DRUG SELECTION AND INITIATION OF TREATMENT Acute Mania The goal of treatment should be to suppress completely all

DRUG SELECTION AND INITIATION OF TREATMENT Acute Mania The goal of treatment should be to suppress completely all

symptoms of mania and return the patient to his or her mental status quo ante. Mood, thinking, and behavior should normalize, though different symptom clusters may improve at different rates. For economic or social reasons, it is sometimes necessary to discharge inpatients with partially remitted mania or hypomania. In this setting, it is imperative to follow such patients closely (perhaps using partial hospitalization or inten- sive outpatient programs) until total remission of symptoms has occurred. In particular, it is important to monitor, and perhaps provide prophylactic pharmacotherapy, for the rapid slide into acute depression that frequently follows mania.

Drug Selection LITHIUM

For many patients with hypomania, lithium by itself can induce

a total remission. Even in acute mania, response rates in clin- ical trials using lithium monotherapy can be as high 80–90%. In everyday clinical practice, however, the use of additional mood stabilizers (anticonvulsants or atypical antipsychotics) may be necessary for remission. In addition, manic psychosis calls for the use of adjunctive antipsychotics and in many patients use of benzodiazepines may be very helpful for symptomatic

MOOD STABILIZERS 91 treatment of agitation and anxiety. Certain clinical features are

somewhat predictive of lower lithium response rates. These include:

• Rapid cycling course • Mixed mania • Greater number of cumulative episodes (> 10 lifetime) • Comorbid anxiety disorders • Comorbid substance abuse

ANTICONVULSANTS Experts usually rank lithium as the treatment of choice for

a patient with classic mania, but divalproex is an acceptable first-line alternative. It may be used singly in patients who cannot tolerate lithium. For patients who do not respond to lithium, there are no secure data on whether divalproex should

be added as an adjunct or substituted, but many psychiatrists would choose the former in a patient who appears to respond at least partially to lithium and the latter in patients for whom lithium seems to afford no benefit. Carbamazepine has also been used in bipolar patients non-responsive to or intolerant of lithium. This use is based upon studies using active compara- tors (including lithium) and demonstrating comparable overall efficacy. Despite being used for decades in this way, it is only recently that FDA approval was sought and obtained for an acute antimanic indication for a slow release form of carbamazepine. Older long prospective studies comparing carbamazepine to lithium suggested a superiority of the anti- convulsant in patients with mixed or dysphoric mania, rapid cycling, or significant comordity. As such, it appears to share a similar profile to divalproex. However, it has a rather different side effect profile, having less risk of weight gain, tremor, or hair loss, but greater risk of neurological side effects, such as ataxia, vertigo, and diplopia. Two other liabilities associated with carbamazepine include an increased risk of agranulocy- tosis and a robust induction of hepatic enzymes. The latter often results in more frequent blood level monitor and the need to compensate for dropping carbamazepine levels. In addition, the dosing of other medications must often be adjusted after addition of carbamazepine.

92 HANDBOOK OF PSYCHIATRIC DRUGS ATYPICAL ANTIPSYCHOTICS

With the exception of clozapine, all other atypical antipsy- chotic drugs have received approval by the FDA for use as monotherapy treatments for acute mania. Clozapine has been shown to be effective in patients with treatment-resistant symptoms but other atypicals with fewer serious adverse effects are preferred for routine use. Placebo-controlled monotherapy trials have demonstrated efficacy for olanza- pine at 10 or 15 mg/day, risperidone at 3–6 mg/day, quetiapine at 600 mg/day, ziprasidone at mean doses of either 112 or 130 mg/day, and aripiprazole at 10–15 mg/day. The presence or absence of psychosis has not been shown to influence antipsy- chotic efficacy in mania.