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Headache and the Contribution of Anxiety

and Mood Disorders

Randall Weeks, Ph.D.

New England Institute for Neurology & HA

Stamford, CT

HCOP

January 27, 2018

Disclosures…

Speakers’ bureau, AdBoard, Consultant…

Alder

Allergan

Pernix

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Why Study Comorbidity?

� Complicates differential diagnosis

� Could contribute to disease burden

� May affect treatment adherence

� Creates therapeutic opportunities

� Imposes therapeutic limitations

� Allows treatment of the “whole person”

Methodological Issues

� Selection bias—has to do with the deviation of results from a true value because of differences in characteristics between those selected to be investigated and those that are not studied

� Berkson’s bias (paradox)—is the non-random co-occurrence of two conditions attributed to the methodology employed

� Measurement (assessment) bias—occurs when there is systematic error arising from inaccurate measurement or classification of subjects

Methodological Issues

� Disproportionately more individuals with comorbid disorders are included in clinical samples than in community studies

� Clinic-based studies should be hypothesis generators

� Comorbidity studies are most valid when representative samples of the general population are used

Hamelsky SW, Lipton RB. Psychiatric comorbidity of migraine. Headache 2006, 46, 1327-1333.

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Methodological Issues

� Cross-sectional studies demonstrate associations (not directionality)

� Only longitudinal studies can indicate directionality to demonstrate whether one condition predisposes to another or whether the relationship is bidirectional

� Directionality has implications for clinical practice and understanding of mechanisms

Hamelsky SW, Lipton RB. Psychiatric comorbidity of migraine. Headache 2006, 46, 1327-1333.

Migraine Comorbidity Constellations

� Group 1—Defined by hypertension, hyperlipidemia, diabetes mellitus, and

hypothyroidism

� Group 2—Defined by depression, anxiety, and

fibromyalgia

� Group 3—The absence of defining comorbidities

Tietjen GE, Herial NA et al. Migraine comorbidity constellations.

Headache 2007; 47(6):857-865.

Comorbid Psychiatric Disorders

� > number predict refractory HA

� > number predict > ER visits

� > number predict > brain imaging & narcotics

� Multiaxial dx’s predict HA chronification & MOH

Guidetti V et al. Cephalalgia, 1998,18(7):455-462.

Minen MT et al. Gen Hospital Psychiatry, 2014,36(5):533-8.

Sheftell FD, Atlas SJ. Headache 2002; 42: 934-944.

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Depression

Association Between Migraine and Depression: IHS-Based Community

StudiesReference Odds Ratio

Breslau (1998)

Migraine w/ aura 4.0

Migraine w/out aura 2.2

Swartz, et al (2000) 2.3

Breslau, et al (2000) 3.5

Low NCP, Merikangas KR. The comMorbidity of migraine. CNS

Spectrums 2003;8(6):433-444.

Martin PR, et al, Behav Res Ther. 2015,73:8-18.

Depression & Migraine—International Studies

� Canada—M’s 60% more likely to dev dep/D’s 40% more likely to dev M

� Brazil—Increased OR’s moving from no M to > freq of M

� Europe—3.5% vs. 6.9% prev in no HA vs M

Mogdill G et al. Headache, 2012;52:422-32.

Goulart AC et al. Headache, 2014;54(8):1310-9.

Lampl C et al. J Headache Pain. 2016;17:59.

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Depression & Migraine (Bidirectional Relationship)

� Two year, longitudinal population based study

� Subjects with Major Depression increased the risk of migraine 3.4 fold

� Subjects with Migraine increased the risk of depression 5.8 fold

Breslau et al. Comorbidity of migraine and depression. Neurology.

2003;60:1308-1312.

Depression & Migraine (Bidirectional Relationship???)

� Shared etiology for M & Dep rather than one causing the other

� May need to look at the severity/degree of comorbid disorders (greater presence of one disorder predicts more robust presentation of the other)

Yang Y et al., Twin Res Hum Genet, 2016,49(10):1493-502.

Swartz KL et al., Arch Gen Psychiatry,2000,57(10):945-50.

Bipolar Disorder

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Bipolar Disorder?

Association Between Migraine and Bipolar Disorder

REFERENCE ODDS RATIO

• IHS-Based

Breslau (1998)Bipolar I Migraine w/ aura 7.3

Migraine without aura 2.4

Bipolar II Migraine w/ aura 5.2 Migraine w/out aura 2.5

• Non IHS-Based

Merikangas, et al (1990)Bipolar spectrum 2.9

Low NCP, Merikangas KR. The comorbidity of migraine. CNS Spectrums 2003;8(6):433-444.

Migraine and Mood Disorders

� There is about a 2.5 to three-fold higher relationship between migraine and bipolar spectrum disorders

� Bipolar spectrum disorders, MDD, recurrent depression, suicide attempts exhibit a stronger relationship for migraine with aura than for migraine without aura.

� Greater in clinic than community; CM associated with higher levels than EM; higher prevalence in MOH

Jette N et al. Headache 2008;48:501-516; Ratcliffe et al. Gen Hospit

Psychiatry 2009;31:14-19; Radat F et al. Cephalalgia 2005;25:519-522;

Swendsen, 2004; Verri, et al, 1998; Juang, et al, 2000; Zwart et al, 2003

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Predictors of Bipolarity in Depressed Patients

� Psychotic symptoms� Family history of bipolar disorder� Early age of onset & high freq of depressive

episodes

� High freq of suicidal thoughts � High rates of divorce, job changes� History of erratic, impulsive behavior

� Quicker onset or improvement of symptoms� Pharmacologic-induced mania or hypomania� Hypersomnia, psychomotor retardation,

profound fatigue, overeating more common

Bowden, 2001; Judd et al, 2002; Frye et al, 2004

Anxiety

Association Between Migraine and Anxiety: Community Studies

REFERENCE ODDS RATI O______

Panic GAD OCD Phobia

Breslau (1998)

Migraine w/ aura 10.4 4.1 5.0 2.9Migraine without aura 3.0 5.5 4.8 1.8

Swartz et al (2000) 3.4 1.3 1.4

Breslau et al (2001) 3.7 Merikangas et al (1990, 1993) 3.3 5.3

McWilliams (2004) 3.9

Saunders et al (2008) 3.6Wang et al (2007) 6.6

Goulart et al (2014) 2.3 4.0

Hamelsky SW, Lipton RB (2006) 3.7

Smitherman TA et al. Headache, 2013,53:23-45.Goulert AC et al. Headache, 2014;54(8):1310-9.

Hamelsky SW & Lipton RB. Headache, 2006,46(9):1327-33.

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Comorbidity Summary

� Migraine has consistently been associated with psychiatric disorders such as depression, anxiety, and bipolar disorders

� For medical patients, treat comorbid psychiatric conditions both pharmacologically and psychologically

� For psychiatric patients, address/treat comorbid medical issues

Migraine Comorbidity

� The number of Migraine comorbities with support from population studies has increased into double digits

� Piecemeal, fragmented, and specialty driven approaches to the migraine comorbidity problem has not served the field or patients well

� Need to identify replicable “essential feature” patient subtypes

� Such subtypes could provide clues to shared pathophysiological mechanisms

Holroyd K. Disentangling the Gordion knot of migraine comorbidity. Headache 2007; 47(6):876-877.

Migraine Comorbities---

Treatment

Now what????

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Monotherapy vs. Polytheraphy

� Idea is to use one drug to treat migraine and associated conditions whenever possible (“two-fer”)

� Simpler, less cost, less AE’s, eliminate potential drug interactions

� Physicians often alter preferred choice for migraine prevention and comorbidity when both present together.

� There is risk of only treating one condition optimally.

� Physicians often sell value of “treating two conditions with one RX” more than controlling both conditions effectively.

Silberstein, Dodick, et al Headache 2007;47:585-599

Likely Will Need More than Pharmacotherapy

Learning, Conditioning, & Cognitive issues

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Biobehavioral Model

� Abandon organic/psychogenic distinction� Conditions that control chronic headache are

multidimensional involving cognitive/emotional/behavioral factors as well as biological processes

� As a headache disorder becomes more severe and chronic, faulty learning and behavior become important maintenance factors.

Psychobiological Model

As a headache disorder becomes more severe and chronic, faulty learning and behavior become important maintenance factors.

“Trait negative affectivity refers to the

predisposition to a wide range of aversive

mood states like anxiety or depresssion,

that are stable across time, independent of objective stress. Trait negative affect,

elevated in chronic headache, is related

to increased intensity of somatic symptoms”.

Watson D, Pennebaker JW. Health complaints, stress, and distress: exploring the central role of negative affectivity. PsycholRev. l989; 96: 234-254.

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Evaluate Pt’s Needs/Concerns

“The actual methods by which physicians may choose, or be forced to treat their patients is, of course, infinitely varied, as are the patients themselves. There is only one cardinal rule: one must always listen to the patient. For if migraine patients have a common and legitimate second complaint besides their migraines, it is that they have not been listened to by physicians. Looked at, investigated, drugged, charged---but not listened to.” (p. 230)

Migraine-Understanding a Common Disorder

Oliver Sacks, M.D. (1985)

Evaluate Pt’s Needs/Concerns

� The “anxious/depressed patient”

� The “co-morbid patient”

� The “angry patient”

� The “defensive patient”

� The “yes/but patient”

� The “show-me patient”

� The “‘slick’ patient”

� The “relieved patient”

Expectancy Model vs. Conditioning Model

Stewart-Williams S & Podd J. Psychological Bulletin. 2004,2:324-340.

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Cognitive Psychology

� S-R model not adequate

� Species specific

behavior

� Genetic/Organismicpredispositions

S-O-R model

Factors Thought to Contribute to Expectancy

� Biological predispositions (co-morbidities)

� Modeling

� Conditioning

� Suggestion

� Motivation

� Anxiety Reduction

Cognitive Rx

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Stimulus Organism Response

Antecedent Belief Consequence

(Behavior)

“If I don’t take the

pills, all my

headaches will

become

incapacitating.”

Julian Rotter

Internal

vs.

External

Locus of Control

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Locus of Control

Internal

� Patient is task-specific

� “Good historian”

� Action-oriented

(“I have a plan”)

� Sets realistic goals

External

� Helplessness (“fix me”)

� Fatalistic/global

� “Suffering” or “hope without action” orientation

� Looking for “magic pill”

� “Yes...but”

“Patients belonging to subgroups

believing that pain was enduring and mysterious were least likely to use

cognitive coping strategies and more

likely to catastrophize with resultant lowering of pain tolerance”.

Williams DA, Keefe FJ. Pain beliefs and the use of cognitive-

behavioral coping strategies. Pain. 1991; 46: 185-190.

Aaron Beck

� Maladaptive Patterns of Thought

� Dichotomous Reasoning

� Arbitrary Inference

� Overgeneralization

� Magnification (catastrophizing)

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Chronic pain patients (across groups)

were significantly different from healthy controls in pain-related negative self- statements, helplessness, and active coping self-statements. Improvement in therapy was associated with lessening of negative cognitions rather than strengthening of positive ones.

Flor H, Behle DJ, & Birbaumer N. Assessment of pain

related cognitions in chronic pain patients. Behav Res

Ther, 1993; 31: 63-73.

“There’s nothing

else that can be

done…I’ve tried

the meds for a

week and my HA’s

are no better…”

M. E. P. Seligman

� Concept of “Learned Helplessness”

� Laboratory analogue of depression

� Expectation of independence between behavior and

outcome (catastrophizing)

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“I should be able

to ignore my

migraines and

work each day…It

is a sign of

weakness ”

Albert Ellis

� Rational Emotive Therapy

� Irrational Beliefs & Self-statements

� Shoulds/Musts

� “Awfulizing” (catastrophizing)

“I woke up with a mild

HA this morning and

decided that I couldn’t

go to school (again)

because I was afraid it

would get worse”

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Wilbert Fordyce

Pain

vs.

Suffering

Get the diagnosis right.

Get the chemicals right.Get the behaviors right.

Get the cognitions, beliefs, & expectations

right.

Thank you for your kind attention…