PSYCHIATRIC COMORBIDITY OF STROKE AND MIGRAINE
From Psychiatric Comorbidities in Mental Disorders, presented by the University of Iowa Roy J. and Lucille A.
Carver College of Medicine and the American Academy of Clinical Psychiatrists
| PSYCHIATRIC COMORBIDITY ASSOCIATED WITH STROKE —Robert G. Robinson, MD, Professor and
Head, Department of Psychiatry, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa
City
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| Effect of depression on stroke outcomes: studies show that, compared to patients with no depression after
stroke, patients with major or minor depression after stroke have 2 to 2.5 times less improvement in activities
of daily living (ADLs), significantly more cognitive impairment, and higher mortality rates
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| Effect of treatment of poststroke depression: trials showed nortriptyline, trazodone, and citalopram better
than placebo in treating poststroke depression; when compared to patients who did not respond to antidepressant,
those who did respond showed improvement in ADLs; patients who responded to treatment, whether antidepressant
or placebo, showed improvement in cognitive function and maintained that improved level over
2-yr follow-up; in trial, depressed and nondepressed patients who had acute stroke received nortriptyline, fluoxetine,
or placebo for 12 wk; during 9-yr follow-up, depressed patients who received active treatment had
better mortality rates than those who received placebo
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| Activities of daily living: patients who received nortriptyline or fluoxetine beginning 1 mo after stroke had
more improvement in ADLs than those whose treatment began 4 mo after stroke; improvement depended on
early treatment after stroke, not on whether patients depressed; speaker suggests that patients, depressed or
not, given antidepressants within first month after stroke recover better than those given antidepressants at
later date; he also questions whether all patients who have had stroke should be evaluated by psychiatrist and
be given antidepressants to help improve recovery
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| Executive function: in same study (depressed or nondepressed patients treated with nortriptyline, fluoxetine, or
placebo after acute stroke), patients who received active treatment improved more than those who received
placebo and maintained that improvement for 21-mo follow-up
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| Morbidity (study 4 wk after stroke; 137 nondepressed patients treated with sertraline or placebo for 1
yr): patients who received placebo had significantly more cardiovascular morbidity and required more hospitalizations
than those who received sertraline; however, not clear that this effect completely nondepression related
because some patients developed depression during 1-yr follow-up; more patients on placebo than on
sertraline developed depression
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| Mortality: depressed and nondepressed patients treated with fluoxetine, nortriptyline, or placebo in double-
blind randomized trial; treated for 12 wk; at end of ≥7-yr follow-up, survival rates significantly higher in
those who received active treatment, whether depressed or nondepressed at beginning of trial; some patients
developed depression after antidepressants discontinued, but their survival rate still higher than that of those
who received placebo; speaker suggests this may be due to effect of antidepressants on neurogenesis, but unknown
exactly what that effect is and where it occurs; 70% of deaths related to cardiovascular disease, but
rate of death much higher in group that received placebo; outcomes not affected by presence of depression at
start of trial, but affected by whether patients received antidepressant or placebo
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| Summary: poststroke depression associated with impaired recovery in ADLs and in cognitive function; increased
risk for death during first 7 yr after stroke; poststroke depression may be treated effectively with citalopram
or nortriptyline; effective treatment significantly improves cognitive function and ADLs and reduces
mortality; beneficial effect of antidepressants on physical and cognitive recovery and mortality after stroke
can be independent of depression and may last for several years; these findings might be construed to indicate
that some neurophysiologic mechanism, perhaps neurogenesis, is turned on or off for extended periods by antidepressants
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| COMORBIDITY OF MIGRAINE WITH MENTAL AND PHYSICAL DISORDERS —James R. Merikangas,
MD, Clinical Professor of Psychiatry and Behavioral Medicine, George Washington University School of Medicine,
Washington, DC
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| Introduction: “migraine is a neurologic disease; it is not just a headache anymore”; major symptom is pain,
which may occur in areas other than head; in United States, 28 million migraineurs >12 yr of age; more common
in women; 1 in 4 households has ≥1 migraineur; most people with migraine 25 to 55 yr of age; 20% of
women have migraine at some time in life; migraine peaks during reproductive years in both sexes; migraine in
children often manifested as gastrointestinal symptoms
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| Characteristics of migraine: imprecise diagnostic criteria; no diagnostic tests; no objective markers; symptoms
may vary from one attack to another; expression age dependent and sex dependent; comorbid with other
disorders; migraine without aura often confused with sinus headache, and many medications that treat sinus
headache (eg, antihistamines, analgesics, caffeine) also treat migraine; migraine usually unilateral (but can
switch sides)
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| Other headaches: cluster headaches—occur in bouts, usually severe, last short time; may occur every day for
1.0 to 1.5 wk once or twice yearly; best and quickest treatment pure oxygen; lithium, even small dose, prophylactic
for cluster headache; eschew narcotics for all headaches in general; hemicrania continua—also
called indomethacin-responsive headache; usually severe, may last long time; treat with daily indomethacin;
physical activity usually makes migraine worse, so if patient “running around in the emergency room, banging
his head” with pain, he or she does not have migraine; tension headache—muscle tension has never been
documented in “tension” headaches; speaker posits that many tension headaches are really due to temporomandibular
joint disorder
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| Features common to migraineurs: hyperosmia; photophobia; phonophobia; visual signs include one-sided
homonymous visual symptoms
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| Red flags: new or different headache; “thunderclap” headache—may be due to intracranial hemorrhage;
worst headache ever—obtain immediate computed tomography (CT; magnetic resonance imaging [MRI]
may provide more accurate diagnosis, but takes too long); obtain CT before doing lumbar puncture; if cerebrospinal
fluid clear, have it centrifuged immediately to look for xanthochromia, which suggests subarachnoid
hemorrhage; focal neurologic signs or symptoms—can occur in conjunction with migraine, but if
sudden and a change, obtain CT; change in existing headaches; new-onset headache after 50 yr of age—“a
brain tumor till you rule it out”; headache associated with systemic symptoms—may be due to cancer or its
treatment
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| Migraine pathophysiology: historically, migraine seen as “nerve storm”; “think of migraine as being on a continuum
from epilepsy, where the nerve storm is sudden and quick, to migraine, where it lasts a little longer, to
manic depression, which is a nerve storm of more duration”; speaker’s current study examines comorbidity of
bipolar illness and migraine; positron emission tomography (PET) and single photon emission computed tomography
(SPECT) show migraine originates deep in brainstem and sends out impulses to dura mater and
covering of blood vessels; study showed that electrical impulses in cortex spread slowly, resulting in visual
disturbances when they arrive at occipital lobe and other disturbances when they arrive at parietal lobes; dilatation
and inflammation of blood vessels causes pain, which is why anti-inflammatory drugs and vasoconstrictors
help
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| Genetic epidemiology: if person has migraine, 3- to 4-fold increased risk that other family members have it;
40% to 50% of variance in familial aggregation of migraine can be attributed to common genes; genetic basis
for familial hemiplegic migraine has been found, but few families have this; if parent has migraine, increased
risk for child having it and with earlier onset
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| Triggers: many patients already know their dietary triggers; fluctuations in reproductive cycle; light, smells,
sounds; changes in sleep; changes in activity and anxiety; exercise; head injury (headache often seen in people
with closed head injury who do not have skull fractures or intracranial bleeding)
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| Migraine in women: incidence increases after puberty; attacks increase during first trimester of pregnancy; attacks
occur on days 2 and 3 of menstrual cycle; increase in attacks associated with oral contraceptives and
hormone replacement therapy; incidence decreases after menopause; studies of hormonal treatment of migraine
conflicting, “sometimes the hormones help, sometimes they make it worse”
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| Comorbidity of migraine: conditions shown to be associated statistically include myocardial infarction, hypertension,
ulcers, colitis, allergies and asthma, epilepsy, and multiple sclerosis
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 | Stroke: in women in general population, prevalence 9 per 100,000; in migraineurs, prevalence 20 per 100,000;
in women who take oral contraceptives, absolute risk 75 per 100,000; greatest risk factor is smoking;
speaker recommends aspirin (81 mg/day) for “everybody” who can take aspirin
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| Migraine and psychiatric disorders: historical descriptions of migraine include observers noting depression,
drowsiness, mild mental and physical depression, sense of apathy, lack of energy, and fatigue; these are also
symptomatic of bipolar depression; speaker observes that in his experience, best prophylactic for migraine is
phenelzine (Nardil), which also treats anxiety and depression; studies show migraine often comorbid with
major depressive disorder, panic disorder, and general anxiety disorder; found that tricyclic antidepressants
especially good treatment in people who have migraine and depression or anxiety; speaker believes that selective
serotonin reuptake inhibitors (SSRIs) ineffective in migraine; manic symptoms, such as restlessness, irritability,
verbosity, driving at excessive speeds, and poor judgment also observed in migraineurs; odds ratio of
family member with affective disorder increased in people with migraine and affective disorder
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| Treatment: include family members in treatment program; eschew narcotics
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| International Headache Society criteria for preventive treatment: ≥2 attacks per month with ≥3 days of
disability per month; failure of or contraindications to treatments for acute migraine; use of abortive medications
>2 times/wk; presence of uncommon migraine (eg, hemiplegic migraine, migrainous infarction);
prophylactic medications include β-blockers, amitriptyline and valproic acid (eg, Depakote); speaker dislikes
because of side-effect profile; anecdotal reports of efficacy of enalapril, but no controlled studies; consider
using monoamine oxidase inhibitor and β-blocker
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| Treatment of migraine and mood disorders: consider amitriptyline (10-150 mg), nortriptyline (10-200 mg),
doxepin (10-150 mg), or phenelzine (15-60 mg); valproic acid or topiramate also may be useful
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| Summary: migraine associated with several physical disorders, particularly allergies and cardiovascular conditions;
onset of allergies and asthma frequently precede that of migraine; migraine is risk factor for stroke and
cardiovascular diseases; mood and anxiety disorders associated with migraine in clinical and community
samples; anxiety disorders associated with migraine in childhood and adolescence, whereas mood disorders,
particularly bipolar spectrum disorders and atypical depression, characterize adults with migraine; migraine
should be included in clinical evaluation and treatment of mood disorders
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Suggested Reading
Abbate-Daga G et al: Anger, depression and personality dimensions in patients with migraine without aura.
Psychother Psychosom 76:122, 2007; Beghi E et al: Headache and anxiety-depressive disorder comorbidity:
the HADAS study. Neurol Sci 28(Suppl 2):S217, 2007; Frediani F, Villani V: Migraine and depression. Neurol
Sci 28(Suppl 2):S161, 2007; Hamelsky SW, Lipton RB: Psychiatric comorbidity of migraine. Headache
46:1327, 2006; Jorge RE et al: Mortality and poststroke depression: a placebo-controlled trial of antidepressants.
Am J Psychiatry 160:1823, 2003; Mongini F et al: Accompanying symptoms and psychiatric comorbidity
in migraine and tension-type headache patients. J Psychosom Res 61:447, 2006; Narushima K et al: Does
cognitive recovery after treatment of poststroke depression last? A 2-year follow-up of cognitive function associated
with poststroke depression. Am J Psychiatry 160:1157, 2003; Narushima K et al: Effect of antidepressant
therapy on executive function after stroke. Br J Psychiatry 190:260, 2007; Narushima K, Robinson RG:
Stroke-related depression. Curr Atheroscler Rep 4:296, 2002; Narushima K, Robinson RG: The effect of
early versus late antidepressant treatment on physical impairment associated with poststroke depression: is
there a time-related therapeutic window? J Nerv Ment Dis 191:645, 2003; Robinson RG: Poststroke depression:
prevalence, diagnosis, treatment, and disease progression. Biol Psychiatry 54:376, 2003; Robinson RG:
Vascular depression and poststroke depression: where do we go from here? Am J Geriatr Psychiatry 13:85,
2005; Spalletta G et al: The etiology of poststroke depression: a review of the literature and a new hypothesis
involving inflammatory cytokines. Mol Psychiatry 11:984, 2006; Torelli P et al: Psychiatric comorbidity and
headache: clinical and therapeutical aspects. Neurol Sci 27(Suppl 2):S73, 2006.
Educational Objectives
| The goal of this program is to improve the management of the psychiatric comorbidities of stroke and migraine.
After hearing and assimilating this program, the clinician will be better able to:
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| 1. Explain the effect of depression on stroke outcomes.
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| 2. Discuss the effect of treatment of depression on poststroke recovery of activities of daily living, cognitive
function, morbidity, and mortality.
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| 3. Compare and contrast migraine symptoms with those of other headaches and other conditions.
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| 4. Describe the pathophysiology of migraine.
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| 5. Prescribe prophylaxis for and treatment of migraine that is comorbid with mood disorders.
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Faculty Disclosure
In adherence to ACCME Standards for Commercial Support, the Audio-Digest Foundation requires all faculty
members to disclose relevant financial relationships within the past 12 months that might create any personal
conflict of interest. Any identified conflicts were resolved to ensure that this educational activity promotes quality
in health care education and not a proprietary business or commercial interest. For this program, Dr. Robinson
disclosed that he is a consultant to Avanir and Hamilton Pharmaceuticals.
Acknowledgements
Drs. Robinson and Merikangas were recorded at Psychiatric Comorbidities in Mental Disorders, held March 31
to April 1, 2007, in Washington, DC, and sponsored by the University of Iowa Roy J. and Lucille A. Carver
College of Medicine and the American Academy of Clinical Psychiatrists. The Audio-Digest Foundation thanks
the speakers and the sponsors for their cooperation in the production of this program.
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