Anxiety II: Agents for PTSD & OCD

Brian J. Piper, Ph.D., M.S.piperbj@husson.edu

Office Hours: T/Th 3-4 or by appointment

February 1, 2013

Objectives

• Pharmacy students should be able to:– List the key characteristics of Post-Traumatic Stress

Disorder & Obsessive Compulsive Disorder– Rank the therapeutic options by efficacy and

differentiate the pharmacotherapies by MOA and adverse events.

Psychotherapy & Anxiety Disorders

Anxiety Disorder Importance of PsychotherapyPhobias Systematic desensitization is gold standard.

Social Anxiety Disorder >50% of patients show response to CBTD

GAD CBT and pharmacotherapy have similar efficacyD

Panic Disorder CBT produces improvements in 75% of patientsD

Obsessive Compulsive Dis CBT (with or without SSRI) is recommended as first-line txD

Post-Traumatic Stress Dis EMDR > fluoxetine in maintaining improvementsD

• Specific therapies, typically brief ( < 12 weeks) have solid empirical support

• Effects are delayed but sustained• Important option for vulnerable populations

DDiPiro et al. (2012). Pharmacotherapy: A Pathophysiologic Approach, Chapters 79 & 80.

Obsessive Compulsive Disorder

Example Patient #1 (0 to 2:50): http://www.youtube.com/watch?v=tPFQMRx2l3Y

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Common Obsessions

1) Dirty 2) Aggression 3) Religion 4) Sex

Famous OCD Cases

Yale Brown Obsessive Compulsive Scale

• Obsessions (5 items)– How much of your time do you occupy with

obsessions? None ------ Extreme (8+ hours/day)– How much do your obsession interfere socially or with

work? Not at all ----- Extreme (Incapacitating)• Compulsions (5 items)– How much time do you spend performing compulsive

behaviors? None ---- 8+ hours/day– How much control do you have over the rituals?

Complete Control ---- No control, unable to even delay

7To take test: http://www.psymed.info/psymed/default.aspx?m=Test&id=52&l=3

OCD Options

2nd Line

1st Line

Modified from Stahl, S. (2008). Essential Psychopharmacology, p. 770.

Fluvoxamine

• MOA: SRI• Indications: FDA approved for OCD (adult & pediatric)• Half-Life: 16 hours• Adverse Effects: nausea, vomiting, weight gain, sexual

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Paradoxical Aggression?• Animal studies demonstrate inverse

relationship between 5-HT & aggression• E.H. receives sertraline, later fluvoxamine• Parents of E.H. sue Solvay• Solvay withdraws fluvoxamine (2002 – 2008)• Aggressive patients -> drug

Drug -> Aggression

http://www.denverpost.com/golf/ci_5094436 1981 - 1999

OCD: SSRI, CBT, or Both?

Baseline Week 8 (Change) Week 16 (Change)

Control (Wait List) 26.8 26.4 (-0.4) NA

CBT (1-16) 25.3 21.5 (-3.8)* 13.5 (11.8)*

FLVX (1-16) + CBT (9-16) 27.2 20.8 (-6.4)* 15.6 (11.6)*

• OCD patients randomized to Cognitive Behavior Therapy (CBT), CBT & Fluvoxamine (50-300, Mean = 235 mg/day), or a wait-list.

• Clinicians completed the Yale-Brown Obsessive Compulsive Scale (0 – 40) – normal = 0-7– mild = 8-15; moderate = 16 -23 – 24-31 = severe– 32-40 = extreme

*p < .01 versus Baseline

Von Balkom et al. (1998). Journal of Nervous & Mental Disease, 186(8), 492-499.

5 Year Follow-Up

CBT (N = 32) CBT + Fluvoxamine (N = 39)

Current YBOCS (SD) 12.3 (8.9) 14.9 (9.1)

YBOCS Improved by >7 78.1% 73.7%

Additional CBT 53% 72%

Using Anti-depressants 19% 51%*

No Longer OCD 62.5% 51.3%

*p < .005

van Oppen et al. (2005). J of Clinical Psychiatry, 66, 1415-1422.

Early OCD Age of Onset

General description (Skip Ad, 0 to 2:25): http://www.youtube.com/watch?v=izT40QNFXuMDelorme et al. (2005). Psychological Medicine, 35(2), 237-243.

Early Onset(N = 141)

Late-onset (N = 20)

MDD 36.2% 66.6%*

ADHD 31.2% 25.0%

Tourette’s 26.9% 0.0%*

GAD 11.3% 41.2%*

* p < .01

Fluvoxamine & Age• Max dose – Adults: 300 mg/day– Adolescents: 300 mg/day– Children: 200 mg/day

• Efficacy: similar across age• Contraindications: MAO-Is• Other: CYP1A2• Adverse Effects: similar across age, transient

gastrointestinalCheer & Figgitt (2002). CNS Drugs, 16(2), 139-144.http://www.pdr.net/drugpages/concisemonograph.aspx?concise=1452

SRIs & Adolescence• The 5-HT system undergoes dynamic changes during adolescence• Does chronic anti-depressant treatment alter neurobehavioral development?• Oral paroxetine (15 mg/kg), but not fluvoxamine (30 mg/kg), from PD 33-62

temporarily, reduced weight.

Jong et al (2006). European Neuropsychopharmacology, 16, 39-48.

SRIs & Adolescence• The 5-HT system undergoes dynamic changes during adolescence• Does chronic anti-depressant treatment alter neurobehavioral development?• After a 23 day drug free period, the rats were tested on the elevated plus maze

V P F

Jong et al (2006). European Neuropsychopharmacology, 16, 39-48.

Common Sexual Effects• Sexual dysfunction (SD) is common among

patients with anxiety & depression• Drug-induced SD is under-reported unless

patients queried directly• SD = ↓ desire, ↓ arousal, ↓ orgasm

SertralineVenlafaxineCitalopramParoxetineFluoxetineImipraminePhenelzineDuloxetineEscitalopramFluvoamine

Serretti et al. (2009). Journal of Clinical Psychopharmacology, 29, 259 – 266.

Males > Females

Serretti et al. (2009). Journal of Clinical Psychopharmacology, 29, 259 – 266.

Post Traumatic Stress Disorder

• A) Exposure to actual or threatened death, serious injury, or sexual violation

• B) Intrusion symptom(s): – spontaneous or cued memories– dreams– flashbacks

• C) Avoidance of stimuli associated with traumatic event

• D) Social or occupational impairmentExample (1st 3 min): http://www.youtube.com/watch?v=7aFs6695VyQSummarized from: http://www.dsm5.org/ProposedRevision/Pages/proposedrevision.aspx?rid=165

Neural Substrate of PTSD?

Stahl et al. (2008). Essential Psychopharmacology, p. 748.

SSRIs increase 5-HT but therapeuticlag

SSRIs increases Brain Derived Neurotrophic Factor (BDNF)

BDNF increases neurogenesis

PTSD & Reduced Hippocampal Volume

Karl et al. (2006). Neuroscience & Biobehavioral Reviews, 30, 104-131.

PTSD Options (DiPiro/Stahl)

Modified from Stahl, S. (2008). Essential Psychopharmacology, p. 770.

*FDA Approvedsertralineparoxetine

*

PTSD Treatment HierarchyDepartment of Defense/Veterans Affairs 2010

• “Psychotherapy is the preferred treatment option.”

• 1st Line Pharmacotherapies: SSRI, SNRI• Not Recommended: Benzos & anti-psychotics

as mono-therapy or used adjunctively

Jeffreys et al. (2012). Journal of Rehabilitation Research & Development, 49(5), 703-715.

Rationale For Avoiding Benzos with PTSDThe veteran was diagnosed with PTSD and panic disorder by a psychiatrist in the PTSD Clinic. He was started on sertraline and after several months at a dose of 200 mg daily, he reported only modest reductions in PTSD symptoms. The panic disorder improved but he continued to take clonazepam 1 mg 1–3 times per week to prevent panic attacks when leaving his home. He was referred for PE (Prolonged Exposure) therapy. Although the PE went well in the initial weeks, both the patient and his therapist noted that he was relatively unaffected by anxiety in some therapy sessions. A careful review of his medication use found he was taking clonazepam prior to driving from his home to the VA medical center because driving alone was a common trigger for panic attacks. He was encouraged to not use clonazepam within 24 hours of a PE session, and after several more weeks, he completed PE without difficulty. The post-PE score on the PCL was below the cutoff for PTSD diagnosis.

Jeffreys et al. (2012). Journal of Rehabilitation Research & Development, 49(5), 703-715.

Summary

• Anxiety Disorders are complex psychiatric conditions that require multi-disciplinary treatment.

• SSRIs are first-line pharmacotherapies for OCD & PTSD although there are substantial differences among members of this class.

Cingulate Cortex

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Anterior Cingulate & OCD

• OCD and controls completed a difficult continuous performance test during fMRI.

• OCD > controls in Anterior Cingulate Cortex

Ursu et al. (2003). Psychological Science, 14, 347-353.

More OCD Patients

• 1st Two Minutes: http://www.youtube.com/watch?v=44DCWslbsNM

• Or: http://www.youtube.com/watch?v=Rn1OYlYzgm8

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