Download Bipolar Disorders

Bipolar Disorders

Thorough 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.
o Most switches from unipolar to bipolar disorder occur within 5 years 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
(egg, antidepressants, phototherapy, sleep deprivation, electroconvulsive therapy), and a family
history of mood disorders for three consecutive generations.
o Between episodes, patients with bipolar disorder exhibit depressive moodiness and sometimes highenergy 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.
o Bipolar I disorder commonly begins with depression and is characterized by at least one manic or
excited period during its course.
o 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).
o During the hypomanic period, mood brightens, the need for sleep decreases, and psychomotor
activity accelerates beyond the patient's usual level.
o Often, the switch is induced by circadian factors (egg, going to bed depressed and waking early in
the morning in a hypomanic state).
o Hypersomnia and overeating are characteristic and may recur seasonally (egg, in autumn or winter);
insomnia and poor appetite occur during the depressive phase.
o For some persons, hypomanic periods are adaptive because they are associated with high energy,
confidence, and supernormal social functioning.
o Many patients who experience pleasant elevation of mood, usually at the end of a depression, do not
report it unless specifically questioned.
o 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 by relatives.

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 (i.e.,
driven, ambitious, and achievement-oriented).
Symptoms and Signs

Symptoms of the depressive phase are similar to those of unipolar depression (see above), 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.
o 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.
o Their lack of insight and their inordinate capacity for activity can lead to a dangerously explosive
psychotic state.
o 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 is difficult to distinguish from the loose associations of the schizophrenic in its
extreme form.
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 (i.e., 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:
o a dysphorically excited mood
o crying
o curtailed sleep
o racing thoughts
o grandiosity
o psychomotor restlessness
o suicidal ideation
o persecutory delusions
o auditory hallucinations
o indecisiveness
o confusion
This presentation is referred to as dysphoric mania, i.e., prominent depressive symptoms superimposed on
manic psychosis.
o Dysphoric mania often develops in women and in persons with a depressive temperament.
o 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 (DSM) are best regarded as intrusions of hypomanic symptoms or hyperthymic traits
into a retarded major depressive episode.
o Antidepressant drugs may aggravate these states by producing a subacute irritable depressive state
that lasts many months.
o 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.
o Patients with a depressive mixed state and those with dysphoric mania are at high risk of suicide
and require expert clinical management.

Mortality from cardiovascular causes is modestly increased in patients with bipolar disorder.
o 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.
o 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.
Treatment
 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.




Lithium is a naturally occurring alkali metal.
Although lithium attenuates bipolar mood swings, it has no effect on normal mood.
It also appears to have an anti-aggressive action, but whether this action occurs in persons without a bipolar
disorder is unclear.
Lithium does not directly produce sedation or, ordinarily, cognitive impairment; if the latter occurs,
lithium-induced hypothyroidism must be ruled out.

Two thirds of patients with uncomplicated bipolar disorder respond to lithium.
o Predictors of a good response include a euphoric manic picture as part of a primary mood disorder
o < 2 episodes a yr
o A personal and family history of response to lithium.
o Lithium is less effective in patients with mixed states, rapid-cycling forms of bipolar disorder,
comorbid anxiety, substance abuse, or a neurologic disorder.

Lithium, usually given as the carbonate, is rapidly and completely absorbed via the GI tract and peaks in
serum in 90 min.
It is not biotransformed; 95% is excreted via the kidneys, a process enhanced by a Na+ load. Thus, use of
diuretics or disorders that lead to Na+ loss pose a risk of toxicity.
The elimination half-life is 24 h, which tends to increase with age. Steady state is reached in 4 to 6 days,
producing a delay in acute antimanic action.
During a manic episode, the patient retains lithium and excretes Na+; oral dosage and the blood level need
to be higher during acute treatment than during maintenance prophylaxis.
Lithium has a narrow therapeutic index, and lithium blood levels must be strictly monitored.













The most common acute, mild adverse effects of lithium are
o fine tremor
o fasciculation
o nausea
o diarrhea
o polyuria
o thirst
o polydipsia
o weight gain (partly attributed to drinking high-calorie beverages).
o These effects are usually transient and often respond to decreasing the dose slightly, dividing the
dose (egg, 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 beta-blocker, such as atenolol 25 mg po daily or bid, can control incapacitating tremor.
Toxic effects are manifested initially by
o gross tremor
o increased deep tendon reflexes
o persistent headache
o vomiting
o mental confusion
o may progress to stupor, seizures, and cardiac arrhythmias
Except for overdose, lithium toxicity is more likely in elderly patients and in patients with decreased
creatinine clearance or with Na+ loss, which may result from fever, vomiting, diarrhea, or use of diuretics.
NSAIDs other than aspirin may contribute to hyperlithemia.
o None of these situations is an absolute contraindication to lithium. However, renal function should
be assessed at baseline and monitored frequently (measuring 24-h urine volume, urine
concentration, and creatinine clearance), and blood lithium should be measured frequently.
o Doses may have to be decreased, and dietary sodium supplementation given.
TSH response to TRH stimulation and other thyroid indexes should be checked when thyroid disease is
suspected.
In patients with relatively stable mood, blood lithium levels and weight should be measured quarterly, and
creatinine and TSH should be measured biannually.
Common chronic adverse effects of lithium are
o exacerbation of acne and psoriasis
o hypothyroidism
o nephrogenic diabetes insipidus (which may respond to dose reduction or temporary interruption of
lithium)
Patients with a history of parenchymal kidney disease may be at risk of structural damage to the distal
tubule.

Acute manic psychosis is being increasingly managed with the atypical antipsychotics risperidone (usually
4 to 8 mg/day po) and olanzapine (usually 5 to 10 mg/day po), because of their minimal risk of
extrapyramidal adverse effects.

Anticonvulsants, especially valproate and carbamazepine, are also widely used.
o Their precise therapeutic action in bipolar disorder is unknown but may involve GABAergic
mechanisms and ultimately G-protein signaling systems.
o Their main advantages over lithium include a wider therapeutic margin and lack of renal toxicity.
o Valproate (especially as divalproex, which has good GI tolerability) is approved for acute mania.
Unlike carbamazepine, divalproex does not suppress the bone marrow, but it may cause liver
damage in children.
o Divalproex may cause weight gain, alopecia, and tremor in adults.
o Common adverse effects of carbamazepine include sedation, vertigo, ataxia, diplopia, and pruritic
rashes. Carbamazepine induces its own catabolism, necessitating frequent increases in dose during
the first months of treatment; divalproex does not.

In patients with bipolar II disorder, any effective antidepressant may cause treatment-emergent hypomania,
but bupropion and paroxetine appear least likely to cause it.

Maintenance therapy: Treatment of an isolated manic episode should continue for at least 6 mo. Most
manias recur as part of a recurrent bipolar disorder.
Maintenance therapy with lithium should be initiated after two classic bipolar episodes < 3 yr apart.
Levels should be maintained between 0.3 and 0.8 mEq/L, usually by giving two to five 300-mg
capsules/day.
Antidepressants should not be used during prophylaxis unless breakthrough depression is severe and, if
used, should be given only for 4 to 12 wk.
When disruptive psychomotor acceleration or mixed states supervene, thioridazine 50 to 300 mg/day po for
1 to 4 wk can restabilize the patient; olanzapine 5 to 10 mg/day may be a viable alternative.





In the noncompliant, cantankerous manic patient, a depot phenothiazine, such as fluphenazine decanoate
12.5 to 25 mg IM q 3 to 4 wk, is customarily given. In patients with bipolar disorder and mood-incongruent
psychotic features beyond the usual boundaries of "pure" mood disorder, intermittent courses of depot
antipsychotics are often necessary.

Prevention of rapid cycling: Antidepressants may induce rapid cycling in some patients (egg, patients
with bipolar II disorder and a cyclothymic temperament), even when given with lithium.
The best strategy is preventive: limiting the use of antidepressants during the depressive phase.
For an established case of rapid cycling, the physician must gradually discontinue all cycling
antidepressants, stimulants, caffeine, benzodiazepines, and alcohol.
Hospitalization may be required.
Lithium (or divalproex) may be given with bupropion.
Because borderline hypothyroidism also predisposes to rapid cycling (especially in women), augmenting
mood stabilizers with hormones (egg, L-thyroxine 100 to 200 g/day po) often helps.
Sometimes carbamazepine can also be useful.
Some experts combine an anticonvulsant with lithium, trying to keep both drugs at 1/2 to 2/3 their usual
dose.
Nimodipine (90 mg bid), a calcium channel blocker, may also help in ultrarapid cycling (i.e., cycling every
few days), but it is not yet an established strategy.














Phototherapy is a relatively new approach for patients with seasonal bipolar or bipolar II disorder (with
autumn-winter depression and spring-summer hypomania).
It is probably most useful as augmentation.
Precautions during pregnancy: Women who wish to have a baby should have at least 2 yr of maintenance
therapy with no episodes before a lithium holiday is prescribed.
Lithium is discontinued in the 1st trimester to avoid the risk of Ebstein's anomaly, a heart defect.
Carbamazepine and divalproex should also be discontinued in the 1st trimester because they may cause
neural tube defects.
For a severe relapse during the 1st trimester, electroconvulsive therapy is safer.














Mood stabilizers, if absolutely necessary, can be used during the 2nd and 3rd trimesters but should be
stopped 1 to 2 wk before delivery and resumed a few days postpartum.
Mothers taking mood stabilizers should not nurse because these drugs pass into the milk.
Psychoeducation and psychotherapy: Enlisting the support of a family member is crucial to prevent major
episodes.
Patients and their significant others are often seen in group therapy, in which they learn about bipolar
disorder, its social sequelae, and the central role of mood stabilizing drugs in its treatment.
Patients, particularly those with bipolar II disorder, may not comply with mood stabilizer regimens because
they report these drugs over control them and make them less alert and creative.
The physician can explain that a decrease in creativity is relatively uncommon, because mood stabilizers
generally offer the opportunity for a more even performance in interpersonal, scholastic, professional, and
artistic pursuits.
Skillful dosing is necessary; the physician must be sensitive to the patient's career while ensuring that
relapses do not occur.
Individual psychotherapy may help patients better cope with problems of daily living and adjust to their
new self-identities.
Patients are unconsciously aware that their periodic tendency to lose control is costly, but they resent being
controlled by the physician. For this reason, when appropriate, the physician should consider fulfilling
some of the patient's requests to modestly reduce the dose of mood stabilizers; the possibly greater risk of
relapse is balanced by better compliance and a trusting relationship.
Small doses of an antipsychotic (egg, thioridazine 50 to 100 mg) can be provided to be taken for a few
nights if impending signs of relapse, such as a decreased need for sleep, occur.
Interventions with the patient's spouse or family can help moderate interpersonal crises.
Patients should be counseled to avoid stimulant drugs and alcohol, to minimize sleep deprivation, and to
recognize early signs of relapse.
If a patient tends to be financially extravagant, finances should be turned over to a trusted family member.
Those with a tendency to sexual excesses should be given information about the conjugal consequences
(divorce) and the infectious risks of promiscuity (particularly AIDS).