Bipolar Disorder: Prevalence
and Illness Characteristics
Bipolar disorder is a recurrent and sometimes
long-term mental illness that can seriously
affect the lives of patients and their
families. The lifetime prevalence of bipolar I
disorder, the most severe form of the illness,
is approximately 1%. The lifetime prevalence
of all forms of the illness, often referred to as
bipolar spectrum disorders, has been estimated
to be 5% in the general population.1,2
Bipolar disorder is characterized by intermittent
episodes of mania and depression.
Symptoms of mania include increased energy,
restlessness, and feelings of euphoria.
States of mania are often characterized by
impulsivity, excessive libido, recklessness,
social intrusiveness, and diminished need for
sleep, all of which may lead patients to inflicting
harm on themselves and others.3 It is not
uncommon for manic patients to find themselves
on spending sprees, to get involved in
reckless behavior, and to start abusing alcohol.
Bipolar depression, on the other hand, is
characterized by depressed mood or loss of or
markedly diminished interest or pleasure in
nearly all activities, significant weight loss
when not dieting or weight gain, insomnia or
hypersomnia nearly every day, psychomotor
agitation or retardation, fatigue or loss of
energy, feelings of worthlessness or excessive
guilt, diminished ability to think or concentrate,
as well as recurrent thoughts of death or
suicidal ideation, or suicide attempt.3 These
symptoms affect the physical, emotional, and
social functioning of an individual and can
have a significant effect on the overall quality
of life.
Impact of Bipolar Disorder
on Patient Lifestyle
Bipolar disorder causes significant psychosocial
morbidity, because it frequently
affects patients' relationships with family
members as well as workplace functioning. A
recent community survey investigated the
impact of bipolar disorder on people's lives,
using the Mood Disorder Questionnaire
(MDQ) as a screening instrument. Subjects
screening positive for bipolar disorder on the
MDQ reported significantly more work and
relationship problems and a greater burden
of comorbid medical illness than subjects
who were negative for bipolar disorder.
Significantly more respondents with positive
screens for bipolar disorder had been arrested,
convicted, or jailed for a crime compared
with respondents with negative screens for
bipolar disorder.4
Another study conducted in a primary
care practice demonstrated that individuals
who screened positive for bipolar disorder
on the MDQ experienced significant disability
in health, social, family, and occupational
functioning. Even after adjusting for the
presence of any current mental condition,
impairment in health-related quality of life,
social activities, and family life remained significantly
associated with a positive screen
for bipolar disorder. Moreover, nearly one
fifth (19%) of those who screened positive for
bipolar disorder in this study reported suicidal
ideation at least some days during the
previous 2 weeks compared with 4% of those
who screened negative.5 Even after remission
of acute episodes, impaired functioning
may persist.6 Many patients with bipolar disorder
do not fully recover the ability to function
in work and social activities, and they
remain impaired even during the stable
phase of their illness.7-11
Research demonstrates that bipolar
depression (and not mania) predicts greater
illness burden and chronicity.12 Depressive
symptoms are more frequent than manic
symptoms and are more likely to disrupt
work as well as social and family life functioning
than manic symptoms. Moreover,
bipolar depressed patients experience significantly
worse depressive symptoms than
unipolar depressed patients.13,14 Bipolar
depressed patients are also more likely to
report being impaired all or most of the time
in their ability to work than unipolar
depressed patients. Despite the central
importance of depression in the overall care
of bipolar patients, this phase of the illness
remains remarkably underinvestigated.15
Options for the treatment of patients with
bipolar depression are particularly limited
when compared with the options available in
the treatment of unipolar depression.
Indeed, until a few years ago, lithium was
the only medical treatment with substantial
research evidence of efficacy in bipolar
depression. More recently, studies of olanzapine,
olanzapine/fluoxetine combination,
quetiapine, lamotrigine, and divalproex
reported on the efficacy of these drugs in
bipolar depression.
Quality of Life in Individuals
With Bipolar Disorder
Quality of life usually refers to satisfaction
with major areas of daily functioning,
including physical, emotional, social, and
spiritual well-being.7,16 Health-related quality
of life is specifically concerned with
those aspects of functioning that can be
directly attributed to illness and consequent
therapy.7
Few studies have evaluated the impact of
bipolar disorder on health-related quality of
life. A systematic review of bipolar disorder
literature covering the period between 1966
and 1998 found 72 articles on studies of
bipolar disorder, of which only 10 included a
health-related quality-of-life assessment.7
When patients with bipolar disorder were
compared with patients with schizophrenia
using the Quality of Life Interview (QLI),
bipolar patients reported significantly less
satisfaction with their quality of life than
patients with schizophrenia. This is particularly
interesting in view of the findings that
on objective measures of life quality (ie,
level of education, financial situation, health
impairment), bipolar patients reported higher
levels of achievement than schizophrenic
patients.17
Among individuals with bipolar disorder,
women reported lower scores on quality-of-life
measures than men.7 When psychotic
patients were compared with nonpsychotic
bipolar patients, it was found that although
the psychotic patients were more symptomatic
than the nonpsychotic group during
the index episode, it did not result in a higher
degree of functional impairment.7
Another recent study compared quality of
life across the mood states of bipolar disorder.18 The manic/hypomanic group manifested
significantly lower self-reported
quality of life than euthymic patients. This
finding refutes the popular conceptualization
that manic/hypomanic patients have an
inflated sense of well-being and subjective
life quality. Also of note is the finding that
depressive symptoms play a key role in
determining the quality of life of bipolar
patients. Specifically in patients in mixed
episode, the depressive component appeared
to predominate in the evaluation of quality
of life.18
Treatment Issues in Bipolar Disorder:
Atypical Antipsychotics
The first drug that was approved by the
US Food and Drug Administration for the
treatment of bipolar mania was lithium in
the early 1970s. Although its efficacy in
bipolar disorder is well established, lithium
is associated with infrequent serious
adverse effects and medical risks, including
tremors, weight gain, gastrointestinal
disturbances, cognitive slowing, neurotoxic effects with overdose, thyroid toxicity,
and diabetes insipidus. Moreover, the
requirement for therapeutic drug monitoring,
including occasional blood tests, to
minimize these risks is unattractive to
patients and physicians.15 More common
adverse events include nausea, vomiting,
diarrhea, sedation, tremor, polyuria, polydipsia,
weight gain, acne, and psoriasis, and
it is these milder but more common side
effects that make lithium less acceptable
over the long term among individuals with
bipolar disorder.
First-generation conventional antipsychotic
drugs, such as chlorpromazine and
haloperidol, are effective in the acute treatment
of mania, but undesirable side effects
(including extrapyramidal side effects and
neuroleptic-induced movement disorders,
such as parkinsonism, dystonia, akathisia,
and tardive dyskinesia)19 limit their use in
bipolar patients. These side effects lead
many patients to discontinue use of these
antipsychotic drugs, despite improvements
in patient symptoms.
Adherence to long-term therapy with
antipsychotic drugs is closely linked to the
incidence and nature of side effects.20 The
rate of discontinuation cannot be solely attributed
to the lack of the patient's insight
into the disorder or the necessity for treatment.
Many factors, such as the positive
influence of a good patient-physician relationship,
are important in compliance with
therapy. However, the patient's initial subjective
experience during treatment with an
antipsychotic drug is a major predictor of
compliance.20 A more favorable benefit-risk
ratio throughout all phases of treatment can
contribute to greater patient adherence and
will help patients adhere to long-term therapy.
Patients' subjective dissatisfaction with
treatment is difficult to capture with objective
examinations, but it is readily reported by
patients on quality-of-life measurements.20
Newer generation atypical antipsychotics
offer several tolerability benefits over conventional
antipsychotics, particularly with
respect to extrapyramidal symptoms, and
are therefore viewed as superior to conventional
antipsychotics in improving quality of
life, particularly from the patient's perspective.20 Indeed, it has been demonstrated that
atypical antipsychotics at low doses can be
efficacious in the treatment of psychosis
without inducing neurotoxic side effects.21
The findings of a large number of studies of
atypical antipsychotics currently on the
market (ie, aripiprazole, clozapine, olanzapine,
quetiapine, risperidone, and ziprasidone)
have now been published and
reviewed.21,22 Atypical antipsychotics are
effective in the treatment of bipolar mania,
either alone or in combination with traditionally used mood stabilizers, such as lithium
and divalproex.
Although a number of studies addressed
the efficacy profile of atypical antipsychotics
in bipolar disorder, very few addressed the
impact of treatment with atypical antipsychotics
on quality of life.
Quality-of-Life Assessments in Individuals
With Bipolar Disorder Treated With
Atypical Antipsychotics
Although social functioning, integration
of patients back into society, and a normalization
of their life situation are the goals of
treatment, few studies include measures of
social functioning and quality of life in their
analyses. In fact, to date no reported studies
of atypical antipsychotics, except the studies
of olanzapine, included psychosocial
functioning and quality-of-life evaluations in
their analyses.
Quality-of-life outcomes were assessed in
patients with the diagnosis of bipolar I disorder
in a manic or mixed episode who were
treated with olanzapine versus placebo in a
3-week acute double-blind study (Table).23
The acute phase was followed by a 49-week
open-label extension during which all
patients were treated with olanzapine.
During the open-label extension, the use of
lithium or fluoxetine was permitted for
patients with breakthrough episodes.
Health-related quality of life was measured
using the Short Form-36 (SF-36) of the
Medical Outcomes Study, a form that covers
multiple dimensions of quality of life.
Olanzapine-treated patients experienced significant
improvements in manic symptoms
as measured by the Young Mania Rating
Scale (YMRS) scores during the 3-week acute
phase compared with the placebo-treated
group, and patients continued to improve
throughout the 49 weeks of open-label olanzapine
treatment. With regard to quality-of-life
outcomes, in the acute phase of the trial,
olanzapine-treated patients improved on all
dimensions of the SF-36, but these improvements
were not significantly different from
improvements in the placebo group, except
for the "physical functioning" dimension of
SF-36, on which olanzapine-treated patients
improved significantly compared with placebo.
However, during this period significantly
more olanzapine-treated than placebo-treated
patients were discharged from the hospital.
During the open-label treatment period,
olanzapine-treated patients showed further
improvements on all SF-36 dimensions compared
with at the end of the acute treatment
period. Moreover, a relationship was determined
between improvements on the YMRS
scale and SF-36, suggesting that as patients
improve clinically during olanzapine treatment,
they may start to experience functional
improvement as well.
A separate study investigated quality-of-life
improvements in patients with bipolar
disorder treated with olanzapine added to
lithium or valproate for 6 weeks (Table).24
Patients receiving olanzapine added to a
mood stabilizer experienced statistically
more significant clinical improvements (as
measured by YMRS and the Hamilton Depression
Scale) than patients treated with a
mood stabilizer alone. These improvements
were complemented by significant improvements
on the measure of quality of life
(Lehman's QLI), and these improvements
were greater in patients treated with olanzapine
added to a mood stabilizer than in
patients treated with a mood stabilizer
alone. This study suggests that as individuals
treated with olanzapine in combination with
a mood stabilizer improve clinically, they
also become more satisfied with their social
functioning, including improvements in
interactions with friends and family, and
their living situation.
Quality of life was measured indirectly in
risperidone studies using the Global Assessment
of Functioning Scale (Table). Assessment
of global functioning was performed in
two 3-week acute studies of risperidone
compared with placebo and in an open-label
9-week extension to these acute trials. In the
acute trial, patients treated with risperidone
improved statistically more significantly
than placebo-treated patients on measures
of global functioning; these improvements
were sustained during the 9 weeks of open-label
treatment with risperidone. At the end
of 12 weeks of treatment with risperidone,
more than 60% of individuals achieved good
global functioning scores.25
Global assessment of functioning was also
performed in a 12-week study of quetiapine
(Table).26 Significant improvements were
seen at 3 and 12 weeks; patients' functioning
improved significantly more in the quetiapine
group than in the placebo group.26
Similarly, global functioning improved significantly
in ziprasidone-treated patients
compared with placebo-treated patients in
a 3-week acute study of ziprasidone versus
placebo (Table).27 Global assessment of
functioning was not included in the published
studies of aripiprazole in bipolar
patients.
Conclusion
When compared with first-generation
antipsychotics, second-generation antipsychotics
improve medication-adherence
behavior, quality of life, and subjective tolerability.
Most published studies on second-generation
antipsychotics have dealt with
issues related to efficacy and safety, but not
quality of life. Few studies have focused on
effectiveness in terms of such important outcomes
as medication-adherence behavior,
quality of life, subjective tolerability, and
overall satisfaction with treatment. Well-designed,
controlled, and adequately powered
studies are urgently needed before any
firm conclusions can be reached.
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