ABSTRACT: The bipolar spectrum has been shown to occur with
increased frequency in migraineurs. Previous studies have primarily focused on bipolar I
and II. The current study also includes the "softer, milder" end of the bipolar spectrum.
Identifying and recognizing bipolar illness is not simply an academic exercise; the clinical
stakes for missing the bipolar diagnosis are enormous. This study, in addition to migraine,
also evaluated the bipolar spectrum in cluster headache, as well as chronic tension headache
1200 consecutive migraine patients were evaluated according to DSM-IV guidelines. Results: Bipolar I:24
Bipolar II:28 Bipolar NOS: 34 Cyclothymia: 17. Total bipolar spectrum for migraineurs:
287 cluster headache patients were seen over 18 years. Results: Episodic cluster (141):
Bipolar I:2 Bipolar II: 4 Bipolar NOS: 1 Cyclothymia: 2 Total episodic: 9 (6.4%).
Chronic cluster (146): Bipolar I:2 Bipolar II:2 (Chronic) Bipolar NOS:2 Cyclothymia: 4
Total chronic: 10 (6.8%). Total bipolar spectrum for cluster patients: 19 (6.6%).
292 patients with chronic tension type headache, without migraine, were evaluated.
Results: Bipolar I:5 Bipolar II:3 Bipolar NOS:3 Cyclothymia:2. Total bipolar
spectrum for chronic tension headache:13 (4.5%).
The bipolar spectrum is seen relatively often in headache patients, particularly among
migraineurs (8.6%). Cluster headache patients had a slightly lower prevalence of
bipolar (6.6%). Chronic tension headache patients, without migraine, had the least
percentage of bipolar, (4.5%).
There has been a great deal of research describing the comorbidity of migraine/tension
headache with anxiety and depression.(1,2,3) Previous studies have documented the increased
association with migraine and the bipolar spectrum.(4,5) Those with bipolar spectrum have
also been shown to be more likely to suffer from migraine.(6,7) For cluster headache, and
chronic tension headache (without migraine), there have been few studies examining the
relationship with bipolar.
The bipolar spectrum tends to be underdiagnosed, with the full clinical spectrum being an
evolving concept. The mild end of the bipolar spectrum (bipolar II, cyclothymia, bipolar NOS)
is often missed. It is likely that 4% (or more) of the general population suffers from the
bipolar spectrum.(8) As bipolar complicates treatment, in a variety of ways, the clinical
stakes for missing bipolar are enormous. Bipolar and migraine share common genetic links,
and both are multifactorial in origin.
This study was done in order to assess the prevalence of bipolar in 3 distinct headache types:
migraine, cluster, and chronic tension (without migraine).
1200 consecutive migraine patients, 275 cluster pts., and 292 pts. with chronic tension
headache, without migraine, were evaluate. The diagnoses were based upon International
Headache Society criteria.(9) They were all patients at our headache center. Evaluation
was accomplished by the following: 1. chart review; 2. Mood Disorder Questionnaire;(10)
3. PHQ-9 patient questionnaire; and 4. interviews with patients and families.
Inclusion criteria included: 1. age 20 or older, and 2. diagnosis of migraine, cluster,
or chronic tension headache (without migraine). The lifetime prevalence of bipolar, including
the milder end of the spectrum, was assessed.
Bipolar illness was defined according to the criteria established by the Diagnostic and
Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV).(11) In addition, t
he modifications to DSM-IV by Akiskal were utilized in defining bipolar disorders.(12,13)
Bipolar I disorder was defined according to the DSM-IV criteria; there had to be at least
one episode, currently or in the past, of true mania.
Bipolar II was assessed according to DSM-IV. There had to have been one or more major
depressive episodes, plus at least one hypomanic episode; no mania or mixed episodes, and
these episodes must have caused significant distress or impairment in patient functioning.
Cyclothymic disorder was defined according to DSM-IV criteria - at least two years of
numerous periods of hypomania and numerous episodes of depressive symptoms that do not
meet criteria for major depressive episode. During the two-year period, the patient
could not have been without the symptoms for more than two months at a time, and no
major depressive episode, manic episode, or mixed episode could have been present during
the first two years of the disturbance. These symptoms had to cause clinically significant
distress or impairment in functioning and were not due to substance abuse or a medical
Bipolar disorder not otherwise specified (NOS) was defined according to DSM-IV, with
additions according to Akiskal.(12,13) Examples of patients included in this category
are those with (i) rapid alterations between manic and depressive symptoms that do not
meet minimal criteria for a full manic episode, or for a major depressive episode; (ii)
recurrent hypomanic episodes without intercurrent depressive symptoms; (iii) a presence of
a hyperthymic temperament as the prevalent, long-term functioning of the person; (iv) the
presence of a persistently agitated, angry, moody personality (temperamental instability),
particularly with a strong family history of bipolar disorder and/or a hypomanic reaction
to an antidepressant (up all night, mind racing, "wired"); (v) increased energy, and
lability of mood also were used as additional indicators of bipolarity. In addition,
criteria that was considered in the diagnosis of the ‘softer’ end of the spectrum include:
early onset of depression (prior to age 25, and certainly prior to age 17), atypical or
psychotic depressive episodes, postpartum depression, and lack of response to 3 or more
MIGRAINE: 1200 consecutive migraine patients were evaluated according to DSM-IV
guidelines. Results: Bipolar I: 24 Bipolar II: 28 Bipolar NOS: 34 Cyclothymia: 17.
Total bipolar spectrum for migraineurs: 103 (8.6% of the total).
CLUSTER: 287 cluster headache patients were seen over 18 years.
Results: Episodic cluster (141): Bipolar I: 2 Bipolar II: 4 Bipolar NOS: 1
Cyclothymia: 2 Total episodic: 9 (6.4%). Chronic cluster (146): Bipolar I: 2
Bipolar II: 2 Bipolar NOS: 2 Cyclothymia: 4 Total chronic: 10 (6.8%). Total bipolar
spectrum for cluster patients: 19 (6.6% of the total).
CHRONIC TENSION (without migraine): 292 patients with chronic tension type
headache, without migraine, were evaluated. Results: Bipolar I: 5 Bipolar II: 3
Bipolar NOS: 3 Cyclothymia: 2. Total bipolar spectrum for chronic tension headache: 13
The bipolar spectrum is seen relatively often in headache patients, particularly among migraineurs.(4,5) The clinical stakes for missing bipolar are enormous; patients tend to bounce from antidepressant to antidepressant, with generally poor results, without being on adequate mood stabilizers. While diagnosis is crucial (see methods section), bipolar is not an easy condition to have, to deal with as a family member, or to treat. Treatment with adequate mood stabilizers may help, but we are often left with less than desirable results. As is the case with headache preventatives, we need better medications for the bipolar spectrum.
The clinical spectrum of bipolar is an evolving concept. Mania is better recognized than is hypomania (with milder bipolar features). Symptoms of mania include: euphoric mood, distractibility, flight of ideas, grandiosity, thoughtlessness or risk-taking, and excessive involvement in pleasurable activities (for example, sex, spending, gambling), pressured speech, an increase in activities, excited (or irritable) energetic mood, and insomnia.(14) Milder hypomanias are often missed, particularly if one relies solely on the patient’s history; it is crucial to talk with a family member or significant other. Hypomania does not meet full criteria for mania, but encompasses the same types of symptoms. In addition, brooding, irritable pessimism may be a manifestation of hypomania. During irritable, angry hypomanias many people will lose jobs or damage relationships. Further complicating diagnosis is the stigma that ‘manic-depression, or bipolar’ carries. Patients and families are often resistant to the diagnosis; there is a need for books that emphasize the milder end of the spectrum, as well as major revisions of nomenclature for the condition.
The comorbidity of migraine with anxiety/depression, and bipolar, has previously been described.(1-5) The lifetime prevalence of bipolar disorder probably is at least 4%.(8) Previous studies have indicated that from 7.2% (127,000 pt. mail survey) to 8.6% (1000 consecutive migraineurs) of migraine patients fit the bipolar spectrum.(4,5) Conversely, in assessing those with bipolar spectrum disorder for migraine, several studies have indicated that there is an increased risk for migraine in the bipolar population.(6,7) One study (n=36,984) indicated that, in the bipolar patients, 14.9% of the men and 34.7% of the women had a lifetime occurrence of migraine.(7) Additional studies in the bipolar population resulted in a migraine lifetime prevalence of 39.8%,(7) and 44%.(15,16)
The therapeutic implications for recognizing bipolarity are enormous. These patients, when not diagnosed, are often given antidepressants alone. While some patients may benefit from antidepressants, they generally are not particularly effective for the bipolar spectrum(17), and may trigger mania or hypomania.(18)
The therapeutic challenge for bipolar has been to find effective therapies for depression; most patients complain primarily of the depression, and fewer medications are effective for the depression than for the hypomania. Rational polypharmacy is often utilized. Lithium has a long, solid track record for the treatment of acute bipolar depression, but much less for the prevention of depression.(19) Lamotrigine has been beneficial for treating acute depression, as well as for prevention.(20) Lamotrigine is generally fairly well tolerated, and may help certain headache types as well. However, the small incidence of the serious drug rash(approximately 1:2000 pts.) has led to an underutilization of lamotrigine for bipolar depression.
Divalproex sodium has been effective for certain headache types, as well as for treating the depression associated with acute mixed mania. It’s efficacy in preventing bipolar depression is less clear. (20)
The atypical (second-generation) antipsychotics may be of benefit for some patients with bipolar depression, as well as treating the mania/hypomania.(21) Quetiapine has the best data at present, but does carry at least a mild to moderate liability for the metabolic syndrome. While this class may help certain aspects of the bipolarity, the medications are probably most useful as adjuncts to lithium or the antiepileptics.
The recognition of the bipolar spectrum is crucial if we are to effectively treat the patient with headaches.
- Baskin SM, et al. Mood and anxiety disorders in chronic headache. Headache. 2006;46 [Suppl 3]:S76-S87.
- Merikangas KR, et al. Comorbidity of migraine and psychiatric disorders. Neurol Clin. 1997;15:115-123.
- Lake AE, et al. Headache and psychiatric comorbidity: Historical context, clinical implications, and research relevance. Headache. 2005;45:493-506.
- Robbins L. Bipolar Spectrum in Cluster Headache Patients. AJPM. 2006;16:44-47.
- Ettinger AB, et al. Prevalence of bipolar symptoms in epilepsy patients vs other chronic health disorders. Neurology. 2005;65:535-540.
- McIntyre RS, et al. The prevalence and impact of migraine headache in bipolar disorder: Results from the Canadian community health survey. Headache. 2006;46:973-982.
- Low NC, et al. Prevalence, clinical correlates, and treatment of migraine in bipolar disorders. Headache. 2003;43:940-949.
- Hirschfeld RM, et al. Screening for bipolar disorder in the community. J Clin Psychiatry. 2003;64:53-59.
- Headache Classification Committee of the International Headache Society. The International Classification of Headache Disorders, 2nd edition. Cephalalgia. 2004;24(suppl 1)1-160.
- Hirschfeld RM, et al. Validity of the mood disorder questionnaire: a general population study. Am J Psychiatry. 2003;160:178-180.
- American Psychiatric Association. Diagnostic and statistical manual of mental disorders, 4th edition. Washington DC: American Psychiatric Association: 1994.
- Akiskal HS, et al. Re-evaluating the prevalence of and diagnostic compostion within the broad clinical spectrum of bipolar disorders. J Affect Disord. 59 (suppl 1):S5-S30,2000.
- Akiskal HS. Classification, diagnosis and boundaries of bipolar disorders, in Bipolar Disorder. Edited by Maj M, Akiskal H, Lopez-Ibor J, et al. London, Wiley, 2002, pp1-52.
- El-Mallakh R, Ghaemi S. Bipolar depression. Washington DC: American Psychiatric Publishing, Inc; 2006: pp 23-26.
- Fasmer OB. The prevalence of migraine in patients with bipolar and unipolar affective disorders. Cephalalgia. 2001;21:894-899.
- Fasmer OB, et al. Laterality of pain in migraine with comorbid unipolar depressive and bipolar II disorders. Bipolar Disord. 2002;4:290-295.
- Sachs G, et al. Effectiveness of adjunctive antidepressant treatment for bipolar depression. The NEJM. 2007;Vol.356,No.17, pp 1711-1722.
- El-Mallakh, et al. Antidepressants in bipolar depression, in El-Mallakh R, Ghaem S. Bipolar Depression. Washington DC, American Psychiatric Publishing, Inc; 2006:167-175.
- El-Mallakh R, Ghaemi S. Bipolar depression. Washington DC: American Psychiatric Publishing, Inc; 2006: pp 148-149.
- El-Mallakh R, Ghaemi S. Bipolar depression. Washington DC: American Psychiatric Publishing, Inc; 2006: pp 149-153.
- Calabrese J, et al. A randomized, double-blind, placebo-controlled trial of quetiapine in the treatment of bipolar I or II depression. Am J Psychiatry. 2005;162:1351-1360.