Nearly one percent of adults in the United States suffer from bipolar
disorder, a severe, chronic, and life-threatening disease. This disord
er involves periodic episodes of mania and depression. At least 80 per
cent of patients who have an initial episode of mania will have one or
more subsequent episodes. Because recurring episodes have a cumulativ
e deteriorative effect on functioning and treatment response, the soon
er bipolar patients are diagnosed and treated, the better their chance
s are for recovery. With optimal treatment, a bipolar patient can rega
in approximately 7 years of life, 10 years of effective major activity
, and 9 years of normal health, which otherwise would have been lost d
ue to the illness. For treatment purposes, bipolar disorder is divided
into three stages: acute mania, acute depression, and maintenance. Li
thium is the standard treatment for acute mania, and its effectiveness
is solidly supported by experimental evidence. Rigorous studies over
the past 40 years involving hundreds of patients have repeatedly shown
the efficacy of lithium therapy, with approximately 80 percent of sub
jects responding favorably. For those who do not, several other drugs
and nonpharmacologic therapies are available that have shown high succ
ess rates in well-standardized trials. The anticonvulsant drug carbama
zepine has been associated with improved symptoms in approximately 60
percent to 70 percent of subjects in double-blind trials comparing it
against placebo, neuroleptics, and/or lithium. Valproate, another anti
convulsant, has been shown to be comparable to lithium and superior to
placebo in treating acute mania in several double-blind, placebo-cont
rolled trials. Electroconvulsive therapy (ECT) is another effective tr
eatment for acute mania, with a positive response rate of approximatel
y 80 percent. Acute bipolar depression has been successfully treated w
ith a number of agents, including monoamine oxidase inhibitors (e.g.,
tranylcypromine), lithium, tricyclic antidepressants, and second-gener
ation antidepressants (e.g., bupropion). Nonpharmacologic approaches s
uch as ECT, sleep deprivation, and light therapy have been effective a
s supplemental therapy in many patients. For maintenance therapy, lith
ium is again the drug of choice. Clinical research has shown that main
tenance lithium lessens the frequency and severity of episodes of mani
a and depression in bipolar patients and helps stabilize mood between
episodes. Long-term lithium treatment also reduces the risk of mortali
ty for bipolar patients: without treatment, mortality is two to three
times higher than that of the general population; with treatment, it i
s not significantly different. Several other drugs have been studied a
s alternatives or adjuncts to lithium therapy. Data from double-blind
trials suggest that carbamazepine is similar to lithium and significan
tly superior to placebo in the maintenance treatment of bipolar disord
er, and several open trials have reported moderate to good results wit
h the combination of valproate and lithium or valproate alone. The tri
cyclic antidepressant imipramine has been found to be less effective t
han lithium in preventing manic episodes but equally as effective in p
reventing depressive episodes. Bupropion and verapamil have also shown
success in preliminary trials.