APA Practice Guidelines

B. Acute Treatment of Bipolar Disorder

cont. from

1. Manic or mixed episodes

For patients experiencing a manic or mixed episode, the primary goal of treatment is the control of symptoms to allow a return to normal levels of psychosocial functioning. The rapid control of agitation, aggression, and impulsivity is particularly important to ensure the safety of patients and those around them.

Lithium, valproate, and antipsychotic medications have shown efficacy in the treatment of acute mania, although the time to onset of action for lithium may be somewhat slower than that for valproate or antipsychotics. The combination of an antipsychotic with either lithium or valproate may be more effective than any of these agents alone. Thus, the first-line pharmacological treatment for patients with severe mania is the initiation of either lithium plus an antipsychotic or valproate plus an antipsychotic. For less ill patients, monotherapy with lithium, valproate, or an antipsychotic such as olanzapine may be sufficient. Alternatives with less supporting evidence for treatment of manic and mixed states include ziprasidone or quetiapine in lieu of another antipsychotic and carbamazepine or oxcarbazepine in lieu of lithium or valproate. (Although efficacy data for oxcarbazepine remain limited, this medication may have equivalent efficacy and better tolerability than carbamazepine.) Short-term adjunctive treatment with a benzodiazepine may also be helpful. In contrast, antidepressants may precipitate or exacerbate manic or mixed episodes and generally should be tapered and discontinued if possible.

Selection of the initial treatment should be guided by clinical factors such as illness severity, by associated features (e.g., rapid cycling, psychosis), and by patient preference where possible, with particular attention to side effect profiles. A number of factors may lead the clinician to choose one particular agent over another. For example, some evidence suggests a greater efficacy of valproate compared with lithium in the treatment of mixed states. Also, severely ill and agitated patients who are unable to take medications by mouth may require antipsychotic medications that can be administered intramuscularly. Because of the more benign side effect profile of atypical antipsychotics, they are preferred over typical antipsychotics such as haloperidol and chlorpromazine. Of the atypical antipsychotics, there is presently more placebo-controlled evidence in support of olanzapine and risperidone.

If psychosocial therapies are used, they should be combined with pharmacotherapy. Perhaps the only indications for psychotherapy alone for patients experiencing acute manic or mixed episodes are when all established treatments have been refused, involuntary treatment is not appropriate, and the primary goals of therapy are focused and crisis-oriented (e.g., resolving ambivalence about taking medication).

For patients who, despite receiving the aforementioned medications, experience a manic or mixed episode (i.e., a "breakthrough" episode), the first-line intervention should be to optimize the medication dose. Optimization of dosage entails ensuring that the blood level is in the therapeutic range and in some cases achieving a higher serum level (although one still within the therapeutic range). Introduction or resumption of an antipsychotic is often necessary. Severely ill or agitated patients may require short-term adjunctive treatment with an antipsychotic agent or benzodiazepine.

With adequate dosing and serum levels, medications for the treatment of mania generally exert some appreciable clinical effect by the 10th to the 14th day of treatment. When first-line medications at optimal doses fail to control symptoms, recommended treatment options include addition of another first-line medication. Alternative treatment options include adding carbamazepine or oxcarbazepine in lieu of an additional first-line medication, adding an antipsychotic if not already prescribed, or changing from one antipsychotic to another. Of the anti-psychotic agents, clozapine may be particularly effective for treatment of refractory illness. As always, caution should be exercised when combining medications, since side effects may be additive and metabolism of other agents may be affected.

Patients displaying psychotic features during a manic episode usually require treatment with an antipsychotic medication. Atypical antipsychotics are favored because of their more benign side effect profile.

continue: Depressive Episodes

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Written 4/02. Reviewed: 03/2006