’re stable and they have their moodstabilizers in place.”

Dr. Selby says if nicotine replacement doesn’t work, he’s

Low-dose nicotine patch as first line treatment

6 n August 2011

C l i n i c a l T r i a l s

n While bupropion has been shown todouble quit rates, an Ontario studyaims to determine whether if cost ofthis medication could be a barrier topatients. The study seeks volunteersover the age of 18 who smoke 10 ormore cigarettes a day who have notenrolled in any of the STOP studyNRT models in the last six months.Subjects will be given bupropion(150 mg) for up to eight weeks, sup-plemented by brief individual coun-selling sessions focused on smokingcessation and relapse prevention.Contact: Centre for Addiction andMental Health, Laurie Zawertailo,PhD, 416-535-8501 ext 7422, [email protected]

—More info on this clinical study

at http://ow.ly/5NKxG

—please turn to page 18

#Any drug you#Any drug youinhale is moreinhale is moreaddictive thanaddictive thananything youanything youinject"inject"

DSM-5 distinguishes between addiction and dependenceADDICTION IS BEING redefined in the DSM-5 according to an articlein Addiction (May 2011: 106(5):866–867).

“The term ‘dependence’, while used in past decades to referto uncontrolled drug-seeking behavior, has an alternative mean-ing—the physiological adaptation that occurs when medicationsacting on the central nervous system are ingested with reboundwhen the medication is abruptly discontinued,” wrote CharlesO’Brien, MD, PhD.

The authors said the dual meanings led to confusion, and mayhave resulted in under treatment of pain as physicians fear creat-ing a physical addiction in their patients by prescribing opioids.

The DSM-5 seeks to address this problem in a chapter called‘addiction and related disorders.’

Dr. O’Brien says that the criteria for diagnosis will remain sim-ilar but for the removal of the ‘committing illegal acts.’

In its place will be the addition of ‘craving’ to the criteria.“The other major change relates to the elimination of the

abuse/dependence dichotomy, given the lack of data supportingan intermediate stage,” he wrote.

“These changes are anticipated to improve clarification anddiagnosis and treatment of substance use and related disorders.”

—Read the study at http://ow.ly/5WlhF

—continued from page 1

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by Louise Gagnon,Correspondent, The Chronicle

UNDERSTANDING THEneurological basis fordrug addiction may lead

to possible treatments fordrug addiction, according to aresearcher at Queen’sUniversity in Kingston, Ont.

“We know some of the riskfactors for drug addiction,such as stress at an early age orexposureto a trau-m a t i cenviron-ment, hasa hugeeffect onyour sus-ceptibilityto devel-op a drug abuse problem laterin life,” said Eric Dumont,PhD, an assistant professor inthe department of anesthesi-ology at Queen’s.

Speaking at a neurosciencesseminar in Toronto highlight-ing neurological research proj-ects where Canada and Franceare collaborating, Dr. Dumontsaid he and co-investigatorsare aiming to identify mecha-nisms that are distinctly linkedwith drug-taking behaviour.They are performing similarexperiments to confirm find-ings and are working in a com-plementary fashion, he said.

“We want to be able to sparenatural motivations to allowsomeone to operate normally,”he said. “We could reducemotivations that affect drug-taking behaviour, but it willalso affect motivations such aswanting to feed one’s self.

Specifically, Dr. Dumontand his collaborators haveidentified that Src, a non-receptor tyrosine kinase, playsa part in drug-taking behav-iours in animal models.Tyrosine kinases play crucialroles in signalling betweencells in multi-cellular animals.

“We see these src tyrosinekinases as only contributing todrug-taking behaviours in ani-mals that have been chronical-ly taken psychostimulants likecocaine or methampheta-mine,” said Dr. Dumont.“This target is uniquely associ-ated with drug-taking behav-iour, and it has nothing to do

with normal motivation.”Src tyrosine kinase (STK)

inhibitors are being exploredin clinical trials as treatmentfor various cancers, he said,

which means that a safety pro-file of the drug is available.

“This may speed upattempts at using them to treataddiction behaviours,”said Dr.

Dumont, who added that as ofnow there is no evidence thatthis drug can be abused.

Dr. Dumont says a poten-tial therapy using STK

inhibitors would assist in curb-ing the use of not only illicitpsychostimulants such ascocaine, but also keep a lid on

Understanding mechanisms of addiction could lead to new therapiesn Queen’s University researcher says that research could disable reward response and avoid addiction in opioid treatments

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Talk to your patients

42815 N_P Chronicle.qxd:42815 N_P Chronicle.qxd 31/08/11 3:48 PM Page 7

Page 8: The Chronicle of Neurology + Psychiatry Aug 30 2011

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by Josh Long, Assistant Editor, The Chronicle

PEOPLE WITH SCHIZOPHRENIA are at significantly greaterrisk for violence and self harm when they have comor-bid substance abuse, according to research presented at

the annual meeting of the Ontario Psychiatric Association. The rate of violence is about 8% among schizophrenia out-

patients but 30% when combined with substance abuse, accord-ing to Dr. Soojin Chun of The Ottawa Hospital, referring to astudy in Hospital and Community Psychiatry(July 1990; 41:761-770).

Dr. Chun also cited a report in thejournal Progress in Neuro-Psychopharmacologyand Biological Psychiatry (June 2006;30(4):586-598), which identified possiblerisk factors for violence and aggression asmales, between the ages of 15 and 24,who are unemployed, have little education, and often haveorganic syndrome and exhibit substance use. Clinical featuresfor violence and aggression from this study included commonauditory hallucination, and paranoid delusions seen in psy-chotic disorders.

“In theory, if no substance [abuse] was involved, the rate of

violence or aggression in psychiatric patients is actually almost[the] same as [the] general population,” she said, referring to astudy (Arch Gen Psychiatry May 1998; 55(5):393-401).

“However when there is substance use, the rate can tripleor even quadruple.”

HARM TO SELFAside from harm to others, Dr. Chun also said that there wasgreater risk of self harm in schizophrenia patients who engage

in substance abuse.Identifying the groups most likely

to commit suicide, Dr. Chun saidthat it varied by gender.

For males, suicide is more likely tooccur in youths with schizophrenia,while for females the most likely is amid-aged single divorced womenwith a mood disorder.

“Ninety per cent of suicides arecommitted by people with [a] docu-mented mental illness or substance useproblem,” she said.

Among conditions commonlyfound in patients with safety issueswere, most commonly, primary mood

disorders, including bipolar affective disorder and major depres-sive disorder. Schizophrenia was the second most common diag-nosis, and the third included delirium, dementia, and other cog-nitive disorders.

—Read more on schizophrenia and patient safety at http://ow.ly/605fY

Substance abuse puts schizophrenia patients at riskn Psychiatrist suggests that treating comorbid drug addiction would improve quality of life

SEEKING TO FIND the mechanisms that cause malfunctions of working memory, semantics, prediction error,and dopamine neuromodulation in schizophrenia, the researchers of a study published in BiologicalPsychiatry created an artificial neural network model and tested it for narrative understanding and recall(May 15, 2011; 69(10):997-1005).

“Findings suggest that exaggerated prediction-error signalling in schizophrenia intermingles and cor-rupts narrative memories when incorporated into long-term storage, thereby disrupting narrative languageand producing fixed delusional narratives,” concluded the authors. “If further validated by clinical studies,these computational patients could provide a platform for developing and testing novel treatments.”

In the study, an artificial neural network “learned sets of autobiographical and impersonal crime sto-ries with associated emotion coding.” The authors then compared these eight illness mechanisms againstsubjects with schizophrenia or schizoaffective patients using a delayed story recall task. Control subjectsalso completed the task.

One of the authors of the study, Dr. Ralph Hoffman of Yale University in New Haven, Conn. explainedwhat they learned from this experiment on National Public Radio’s Science Friday.

“What surfaced was a clear cut, at least a statistical winner,” said Dr. Hoffman. “And that was what wenow term as hyperlearning.”

What this means, he says, is that when the simulated neural network modules were engaged in alearning process—in this case learning the previously described crime stories—the errors that occurredin the simulation were similar to those that were created by schizophrenics.

“If this memory consolidation process was accelerated to an excessive degree that the system beganto confuse different stories or memories and to corrupt these representations in very specific ways,” hesaid, “it seemed to be suggestive of certain language manifestations of schizophrenia.”

—Read this article in Biological Psychiatry at http://ow.ly/52B2M

A possible mechanism of schizophreniaUn

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New quetiapine label in U.S. n Includes more detail on associated heart risksASTRAZENECA REVISED the label for quetiapine in mid-July for theU.S. market, as requested by the FDA.

The passage added to the label is as follows:“The use of quetiapine should be avoided in combination with

other drugs that are known to prolong QTc including Class 1Aantiarrythmics (e.g., quinidine, procainamide) or Class III antiarryth-mics (e.g., amiodarone, sotalol), antipsychotic medications (e.g.,ziprasidone, chlorpromazine, thioridazine), antibiotics (e.g., gati-floxacin, moxifloxacin), or any other class of medications known toprolong the QTc interval (e.g., pentamidine, levomethadyl acetate,methadone).”

In a New York Times interview (July 19, 2011), AstraZenecaspokeswoman Stephanie Andrzejewski said the new warning willprovide additional guidance to physicians treating patients at riskfor QT prolongation. While the old label had mentioned the risk ofa prolonged QT, she said it was not as specific as the current label.

The product information sheet issued by Health Canada forquetiapine was last updated in April 2008.

It says: “Because of its potential for inducing hypotension, que-tiapine may enhance the effects of certain antihypertensive agents.”

—Read all about it at http://nyti.ms/pe3fqy

Dr. Soojin Chun, at the Ontario PsychiatricAssociation meeting

8 n August 2011

#Ninety per cent of suicides are committed bypeople with a documented

mental illness or substanceuse problem"

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by Josh Long, Assistant Editor, The Chronicle

ALCOHOL ADDICTION IN patients with comorbid schizo-phrenia tends to have a high relapse rate, as well as detri-mental effects on schizophrenia-related outcomes. Dr.

Shaul Lev-Ran from the Centre for Addiction and MentalHealth reviewed pharmaceutical options to improve the odds atthe Ontario Psychiatric Association annual meeting in Toronto.

A medication that “seems to stickout,” says Dr. Lev-Ran, is clozapine.

“[Its] particularly good for treatingschizophrenia patients with substance usedisorders and there are a number of casereports and case series that show quitedramatic results when schizophreniapatients with co-morbid substance usedisorders are treated with clozapine,” hesaid. “In one of those studies they weretwice as likely to have remission of their alcohol-use disorder.”As well, he said that a 10-year study, published in theSchizophrenia Bulletin (July 2000; 26(2):441-449), had foundpatients on clozapine had lower relapse rates.

Most studies reporting that clozapine treatment is associatedwith remission of substance use disorders in schizophreniapatients are retrospective, he said, “but just recently there was anRCT showing its efficacy in reducing cannabis smoking amongschizophrenia patients with cannabis use disorders,” he said,referring to a study published in the Journal of Dual Diagnosis(May 2011; 7(1-2): 50-63) that was led by Mary F. Brunette.

Depot antipsychotics, also called long acting injections, havealso shown promise. “There are a few studies of depot antipsy-chotics,” he said, “where schizophrenia patients decreased theiralcohol use.” He added that part of the improvement in alcoholuse outcomes can be attributed to improved compliance totreatment and reduced symptoms of schizophrenia.

“There is also some evidence that long acting risperidoneis more effective than first generation antipsychotics, thoughthis has been shown in schizophrenia patients with sub-

stance use disorders in general, and not specifically for alco-hol dependence.”

Approved pharmacological treatments for alcoholism inthe general population have also been found to be effectiveat treating alcoholism in schizophrenia, he said, particularlydisufiram and naltrexone.

“Disulfiram is actually somewhat surprising as clinicians havebeen afraid to use it in people with schizophrenia because offear that it might increase psychosis,” he said, adding that this ismainly due to clinical reports in the 1970s when the doses ofdisulfiram used were much higher than those suggested today.Recent reports have shown that disulfiram may be safe in indi-viduals with psychiatric disorders, including schizophrenia.

Naltrexone, he said, appears to be both efficacious andsafe, and has been found to reduce alcohol consumptionamong schizophrenia patients in a randomized-controlledtrial (referring to the study conducted by Petrakis(Psychopharmacology; March 2004; 172(3):291-297)).

MORE RESEARCH NEEDEDThough there have been recent reports of successful treat-ment of alcohol dependence in schizophrenia patients usingacamprosate, much more research is needed. Other promis-ing medications, particularly topiramate, have not beeninvestigated yet in this patient population and currently onlycase reports showing its efficacy in schizophrenia patientswith alcohol dependence are available.

“The bottom line is that conventional drugs for treating alco-hol dependence are probably effective in schizophrenia patientsas well, though more evidence is needed in order to guide clini-cal decision making. Regarding antipsychotic medications, cloza-pine and long-acting antipsychotics seem to be particularly effec-tive. Finally, though effective treatment of schizophrenia symp-toms is necessary to improve alcohol use outcomes, it may notbe enough; targeting the alcohol use disorder with proper med-ications can have significant effects on outcomes.”

—Read more on alcohol addiction in schizophrenia at http://ow.ly/66YXL

August 2011 n 9

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United Kingdom Cognitive behaviouraltherapy may be no more efficaciousthan other simpler strategies, accord-ing to the Cochrane Database ofSystemic Reviews (April 13, 2011).“Trial-based evidence suggests noclear and convincing advantage forcognitive behavioural therapy overother and sometime much less sophis-ticated therapies for people with schiz-ophrenia,” wrote the authors.Compared to other psychotherapies,there was no difference in outcome interms of relevant adverse events, norin relapse rates over any time period,or rehospitalization. “Various globalmental state measures failed to showdifference (4 RCTs, n=244, RR noimportant change in mental state 0.84CI 0.64 to 1.09). More specific meas-ures of mental state failed to show dif-ferential effects on positive or negativesymptoms of schizophrenia but there

may be some longer term effect foraffective symptoms (2 RCTs, n=105,MD BDI -6.21 CI -10.81 to -1.61).”

—Read more at http://ow.ly/51Xzs

China The reliability of the Symbol DigitModalities Test (SDMT) and the DigitVigilance Test (DVT) was clarified inthe Archive of Clinical Neuro-psychology (August 2011; 26(5):405-411). “The SDMT and DVT are reliablefor a group of subjects but limited forindividual subjects with schizophreniain 1-week interval clinical trials,” wrotethe authors. The study was conductedon 147 participants with schizophrenia.Each subject had both tests adminis-tered twice at one week intervals.“Test-retest reliability was determinedthrough the calculation of the intra-class correlation coefficient (ICC),”wrote the authors, who also used the

Bland-Altman analy-sis which included ascatter plot of the dif-ferences between testand retest against theirmean. Using a paired t-test,researchers evaluated system bias.“The ICC for the SDMT was 0.87 andthat for the DVT was 0.83,” wrote theauthors. “The mean difference scoresof the SDMT and DVT were 1.5 (4.7%of the first session mean; p= .002) and-46.4 (7.6% of the first session mean;p< .001).” The ICCs show both tests tobe stable measures but “the paired t-test indicates a practice effect, and theLOAs show large variations. Thus, theSDMT and DVT are reliable for a groupof subjects but limited for individualsubjects with schizophrenia in 1-weekinterval clinical trials.”

—Read more at http://ow.ly/671eD

W o r l d B r i e f s i n S c h i z o p h r e n i a

C l i n i c a l T r i a l s

n Magnetic pulses are being tested inschizophrenia patients to determinewhether they have an effect on audi-tory hallucinations. Suitable candi-dates must have auditory hallucina-tions more than five times a day,have been on antipsychotic medica-tion including one atypical medica-tion for six weeks or longer, andhave been on stable medication forfour weeks prior to the start of thestudy. Candidates may not haveeither a personal or family history ofseizure disorder in first degree rela-tives, nor may they have had recenthead injury, acute suicidality, sub-stance abuse, an implanted pace-maker or metal in the head or neck.Patients may not be pregnant.Contact: St. Joseph’s Healthcare,Rose Marie Mueller, RN 905 -522 -1155 ext 36629

—More info including full eligibility critieria is available

at http://ow.ly/4YG82

n Patients with metabolic syndrome arebeing recruited for a one year trial oforal ziprasidone. The purpose of thestudy is determine ziprasidone’seffect on the distribution of risk fac-tors associated with metabolicsydrome in patients presenting withgulcose intolerance, dylipidemaand/or elevated waist circumferenceassociated with their current antipsy-chotic medication. Patients areexcluded if they have a history oftreatment resistance, contraindica-tions to the use of ziprasidoneaccording to Canadian prescribinginformation, or have a medical con-dition. Eligible patients also mustalso have a minimum of 40 BMI atbaseline. Contact: Pfizer CT.gov CallCenter, 1-800-718-1021

—More info including full eligibility critieria is available

at http://ow.ly/4YG61

n Cognitive remediation is being testedin a randomized trial to see whetherit is more effective when comparedwith a social and functional compo-nent. There will be three arms. Onearm is experimental cognitive reme-diation, another with functionaladaptive skills training with social skills group treatment. The third arm will include combined cognitive remediation and functional adaptive skills training. Contact: Queen’s University, Christopher R. Bowie, 613-533-3347, [email protected]

—More info including full eligibility critieria is available

at http://ow.ly/60b0L

Treating alcohol use disorders in schizophrenian Pharmacological interventions identified at Ontario Psychiatric Association meeting

Dr. Shaul Lev-RanDr. Shaul Lev-Ran

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while those with severe or class IIobesity (BMI 35-39.9) had a 200% increased odds, and thosewith morbid or class III obesity (BMI =40) had a 275%increased odds of migraine.

“These findings are interesting because it suggests thatpeople who have migraines have greater risk of gaining weightthan women who don’t have migraines and that the risk ofmigraine increases with increasing weight gain,” she said.

So it’s possible that migraine contributes to weight gain or thatweight gain contributes to migraine, but more data is needed.

“Further research is needed to determine if migraine cancontribute to causing obesity and/or ifobesity contributes to causingmigraine,” she said. “It is possible bothdisorders share common pathophysio-logical abnormalities.”

To address obesity in people whohave migraine, Dr. Peterlin noted thatevidence suggests lack of exercise maybe one trigger of migraine headaches,citing an article published in Cephalalgia(April 2007; 27(4):304-314) by Dr.Wober and colleagues.

Dr. Wober’s study demonstrated that the lack of physicalactivity was associated with a 21% increased risk of headacheattacks in adult migraineurs and a 50% increased risk ofmigraine in adolescents. In addition, limited data suggest aerobicactivity may reduce headache frequency in episodic migraineurs.

Further evidence suggesting a relationship between obesi-ty and episodic migraine keeps popping up. A recent studypublished in the journal Neurology (Mar. 29, 2011; 76(13):1135-1138), found that when a group of 24 severely obese patientswith infrequent episodic migraine underwent bariatric bypasssurgery, their headache frequency was significantly reduced.Specifically, following surgery, migraineurs went from about 4headaches per month to about 2 headache days per month.

“The odds of experiencing a 50% reduction in headachedays was related to greater [mean percent excess weight loss],independent of surgery type (p<0.05),” wrote the authors.“Reductions in severity were also observed (p<0.05) and thenumber of patients reporting moderate to severe disability

decreased from 12 (50.0%) before surgery to three (12.5%)after surgery (p<0.01).”

Research presented at the American Society for Metabolicand Bariatric Surgery’s 28th Annual Meeting in Orlando, Fla. inJune provides additional supporting evidence.

In the research, 81 morbidly obese patients with migrainesunderwent gastric bypass surgery, and lost 55% of their excessweight on average. In all, 89% of the patients experienced report-ed significant improvement in migraine headaches, while 57 of 81reported complete resolution. Nine per cent reported no change.

Research lead by Dr. Peterlin suggests the possibility thatproteins produced byfat itself could be acontributing mecha-nism for developingmigraine.

Adipose tissue is adynamic neuroen-docrine organ thatparticipates in multiplephysiological andpathological processes

including inflammation. A manuscript by Dr. Peterlin sug-gests it is associated with migraine.

“Clinical, population-based, translational, and basic scienceresearch show multiple areas of overlap between the central andperipheral pathways regulating feeding and migraine pathophysi-ology. The current epidemiological research suggests that chron-ic daily headache prevalence is increased in adults with obesityand that the prevalence of episodic headaches may be increasedin reproductive aged adults with obesity as well,” she wrote in themanuscript published in Headache (April 2010; 50(4):631-648).

“In addition to the epidemiological associations, basic andtranslational research has suggested that several proteins and neu-rotransmitters, which modulate the pathways regulating feedingand energy homeostasis, may also play a role in migraine patho-physiology, including serotonin, orexin, and adipocytokines.”

To be certain of this association, Dr. Peterlin said it wouldbe necessary to conduct a longitudinal study on people who donot have headaches and are obese at baseline to determinewhether obesity causes

Link between migraine and obesity unclear, say specialists

#Obesity and migraineheadaches are related,"said Dr. Lee Peterlin, anassistant professor atJohns Hopkins UniversitySchool of Medicine.

10 n August 2011

Dr. Lee Peterlin

—please turn to page 17

—continued from page 1

Spain Risk factors that may cause a patient to drop outof preventive treatment for migraines include thedrug used as preventive treatment, side effects, ayounger age of the patient and a lower number ofseizures, according to a study published in Revistade Neurologia (August 16, 2011; 53(4):201-208).The researchers conducted a prospective study ofpatients who had migraines requiring preventivetreatment. They were treated with one of the topthree drugs including nadolol; a beta blocker, topira-mate; a neuromodulator, and flunarizine; a calciumantagonist. “Of 800 patients with migraine whorequired preventive treatment for the first time, thedrop-out rate was 19.7%. In the drop-out group, thevariables ‘age’, ‘number of seizures’, ‘number of

seizures prior to preventive treatment’ and ‘sideeffects’ showed significant differences with thosefrom the group of patients who did not drop out ofpreventive treatment,” the authors wrote. Preventivemeasures for migraines have a drop out rate of 30%.

—Read moreat http://ow.ly/671mk

China Women using triptans or ergots during pregnan-cy were found to have low risk for adverse events indelivery outcome, according to a study in DrugSafety (August 2011; 34(8):691-703), though dataon triptans other than sumatriptan is lacking. Theregister study was conducted. Exposure to migrainemedication was determined from interviews con-

ducted by the attending midwifeand medical records in antenatalcare (1995-2008) and partly by link-age to the Prescribed Drug Register (2005-2008).“Use of ergots or triptans during early pregnancy(first trimester) occurred in 3,286 women with 3,327infants, while use after the first trimester occurred in1,394 women with 1,419 infants,” wrote the authors.“Women using drugs for migraine had not previous-ly had more miscarriages than expected.” Womenthat were using such drugs for migraine were older,had no previous infants, and more often had a highbody mass index.

—Read moreat http://ow.ly/671pl

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SURGICAL INTERVENTION CAN treat migraine in patientswho do not respond to standard therapies, according toresearch presented at the annual meeting of the

American Society of Aesthetic and Plastic Surgery in Toronto.“We had a high success rate

at five-year follow up,” said Dr.Bahman Guyuron, the chair ofthe department of plastic sur-gery at Case WesternUniversity in Cleveland.

A study of 125 patients ran-domized 100 patients to surgi-cal deactivation of migraineheadache trigger sites while 25patients served as control subjects. This ratio was used in accor-dance with the study’s biostatistician using the envelope techniqueto determine the size of the control group and the interventiongroup (Plast Reconstr Surg Feb. 2011; 127(2):603-608).

Of 100 patients, 89 underwent surgical deactivation ofmigraine trigger sites, and 79 were followed for five years. Ofthe 79 patients, Dr. Guyuron noted that 10 patients underwentdeactivation of additional trigger sites, and were not includedin the five-year analysis, leaving 69 patients for analysis.

A total of 20 patients experienced complete elimination oftheir migraines, 41 patients experienced a significant declinein the frequency and severity of their migraines (at least 50%reduction), and eight patients had no significant change,defined as less than 50% improvement.

“When compared with the baseline values, all measuredvariables at 60 months improved significantly (p<0.0001),”wrote the authors of the article in Plastic & ReconstructiveSurgery. “The results of this five-year analysis were not com-pared with the control group who were only followed for oneyear. Based on the design of the initial study, most patients inthe control group underwent surgical treatment at one year.”

There have been advances in the medical management ofpatients with migraine, but there continue to be patients whodo not respond to medical management or who do not toler-ate the side effects of standard pharmacotherapies. In theU.S., for instance, it is estimated 30 million patients withmigraine are not aided by standard management.

“The typical medications that are used to treat migrainesare triptans,” said Dr. Guyuron. “But these medications haveside effects and not every patient can tolerate them.”

SURGERY AN OPTIONSurgery is a good option for patients with migraines who failto respond to medical management, noted Dr. Guyuron, cit-ing a study he co-authored that was published in Plastic &Reconstructive Surgery (Jan. 2005; 115(1):1-9), which found that

“surgical deactivation of migraine trigger sites can eliminateor significantly reduce migraine symptoms.”

The motivation to explore the impact of surgical interventioncame when he noticed that patients who had undergone fore-head rejuvenation as a cosmetic procedure also enjoyed the ancil-lary benefit of a decrease in headaches or migraines.

“The idea for surgical treat-ment started when I reviewedresults from a retrospectivestudy of patients who hadforehead lifts and reported thattheir headaches went away afterthe esthetic procedure,” hesaid. “This led to a pilotprospective study to see theimpact on treating migraines.”

FACTORS LEADING TO A MORE POSITIVE OUTCOMEIn further investigation, Dr. Guyuron has found that a higherrate of use of over-the-counter medications, a higher rate ofhead and neck injury, and older age increase the chances of asuccessful surgical intervention.

By contrast, he said, patients who have had a younger ageof onset of migraines are less likely to benefit from surgicaltreatment for migraines.

“If the headaches are occurring when they are younger, [itis] more likely the migraines are being triggered from the noseand from the septum,” he said, citing the 2005 article in Plastic& Reconstructive Surgery. “The chance of success for those whohave nose-related migraine headaches is slightly less than thosewho have migraines triggered from other sites.”

SOME TRIGGER SITES MORE RESPONSIVEOther sites that are more usually responsible to elicit migrainesare the frontal, temporal, and occipital sites. Dr. Guyuronremoves the corrugator supercilii muscles in the forehead toaddress the frontal migraine trigger, and where patients haveoccipital migraine headaches, he removes a small piece of mus-cle encasing the nerve and replaces it with a soft tissue flap.

Dr. Guyuron said his experience to date has shown that heneeds to be more surgically aggressive in treating patientswhose trigger sites lie in the nose.

Botulinum toxin type A has been applied as a therapy totreat migraine headaches, noted Dr. Guyuron, and wasapproved for the indication in Canada in 2011.

“It paralyzes the muscles,” he said, noting Botox can also beused for other purposes, such as identification of trigger sites.

“Botox can be used to confirm the trigger sites,” he said. “Wehave also put together a constellation of symptoms that repre-sent specific trigger sites.”

Some trigger sites include frontal, temporal, and occipital sites.In another study of 75 patients

Surgical intervention and migraine treatmentn Shows promise in patients who do not respond to traditional therapies, says plastic surgeon

C l i n i c a l T r i a l s

n A clinical trial is being conducted toevaluate whether the frequency ofmigraine headaches can be con-trolled in migraineurs with aura anda patent foramen ovale. Patent fora-men ovale is a slit-like openingbetween the right and left atria whichnormally close at or soon after birth.Patients are randomized to have theovale closed, or to continue withstandard medical treatment. Primaryoutcome measures includeheadache frequency before andafter ovale closure, secondary out-come measures include acutemigraine medication use, quality oflife evaluations, the effects of anti-thrombotic medication, adverseevents, and patent foramen ovaleclosure. Patients must be between18 and 65, have migraineheadaches with aura diagnosed by aphysician, who have not respondedto or cannot take migraine preventa-tive medications. Patients areexcluded if they have a clinical histo-ry of stroke, if they cannot take ASAor clopidogrel, or if they are pregnantor wish to become pregnant withinthe next year. Contact: Contact:PRIMA Trial [email protected]

—Full study criteria includingtrial locations is available at

http://ow.ly/5Nzwz

n Intravenous fluid hydration is beingstudied to determine whether it maybe used to reduce headache pain inemergency room pediatrics. “Theinvestigators propose a study toexamine the response to intra-venous fluid hydration as initial ther-apy comparing a group with expec-tation of medication and anothergroup without the initial expectationof medication,” wrote the authors.The intervention is 0.9% salineadministered over a period of 30minutes, with primary outcomemeasures being the nine faces painscale, the visual analogue scale,and four categories (none, mild,moderate, or severe). Secondaryoutcomes are nausea and/or vomit-ing within 30 minutes, headacherecurrence or worsening within 24hours after leaving the emergencydepartment, or returning to theemergency department. Patientsmust be between five and 17 yearsof age. Contact: Stollery Children’sHospital Emergency Department,Edmonton, Lawrence P Richer, MD,MSc 780-407-7329 [email protected]

—Full study criteria includingtrial locations is available at

http://ow.ly/5NBvG

ALMOST HALF OF all adults have headachedisorders such as migraine and tensionheadache resulting in an economic burden,according to the World Health Organization.

“Migraine alone is the cause of an esti-mated 400,000 lost days from work or schoolevery year per million of the population indeveloped countries, and in the EU, the totalannual cost of all headache has recentlybeen estimated at 155 billion euros ($219 bil-lion),” reports Reuters (May 4, 2011).

"The financial costs to society throughlost productivity are enormous," wrote theauthors of this study.

“Headache and migraine disorders aregreatly underrated and underreported byhealth systems and receive too little atten-tion,” said Dr. Shekhar Saxena, the WorldHealth Organization's director of mentalhealth and substance abuse disorders,said in a press release.

“Headaches can be debilitating for

many people, rendering them unable towork. During migraine attacks, 90 per centof people postpone household chores,almost three-quarters have limited ability towork and half of them miss work entirely.”

The study also found that 47% of adultshave a headache disorder, and thatheadaches are under-recognized, under-diagnosed, and under-treated.

— Read this study online athttp://ow.ly/671ss

Headache disorders are economic burden, says WHO

—please turn to page 17

Dr. BahmanDr. BahmanGuyuronGuyuron

# The typical medications thatare used to treat migraines are

triptans," said Dr. Guyuron.#But these medications have

side effects and not every patient can tolerate them."

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by Josh Long, Assistant Editor, The Chronicle

AN EFFECTIVE MEASURE to assist in diagnosis of parkin-sonian syndromes in clinically uncertain cases is 123I-ioflupane, according to research presented at the annual

American Academy of Neurologymeeting in Honolulu, Hawaii.

The research found that of thepatients who had a management planwhen they started the study, signifi-cantly more patients who had taken123I-ioflupane had management planchanges in 12 weeks, compared tothe control group (p=0.004).

“In the imaging and control group,the movement disorder specialistwould see them at four weeks, and 12 weeks,” said Dr. FrederickWeiland, Sutter Medical Group Diagnostic Medical Imaging co-director of nuclear medicine in Sacramento, Calif. and co-authorof this presentation. “There was management plan change in 49per cent of patients over 12 weeks if they had [123I-ioflupane ]and 31 per cent if they did not have the [123I-ioflupane] results.”

He said this diagnostic tool could lead to a quicker and moreaccurate diagnosis in patients with a clinically uncertain parkin-sonian syndrome (44% in the imaging group vs. 12% in thecontrol group had changes in diagnosis at 12 weeks, p<0.001),and that could bring more appropriate treatment faster.

“[123I-ioflupane] provides objective versus subjective evidence.Early evaluations can lead to misdiagnosis even in the best ofhands,” he said, citing a study in Movement Disorders (Oct. 2004;19(10):1175-1182) that found that confidence in a diagnosis ofpresynaptic parkinsonian syndromes was increased from 58.4 ±22.2% at baseline to 88.4 ±14.1% when 123I-ioflupane was used.

“Recently, we tested 20 patients that were referred by move-ment disorder specialists because they had suspectedParkinson’s disease (PD) and 12 patients had normal scans.This means that only eight patients had abnormal scan resultssuggesting PD. The neurologists that I work with tend to treatpatients with negative scans very conservatively and will typi-cally stay away from prescribing PD drugs.”

He said in cases where the diagnosis is unclear and the 123I-ioflupane radiological examination is unavailable, the only way to

be sure patient has Parkinson’s disease is to treat them, and seeif they improve. The sensitivity of this procedure is between 95and 97%, while the specificity is between 93 and 100%.

He also said that 123I-ioflupane shows the loss of dopaminetransporters that are the hallmark ofParkinson’s disease, permitting a diagnosis tobe confirmed more quickly. “By virtue ofwhat it is, [123I-ioflupane] is a very elegantindicator of the loss of functional striataldopaminergic neuron terminals in patientswith degenerative forms of parkinsonian syn-drome” he said. “You have to have 60 to 80per cent loss of nigro-striatal dopaminergicneuron function before symptoms manifestthemselves,” citing an article in the Journal of

Neurology (2006; 253:IV/2-IV/7).He says that in this procedure significant loss of these trans-

porters is easily visible to a trained nuclear medicine physician.

CONTROVERSYNews that U.S. FDA approved 123I-ioflupane for this purpose wasaccompanied by criticism from Dr. William Weiner, director of theMaryland Parkinson’s Disease and Movement Disorders Center.

In a Neurology Today article, Dr. Weiner was quoted as saying“quite honestly, we expect medical students to be able to dif-ferentiate between essential tremor and parkinsonism.”

In an interview with THE CHRONICLE, Dr. Anthony Lang,director of the Morton and Gloria Shulman Movement DisordersCentre in Toronto and officer of the Order of Canada, said Dr.Weiner’s comments should be taken with a grain of salt.

“There is some validity in his opinion,” he said, “but [...]whilehopefully most medical students can differentiate between gardenvariety essential tremor and garden variety Parkinson’s disease, westill commonly see errors in diagnosis in both directions.”

Though this diagnostic adjunct is not yet available inCanada, Dr. Lang said he was optimistic about its growing use.

“I think that this tool would be very useful. In fact I woulduse it in my own practice periodically,” he said. “One wouldnot like to see this tool used to the exclusion of actually think-ing about the problem clinically.”

—Read more on 123I-ioflupane at http://ow.ly/5Uvhi

Radiological test shows promise as diagnostic adjunct n Results presented at the annual American Academy of Neurology meeting in Hawaii

C l i n i c a l T r i a l

n ELND002 is being tested for safety andtolerability in patients with multiplesclerosis, with the possibility that itmay reduce clinical relapses. The12-week study requires patientsbetween the ages of 18 and 65, whohave a documented medical historyof relapse in the last year, an inade-quate response or intolerability tointerferon and/or glatiramer acetate,and who are able to undergo GDadministration and repeat MRI test-ing. Patients are excluded if theyhave primary progressive MS, a his-tory of treatment with recombinanthumanized monoclonal antibodies,have received treatment withimmunosuppressant medications orany component of the investigationaldrug, a medical history that wouldimpact outcome, or any other clini-cally significant abnormality thatwould affect physical, neurological,laboratory, or ECG examination.Contact: Elan Pharmaceuticals,Lacey Powers, 469-916-8641, [email protected]

—More information on this clinical trial at http://ow.ly/4YFe5

12 n August 2011

W o r l d B r i e f s i n M o v e m e n t D i s o r d e r sUSA Functional loss occurs at different points

in the progress of Parkinson’s diseasewhich can be used to monitor the statusof patients, says a study in PhysicalTherapy (July 21, 2011). In the study, 339patients had their disease severity evalu-ated using the Unified Parkinson’sDisease Rating Scale motor score. Themean score for the sample was 39.2(SD=12.93). “At each stage of PD (fromleast to most involved), scores on func-tional measures indicated a significantand progressively reduced functional sta-tus,” wrote the authors. They noted thatlimitations began early in the diseasefrom measurements for functional capac-

ity using the Continuous Scale PhysicalFunctional Performance Test, and withfunctional axial rotation. Both of thesemeasures were found to mark consistentloss of performance throughout all stagesof the disease.

—More info at http://ow.ly/670Pe

United Kingdom Impulse control disorderswere associated with Tourette syndromein a study published in the Journal of theNeurological Sciences (July 6, 2011).The study included 31 patients with aTourette syndrome diagnosis who werescreened for impulse control disordersusing the Minnesota Impulse DisordersInterview. The Health Related Quality of

Life was assessed usingthe Medical OutcomesStudy 36-Item Short-FormHealth Survey and the Gilles de laTourette Syndrome Quality of Life Scale.“Twenty-three out of 31 participants(74.2%) had at least one ICD. The mostcommon ICDs were intermittent explo-sive disorder (51.6%) and compulsivebuying disorder (41.9%),” wrote theauthors, who also noted that the numberof impulse control disorders significantlycorrelated with a reduced health relatedquality of life (p=0.011) as measured bythe Gilles de la Tourette SyndromeQuality of Life Scale.

—More info at http://ow.ly/670QT

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42815 N_P Chronicle.qxd:42815 N_P Chronicle.qxd 31/08/11 3:48 PM Page 12

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by Kristina Fiore, Special to The Chronicle

PATIENTS WHO ABUSE methamphetamine and other relatedstimulants may be increasing their chances of developingParkinson’s disease, researchers have found.

Those hospitalized in California formethamphetamine or other ampheta-mine-related conditions had a significant-ly greater risk of developing the neurolog-ical condition than those admitted forappendicitis or cocaine use, Dr. RussellCallaghan, of the University of Toronto,and colleagues reported online in Drug andAlcohol Dependence.

The findings “support the long-hypothesized notion, based on animaldata, that meth/amphetamine exposure might lead to enduringdamage of brain dopamine neurons in humans,” they wrote.

Research has shown that methamphetamine and otheramphetamine-type stimulants can damage dopaminergic neu-rons, and scientists have long suspected that the drugs can pre-dispose users to Parkinson’s disease, a dopamine-deficiency dis-order. Recently, Kaiser Permanente researchers found in anobservational study that amphetamine sulfate and dextroam-phetamine sulfate abuse can increase the risk of the disease.

So Dr. Callaghan and colleagues conducted a retrospectivecohort study using all linked statewide California inpatient hos-pital episodes and death records via the California PatientDischarge Database and Vital Statistics Database from Jan. 1,1990 through Dec. 31, 2005.

They compared the 40,472 patients admitted for ampheta-mine-related conditions with the 207,831 patients admitted forappendicitis and with the 35,335 admitted for cocaine-use disor-ders. Patients were at least 30 years old and were followed for up

to 16 years. The researchers found that the amphetamine cohorthad a greater risk of Parkinson’s than either control group.

They had a 76% increased risk of developing the diseasecompared with the appendicitis patients (95% CI 1.12 to 2.76,p=0.014) and almost a 2.5-fold greater risk than cocaine users(HR 2.41, 95% CI 1.32 to 4.41, p=0.004).

They noted that the cocaine cohort didn’t have a significantlyincreased risk of disease compared with the appendicitis patients.

Cocaine and amphetamines are both dopaminergic stimu-lants, the researchers explained, but they have a different pri-mary mechanism of action. Cocaine is active in monoamineneurotransmitter transporter blockade, while methampheta-mine is active in monoamine neurotransmitter release andtransporter blockade. The findings coincide with animal mod-els that haven’t shown dopamine neuron toxicity after expo-sure to cocaine.

Dr. Callaghan and colleagues wrote that the work extendsan earlier study they performed, by including a longer follow-up time, a younger and larger sample, and linked mortalityinformation. They also noted that their study was subject tothe usual limitations of a retrospective study relying on admin-istrative diagnostic codes.

The investigators cautioned that the findings likely only pertainto high-dose meth/amphetamine users, as 96% of patients in thatcohort were diagnosed with abuse or dependence at admission.

“While our study does raise the question of whether licitamphetamines might also increase the risk of Parkinson’s dis-ease,” they wrote, “it is important to emphasize that our find-ings might not at all relate to those individuals who take muchlower doses of amphetamine drugs for therapeutic purposes.”

Copyright Med Page Today, LLC. All rights reserved. Reprinted withpermission. www..medpagetoday.com

Stimulants increase likelihood of developing Parkinson’s n Hypothesis linking stimulant usage and Parkinson’s confirmed in University of Toronto study

(Clostridium Botulinum Neurotoxin Type A [150 kD], free from complexing proteins)XEOMIN® is indicated for blepharospasm, cervical dystonia of a predominantly rotational form (spasmodic torticollis) and post-stroke spasticity of the upper limb.

Merz Pharma Canada Ltd. wishes to inform physicians of the This new program is designed to make it easier for

patients in need of XEOMIN® by paying up to 20% of the

total prescription costs.

For more information contact your Merz Pharma Canada

representative, call us at 1-866-RxHelp4 (1-866-794-3574)

or go to www.iTrialRx.comAdvantage Program –

XEOMIN® Patient Assistance Plan

New

L a y p r e s s

n Lewy body dementia is discussed by aphysician who has the condition him-self. Dr. Geoff Kalchman, a retiredphysician in Toronto, talks about hisexperiences with the condition thatled to him having several car acci-dents. His wife discusses how a lackof facial expression symptomatic ofthe condition caused her some dis-turbance over the years that the con-dition progressed undiagnosed andunrecognized.

—Watch the CTV news item athttp://ow.ly/4WvbH

n Clinics outside of Canada are capitaliz-ing on impatient patients who wantCCSVI treatment immediately,reports the Globe and Mail (May, 10,2011). Patients are paying upwardsof tens of thousands of dollars torecieve the treatment in the U.S.,Costa Rica and Bulgaria, for whatwould cost around $6,300 in Ontario.“The fact that patients are beingcharged for a procedure that is notyet validated, that it involves seriousrisks and that there isn’t systematiccollection of information about thesafety and efficacy raises major redflags,” said Jonathan Kimmelman,associate professor of biomedicalethics at McGill University in thenewspaper article.

—Read this Globe and Mailarticle at http://ow.ly/5WmBJ

n Using small-angle neutron scatteringequipment at the laboratory’s highflux isotope reactor, researchers atthe Oak Ridge National Laboratoryand the University of Tennessee.have identified the “earliest aggre-gate species of the protein that arebelieved to be the most toxic,”Science Daily reports, (May 19,2011). Researchers say the next stepis to take drug molecules and seehow they can interact and affectthese structures in the hope that adrug could prevent neurdegenerationassociated with Huntington’s dis-ease.

—Read this article athttp://ow.ly/5WmFy

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HALF OF MULTIPLE SCLEROSIS patients on dis-ease modifying drugs (DMD) cease adher-ence after two years, suggests a study inthe Canadian Journal of NeurologicalSciences (May 2011; 38(3):429-433).

“Adherence to [disease-modifyingdrugs] in adult MS patients in Ontario ispoor, which is consistent with previouslyreported adherence rates to MS [disease-modifying drugs] in other regions. No sig-nificant differences in adherence existbetween the DMD evaluated in this study,”wrote the authors.

The study looked at four different inter-feron-based drugs included in this study:intramuscular interferon beta-1a (i.m.IFNß-1a, Avonex), subcutaneous interfer-

on beta-1a (s.c. IFNß-1a, Rebif), subcuta-neous interferon beta-1b (IFNß-1b,Betaseron) and glatiramer acetate(Copaxone).

The data was collected from an Ontariodrug-coverage database which identified682 people newly prescribed multiple scle-rosis medications. The researchers fol-lowed their progress from April 2006 untilMarch 2008.

“Cumulative persistence rates wereanalysed by the Kaplan-Meier method.The proportion of patients reaching thestudy endpoints after the two year follow-up period was also calculated,” wrote theauthors of the study.

Though 56% had stopped their medica-

tion after two years, this finding marked atrend in nonadherence that started aftersix months.

“Cumulative persistence rates for allfour [disease-modifying drugs] were similarover time (p=0.80), ranging from 73.6-79.1% at six months, 59.1-63.1% at oneyear and 41.5-47.4% at two years. Aftertwo years, the proportion of patients whohad discontinued treatment, switched toanother DMD or died was similar amongDMDs (p=0.79, Fisher’s exact test).Switching between [disease-modifyingdrug] types was low and occurred in 3.4-6.5% of new DMD users.

— Read this study online athttp://ow.ly/670SU

Adherence to MS meds less than half after 2 years

Dr. RusselCallaghan

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by Louise Gagnon, Correspondent, The Chronicle

HYPOMANIA IS AN effective response to combat depres-sive episodes that occur in bipolar depression, anddoes not need to be treated,

according to a Toronto psychiatrist inprivate practice.

“It is a short-term effective treatmentthat helps people deal with depressivestates,” said Dr. Brad Bowins in an inter-view with THE CHRONICLE OFNEUROLOGY & PSYCHIATRY.

Most clinicians miss hypomaniabecause they rely on the definition ofhypomania as outlined in the fourth edi-tion of the Diagnostic and Statistical Manual of MentalDisorder (DSM-IV), which states it has to be present for atleast four days, noted Dr. Bowins.

“If people are going by the manual, they are missing themajority of what is out there,” said Dr. Bowins. “It is very oftenout there if you look for it. It can take place for a few hours tothree days. It is more of a spectrum than a discreet entity.”

HYPOMANIA USUALLY ACCOMPANIES DEPRESSIONWhen hypomania is activated in one to three days, depressivesymptoms are not usually eliminated altogether, according toseveral studies in the literature. Research indicates that hypo-mania is as prevalent as depression, and mania is far less com-mon, said Dr. Bowins. What is usually present is a mixture ofhypomanic and depressive symptoms.

When depression co-exists with hypomania, there can beextraordinary periods of functioning for individuals in whichthey rebound from their distressing periods.

Depressive inhibitions impair motivation, physical behav-iour, and cognition, said Dr. Bowins. In addition, depressiveinhibitions engender social avoidance.

“Depressive inhibitions are very much linked to social inhi-bitions or social anxiety,” said Dr. Bowins. “When individualsare depressed, there is usually reduced social extroversion.When there is less social inhibition, there is better social func-tioning and greater social extroversion.”

Hypomania, however, can act as a defense mechanismwhich overrides depressive inhibition. Given it has that ability,clinicians should encourage their patients who report that they

are depressed to engage in more mental and physical activity asways of coping with their depression, said Dr. Bowins.

“It is worthwhile to try to engage patients in social activity,but not in an overwhelming sense,” said Dr. Bowins.

Studies show that theworse an individual is atbaseline in terms oftheir depressive state,the more that the indi-vidual can benefit fromhypomania, said Dr.Bowins. “The lower thefunctioning of the indi-vidual to begin with, thehigher the impact that

hypomania will have,” he said.

PHARMACOTHERAPY MAY NOT BE NECESSARYIn one small study, monoamine oxidase inhibitors inducedhypomania, and optimal social adaptation, and optimal adapta-tion was achieved in about half of the patients.Pharmacotherapy is not necessary to induce hypomania inpatients, noted Dr. Bowins.

Clinicians do not need fear induction of hypomania in anindividual with depression. “The vast majority do not go intoa manic state,” he said, adding that many of those who experi-ence manic episodes also have hypomanic episodes that do notprogress to mania. “There is a tremendous upside and limiteddownside to get people [who are depressed] into a hypomanicstate.”

If an individual has a predisposition to mania, it would bewise to prescribe a mood stabilizer as well as an antidepressant,said Dr. Bowins.

Contemporary culture values hyperthymic personalities,where individuals are perpetually in a hypomanic state, arehighly productive, engaging, and are tireless, notes Dr. Bowins.

“About one per cent of the population is this type of per-sonality, but there is an increasing frequency,” he said. “Intoday’s society, to be ‘on’ is a good thing. Many people aredrinking coffee and other stimulating drinks like Red Bull,pushing themselves to adopt a hyperthymic personality.”—Read Dr. Brad Bowin’s special review article in the Journal

of Affective Disorders at http://ow.ly/5W7jT

Hypomania could be the body’s way to combat depression n Private practitioner says psychiatrists shouldn’t rely on DSM-IV to diagnose hypomania

#Studies show that theworse an individual is atbaseline in terms of theirdepressive state, the morethat the individual canbenefit from hypomania,"said Dr. Bowins.

n Oral OPC-34712 will be tested as an adjunctive therapy in adults with majordepressive disorder. The non-randomized study will attempt to measure the safe-ty and tolerability of the drug by examining frequency and severity of adverseevents. It will also determine the change from baseline in the Sheehan DisabilityScale, the Inventory of Depressive Symptomatology, and the Clinical GlobalImpression—Severity of Illness scales. Patients must be between 18 and 65years of age to qualify. The study will begin in October 2011. Contact: SusanHonn, 512-579-4714, [email protected].

—Full study criteria available at http://ow.ly/5T7Sv

n Mindfulness-based cognitive therapy (MBCT) and its contribution to combating depres-sion in patients with a traumatic brain disorder is being examined at LakeheadUniversity. Outcome measures include evidence of decreased depression symptomsas measured by several scales. Secondary outcome measures include improvementof pain intensity, attention/concentration, satisfaction with life and other psychologicalsymptoms. There are two arms to the study, a control arm and MBCT. In the non-con-trolled MBCT arm, subjects participate in weekly one and a half hour group sessionsover a period of 10 weeks. These sessions include exercises such as meditation,awareness, and breathing techniques, which subjects are encouraged to practice out-side of the sessions. Contact: Lakehead University, Michel Bédard, PhD, 807-343-8630 [email protected] —Full study criteria available

at http://ow.ly/5TaWb

C l i n i c a l T r i a l s

Dr. Brad Bowins

14 n August 2011

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August 2011 n 15

by Josh Long, Assistant Editor, The Chronicle

Anew clinic is opening up to treat the after effectsof intimate partner violence in London, Ont atthe Merrymount Family Support and Crisis

Centre.Marilyn Ford-Gilboe, PhD, is a registered nurse and

professor at the University of Western Ontario inLondon, Ont., and Faculty Scholar and Echo Chair inRural Women’s Health Research.

She has recently entered into a partnership withLondon Middlesex Housing Corporation to open thisclinic.

She says that while the clinic will be open to every-one, it has been designed to be of particular service towomen who are in various stages of removing them-selves from a situation where they are experiencingintimate partner violence.

“There are a wide range of issues that are all docu-mented in research literature [for which] the nursepractitioner and the rest of the staff who work in thisclinic will be supporting women,” she said.

Along with a wide range of physical health symp-toms that women typically report after intimate part-ner violence are physical fatigue, anxiety, depression,and chronic pain.

“So there'll be counselling services available forwomen with these issues,” she said.

PAIN A CONTINUING SYMPTOMDr. Norman Buckley is the founder and director ofthe Pain Management Centre for Hamilton HealthSciences and McMaster University. He said that whilehe is not a specialist in chronic pain resulting fromdomestic violence, he has heard of cases where chron-ic pain has conicided with psychiatric symptoms fol-

lowing intimate partner violence. “There was one woman who had an anxiety disor-

der that manifested itself in non-specific pain,” saidDr. Buckley, who also said this anxiety began occur-ring after having her life was put in jeopardy by herspouse. Another had pain persisting in the scars ofknife wounds. One mode of treatment is to offerinjections of local anesthetic and steroids, he said, buteven thoughthe treat-m e n treduced thepain thep a t i e n tfound thatthe processof injectionconsistentlyc r e a t e d‘flashbacks’ which elevated her anxiety.

Chronic pain, he said, is a symptom associated withdepression.

FINANCIAL BARRIERS A BARRIER TO TREATMENTFinancial barriers can be an obstacle to women whoare experiencing or have experienced intimate partnerviolence, but it’s not the only one that is at play forwomen experiencing intimate partner violence..

“It’s currently difficult for women without financialresources to access any kind of psychological coun-selling,” said Dr. Robin Mason, PhD, a psychologist atthe Women’s College Research Institute in Toronto.

She has studied domestic violence for 10 years andhas developed an education program to help physi-cians and other clinicians learn how to work with

patients who may be undergoing intimate partner vio-lence.

She said the added stress of trying to maintainthemselves financially is one of many barriers to seek-ing help before and after leaving an abusive relation-ship.

In addition, she said, many may feel that seekingmedical help suggests a problem exists within them-

selves, andso they mayavoid treat-ment alto-gether.

“ M a n ychoose notto see psy-c h i a t r i s t sbecause itfeels like it’s

medicalizing them, like they have become the problemin some way,” Dr. Mason said.

This may make it difficult for a patient to recognizethey are experiencing the after effects of an abusiverelationship that may require psychiatric assistance.

Dr. Mason also said that while the results of thisstudy may be useful, physicians should consider thateach case is unique.

“It’s important to recognize women are also enor-mously resilient, and not all women have that sametrajectory of experience,” she said, adding that this isparticularly true in patients who have quickly removedthemselves from a situation where they may haveexperienced intimate partner violence.

—Read a recent study by Dr. Ford-Gilboe at http://ow.ly/673Gf

Treating the long-term effects of intimate partner violencen Women’s health researcher intends for clinic to be accessible to women after intimate partner violence

Identifying suspected intimate partner violenceTHERE MAY BE LESS obvious signs a patientmay be experiencing an abusive relation-ship, said Robin Mason, PhD.

She’s a psychologist who has studieddomestic violence and developed an edu-cation program to help physicians andother clinicians learn how to work withpatients who may be undergoing intimatepartner violence.

She said the signs of abuse may vary.“It depends on the kind of abuse in the

relationship, because not all abuseincludes physical abuse. There are alsovery abusive relationships with psycho-logical or emotional abuse.”

Emotional or psychological abuse maybe more difficult to diagnose, said Dr.Mason, and more difficult to recover from.

“If you have a physical episode, aphysical assault, it’s very clear somethinghas happened. But if someone is erodingyour self-esteem in a very continuousform, minimizing your experiences,devaluing your opinion and experiences,it’s a slow erosion of the self that’s hard toput your finger on.”

She said self doubting, having difficul-

ty identifying feelings, or describing one’sself as incompetent may be red flags. Aswell, she said, a patient may be very anx-ious about her partner finding out that sheis seeking help and thereby exposing theabuse.

Another sign is substance abuse,which she said may make people sus-ceptible to abuse, as well as be a form ofself-medicating to lessen the symptomsof abuse.

Dr. Mason provided a sample script ofwhat she might say to a patient who shesuspects may be experiencing intimatepartner violence.

“Sometimes when I see this sort of pic-ture I begin to wonder about what’s goingon in this person’s life and this person’srelationship so I’m going to ask you somequestions about your relationship withyour partner.”

She said techniques like these may benecessary for patients who are reluctantto recognize a problem with their relation-ship. Even after a problem is identified,intimate partner violence can continue.

One reason is that those experiencing

intimate partner violence may remain withtheir partner, said Dr. Mason.

“It can take a really long time to extri-cate from these relationships for a wholehost of reasons,” she said.

“When you add to that the lack of afford-able housing, whether she has access tofinancial means or not, having to take herkids out of school to relocate, the harass-ment that can develop as these cases gothrough the court system, it’s not surprisingit takes so long for these women to extri-cate,” she said. “Women are beingharassed for a long time on their way out ofa relationship.”

Dr. Mason has developed an interac-tive online video gaming platform to teachintimate partner violence in many mani-festations. It currently comprises 17 sep-arate units, with each divided into threeparts: an interactive didactic section, asection that uses a simulated patientavatar, and a quiz.

“It’s available free, and paid for by theprovince of Ontario. And there are CMEcredits attached to it,” she said.—Read more at www.dveducation.ca

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n A study led by Dr. Jeffrey Meyer, whoholds a Canada Research Chair inthe Neurochemistry of MajorDepression, may explain the linkbetween depression and smokingcessation, e! Science News reports(Aug. 2, 2011). MAO-A is a chemicalfound in cigarettes that helps main-tain a normal mood. “When MAO-Alevels are higher as in early cigarettewithdrawal, it means that this removalprocess is overly active, making peo-ple feel sad,” wrote the author.“During active smoking, harmanattaches to MAO-A. During earlywithdrawal in heavy smokers whohad 25 or more cigarettes a day,MAO-A levels rose rapidly to a levelbeyond that seen in the healthy com-parison group.” CAMH used the onlyPET scanner in the world specificallydedicated to research in mentalhealth and addiction to complete thisstudy.

—Read this news report on addiction and depression

at http://ow.ly/5W9pP

Dr. Norm Buckley Dr. Robin Mason

#It’s currently difficult forwomen without financial resources toaccess any kind of psychological counselling,"said Dr.Robin Mason.

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Speech enabling smartphone app now freely availablewhich they can download at will,called the bookshelf tool.

“These books are hand-crafted collections of wordsand phrases about specificsubjects,” said Levy. “Supposeyou’re interested in cookingfor example. For the purposesof chatting with your friendsabout recipes, you couldpainstakingly add every ingre-dient that you needed to dis-cuss, but the bookshelf letsyou do the same thing in sec-onds.”

The phone must haveaccess to a data plan or wire-less connection to download abook, or the customizedvocabulary.

However, already down-loaded content is accessiblewhen offline, Levy says.

Alexandra Carling-Rowland, PhD, is an aphasia researcher at the University ofToronto who has recently joined this project. She said that she

will examine the effectiveness of MyVoice technology.“When you’re living with a severe communication barrier,

you can become very isolated andyou can really begin to lose your con-fidence,” she said. “What we’re goingto do is look at those two areas. DoesMyVoice increase someone’s com-munication confidence? Does it helpthem participate more in life anddoes it help them to become moreindependent?”

Dr. Carling-Rowland also said thisresearch would be conducted in col-laboration with partners fromSunnybrook Health Sciences, theToronto Rehabilitation Institute andthe Aphasia Institute, all located inToronto.

The application is currently avail-able for the iPhone and Android.Research in Motion recentlyannounced future versions of theBlackberry would support Androidapplications, and so the application

will work on these phones as well. —More info on this app at http://myvoiceaac.com/

THE NEXT CANADIAN PsychiatricAssociation meeting is being held thisOctober in Vancouver. �

This year’s expert psychiatry serieswill be on Emerging Trends in GeriatricPsychiatry: From Personality DisordersTo Electroconvulsive Therapy, featuringDrs. Caroline Gosselin and Joel Sadavoy.

Guest speakers include Dr. AnthonyPhillips, the scientific director of CIHR’sinstitute of neurosciences, MentalHealth and Addiction, who has a presen-tation called “Harnessing a Window ofOpportunity to Transform MentalHealth Research in Canada.”

Named for the Canadian PsychiatricAssociation founding president, the R.O.Jones Memorial Lecture will be “Settingthe Balance: Energy Metabolism inMood Disorders” lead by Dr. TrevorYoung, the chair of the University ofToronto psychiatry department.

Dr. Matthew Hill from the Universityof Calgary’s psychiatry department will bepresenting “Structural Remodelling in

Cortico-Limbic Circuts Following ChronicStress Mechanisms and Implications.”

Two distinguished member lecturersinclude Dr. Gary Chiamowitz fromMcMaster University in Hamilton, andDr. Harry Karlinsky.

In addition to his work as a clinicalprofessor in the deptartment of psychia-try at the University of BritishColumbia, Dr. Karlinsky is also an nov-elist, having written a biography ofThomas Darwin, the son of CharlesDarwin who in 1879 was involuntarilyadmitted to the London Aslym inOntario. At the Canadian PsyciatricAssociation meeting, he’ll be moderatinga discussion on the documentary film“Suicide Tourist” about people whotravel to Zurich, Switzerland seekingassisted suicide.

Dr. Chiamowitz’s presentation iscalled “The Criminalization of theSeriously Mentally Ill: The Need forCentres of Humility.”

This meeting marks the 60th anniver-

sary of the CPA, a milestone that will bemarked by the organizers.

“In celebration of this year being the60th anniversary of the CPA, our open-ing reception and closing gala will beextra special. The opening reception willhave a ‘Happy Days are Here Again’theme in our 1950s diner so it is highlyrecommended you find those poodleskirts and letter sweaters and there willbe costume judging,” said a letter in thepreliminary program signed by Drs.Nancy Brager and Glendon Tait, co-chairs of the organizing committee.

“If you have never been to the closinggala, you will not want to miss this year’s‘B.C. Food and Wine Extravaganza’where Chef Robert Lecrom of HotelVancouver will spoil us with delectablefood and especially chosen wine pairingsfor every course, on what will be one ofhis final events. This feast will truly befitour 60th anniversary!”

—More on the CPAat http://www.cpa-apc.org

Mian

—continued from page 5Agenda

Oct. 13-15, 2011Canadian Psychiatric Association’s

Annual ConferenceVancouver

Phone: 613-234-2815 Fax: 613-234-9857

Email: [email protected]

Oct. 14-16, 2011 ADHD Research into Practice:

A Global ViewInternational conference on

ADHD research and practiceToronto

Website: www.caddra.caPhone: 416-637-8583

Fax: 905-475-3232

Oct. 15-18, 2011Academy Of Aphasia 49th Annual

Meeting 2011Montreal

Website: www.academyofaphasia.orgEmail: [email protected]

Phone: 952-920-0484

Oct. 27-29, 20116th Canadian Conference on Dementia

MontrealWebsite:

canadianconferenceondementia.comEmail: [email protected]

Phone: 416-597-3422, ext. 3693Fax: 416-597-6202

Oct. 28, 2011 Child and Youth Mental Illness:

Cultural Competency and Pathwaysto Reduce Recidivism

TorontoEmail: [email protected]

Website: www.careconferences.comPhone: 416-444-8455

Fax 416-391-5984

Feb. 15—18, 2012INS - International Neuropsychological

Society Annual MeetingMontreal

Website: www.the-ins.org/Phone: 614-263-4200

Fax: 614-263-4366

—Let us know about upcoming conferences

of interest. Contact us [email protected]

Canadian Psychiatric Association’s annual congress n The 60th annual conference will be held in Vancouver from Oct. 13 to 15

AakashSahney

Dr. AlexandraCarling-Rowland

AlexanderLevy

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migraine or vice-versa.Another way to interpret the

results is that people who areless obese simply eat lessmigraine triggering food, saidDr. William Pryse-Phillips, aneurologist and former profes-sor at the Memorial Universityof Newfoundland’s faculty ofmedicine in St. John’s.

“We should point out thatcheese, chicken liver, mono -sodium glutamate, nitrites of allkinds in hotdogs, in hamburg-ers, [...] beer, red wine, and insome people things like choco-late, nuts and so on [are] well-documented precipitants ofmigraine headaches-usuallywithin the next 12 [to] 24 hoursof ingestion in those peoplewho are susceptible,” he said.

He also said that in theNeurology study, the improvedcondition of the migraineurscould have been a secondaryoutcome in patients whounderwent lap-band surgery.

“My suspicion is that this isslightly due to the reduction ofthe ingestion of migraine-pre-cipitating foods as anythingelse,” said Dr. Pryse-Phillips.“And if they’re eating less, thenthey’re eating less of thosefoods that can, in some people,precipitate migraine head aches.”

However, Dr. Peterlin notedthat while food choices maytrigger migraines and manypatients do report food triggers,with the exception of alcoholand nitrite ingestion, most havenot been well substantiated byresearch, including chocolate.

She suggested that patientscan keep a headache and foodjournal that tracks what foodsthey eat and if they suspectfood could be a trigger toremove that food. She also saidpatients with migraine and obe-sity should be educated on thelink between these two condi-tions, and tailor choices ofmigraine preventive medica-tions based on patients obesitystatus. Furthermore, she said,clinicians should promote thatpatients maintain healthylifestyle choices in both dietand exercise routines.

—More on obesity andmigraine at http://ow.ly/65Orm

THERAPEUTIC CLASSIFICATION Antidepressant/Anxiolytic/Antiobsessional

INDICATIONS AND CLINICAL USEAdults Cipralex® (escitalopram oxalate) is indicated for the symptomatic relief of Major Depressive Disorder (MDD).Cipralex® is indicated for the symptomatic relief of anxiety causing clinically significant distress in patients withGeneralized Anxiety Disorder (GAD). Cipralex® is indicated for the symptomatic relief of obsessive-compulsive disorder(OCD). The obsessions and compulsions must be experienced as intrusive, markedly distressing, time consumingor interfering significantly with the person’s social or occupational functioning. Physicians who elect to use Cipralex®

for extended periods should periodically re-evaluate the usefulness of the drug for individual patients.Geriatrics Although there was no evidence from clinical studies suggesting that use in geriatric populations isassociated with differences in safety and effectiveness, a greater sensitivity of some older individuals to effects ofescitalopram cannot be ruled out (see ADMINISTRATION). Pediatrics Escitalopram is not indicated for use in patientsbelow the age of 18 (see WARNINGS AND PRECAUTIONS – General, Potential Association with Behavioural andEmotional Changes, Including Self-Harm).CONTRAINDICATIONS Cipralex® (escitalopram oxalate) is contraindicated in patients with known hypersensitivityto escitalopram or any of the excipients of the drug product. Monoamine Oxidase Inhibitors (MAOIs) Escitalopramshould not be used in combination with a MAOI or within 14 days of discontinuing treatment with a MAOI. Similarly, atleast 14 days should elapse after discontinuing escitalopram treatment before starting a MAOI. Pimozide Escitalopramshould not be used in combination with the antipsychotic drug pimozide, as results from a controlled study with citalopramindicate that concomitant use is associated with an increased risk of QTc prolongation compared to pimozide alone.

WARNINGS AND PRECAUTIONSGeneralPOTENTIAL ASSOCIATION WITH BEHAVIOURAL AND EMOTIONAL CHANGES, INCLUDINGSELF-HARM Pediatrics: Placebo-Controlled Clinical Trial Data Recent analyses of placebo-controlledclinical trial safety databases from SSRIs and other newer antidepressants suggest that use ofthese drugs in patients under the age of 18 may be associated with behavioural and emotionalchanges, including an increased risk of suicidal ideation and behaviour over that of placebo.The small denominators in the clinical trial database, as well as the variability in placebo rates,preclude reliable conclusions on the relative safety profiles among these drugs. Adults andPediatrics: Additional Data There are clinical trials and post-marketing reports with SSRIs andother newer antidepressants, in both pediatrics and adults, of severe agitation-type adverseevents coupled with self-harm and harm to others. The agitation-type events include: akathisia,agitation, emotional lability, hostility, aggression, depersonalization. In some cases, the eventsoccurred within several weeks of starting treatment. Rigorous clinical monitoring for suicidalideation or other indicators of potential for suicidal behaviour is advised in patients of all ages.This includes monitoring for agitation-type emotional and behavioural changes. DiscontinuationSymptoms Patients currently taking escitalopram should NOT be discontinued abruptly, due torisk of discontinuation symptoms. At the time that a medical decision is made to discontinue anSSRI or other newer antidepressant drug, a gradual reduction in the dose rather than an abruptcessation is recommended.Discontinuation of Treatment with Escitalopram When discontinuing treatment, patients should be monitoredfor symptoms that may be associated with discontinuation (e.g., dizziness, abnormal dreams, sensory disturbances[including paraesthesias and electric shock sensations], agitation, anxiety, emotional indifference, impaired concentration,headache, migraine, tremor, nausea, vomiting and sweating) or other symptoms that may be of clinical significance.A gradual reduction in the dosage over several weeks, rather than abrupt cessation is recommended whenever possible.If intolerable symptoms occur following a decrease in the dose or upon discontinuation of treatment, dose titration shouldbe managed on the basis of the patient’s clinical response (see ADVERSE REACTIONS). Escitalopram Treatmentduring Pregnancy-Effects on Newborns Post-marketing reports indicate that some neonates exposed to SSRIssuch as escitalopram and other antidepressants late in the third trimester have developed complications requiring prolongedhospitalization, respiratory support, and tube feeding. Such complications can arise immediately upon delivery. Whentreating a pregnant woman with escitalopram during the third trimester, the physician should carefully consider the potential

risks and benefits of treatment. The physician may consider tapering Cipralex® in the third trimester. Interference withCognitive and Motor Performance In a study with healthy volunteers, citalopram did not impair cognitive functionor psychomotor performance. However, psychotropic medications may impair judgement, thinking or motor skills.Consequently, patients should be cautioned against driving a car or operating hazardous machinery until they arereasonably certain that escitalopram does not affect them adversely.

ADDITIONAL PRECAUTIONS For complete details on the following precautions, please refer to the SUPPLEMENTALPRODUCT INFORMATION section: Carcinogenesis and Mutagenesis, Cardiovascular (Patients with Cardiac Disease), Endocrineand Metabolism (Diabetic Patients), Hematologic (Bleeding Disorders), Hepatic/Biliary/Pancreatic (Hepatic Impairment),Neurologic (Seizures, Serotonin Syndrome/Neuroleptic Malignant Syndrome (NMS)- like events), Psychiatric (Suicide,Activation of Mania/Hypomania, Electroconvulsive Therapy (ECT), Renal (Hyponatremia, Renal Impairment), SpecialPopulations (Pregnant and Nursing Women, Complications following late third trimester exposure to SSRIs, Risk of PPHNand exposure to SSRIs, Pediatrics, Geriatrics).

ADVERSE REACTIONS Adverse Events Observed in Controlled Trials Adverse Events Associatedwith Discontinuation of Treatment: MDD Discontinuation due to adverse events was more common in the activetreatment groups (5.9% in escitalopram and 5.4% in citalopram) than in the placebo group (2.2%). The events that wereassociated with discontinuation of escitalopram in 1% or more of patients at a rate of at least twice that of placebo were:nausea (1.7% vs. 0.2%) and ejaculation failure (1.8% vs. 0.0% of male patients). GAD In GAD trials, 7.8% discontinuedtreatment due to an adverse event, as compared to 3.2% of patients receiving placebo. Adverse events that were associatedwith the discontinuation of at least 1% of patients treated with escitalopram, and for which the rate was higher than theplacebo rate, were: dizziness (1.2% vs. 0.2%), fatigue (1.1% vs. 0.2%) and nausea (1.8% vs. 0.2%). OCD In OCDtrials, discontinuation of treatment due to adverse events was reported for 9% and 11% of patients who were treatedwith 10 mg/day or 20 mg/day escitalopram, respectively, compared to 5% receiving placebo. Adverse events that wereassociated with discontinuation of at least 1% of patients treated with escitalopram, and for which the rate was higherthan the placebo rate, were: nausea (1.8% vs. 0.0%), insomnia (1.8% vs. 0.9%), and erectile dysfunction (1.1% vs. 0.0%).Clinical Trial Adverse Drug Reactions Because clinical trials are conducted under very specific conditions theadverse reaction rates observed in the clinical trials may not reflect the rates observed in practice and should not becompared to the rates in the clinical trials of another drug. Adverse drug reaction information from clinical trials is usefulfor identifying drug-related adverse events and for approximating rates. Treatment-emergent adverse events in placebo-controlled clinical trials for MDD: The most commonly observed adverse events (>5% and twice the rate of that seen inplacebo) in escitalopram-treated patients was: insomnia. Adverse reactions observed with escitalopram are in general mildand transient. Treatment-emergent adverse events in placebo-controlled clinical trials for GAD: The most commonlyobserved adverse events (>5% and twice the rate of that seen in placebo) in escitalopram-treated patients were: nausea,fatigue, insomnia, delayed ejaculation. Treatment-emergent adverse events in placebo-controlled clinical trials for OCD:The most commonly observed adverse events (>5% and twice the rate of that seen in placebo) in escitalopram-treatedpatients were: fatigue, delayed ejaculation, hyperhidrosis. Weight Changes: Patients treated with escitalopram in short-termcontrolled trials did not differ from placebo-treated patients with regards to clinically important change in body weight. Inone 24-week randomized clinical trial in patients with Social Anxiety Disorder, 8.0% of patients treated with escitalopramand 3.2% of patients treated with placebo experienced weight gain of 7% or more. For more details on adverse eventsreported during clinical trials or in post-marketing, see ADVERSE REACTIONS in the Product Monograph available on request.To report suspected adverse reactions, contact Lundbeck Canada Medical Information & Pharmacovigilance at1 866 880-4636 or (514) 844-8088. Suspected adverse reactions can also be reported to Health Canada at1 866 234-2345 or faxed at 1 866 678-6789 or emailed at [email protected]. They can also be mailed to:Canada Vigilance National Office, Marketed Health Products Safety and Effectiveness Information Division, MarketedHealth Products Directorate, Health Products and Food Branch, Health Canada, Tunney's Pasture AL 0701C, Ottawa,Ontario, K1A 0K9.

DRUG INTERACTIONS

Serious Drug Interactions– Monoamine Oxidase Inhibitors: see CONTRAINDICATIONS.– Pimozide: see CONTRAINDICATIONS.

Drug-Drug Interactions Monoamine Oxidase Inhibitors (MAOIs) Combined use of escitalopram and MAOinhibitors is contraindicated (see CONTRAINDICATIONS; PRECAUTIONS – Serotonin Syndrome/Neuroleptic MalignantSyndrome (NMS)- like events). Cytochrome P450 Isozymes: Escitalopram: Using in vitro models of human livermicrosomes, the biotransformation of escitalopram to its demethylated metabolites was shown to depend on three parallelpathways (CYP2C19, CYP3A4 with a smaller contribution from CYP2D6)(see ADMINISTRATION, CYP2C19 Poor metabolizers).Studies also indicate that escitalopram is a very weak or negligible inhibitor of human hepatic isoenzyme CYP1A2, 2C9,2C19, 2E1, and 3A4, and a weak inhibitor of 2D6. Although escitalopram has a low potential for clinically significant druginteractions, caution is recommended, when escitalopram is co-administered with drugs that are mainly metabolized byCYP2D6, and that have a narrow therapeutic index. The possibility that the clearance of escitalopram will be decreasedwhen administered with the following drugs in a multiple-dose regimen should be considered: potent inhibitors of CYP3A4(e.g., fluconazole, ketoconazole, itraconazole, erythromycin), or potent inhibitors of CYP2C19 (e.g., omeprazole,esomeprazole, fluvoxamine, lansoprazole, ticlopidine). Caution should be exercised at the upper end of the dosage rangeof escitalopram when it is co-administered with CYP2C19 inhibitors. In addition, a single-dose study of escitalopramco-administered with a multiple-dose regimen of cimetidine led to significant changes in most of the pharmacokineticparameters of escitalopram. The overall metabolic pathways for escitalopram and citalopram are qualitatively similar and theinteraction potential for escitalopram is expected to closely resemble that of citalopram. Thus, this allows for extrapolationto previous studies with citalopram. CNS drugs Drug interactions have not been specifically studied between eitherescitalopram or racemic citalopram and other centrally acting drugs. Given the primary CNS effects of escitalopram, cautionshould be used as with other SSRIs when escitalopram is taken in combination with other centrally acting drugs.Serotonergic Drugs: Based on the mechanism of action of escitalopram and the potential for serotonin syndrome,caution is advised when Cipralex® is coadministered with other drugs or agents that may affect the serotonergicneurotransmitter systems, such as tryptophan, triptans, serotonin reuptake inhibitors, lithium, tramadol, or St. John's Wort(see SUPPLEMENTAL PRODUCT INFORMATION, PRECAUTIONS – Serotonin Syndrome/Neuroleptic Malignant Syndrome

Patient Selection Criteria

Safety Information

Prescribing Summary

10 mg and 20 mg tablets

Considering surgery in treatment resistant migraine patients

August 2011 n 17

—continued from page 10

(Plast Reconstr Surg Aug. 2009;124(2):461-468.), those who hadsuch trigger sites were random-ized in double-blind fashion foreither sham or actual surgery.

While patients in both studyarms experienced at least 50%

reduction in migraine head ache,there was a statistically significantdifference (p<0.05) between thetwo groups on that outcome, adifference that favoured thosewho had actual surgery.

Moreover, there was a highlystatistically significant differ-

ence across the two groups inthose patients who had com-plete elimination of migraineheadaches, favouring thosewho underwent surgicaldecompression, p<0.001.

“Multiple basic science stud-ies are underway in our lab to

shed some light into the ration-al for the efficacy of the surgi-cal treatment of migraineheadaches,” he said.

Non-proprietary names of ther-apies: Botulinum Toxin Type A,(Botox, Allergan)

Migraineand obesity

—continued from page 11

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18 n August 2011

done.”“If people use nicotine

replacement after they’ve start-ed varenicline, theoretically itwill block nicotine replace-ment,” he said, but he addedthat anecdotal evidence sug-gests some effectiveness whencombined with nicotine gum orlozenges for the patient whohas only the occasional ciga-rette while on varenicline.

He emphasized though thatin general, varenicline shouldnot be used with nicotinereplacement therapy.

“Varenicline generallyshould be used by itself. Youcan make a case for its combi-nation with bupropion, but it’svery difficult to make a case forits use during nicotine replace-ment,” he said.

Between the two approach-es, he said, each has advantages.

“From a safety profile, nico-tine replacement wins handsdown,” said Dr. Selby.

“And from an efficacy per-spective, though we don’t havea good head to head compari-son study... varenicline appearsto be the most effective.”

—Read about Dr. Selbyin the news at

http://ow.ly/65C3P

Mechanismsof addiction

Nicotine replacement therapy and its role in pharmacological treatmentsprepared to use varenicline.

“If they’ve tried NRT,bupropion, and they have areally compelling need to stop,such as COPD, then I’m goingto bring out the big guns.”

He said that varenicline is gen-erally contraindicated with nico-tine replacement therapy, since itacts as an antagonist to block thenicotine receptors if given afterthe person is on the patch.

“It doesn’t make a whole lot

of sense, because with the stan-dard dosing of varenicline,almost all the nicotinic recep-tors are saturated. But, that’snot definitive,” said Dr. Selby.

Varenicline is a partial agonistof the a4ß2 subtype of the nico-

tinic acetylcholine receptor. Italso acts on a3ß4 and weakly ona3ß2 and a6-containing receptors.

“There may be other recep-tors subtypes that may not beblocked by varenicline, butthose studies haven’t been

—continued from page 6

(NMS)- like events). Concomitant use of Cipralex® and MAO inhibitors (including linezolid, an antibiotic which is areversible non-selective MAO inhibitor) is contraindicated (see CONTRAINDICATIONS). Triptans (5HT1 agonists):Cases of life-threatening serotonin syndrome have been reported during combined use of selective serotonin reuptakeinhibitors (SSRIs)/serotonin norepinephrine reuptake inhibitors (SNRIs) and triptans. If concomitant treatmentwith Cipralex® and a triptan is clinically warranted, careful observation of the patient is advised, particularly duringtreatment initiation and dose increases (see SUPPLEMENTAL PRODUCT INFORMATION, PRECAUTIONS – SerotoninSyndrome/Neuroleptic Malignant Syndrome (NMS)- like events). Racemic Citalopram As escitalopram (Cipralex®)is the active isomer of citalopram (Celexa®), the two drugs should not be taken together. Alcohol use Althoughcitalopram did not potentiate the cognitive and psychomotor effects of alcohol in volunteers, the concomitant use ofalcohol in depressed patients taking escitalopram is not recommended. Polymorphism It has been observed that poormetabolisers with respect to CYP2C19 have twice as high a plasma concentration of escitalopram as extensivemetabolisers (see ADMINISTRATION, CYP2C19 Poor metabolizers). Although no significant change in exposure wasobserved in poor metabolizers with respect to CYP2D6, caution is recommended when escitalopram is co-administeredwith medicinal products that are mainly metabolised by this enzyme, and that have a narrow therapeutic index.Established or Predicted Drug-Drug Interactions with Escitalopram Cimetidine: Caution should beexercised when used concomitantly with cimetidine. A reduction in the dose of escitalopram may be necessary basedon clinical judgement. Imipramine/Desipramine: substrate for CYP2D6: Resulted in a 50% increase ofdesipramine concentrations. Concomitant treatment with escitalopram and imipramine/desipramine should be undertakenwith caution. Metoprolol: substrate for CYP2D6: Resulted in a 50% increase in the peak plasma levels of theß-adrenergic blocker with no clinically significant effects on blood pressure or heart rate. Omeprazole: CYP2C19inhibitor: Caution should be exercised when used concomitantly with CYP2C19 inhibitors (e.g. omeprazole). A reductionin the dose of escitalopram may be necessary based on clinical judgement. Ritonavir: substrate for CYP3A4:Combined administration did not affect the pharmacokinetics of either ritonavir or escitalopram. Carbamazepine: Sincecarbamazepine is a microsomal enzyme inducer, the possibility that carbamazepine may increase the clearance ofescitalopram should be considered if the two drugs are given concomitantly. Lithium: Since lithium may increaseserotonergic neurotransmission, concomitant treatment with escitalopram should be undertaken with caution. Drug-FoodInteraction Although there is a theoretical possibility of pharmacokinetic drug interactions resulting from co-administrationof escitalopram with grapefruit juice, the onset of an interaction is considered unlikely. Drug-Herb Interactions St-John’sWort: In common with other SSRIs and newer antidepressants, pharmacodynamic interactions between escitalopram andthe herbal remedy St-John’s Wort may occur and may result in undesirable side effects.

Dosing Consideration Cipralex® (escitalopram oxalate) is not indicated for use in children under18 years of age (see WARNINGS AND PRECAUTIONS – Potential Association with Behavioural and Emotional Changes,Including Self-Harm). General: Escitalopram should be administered as a single daily dose, with or without food.Recommended Dose and Dosage Adjustment Adults MDD/GAD/OCD Escitalopram should be administeredas a single oral dose of 10 mg daily. Depending on individual patient response, an increase in the dose to a maximum of20 mg daily should be considered. Where initial sensitivity to adverse events may be a concern, escitalopram could bestarted at 5 mg daily and titrated upwards as tolerated. Treatment of Pregnant Women During the ThirdTrimester (see WARNINGS AND PRECAUTIONS). Elderly Patients A longer half-life and decreased clearance have beendemonstrated in the elderly, therefore lower doses and a lower maximum dose should be considered. It may be desirable tostart at 5 mg daily and titrate upwards as needed and tolerated. Renal Impairment No dosage adjustment is necessaryfor patients with mild or moderate renal impairment. Since no information is available on the pharmacokinetic or pharma-codynamic effects of either escitalopram or citalopram in patients with severely reduced renal function (creatinine clearance<30mL/min), escitalopram should be used with caution in these patients. Hepatic Impairment Dosages should berestricted to the lower end of the dose range in patients with mild to moderate hepatic insufficiency. Accordingly, an initialsingle oral dose of 5 mg daily is recommended. Subsequently, the dose may be increased based on the patient’s response andclinical judgement. A daily dose of 10 mg is the recommended maximum dose for most patients with hepatic impairment.No information is available about the pharmacokinetics of escitalopram in patients with severe hepatic impairment (Child-PughCriteria C). Escitalopram should be used with additional caution in patients with severe hepatic impairment. CYP2C19 Poormetabolizers The metabolism of escitalopram is mainly mediated by CYP2C19. For patients who are known to be poormetabolizers with respect to CYP2C19, an initial dose of 5 mg daily is recommended. The dose may be increased basedon the patient’s response and clinical judgement. Long-Term Treatment During long-term therapy, the dosage should bemaintained at the lowest effective level and patients should be periodically reassessed to determine the need to continue treat-ment. Switching Patients To or From a Monoamine Oxidase Inhibitor (MAOI) (see CONTRAINDICATIONS).Discontinuation of Escitalopram Treatment Symptoms associated with the discontinuation or dosage reduction ofescitalopram have been reported. Patients should be monitored for these and other symptoms when discontinuing treatmentor during dosage reduction (see WARNINGS AND PRECAUTIONS and ADVERSE REACTIONS). Children (see WARNINGSAND PRECAUTIONS – General, Potential Association with Behavioural and Emotional Changes, Including Self-Harm).Missed Dose In the event that a dose is missed, the patient should take the next dose when it is due.OVERDOSAGE: See SUPPLEMENTAL PRODUCT INFORMATION section.STORAGE AND STABILITY: Escitalopram tablets should be stored in a dry place at room temperature (15° and 30°C).DOSAGE FORMS, COMPOSITION AND PACKAGING: Escitalopram tablets contain escitalopram oxalatecorresponding to 10 mg or 20 mg escitalopram, and the following non medicinal ingredients: colloidal silicondioxide, croscarmellose sodium, hydroxypropyl methyl cellulose, magnesium stearate, microcrystalline cellulose,polyethylene glycol 400, talc, titanium dioxide (white E-171). Availability of dosage forms: 10 mg tablets:Each film-coated, white, oval, scored tablet, marked with “EL” on one side, contains: escitalopram 10 mg (as escitalopramoxalate). Blister packages of 7 and 30. Bottle of 100. 20 mg tablets: Each film-coated, white, oval, scored tablet,marked with “EN” on one side, contains: escitalopram 20 mg (as escitalopram oxalate). Blister packages of 30.Consult Product Monograph for full prescribing information.

SUPPLEMENTAL PRODUCT INFORMATIONCONTRAINDICATIONS: Monoamine Oxidase Inhibitors Cases of serious reactions have been reported in patients receiving selective serotonin reuptakeinhibitors (SSRIs) in combination with a monoamine oxidase inhibitor (MAOI) or the reversible MAOI (RIMA), moclobemide, and in patients who have recently discontinuedan SSRI and have been started on a MAOI (see DRUG INTERACTIONS). With the co-administration of an SSRI with MAOI, there have been reports of serious, sometimesfatal reactions including hyperthermia, rigidity, myoclonus, autonomic instability with possible fluctuations of vital signs, and mental status changes, including extremeagitation progressing to delirium and coma. Some cases presented with features resembling serotonin syndrome.PRECAUTIONS The following additional precautions are listed alphabetically. Carcinogenesis and Mutagenesis See complete product monograph.Cardiovascular Patients with Cardiac Disease Neither escitalopram nor racemic citalopram has been systematically evaluated in patients with a recent historyof myocardial infarction or unstable heart disease. In line with other SSRIs, including racemic citalopram, escitalopram causes statistically significant, but clinicallyunimportant decrease in heart rate. In patients <60 years old, the mean decrease with escitalopram was approximately 2.3 bpm, while in patients ≥60 years old, themean decrease was approximately 0.6 bpm. Endocrine and Metabolism Diabetic Patients Neither escitalopram nor racemic citalopram has been systematicallyevaluated in diabetic patients; in the case of citalopram, diabetes constituted an exclusion criterion. Rare events of hypoglycaemia were reported for citalopram. Treatmentwith an SSRI in patients with diabetes may alter glycaemic control (hypoglycaemia and hyperglycaemia). Escitalopram should be used with caution in diabetic patients oninsulin or oral hypoglycaemic drugs. Hematologic Bleeding Disorders SSRIs and serotonin/norepinephrine reuptake inhibitors (SNRIs), including Cipralex®, mayincrease the risk of bleeding events. Concomitant use of aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), warfarin, and other anticoagulants may add to this risk.Case reports and epidemiological studies (case-control and cohort design) have demonstrated an association between use of drugs that interfere with serotonin reuptakeand the occurrence of gastrointestinal bleeding. There have been reports of bleeding events ranging from ecchymoses, hematomas, epistaxis, and petechiae tolife-threatening haemorrhages, associated with treatment with SSRIs and SNRIs. Caution is advised in patients taking SSRIs and SNRIs, particularly in concomitant usewith drugs known to affect platelet function (e.g. atypical antipsychotics and phenothiazines, most tricyclic antidepressants, anticoagulants, platelet aggregationinhibitors, acetylsalicylic acid and NSAIDs), as well as in patients with a history of bleeding disorders or predisposing conditions (e.g., thrombocytopenia).Hepatic/Biliary/Pancreatic Hepatic Impairment Based on a study conducted with escitalopram in patients with mild to moderate hepatic impairment, thehalf-life was approximately doubled and the exposure was increased by approximately two third, compared to subjects with normal liver function. Consequently, the useof escitalopram in hepatically impaired patients should be approached with caution and a lower dosage is recommended (see ADMINISTRATION). Neurologic SeizuresEscitalopram has not been systematically evaluated in patients with a seizure disorder. These patients were excluded from the clinical studies. In clinical trials withescitalopram, convulsions have been reported very rarely (2 out of 3981 patients) in association with treatment with escitalopram. From post-marketing data, the reportingof seizures with escitalopram is comparable to that of other antidepressants. Like other antidepressants, escitalopram should be used with caution in patients with a historyof seizure disorder. Serotonin Syndrome/Neuroleptic Malignant Syndrome (NMS)-like events On rare occasions serotonin syndrome or neurolepticmalignant syndrome-like events have occurred in association with treatment with SSRIs, including escitalopram, particularly when given in combination with otherserotonergic and/or neuroleptic drugs. As these syndromes may result in potentially life-threatening conditions, treatment with Cipralex® should be discontinued if such events(characterized by clusters of symptoms such as hyperthermia, rigidity, myoclonus, autonomic instability with possible rapid fluctuations of vital signs, mental status changesincluding confusion, irritability, extreme agitation progressing to delirium and coma) occur and supportive symptomatic treatment should be initiated. Cipralex® should notbe used in combination with MAO inhibitors or serotonin-precursors (such as L-tryptophan, oxitriptan) and should be used with caution in combination with other serotonergicdrugs (triptans, certain tricyclic antidepressants, lithium, tramadol, St. John’s Wort) due to the risk of serotonergic syndrome (see CONTRAINDICATIONS and DRUGINTERACTIONS, Serotonergic Drugs, Triptans). Psychiatric Suicide The possibility of a suicide attempt is inherent in depression and may persist until remission occurs.Therefore, high-risk patients should be closely supervised throughout therapy with consideration to the possible need for hospitalization. In order to minimize the opportunityfor overdosage, prescription for escitalopram should be written for the smallest quantity of drug consistent with good patient management. Because of the well establishedcomorbidity between depression and other psychiatric disorders, the same precautions observed when treating patients with depression should be observed when treatingpatients with other psychiatric disorders (see WARNINGS AND PRECAUTIONS – General, Potential Association with Behavioural and Emotional Changes, Including Self-Harm). Activation of Mania/Hypomania In placebo-controlled trials of escitalopram oxalate activation of mania/hypomania was reported in one patient of then=715, treated with escitalopram and in a small proportion of patients treated with citalopram, and with other marketed antidepressants. Escitalopram should be usedwith caution in patients with a history of mania/hypomania. Electroconvulsive Therapy (ECT) The safety and efficacy of the concurrent use of either escitalopramor citalopram and ECT have not been studied. Renal Hyponatremia As with other antidepressants, cases of hyponatremia and SIADH (syndrome of inappropriateantidiuretic hormone secretion) have been reported with escitalopram and racemic citalopram as a rare adverse event. The majority of these occurrences have beenin elderly individuals, some in patients taking diuretics or who were otherwise volume-depleted. Elderly female patients in particular seem to be a group at risk.Renal Impairment (see ADMINISTRATION). Special Populations Pregnant and Nursing Women: The safety of escitalopram during human pregnancy andlactation has not been established. Therefore, escitalopram should not be used during pregnancy, unless the potential benefit to the patient outweighs the possible risk tothe foetus. Studies with escitalopram have not been performed in nursing mothers, but it is known that citalopram is excreted in human milk and it is expected thatescitalopram is also excreted into breast milk. Escitalopram should not be administered to nursing mothers unless the expected benefits to the patient outweigh the possiblerisk to the child. Complications following late third trimester exposure to SSRIs: Post-marketing reports indicate that some neonates exposed to SSRIssuch as Cipralex® and other antidepressants late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tubefeeding. Such complications can arise immediately upon delivery. Reported clinical findings have included respiratory distress, cyanosis, apnoea, seizures, temperatureinstability, feeding difficulty, vomiting, hypoglycaemia, hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, irritability, and constant crying. These features are consistentwith either a direct toxic effect of SSRIs and other newer antidepressants, or, possibly, a drug discontinuation syndrome. It should be noted that, in some cases, the clinicalpicture is consistent with serotonin syndrome (see SUPPLEMENTAL PRODUCT INFORMATION, PRECAUTIONS – Serotonin Syndrome/Neuroleptic Malignant Syndrome(NMS)- like events). Risk of PPHN and exposure to SSRIs: In one epidemiological case-control study on persistent pulmonary hypertension (PPHN) with n = 377infants with PPHN and n = 836 matched control infants, PPHN was six times more common in babies whose mothers took an SSRI antidepressant after the 20th weekof pregnancy compared to babies whose mothers did not take an antidepressant. The study was too small to determine relative risks among the specific SSRIs. Thisinformation is considered to be preliminary at this time. The absolute risk of PPHN in the general population is reported to be 1 – 2 per 1000. Pediatrics (see WARNINGSAND PRECAUTIONS, General, Potential Association with Behavioural and Emotional Changes, Including Self-Harm). Geriatrics (see ADMINISTRATION).OVERDOSAGE Clinical data on escitalopram overdose are limited and many cases involve concomitant overdoses of other drugs. In the majority of cases mild or nosymptoms have been reported. Fatal cases of escitalopram overdose have rarely been reported with escitalopram alone (doses unknown); the majority of cases have involvedmultiple drug overdose. Doses up to 800 mg of escitalopram alone have been taken without any severe symptoms. In clinical trials with citalopram, there were no reportsof fatal citalopram overdoses of up to 2000 mg. Post-marketing reports of drug overdoses involving racemic citalopram have included fatalities with citalopram alone. Inmany cases, details regarding the precise dose of racemic citalopram or combination with other drugs and/or alcohol are often lacking. However, three fatalities with knownoverdoses of citalopram alone have been reported in the literature, (doses of 2800 mg, 2880 mg, and 3920 mg) although survival has also been reported with overdosesof up to 5200 mg. In comparing the data from racemic citalopram with that of escitalopram, it is important to be aware that the latter product is expected to have similarpharmacodynamic effects at a lower dose of the racemic product. Fatal cases of serotonin syndrome have been reported in patients who took overdoses of moclobemide(Manerix®) and racemic citalopram. Symptoms most often accompanying overdose of racemic citalopram included dizziness, sweating, nausea, vomiting, tremor, andsomnolence. In more rare cases, observed symptoms included confusion, loss of consciousness, convulsions, coma, sinus tachycardia, cyanosis, hyperventilation andrhabdomyolysis and ECG changes (including QTc prolongation, nodal rhythm, ventricular arrhythmia, and one possible case of Torsades de pointes). Management ofOverdose As with racemic citalopram, there is no specific antidote to escitalopram. Treatment is symptomatic and supportive. Establish and maintain an airway to ensureadequate ventilation and oxygenation. Gastric lavage and use of activated charcoal should be considered as soon as possible after oral ingestion. Cardiac and vital signmonitoring are recommended, along with general symptomatic and supportive measures. Due to the large volume of distribution of escitalopram, forced diuresis, dialysis,haemoperfusion and exchange transfusion are unlikely to be of benefit. In managing overdosage, the possibility of multiple drug involvement must be considered.For management of a suspected drug overdose, contact your regional Poison Control Centre.

Cipralex® tablets are made by:H. Lundbeck A/S, Ottiliavej 9, DK-2500, Copenhagen, DenmarkProduct License Holder/Distributor:Lundbeck Canada Inc., 1000 de la Gauchetière Street West, Suite 500, Montreal (Quebec), H3B 4W5, Canada 1-800-586-2325 www.lundbeck.caProduct Monograph available on request.Reference: 1. Cipralex Product Monograph, June 12, 2009. Lundbeck Canada Inc.

® Registered trademark of Lundbeck Canada Inc.

ADMINISTRATION

CIP-253-09E

the use of prescription thera-pies, such as opioids.

Current responses to drugaddiction like methadone arepalliative, and not actually treat-ment for drug addiction. “Wewant to aim at reversing what ishappening in the brain,” saidDr. Dumont.

The potential therapy heenvisions could be added to anexisting drug like oxycodone,according to Dr. Dumont.

“It could be an adjuvant to apainkiller,” said Dr. Dumont.“It would not interfere with thepainkiller’s ability to reducepain, but it would reduce itsaddictive properties.”

—Read a recent article byDr. Dumont at

http://ow.ly/65Bkz

—continued from page 7

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PRESCRIBING SUMMARY

THERAPEUTIC CLASSIFICATION

Muscle relaxant, peripherally acting agent

INDICATIONS AND CLINICAL USEXEOMIN® is indicated in adults for the symptomatic management of: blepharospasm; cervical dystonia of a predominantly rotational form (spasmodic torticollis); post-stroke spasticity of the upper limb.XEOMIN® as a treatment for focal spasticity has been studied in association with usual standard care regimens and is not intended as a replacement for these treat-ment modalities. XEOMIN® is not likely to be effective at a joint affected by a fixed contracture.XEOMIN® may only be used by physicians with suitable qualifications and proven experience in the application of Botulinum toxin type A and in the use of the neces-sary equipment, e.g. EMG (electromyography).

CONTRAINDICATIONSHypersensitivity to Botulinum neurotoxin type A or to any of the excipients. Gen-eralised disorders of muscle activity (e.g. myasthenia gravis, Lambert-Eaton syn-drome). Presence of infection at the proposed injection site.

SERIOUS WARNINGS AND PRECAUTIONS

-ment of toxin activity that is unique to XEOMIN®

used to describe XEOMIN® activity are different from those used to describe that of other botulinum toxin preparations and the units representing XEOMIN® activity are not interchangeable with other products.

® (See DOSAGE AND ADMINISTRATION).

GeneralPatients and caregivers should be advised to seek immediate medical consultation if swallowing, speech, or respiratory disorders arise. In very rare cases severe adverse events like muscle weakness, dysphagia or aspiration pneumonia with a suspected causal relationship to toxin spread have been reported with the use of botulinum toxin. Also very rare cases of adverse events with a fatal outcome have been reported. Patients with a neurological underlying disease or swallowing, speech or respiratory difficulties have an increased risk for these adverse drug reactions and should be treated and supervised very carefully. An anaphylactic reaction may occur rarely after injection of Botulinum neurotoxin

anaphylaxis should be available. Extra caution is required when injecting at sites close to sensitive structures such as the carotid artery and lung apices. XEOMIN® should be used with caution: in patients suffering from amyotrophic lateral sclerosis or other diseases which result in peripheral neuromuscular dysfunction; in targeted muscles which display pronounced weakness or atrophy.

GASTROINTESTINAL

Spasmodic torticollisPatients should be informed that injections of XEOMIN® for the management of spasmodic torticollis may cause mild to severe dysphagia with the risk of aspiration and dyspnoea. Medical intervention may be necessary (e.g. in the form of a gas-

three weeks after injection. Patients with smaller neck muscle mass, or patients who require bilateral injections into the sternocleidomastoid muscles are at greater risk.

-fect of Botulinum toxin as the result of the neurotoxin spread into the oesophageal musculature.

HematologicXEOMIN® should be used with caution if bleeding disorders of any type occur. It should be used with caution in patients receiving anticoagulant therapy.

OPHTHALMOLOGIC

BlepharospasmBecause of the anticholinergic effect of Botulinum toxin type A, XEOMIN® should be used with caution in patients at risk of developing an angle closure glaucoma.In order to prevent ectropion, injections into the lower lid area should be avoided, and

drops, ointments, soft bandage contact lenses, or closure of the eye by patching or similar means.Reduced blinking following XEOMIN® injection into the orbicularis muscle can lead to corneal exposure, persistent epithelial defects and corneal ulceration, especially in patients with cranial nerve disorders (facial nerve). Careful testing of cor-neal sensation should be performed in patients with previous eye operations. Ecchymosis easily occurs in the soft tissues of the eyelid. Immediate gentle pressure at the injection site can limit that risk.

SPECIAL POPULATIONS

Pregnant Women:

unknown. XEOMIN® should not be used during pregnancy unless clearly necessary and unless the potential benefit justifies the risk.

Nursing Women:-

fore, the use of XEOMIN® during lactation is not recommended.

Pediatrics (<18 years of age):No data is available on the use of XEOMIN® in children and it is therefore not currently recommended in this age group.

Geriatrics (>65 years of age):Although clinical studies included a number of patients over the age of 65, no clinical trials specifically designed for elderly patients have been performed. Initial dosing should begin at the lowest recommended dose for the specific indi-cation and be cautiously titrated within the recommended range for optimal patient outcome.

ADVERSE REACTIONS

Adverse Drug Reaction Overview

A are mainly related to the diffusion of Botulinum neurotoxin type A from the tar-get muscle to adjacent muscles. Such undesirable effects are rare, and most are localized in close proximity to the injection site; systemic side effects are un-common. Intramuscular injection into neck muscles for treatment of cervical dystonia occasionally results in transient dysphagia and a general weakness in the

ptosis and diplopia. Intramuscular injections of Botulinum toxin type A for up-per limb spasticity were reported to be commonly associated with local reac-tions like hypertonia, ecchymosis, purpura, pain in shoulder, arm or hand, muscle weakness, bleeding and itching after administration at the injection site.

Clinical Trial Adverse Drug Reactions Because clinical trials are conducted under very specific conditions the adverse reac-tion rates observed in the clinical trials may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug. Adverse drug reaction information from clinical trials is useful for identifying drug-related ad-verse events and for approximating rates.In the 6 studies conducted to provide data on the safety of XEOMIN® 1082 subjects were treated with trial medications (XEOMIN®, active comparator or placebo). See product monograph for study parameters.

Table 1: Adverse Drug Reactions Reported in 1% of Cervical Dystonia Patients

System organ classPreferred term

Number of subjects (%)

XEOMIN® N=272

Active Comparator 1 (Botulinum toxin type A-complex)

N=244

Gastrointestinal disorders 24 (8.8) 15 (6.1)

Dysphagia 24 (8.8) 15 (6.1)

Musculoskeletal & connective tissue disorders 9 (3.3) 2 ( 1)

Muscular weakness 4 (1.5) 1 ( 1)

Neck pain 5 (1.8) 1 ( 1)

Powder for solution for injection, 100 LD50 units per vial

Prescribing Summary

Patient Selection Criteria

Safety Information

(Clostridium Botulinum Neurotoxin Type A (150 kD), free from complexing proteins)

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42815 N_P Chronicle.qxd:42815 N_P Chronicle.qxd 31/08/11 3:48 PM Page 19

Page 20: The Chronicle of Neurology + Psychiatry Aug 30 2011

Table 2: Adverse Drug Reactions Reported in 1% of Blepharospasm Patients

System organ classPreferred term

Number of subjects (%)

XEOMIN® N=148

Active Comparator 1 (Botulinum toxin type A-complex)

N=152

Eye disorders 12 (8.1) 12 (7.9)

Dry eye 3 (2.0) 0 (0.0)

Eyelid oedema 0 (0.0) 2 (1.3)

Eyelid ptosis 9 (6.1) 7 (4.6)

Vision blurred 0 (0.0) 3 (2.0)

Table 3: Adverse Drug Reactions Reported in 1% of Patients with Post-stroke Spasticity of the Upper Limb (Double-blind Period)

System organ classPreferred term

Number of subjects (%)

XEOMIN® N=73

Placebo N=75

Gastrointestinal disorders 0 (0.0) 1 (1.3)

Dysphagia 0 (0.0) 1 (1.3)

General dis. & admin. site conditions 0 (0.0) 1 (1.3)

Injection site pain 0 (0.0) 1 (1.3)

Nervous system dis. 1 (1.4) 0 (0.0)

Headache 1 (1.4) 0 (0.0)

Table 4: Adverse Drug Reactions Reported in 1% of Patients with Post-Stroke Spasticity of the Upper Limb (Open-Label Extension Period)

System organ classPreferred term

XEOMIN®

Number of Subjects (%) N= 145

Gastrointestinal disorders

Dysphagia 2 (1.4)

General dis. & admin. site conditions

Injection site pain 4 (2.8)

Musculoskeletal and connective tissue disorders

Muscular weakness 5 (3.4)

Pain in extremity 2 (1.4)

MERZ Canada at 1-866-815-8715.

Drug-Drug Interactions-

biotics or other medicinal products that interfere with neuromuscular transmission, e.g. tubocurarine-type muscle relaxants.

® with aminoglycosides, polymyxins, tetracyclines, linomycin, spectinomycin or any other drugs that interfere with neuro-muscular transmission requires special care. Peripheral muscle relaxants should be used with caution, if necessary reducing the starting dose of relaxant, or using an intermediate-acting substance such as vecuronium or atracurium rather than sub-stances with longer lasting effects. 4-Aminochinolines may reduce the effect of XEOMIN®.

Recommended Dose and Dosage Adjustment

Blepharospasm

treatment session is recommended to be at least every 12 weeks.

patients and in long-term repeat-dose treatment.At repeat treatment sessions, the dose may be increased up to two-fold (as long as

-sidered insufficient – usually defined as an effect that does not last longer than two months. However, there appears to be no additional benefit obtainable from injecting

frequently than every three months.

Spasmodic torticollisIn the management of spasmodic torticollis, XEOMIN® dosing must be tailored to the individual patient, based on the patient’s head and neck position, loca-tion of possible pain, muscle hypertrophy, patient’s body weight, and response to the injection. A suitable sterile needle (e.g. 25-30 gauge/0.30-0.50 mm) is used for injections into superficial muscles, and an e.g. 22 gauge/0.70 mm nee-dle may be used for injections into deeper musculature. An injection volume of approximately 0.1 to 0.5 mL per injection site is recommended.

effect of each treatment generally lasts approximately 3-4 months; however, it may

patients and in long-term repeat-dose treatment.

Post-stroke Spasticity of the Upper LimbReconstituted XEOMIN® is injected using a suitable sterile needle (e.g. 26 gauge/0.45 mm diameter/37 mm length, for superficial muscles and a longer needle, e.g. 22 gauge/0.7 mm diameter/75 mm length, for deeper musculature). An injection volume of approximately 0.2 to 1 mL per injection site is recommended, but it can be exceeded to 1.5 mL in selected cases.

Table 5: Dosage guide for the management of post-stroke spasticity of the up-per limb

Clinical Pattern Muscle

Units

Flexed Wrist (Total) 90

Flexor carpi radialis 50

Flexor carpi ulnaris 40

Clenched Fist (Total) 80

Flexor digitorum superficialis 40

Flexor digitorum profundus 40

Flexed Elbow (Total) 130-190

Brachioradialis 60

Biceps 80

Brachialis 50

Pronated Forearm (Total) 25-65

Pronator quadratus 25

Pronator teres 40

humb-in-Palm (Total) 10-40

Flexor pollicis longus 20

Adductor pollicis 10

Flexor pollicis brevis/ Opponens pollicis 10

different muscles. Initial dosing should begin at the lowest recommended dose for the specif-ic indication and be cautiously titrated within recommended dose range for optimal patient outcome.

is recommended to be at least 12 weeks.

innervation zones can reduce undesirable effects and, at the same time, may reach more intrafusal fibres.

BlepharospasmAfter reconstitution, the XEOMIN® solution is injected using a suitable sterile needle (e.g. 27-30 gauge/0.30-0.40 mm). Electromyographic guidance is not necessary. An injection volume of approximately 0.05 to 0.1 mL is recommended.XEOMIN® is injected into the medial and lateral orbicularis oculi of the upper lid and the lateral orbicularis oculi of the lower lid. Additional sites in the brow area, the lateral orbicularis and in the upper facial area may also be injected if spasms here interfere with vision.

Administration

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Injections near the levator palpebrae superioris should be avoided to reduce the oc-currence of ptosis. Diplopia may develop as a result of Botulinum neurotoxin type A diffusion into the inferior oblique. Avoiding medial injections into the lower lid may reduce this adverse reaction.

Spasmodic torticollisIn the management of spasmodic torticollis, XEOMIN® is usually injected into the sternocleidomastoid, levator scapulae, scalenus, splenius capitis, and/

responsible for controlling head position may be involved and therefore require treatment. If difficulties arise isolating single muscles, injec-

mass and the degree of hypertrophy or atrophy are factors to be taken into consideration when selecting the appropriate dose.Multiple injection sites permit XEOMIN® more uniform coverage of the innervated areas

number of injection sites is dependent upon the size of the muscle to be chemically denervated.

increased risk of adverse reactions (in particular dysphagia) when bilateral injec-

Post-stroke Spasticity of the Upper LimbLocalisation of the involved muscles with electromyographic guidance or nerve stimulation techniques may be necessary. Multiple injection sites may allow XEOMIN® to have more uniform contact with the innervation areas of the muscle and are especially useful when larger muscles are injected.

-tient based on the size, number and location of muscles to be treated, the severity of spasticity, and the presence of local muscle weakness. Initial dosing should begin at the lowest recommended dose and be cautiously titrated within the recommended dose range for optimal patient outcome.

Reconstitution

except those mentioned below.XEOMIN® is reconstituted prior to use with sterile unpreserved sodium chloride 9 mg/mL (0.9%) solution for injection. Reconstitution and dilution should be performed in accordance with good clinical practice guidelines, particularly with respect to asepsis.It is good practice to perform vial reconstitution and syringe preparation over plastic-lined paper towels to catch any spillage. An appropriate amount

rubber stopper of the vial is cleaned with alcohol (70%) prior to insertion of the

if the vacuum does not pull the solvent into the vial. Reconstituted XEOMIN® is a clear colourless solution free of particulate matter. XEOMIN® should not be used if the reconstituted solution (prepared as above) has a cloudy appearance or contains floccular or particulate matter.

Table 6: Possible Dilutions of XEOMIN® in the Reconstituted Solution

Solvent added(sodium chloride 9 mg/mL (0.9%)

solution for injection

Resulting dose in units per 0.1 mL

0.5 mL1.0 mL2.0 mL4.0 mL8.0 mL

20.010.0 5.02.5

1.25

Any solution for injection that has been stored for more than 24 hours as well as

reconstituted solution, see SPECIAL HANDLING INSTRUCTIONS

SUPPLEMENTAL PRODUCT INFORMATION

Dosing ConsiderationsUnit doses recommended for XEOMIN® are not interchangeable with those for other preparations of Botulinum toxin.

XEOMIN® may only be used by physicians with suitable qualifications and proven experience in the application of Botulinum toxin and in the use of the necessary equipment, e.g. EMG (electromyography).Reconstituted XEOMIN® is intended for intramuscular injection. After reconstitution, XEOMIN® should be used for only one injection session and for only one patient.

® should be as recommended for the specific indica-tion.

for each patient. A titration of the dose should be performed.A decrease or increase in the XEOMIN® dose is possible by administering a smaller or larger injection volume. Initial dosing should begin at the lowest recommended dose for the specific indication and be cautiously titrated within the recommended range for optimal patient outcome. If no treatment effect occurs within one month after the initial injection, the following measures should be taken:

facility.

injection technique, fixed contracture, too weak antagonist, possible development of antibodies.

performed under the following conditions: 1) dose adjustment with regard to analysis of the most recent therapy failure, 2) EMG-guidance, 3) the recommended minimum interval between the initial and repeat treatment is followed

not been investigated whether secondary non-response due to the development of antibodies is less frequent under XEOMIN® therapy than under treatment with conventional preparations containing the Botulinum toxin type A complex. In cases of non-response, alternative therapies should be considered.XEOMIN® has not been studied in the paediatric population and is therefore not recommended in the paediatric age group until further data become available.Prior to administering XEOMIN®, the physician must familiarise himself/herself with the patient’s anatomy and any alterations to the anatomy due to prior surgical procedures. Extra caution is required when injecting at sites close to sensitive structures

--

ment and in treatment-naive patients for post-stroke spasticity of the upper limb.Clinical effects of XEOMIN® may increase or decrease with repeated injections. Possible reasons for change in clinical effect are different techniques of reconstitution, the chosen injection intervals, the injected muscles and marginally varying toxin activity resulting from the biological testing pro-cedure employed or secondary non-response. Previously akinetic or sedentary patients should be reminded to gradually re-sume activities following the injection of XEOMIN®. XEOMIN® contains albumin, a derivative of human blood. Standard meas-ures to prevent infections resulting from the use of medicinal products prepared from human blood or plasma include careful selection of donors, screening of individual donations and plasma pools for specific markers of infection and the inclusion of effective manufacturing steps for the inactivation/removal of viruses. Despite this, when medi-cinal products prepared from human blood or plasma are administered, the possibility of transmitting infective

no reports of viral transmissions with albumin manufactured to European Pharmacopoeia specifications by established processes.

Immune

young age at disease onset, and higher total dosage received of Botulinum toxin. Antibody development may lead to treat-

Less Common Clinical Trial Adverse Drug Reactions (<1%) Cervical Dystonia: eye pain, diarrhoea, dry mouth, vomiting, colitis, asthenia, injection site inflammation, injection site tender-ness, skeletal pain, myalgia, headache, tremor, dysphonia, skin rash, erythema, pruritus, sweating increased. Blepharospasm: conjunctivitis, dry mouth, inflicted injury, muscle weakness, paraesthesia, headache, skin rash.Post-stroke Spasticity

Abnormal Hematologic and Clinical Chemistry Findings In all clinical trials, there were no findings indicative of underlying pathological changes as a result of trial medication, both with regard to the incidence of abnormal hematologic and clinical chemistry values and with regard to the mean change in laboratory values for either treatment group.

Post-Market Adverse Drug Reactions ® has been marketed: eye swelling, eyelid

edema, madarosis, vision blurred; injection site reactions; asthenia, fatigue; dysphagia, nausea, abdominal disten-sion; hypersensitivity including allergic dermatitis, skin rash, erythema, drug eruptions, lymphadenopathy, alopecia; dysphonia, cough, dyspnoea, asthma; herpes zoster; muscular weakness, muscle spasm, myalgia, trismus; dysarthria, headache, somnolence; cardiovascular insufficiency, circulatory collapse; abnormal dreams. Side effects related to spread of toxin distant from the site of administration have been reported very rarely (exaggerated muscle weakness, dysphagia, and aspiration pneumonitis with fatal outcome in some cases).

events have been reported following administration of conventional Botulinum toxin type A complex: dysarthria, abdominal pain, hyperhidrosis, anorexia, hypoacusis, tinnitus, radiculopathy, and syncope.

and myocardial infarction, some with fatal outcomes. It remains unclear whether these deaths were induced by conventional preparations containing the Botulinum toxin type A complex or whether these were caused by pre-existing cardiovascular disease. Serious and/or immediate hypersensitivity reactions have been rarely reported, includ-ing anaphylaxis, serum sickness, urticaria, soft tissue oedema, and dyspnoea. Some of these reactions have been reported following the use of conventional Botulinum toxin type A complex either alone or in combination with other agents known to cause similar reactions.

® in clin-ical studies with blepharospasm and cervical dystonia patients. However, these findings were not considered clinically relevant in the opinion of the treating cardiologist and the exact relationship of these events to XEOMIN® is un-known. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

OTHER INTERACTIONS

Drug-Food InteractionsInteractions with food are not relevant.

Drug-Herb InteractionsInteractions with herbal products have not been established.

Drug-Laboratory InteractionsInteractions with results of laboratory tests have not been established.

Drug-Lifestyle Interactions XEOMIN®

the therapeutic and/or adverse effects of XEOMIN®, which may also interfere with the ability to drive and operate machinery. Consequently affected persons should avoid these tasks until their faculties are fully recovered.

OVERDOSAGE:Increased doses of Botulinum neurotoxin type A may result in pronounced neuromuscular paralysis distant from the injec-

exposure. Signs of overdose may include general weakness, ptosis, diplopia, swallowing and speech difficulties, or paralysis of the respiratory muscles resulting in an aspiration pneumonia. In case of an overdose, the patient must be monitored medically for several days. If signs of intoxication appear, hospitalisation with general supportive measures is necessary. Intubation and assisted ventilation will become necessary until improvement if paralysis of the respiratory muscles occurs.

® contains 0.6 ng Botu-

application.® XEOMIN® is a registered trademark of Merz GmbH.

MERZ PHARMA CANADA

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22 n August 2011

Psychiatrist Dr. Steven Cohen has beenon missions with Médecins SansFrontières, or Doctors Without

Borders, in both Chad and Sudan. InDarfur, Dr. Cohen helped develop a basicmedication management program to trainlocal physicians how to diagnose and treatsevere mental illness, focusing mainly onschizophrenia. In Chad he worked with ateam of nine Sudanese refugee counselorsand 26 local community health workers. Together, his mental healthtreatment group had about 500 patient encounters per month.

Q:Has there been a case that particularly struckyou in your travels?

A:While I was in Sudan I saw one fellow with schiz-ophrenia who had unfortunately become psychot-

ic. In a violent rage while very ill he killed his brother.The family and the community were fairly sophisticated.They recognized that while he did this horrific act, hewas not thinking clearly, and did not know right fromwrong. They continued to support him, but realized thatthey had to keep him from hurting others. He waschained to a big log, so that he couldn’t walk very quick-ly. It seemed to be barbaric and quite inhumane, butover time and after many discussion with local careworkers, I got a sense that it was actually a tenable, if farfrom ideal, short-term solution in that region.

We prescribed haloperiodol 0.5 mg twice daily andeventually titrated him up to 1 mg twice a day, a remarkablylow dose, but enough to resolve this man’s acute psychosis.

He improved quickly, over the span of a month ortwo, and became well enough to take part in the familybusiness, take on familial responsibilities, and, at the

time that I left the region, was engaged to a woman andplanning a marriage.

Q:So you get off the airplane in Chad. What hap-pens then?

A:When I went to Chad, it took about over twoweeks to get to that small camp where the MSF

project was located. I flew into the capital, N’Djamena.There’s a bus that picks you up and drives you to theterminal even though you could probably walk it faster.And then you walk out of the small terminal, it’s just asea of white Land Cruisers.

These vehicles are the hallmark of most of theNGOs who are in that region. And, because nobodyelse wants to be targeted as being part of an oil consor-tium or somebody who has money, other groups startusing them. Quite despicably, even the military has, atsome points, used white Land Cruisers, as [the vehicle]provides them some protection against being targeted.This is not good for humanitarians, you can see.

Q:What was it like in Sudan?

A:There was, of course, a genocide in Darfur thathad started about 2003, leading to a large number

of people being killed, displaced within Sudan, andfleeing to neighbouring countries, such as Chad.

There were ongoing acts of violence where villageswere razed and families decimated—whole villageswould be burned down and women were systematical-ly raped as an act of war. Men would have their live-stock stolen or be beaten. It was not unusual to havetheir teeth cracked. That was still going on but it wasgoing on a smaller scale than years before. It is hard to

treat stress-born illness in the context of an ongoing,unstable, and dangerous conflict.

Q:Did you see many PTSD patients?

A:I thought that when I arrived in Chad and Sudan,that there would be many people with PTSD,

maybe even an epidemic, but we didn’t see that much ofit. By the time that I had arrived, the heart of the crisishad been over for about three and a half to four years.

Many had navigated through that crisis phase andwere rebuilding their lives. Religious groups, sportingactivities, family occasions—people found support andmeaning in them.

Q:You were surprised by how few cases of PTSDthere were. Can you speculate as to why that

would be?

A:I think it’s human resilience. People get better.PTSD is a transient illness, in large part. The trau-

ma never leaves entirely, but with the passage of timeand the budding of new and healthy experiences, itbecomes less prominent. I’ve never seen communitiesas strong those among the Sudanese. It makes a worldof difference.

Dr. Steven Cohen is now a staff psychiatrist at the CAMH lawand mental health program in Toronto. He trained as a physicianat the University of Calgary and spoke with CHRONICLEassistant editor Josh Long.

—Who’s making a difference near you? Tell The Chronicle, so we can tell our readers.

Write us at [email protected]

Psychiatry without bordersn IInn ccoonnvveerrssaattiioonn SStteevveenn CCoohheenn,, aa ppssyycchhiiaattrriisstt wwhhoo vvoolluunntteeeerrss ffoorr tthhee ggrroouupp DDooccttoorrss wwiitthhoouutt BBoorrddeerrss

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“If the nineteenth century was the age of the editorialchair, ours is the century of the psychiatrist’s couch..”

— Marshall McLuhan (1911-1980) Canadian communicationstheorist and educator.

Dr. Steven CohenDr. Steven Cohen

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oing,

udan,TSD,ch ofcrisisears.

andrtingt and

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you? ders. e.org

Introducing the greenChronicleComing soon: A bimonthly electronic supplement to The Chronicle with original multimedia content inevery issue. Optimized for iPad, and readable on your computer, e-reader and electronic device.Interactive, real-time news, opinion and education in the CNS sciences, with two intriguing value-addedfeatures: It’s free. And no trees were harmed in the preparation of this journal.

Sign up for your free subscription now at www.chronicle.ca, and be among the first to receive the revolu-tionary greenChronicle. And while you’re at it, why not follow us on Twitter and Facebook?

Your device. Our content.(This could be the ultimate word-association.)

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orialch..”tions

cator.

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See prescribing summary on page xxx

References: 1. Cipralex Product Monograph, February 2010. Lundbeck Canada Inc.2. Data on file. Lundbeck Canada Inc.

CIP-342-11E

®Registered trademark of Lundbeck Canada Inc.

For more information, please refer tothe complete Cipralex Product Monograph.

Discover the Power of Cipralex

In Depressionand in GAD

Most common adverse events reported by patients treated with Cipralex® (escitalopram oxalate) for Major Depressive Disorder (MDD)were mild and transient in nature and included: headache (15.8% vs. 16.4% placebo) and nausea (15.2% vs. 8.1% placebo). The mostcommon adverse events reported by patients treated with Cipralex for GeneralizedAnxiety Disorder (GAD) were mild and transient innature and included: headache (23.7% vs. 18.6% placebo), nausea (19.4% vs. 9.0% placebo) and insomnia (10.1% vs. 3.7% placebo).Cipralex is indicated for the symptomatic relief of MDD. The efficacy of Cipralex in maintaining an antidepressant response, in patients with MDD who respondedduring an 8-week, acute-treatment phase while taking Cipralex and were then observed for relapse during a period of up to 36 weeks, was demonstrated in aplacebo-controlled trial. Cipralex is indicated for the symptomatic relief of anxiety causing clinically significant distress in patients with GAD. The efficacy ofCipralex in maintaining anxiolytic response for at least 6 months in patients with GAD was demonstrated in a long-term placebo-controlled trial (in patients whohad initially responded to Cipralex during a 12-week open-label phase). Physicians who elect to use Cipralex for extended periods should periodicallyre-evaluate the usefulness of the drug for individual patients.

Cipralex should not be used in combination with an MAOI or within 14 days of discontinuing treatment with an MAOI. Similarly, at least 14 days shouldelapse after discontinuing Cipralex treatment before starting an MAOI. Cipralex should not be used in combination with the antipsychotic drug pimozide.

Cipralex is not indicated for use in patients under 18 years of age. In these patients, the use of SSRIs and other newer antidepressants may be associated withbehavioural and emotional changes, including an increased risk of suicidal ideation and behaviour over that of placebo.

In both pediatrics and adults, there have been reports of severe agitation-type adverse events coupled with self-harm and harm to others with SSRIs andother newer antidepressants. The agitation-type events include:akathisia, agitation, emotional lability, hostility, aggression,depersonalization. In some cases, the events occurred withinseveral weeks of starting treatment. Patients currently takingCipralex should NOT be discontinued abruptly, due to riskof discontinuation symptoms. A gradual reduction in the doseis recommended.

See prescribing summary on page 17

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