Epilepsia, 46(Suppl.
4):8–13, 2005
Blackwell Publishing, Inc.


C International League Against Epilepsy
Epidemiology of Bipolar Disorders
Michael Bauer and Andrea Pfennig
Charité-University Medicine Berlin, Campus Charité Mitte (CCM), Department of Psychiatry and Psychotherapy, Berlin, Germany
Summary: Bipolar, or manic–depressive, disorders are frequent
and severe mental illnesses associated with considerable morbid-
ity and mortality. Epilepsy and bipolar disorder could probably
share some aspects of pathophysiology because manic as well
as depressive symptoms are seen in patients with seizures, and
a number of antiepileptic drugs are effectively used in the acute
and prophylactic treatment of bipolar disorder. Epidemiologic
research suggests a dimensional composition of bipolar illness
at the population level. Apart from the DSM-IV diagnostic fea-
tures of bipolar I (mania and depression) and bipolar II (hypoma-
nia and depression), the concept of bipolar spectrum disorders
comprises a range of bipolar conditions with less obvious mani-
festations with estimated lifetime prevalence rates ranging from
2.8 to 6.5%. Expanding the definition of bipolar II disorders
shows that half of the patients currently diagnosed with a unipo-
lar depressive episode could suffer from unrecognized bipolar II
disorder, and about the same number of mild depressive patients
Bipolar, or manic–depressive, disorders are frequent,
severe, and often chronic mental illnesses. They are asso-
ciated with considerable morbidity and mortality, and for
many patients, an initial episode of mania or depression
evolves into a life-long illness. To prevent recurrence, sui-
cidal behavior, and chronicity, long-term pharmacologic
treatment is indicated early in the course of the disease.
Population data suggest an increased prevalence of de-
pression and bipolar disorders in patients with seizures,
and a number of antiepileptic drugs (AEDs) are used,
apart from lithium, in the short-term therapy and as long-
term mood stabilizers. Important epidemiologic aspects
of bipolar disorders are discussed in this article.
DISEASE CLASSIFICATION AND LIFETIME
PREVALENCE RATES
Bipolar disorders are classified within the framework of
the Diagnostic and Statistical Manual of Mental Disorders,
Fourth Edition (DSM-IV, published by the American Psy-
chiatric Association), which differentiates between Bipo-
Address correspondence and reprint requests to Dr. M. Bauer at De-
partment of Psychiatry and Psychotherapy, Charité-University Medicine
Berlin, Campus Charité Mitte (CCM), Schumannstrasse 20/21, 10117
Berlin, Germany. E-mail: michael.bauer@charite.de
8
could be minor bipolars. Research efforts to refine the diagnostic
criteria of bipolar disorder aim at an earlier and complete recog-
nition of the disease to provide appropriate pharmacological and
nonpharmacological treatment early in the course of the illness to
anticipate individual suffering, suicidal behavior, and increased
socioeconomic costs for society. This article also discusses risk
factors, comorbid conditions, course of illness, as well as the
individual and socioeconomic impact of bipolar disorders.
Conclusions: The findings suggest reconceptualizing bipo-
lar illnesses as highly recurrent, malignant disorders that oc-
cur far more frequently than previously thought. Interdisci-
plinary knowledge transfer could help to increase our under-
standing of the pathophysiology of these disorders as well as
provide grounds for better recognition and treatment of patients
with manic and/or depressive symptoms. Key Words: Bipolar
disorders—Manic–depressive disorders—Epidemiology, Mood
stabilizer.
lar I (manic or mixed episodes in the course of disease
apart from depressive episodes), Bipolar II disorder (hy-
pomania for ≥4 days but no manic states in the course of
disease, apart from depressive episodes), and bipolar dis-
order not otherwise specified (Bipolar NOS) (1). The last
mentioned includes patients experiencing bipolar features
that do not meet the criteria for bipolar disorder (i.e., hy-
pomania without depressive episodes or bipolar disorder
due to medical conditions). Cyclothymia forms a distinct
diagnosis requiring ≥2 years of fluctuating mood distur-
bances with hypomanic and depressive states insufficient
in severity to meet the criteria for Bipolar I or II.
According to the International Statistical Classification
of Diseases and Related Health Problems, 10th Revision
(ICD-10; 2), a diagnosis of bipolar affective disorder re-
quires manic, hypomanic, or mixed episodes. The term
“other bipolar affective disorders” includes Bipolar II and
recurrent manic episodes, and Bipolar NOS again com-
prises patients experiencing bipolar features that do not
meet the criteria for bipolar disorder. A separate classi-
fication exists for manic episodes independent of bipo-
lar disorder available in case only one manic episode has
been observed. Cyclothymia is defined as persistent in-
stability of mood involving mild depression and mood
elations.
 15281167, 2005, s4, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/j.1528-1167.2005.463003.x by Muni University, Wiley Online Library on [03/03/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
EPIDEMIOLOGY OF BIPOLAR DISORDERS 9

TABLE 1. Lifetime prevalence rates of bipolar disorders

Diagnosis (DSM-IV) Study/author Year Country Lifetime prevalence

Bipolar I NCS/Kessler et al. 1994 U.S.A. 0.4

Bipolar I and II ECA/Regier et al. 1988 U.S.A. 1.2
NCS/Kessler et al. 1994 U.S.A 1.6
Weissman et al. 1996 Cross-national 0.3–1.5
NHANES III/Jonas et al. 2003 U.S.A. 1.6
Bipolar II Oliver and Simmons 1985 U.S.A. 3.0
Weissman et al. 1991 U.S.A. 0.6
Stefansson et al. 1991 Iceland 0.5
Bipolar spectrum Weissman and Myers 1978 U.S.A. 3.0
Oliver and Simmons 1985 U.S.A. 3.3
Heun and Maier 1993 Germany 6.5
Angst 1998 Switzerland 2.8

NCS, National Comorbidity Study; ECA, Epidemiologic Catchment Area study; NHANES III, 3rd National Health and Nutrition Examination Survey.

Rapid-cycling bipolar disorder is a malignant form
of bipolar illness characterized by four or more disease
episodes during the previous 12-month period (3). Rapid
cycling affects ∼15% of bipolar patients and is established
either from the beginning or develops in the course of the
disease. This subtype is associated with increased depres-
sive symptoms and risk for suicidal behavior (4).
Lifetime prevalence rates of bipolar disorder are esti-
mated to range from 1 to 5% in the general population
(5–8). The median lifetime prevalence found in 11 stud-
ies reviewed by Wittchen (9) is 1.3% (range, 0.6–3.3).
Lifetime prevalence of Bipolar II disorder is suggested to
range from 0.5 to 3.0% (10–14, see Table 1 for prevalence
rates estimated in different studies).
Epidemiologic research suggests a dimensional compo-
sition of bipolar illness at the population level. The concept
of bipolar spectrum disorders (proposed by 15; refined by
16 and 17) comprises a range of bipolar conditions with
less-obvious manifestations. Estimates of lifetime preva-
lence rates for bipolar spectrum disorders range from 2.8
to 6.5% (10,11,18–20). Table 2 shows the classification
approach used by Angst in 2003 (21).
TABLE 2. Bipolar spectrum conceptualized by Angst et al.
2003 (ref. 21)
Classification Description
Bipolar I Hospitalized mania plus major depression
Bipolar II DSM-III-R major depressive episodes associated
with
(a) a hypomanic syndrome as defined above, or
(b) hypomanic symptoms only
Minor bipolar Dysthymia, minor depression, or recurrent brief de-
disorder pression associated with
(a) the hypomanic syndrome or
(b) hypomanic symptoms only
Pure hypomania (a) a hypomanic syndrome without any diagno-
sis of depression, and
(b) hypomanic symptoms only
DSM-III-R, Diagnostic and Statistical Manual of Mental Disorders,
3rd revised edition.
Strong support has been given for expanding the def-
inition of bipolar II disorders (22–24). In an attempt to
validate the Zurich study data, Angst et al. challenged the
DSM-IV diagnostic requirements for hypomania, suggest-
ing that the demanded length of the hypomanic state of ≥4
days may be too restrictive. With the established DSM-IV
criteria, 0.5% of patients had Bipolar I disorder, 1.7% had
Bipolar II disorder, and 21.3% had Major depressive dis-
order. With newly defined “hard” and “soft” Zurich crite-
ria, the prevalence of patients with Bipolar II was 5.3 and
11.0%, respectively, and the percentage of patients with
Major depressive disorder was reduced to 17.1 and 11.4%.
The findings imply that up to half of the patients currently
diagnosed with a unipolar depressive episode could suffer
from unrecognized Bipolar II disorder and about the same
proportion of mild depressive patients from minor bipolar
disorder (21).
THE CHALLENGE OF RECOGNIZING BIPOLAR
DISORDERS
Bipolar disorders are not easy to recognize because
many symptoms overlap with other psychiatric disorders,
comorbidity is common (both psychiatric and somatic),
patients often lack insight into their illness (especially for
hypomanic states), and stigmatizing societal environments
are only slowly changing (see also 25,26). In a recent
survey using a validated screening instrument (the Mood
Disorder Questionnaire) in 127,000 adult U.S. citizens,
the overall rate for Bipolar I and II disorders, weighted
to match the 2000 U.S. Census demographics, was 3.4%
(3.7% after adjustment for nonresponse bias). Supporting
previous findings, only 19.8% of individuals with posi-
tive screening reported having previously been diagnosed
with bipolar disorders by a physician, whereas 31.2% re-
ported having received a diagnosis of unipolar depression
(27; see also 28). Identifying hypomanic episodes is not
an easy task because patients are usually not functionally
impaired; instead, they often show increased achievement
potential. However, hypomania is by no means benign, as

Epilepsia, Vol. 46, Suppl. 4, 2005


10 M. BAUER AND A. PFENNIG
it is accompanied by a high risk for suicidal behavior and
social impairment and is followed by manic episodes in
10–15% of cases in the course of illness (21,29).
The scientific and clinical endeavors to refine the di-
agnostic criteria of bipolar disorders aim at building the
groundwork for an earlier and complete recognition of
the disease. This provides the chance for choosing the ap-
propriate pharmacological and nonpharmacological treat-
ment early in the course of the disease to anticipate
individual suffering, suicidal behavior, and increased so-
cioeconomic costs for society.
Pathophysiology
Despite major research achievements, the underlying
pathophysiology of bipolar disorders, including molecular
causes and mechanisms, is still obscure. Imaging studies
(reviewed by Bruno in this volume) have been variable,
with suggested abnormalities in prefrontal cortex, lim-
bic regions, striatum, ventricular volume, and in some in-
stances, cerebellum (30–34). With proton resonance spec-
troscopy, reduced levels of a potential marker for neuronal
density and viability were found in the dorsolateral pre-
frontal cortex of euthymic bipolar patients (35,36). Neu-
roanatomic studies show decreased neuronal and glial den-
sity in prefrontal cortex that appears to be more exten-
sive than in unipolar depression (37–40). Neurotransmit-
ter systems probably involved in the pathophysiology of
bipolar illnesses include serotonergic pathways, as well
as the hypothalamic–pituitary–thyroid and –adrenal sys-
tems (41–44). Examining the mechanisms of action of
mood stabilizers has provided clues to potential underly-
ing neurobiologic abnormalities in bipolar disorders (see
also 45,46).
Family studies have consistently demonstrated the ge-
netic liability of bipolar disorders. First-degree relatives of
affected individuals have a 10-fold increased risk for de-
veloping the disease compared to relatives of unaffected
controls (47). Twin and adoption studies have provided
evidence that genes strongly contribute to familial trans-
mission of the illness. Early-onset bipolar disorder appears
to be associated with increased familial risk, and studies
have identified other putative familial subtypes, includ-
ing lithium-responsive bipolar disorder and bipolar dis-
order with psychosis or comorbid panic disorder (48,49).
McGuffin et al. (50) applied statistical models to the data
of 67 twin pairs, estimating a heritability of 85% for bipo-
lar disorder, leaving only 15% of variance to individual
specific and/or nonfamilial environmental effects. They
estimated the genetic correlation of bipolar disorder and
depression to be 0.65 and of nonfamilial environment to be
0.59. Interestingly, 71% of the genetic variance in liability
to mania was not shared by depression (50).
Implications of gender
Gender influences both presentation and course of bipo-
lar disorders. Bipolar I disorder affects men and women
Epilepsia, Vol. 46, Suppl. 4, 2005
15281167, 2005, s4, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/j.1528-1167.2005.463003.x by Muni University, Wiley Online Library on [03/03/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
with equal frequencies. However, Bipolar II appears to be
more common in women. About 80–90% of patients with
the malignant type of rapid-cycling bipolar disorder are
women (51). Additionally, women are more likely to ex-
perience mixed mania and manic switches during antide-
pressant treatment (51). Comorbidity of somatic and psy-
chiatric disorders is more common in women than in men
(52). Finding the right treatment regimen can be challeng-
ing in women who wish to conceive as well as in pregnancy
and breast-feeding periods. Individualized risk–benefit as-
sessments are required to promote the health of the woman
and avoid or limit exposure of the fetus or infant to poten-
tial adverse effects of medication (52).
Psychiatric and somatic comorbidities
Lifetime prevalence rates of comorbid psychiatric and
medical conditions are increased in patients with bipolar
disorders, complicating the treatment and overall man-
agement of the disorder (53). About 22% of bipolar pa-
tients have an additional somatic condition, and 39% a
second psychiatric one (of that, two thirds are related to
substance abuse; 54). The Epidemiologic Catchment Area
(ECA) study demonstrated that a diagnosis of substance
abuse or dependence is found more often in bipolar pa-
tients than in those with any other Axis I disorder (12).
Substance-abusing bipolar patients show higher rates of
suicide attempts, panic attacks, and very fast cycling (55).
Goodwin and Hoven (56) found that the co-occurrence of
bipolar disorders and panic attacks was associated with
an earlier onset and more severe expression of the panic
disorder.
Prevalence rates of both depressive and bipolar spec-
trum disorders in persons with epilepsy appear to be higher
than those in the general population. Recent data from
community samples show rates significantly above those
in patients with and without other chronic diseases (57).
Mania is reported less frequently than depression (58).
Age at onset and course of disease
Unlike unipolar depression, bipolar disorders are man-
ifested to a great extent in the adolescent and young-adult
years (see 59). The peak age at onset of the first symp-
toms of bipolar disorder is between age 15 and 19. The
median age at onset of 2,839 patients with bipolar dis-
orders recorded by the Stanley Center Bipolar Disorder
Registry was 17.5 years (mean, 19.8 years; 60). Bipolar
disorders can appear before puberty; however, this is rare
and difficult to distinguish from other severe psychiatric
disorders such as schizophrenia, unipolar depression, and
attention-deficit/hyperactivity disorder (ADHD) (61,62).
Elderly patients also can have symptoms of bipolar dis-
orders for the first time in old age. However, manic and
depressive symptoms in this age group have usually been
present for many years, and in mild cases, have often gone
untreated. Onset of mania after age 60 is less likely to be
associated with a family history of bipolar disorder and

EPIDEMIOLOGY OF BIPOLAR DISORDERS
more likely secondary to medical causes other than bipo-
lar disorders [e.g., neurologic (trauma, neoplasm, multiple
sclerosis, stroke, epilepsy), endocrine (hyperthyroidism,
Cushing disease), infectious (AIDS), and inflammatory
(systemic lupus erythematosus) disorders (63)].
Usually a delay of 5–10 years is found between the first
episode of a bipolar disorder and the age at first treatment
or hospitalization (64). In a study of 450 bipolar patients,
the observed latency from the first episode of bipolar ill-
ness to the start of maintenance treatment averaged 7.8
years (median, 5 years), during which time patients expe-
rienced a mean of 9.4 episodes (median, five episodes).
In the years before maintenance treatment, patients were
ill ∼46.5% of the time, and 28.7% of subjects had at least
two episodes per year (65). Leverich et al. (66) found a
mean age at first treatment of 29.2 years in their sample
of 631 bipolar patients.
Manic–depressive disorders have a high rate of recur-
rence (>90% of individuals who have a single manic
episode will have future episodes). The natural course of
the illness and its phenotypic expression are highly vari-
able. It has been estimated that without adequate treat-
ment, the average patient experiencing the onset of bipo-
lar disorders at age 25 years will have a few episodes;
however, 10–15% of patients will undergo >10 episodes
(64,67). The prevalence of residual depressive symptoms
was estimated to be 40–85% in bipolar patients, showing
positive associations with recurrences (68).
An early onset of bipolar disorders increases the risk for
a severe course and poor outcome of the disease. The risk
for having the rapid-cycling type (69), suicidal ideation,
and comorbidity with substance abuse–related disorders
also is increased (69–71). Other predictors of poor out-
come include childhood psychopathology (72), being fe-
male (see gender differences and 73), and poor adherence
to treatment (74).
Increased suicide risk
Suicidal behavior is the most serious consequence of
bipolar disorders, reaching a lifetime prevalence of suicide
attempts of up to 30% (5,75,76). The odds ratio for sui-
cide attempts was 6.2 in the subjects of the ECA database
versus controls (compared with 3.1 in unipolar depres-
sion (77,78). Up to 20% of bipolar patients die of suicide.
Data from the Stanley Foundation Bipolar Network show
that several factors are associated with an increased risk
for suicidal behavior in bipolar patients, including genetic
and familial variables, childhood and recent environmen-
tal adversities, loss of social and medical support, psy-
chiatric comorbidity, and a more severe course of bipolar
illness (79). An early and appropriate treatment provides
the background for effective prevention of suicidal mor-
tality (5). Lithium proved to be the most efficient drug
in long-term treatment of both unipolar and bipolar pa-
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11
tients, reducing the risk for suicidal acts in Bipolar I and
II patients by 82 and 67% (80).
HEALTH-RELATED QUALITY OF LIFE AND
SOCIOECONOMIC BURDEN
Studies assessing the impact of bipolar disorders on the
health-related quality of life show outcomes resembling or
even worse than that seen in patients with chronic somatic
and some other psychiatric diseases (81–84).
Adding to the suffering of bipolar patients and their
families, the condition significantly increases costs for
society (85). At present, estimated annual total disease
costs in Germany amount to ∼Euro 5.9 billion, mainly
arising from indirect costs (86); in the United States, the
costs for society in 1991 were calculated to reach ∼US$
45 billion (87). Work impairment in bipolar patients is
even greater than that seen in unipolar depressed patients
(88–90).
NEEDS AND PERSPECTIVES
The findings discussed suggest a reconceptualization of
bipolar illnesses as highly recurrent and malignant disor-
ders that occur more frequently than previously thought.
Because early recognition and intervention may be able
to ameliorate adverse outcomes, efforts should be taken
to implement structured screening and diagnosis tools and
treatment guidelines, including both pharmacological and
nonpharmacological strategies into research and clinical
practice. Interdisciplinary transfer of knowledge is re-
quired, bearing in mind high comorbidity rates of bipolar
disorders with other medical, neurologic, and psychiatric
illnesses and the likely shared aspects of pathophysiol-
ogy.
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Epilepsia, Vol. 46, Suppl. 4, 2005