Bipolar DisordersThorough evaluation of many persons with depression reveals bipolar traits, and as many as one in five patients with
a depressive disorder also develops frank hypomania or mania. Most switches from unipolar to bipolar disorder occur
within 5 yr of the onset of depressive manifestations. Predictors of a switch include early onset of depression (< 25 yr old),
postpartum depression, frequent episodes of depression, quick brightening of mood with somatic treatments
(eg, antidepressants, phototherapy, sleep deprivation, electroconvulsive therapy), and a family history of mood
disorders for three consecutive generations.
Between episodes, patients with bipolar disorder exhibit depressive moodiness and sometimes high-energy
activity; disruption in developmental and social functioning is more common than in unipolar disorder. In bipolar disorder,
episodes are shorter (3 to 6 mo), age of onset is younger, onset of episodes is more abrupt, and cycles (time from onset of
one episode to that of the next) are shorter than in unipolar disorder. Cyclicity is particularly accentuated in rapid-cycling forms
of bipolar disorder (usually defined as >= 4 episodes/yr).
In bipolar I disorder, full-fledged manic and major depressive episodes alternate. Bipolar I disorder commonly begins with
depression and is characterized by at least one manic or excited period during its course. The depressive phase can be an
immediate prelude or aftermath of mania, or depression and mania can be separated by months or years.
In bipolar II disorder, depressive episodes alternate with hypomanias (relatively mild, nonpsychotic periods of usually
< 1 wk). During the hypomanic period, mood brightens, the need for sleep decreases, and psychomotor activity
accelerates beyond the patient's usual level. Often, the switch is induced by circadian factors (eg, going to bed depressed
and waking early in the morning in a hypomanic state). Hypersomnia and overeating are characteristic and may
recur seasonally (eg, in autumn or winter); insomnia and poor appetite occur during the depressive phase. For
some persons, hypomanic periods are adaptive because they are associated with high energy, confidence, and
supernormal social functioning. Many patients who experience pleasant elevation of mood, usually at the end of a
depression, do not report it unless specifically questioned. Skillful questioning may reveal morbid signs, such as excesses
in spending, impulsive sexual escapades, and stimulant drug abuse. Such information is more likely to be provided
Patients with major depressive episodes and a family history of bipolar disorders (unofficially called bipolar III)
often exhibit subtle hypomanic tendencies; their temperament is termed hyperthymic (ie, driven, ambitious, and
Symptoms and Signs
Symptoms of the depressive phase are similar to those of unipolar depression, except that psychomotor retardation,
hypersomnia, and, in extreme cases, stupor are more characteristic. In full-blown manic psychosis, the mood is
usually elation, but irritability and frank hostility with cantankerousness are not uncommon. Typically, manic patients
are exuberant and flamboyantly or colorfully dressed; they have an authoritative manner with a rapid, unstoppable flow
of speech. They tend to believe they are in their best mental state. Their lack of insight and their inordinate capacity for activity
can lead to a dangerously explosive psychotic state. Interpersonal friction results and may lead to paranoid delusions that they
are being unjustly treated or persecuted.
Accelerated mental activity is experienced as racing thoughts by the patient, is observed as flights of ideas by the
physician, and, in its extreme form, is difficult to distinguish from the loose associations of the schizophrenic. Easily
distracted, patients may constantly shift from one theme or endeavor to another. Thoughts and activities are expansive
and may progress into frank delusional grandiosity (ie, false conviction of personal wealth, power, inventiveness, and genius
or temporary assumption of a grandiose identity). Some patients believe they are being assisted by external agents.
Auditory and visual hallucinations sometimes occur. The need for sleep is decreased. Manic patients are inexhaustibly,
excessively, and impulsively involved in various activities without recognizing the inherent social dangers. In the extreme,
psychomotor activity is so frenzied that any understandable link between mood and behavior is lost; this senseless agitation
is known as delirious mania, which is the counterpart of depressive stupor. Rarely seen in psychiatric practice today,
delirious mania constitutes a medical emergency, because patients may die from sheer physical exhaustion.
Mixed states are blends of depressive and manic (or hypomanic) manifestations and distinguish bipolar disorders
from their unipolar counterparts. The most typical examples include momentary switches to tearfulness during the
height of mania or racing thoughts during a depressive period. In at least 1/3 of persons with bipolar disorders, the entire
attack--or a succession of attacks--occurs as a mixed episode. A common presentation consists of a dysphorically excited
mood, crying, curtailed sleep, racing thoughts, grandiosity, psychomotor restlessness, suicidal ideation, persecutory
delusions, auditory hallucinations, indecisiveness, and confusion. This presentation is referred to as dysphoric mania,
ie, prominent depressive symptoms superimposed on manic psychosis. Dysphoric mania often develops in women and
in persons with a depressive temperament. Alcohol and sedative-hypnotic abuse contributes to the development or
aggravation of mixed states.
Depressive mixed states, which are not specifically characterized in the Diagnostic and Statistical Manual of Mental
Disorders, 4th edition, are best regarded as intrusions of hypomanic symptoms or hyperthymic traits into a retarded
major depressive episode. Antidepressant drugs may aggravate these states by producing a subacute irritable depressive
state that lasts many months. The clinical picture consists of irritability, pressure of speech against a background of
retardation, extreme fatigue, guilty ruminations, free-floating anxiety, panic attacks, intractable insomnia, increased libido,
histrionic appearance yet genuine expressions of depressive suffering, and, in the extreme, suicidal obsessions and impulses.
Patients with a depressive mixed state and those with dysphoric mania are at high risk of suicide and require expert clinical
Mortality from cardiovascular causes is modestly increased in patients with bipolar disorder; the increase is not
explained by cardiotoxicity from lithium or tricyclic antidepressants and tends to also occur in first-degree biologic
relatives who do not have frank affective episodes. The increase is probably related to comorbid hypertension, diabetes,
and coronary artery disease, all of which are aggravated by nicotine and alcohol dependence, which are prevalent in patients
with bipolar disorder.
Acute management: Classic euphoric mania often presents as a social emergency and is preferably managed
on an inpatient basis. Lithium works best in uncomplicated euphoric mania. After baseline laboratory tests (CBC,
urinalysis, thyroxine, TSH, serum electrolytes, creatinine, and BUN) are performed, lithium carbonate 300 mg po
bid or tid is given, and the dose is increased over 7 to 10 days until a blood level of 0.8 to 1.2 mEq/L is reached.
Patients with acute mania have a high tolerance for lithium and preferentially retain it during the first 10 days
while excreting Na+. A regular diet is recommended. Teenagers, whose glomerular function is excellent, need
higher doses of lithium to achieve the same level; elderly patients need lower doses. Because lithium's onset of
action has a 4- to 10-day latency period, haloperidol 5 to 10 mg po or IM (up to 30 mg/day) or another antipsychotic
is sometimes also necessary initially; it is given as needed until the manic stage is controlled. For extremely
hyperactive psychotic patients with poor food and fluid intake, giving an antipsychotic IM with supportive care
for a week before initiating lithium is preferable. Lorazepam or clonazepam 2 to 4 mg tid IM or po given early
in acute management can boost the antipsychotic's effects so that its dose can be reduced.
Two thirds of patients with uncomplicated bipolar disorder respond to lithium. Predictors of a good response
include a euphoric manic picture as part of a primary mood disorder, < 2 episodes a yr, and a personal and family
history of response to lithium. Lithium is less effective in patients with mixed states, rapid-cycling forms of bipolar
disorder, comorbid anxiety, substance abuse, or a neurologic disorder.
The most common acute, mild adverse effects of lithium are fine tremor, fasciculation, nausea, diarrhea, polyuria,
thirst, polydipsia, and weight gain (partly attributed to drinking high-calorie beverages). These effects are usually
transient and often respond to decreasing the dose slightly, dividing the dose (eg, tid), or using slow-release forms.
Once dosage is established, the entire dose should be given after the evening meal. This dosing may improve
compliance, and the troughs in blood levels are believed to protect the kidneys. A blocker, such as atenolol 25
mg po daily or bid, can control incapacitating tremor.