A second meta-analysis of antimanic treatments, conducted by Yildiz et al,6 focused on direct comparisons of individual medications and on effects of classes of medication. Second-generation antipsychotic medications in general and haloperidol (a first-generation antipsychotic) proved more effective than mood stabilizers (lithium, valproate, and carbamazepine) for the treatment of acute mania. The differences in efficacy among the antipsychotics were inconclusive for recommending specific medications.

Persons with acute mania can present in either inpatient and outpatient settings. Patients with a previous diagnosis of bipolar disorder may present with severe manic episodes, defined by suicidal ideation, homicidal ideation, psychosis, or aggression. For these patients, continuance of their mood stabilizer (typically lithium or valproate) plus the addition of an antipsychotic leads to a 20% higher rate of response.7 For patients whose symptoms are resistant to treatment, different combinations of medications are recommended. For example, a patient can switch from lithium to valproate (or vice versa) and/or can change from one antipsychotic medication to another among the choice of haloperidol, olanzapine, quetiapine, and risperidone.7 Electroconvulsive therapy (ECT) can be reserved as a treatment of last resort for patients with refractory symptoms who have failed a minimum of 4 to 6 combinations of medications.7

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Treatment of depression in patients with  bipolar disorder

Patients who have bipolar disorder and present with major depressive symptoms face a difficult situation because treatment with regular antidepressants can precipitate a swing into a state of mania or rapid cycling between manic and depressive symptoms. Bobo and Shelton8 present clinical trial evidence against the use of antidepressants as monotherapy in patients with bipolar disorder. However, these authors also present evidence for the limited use of antidepressants in conjunction with a mood stabilizer or antipsychotic. The best-studied therapy with effective results for the treatment of depression in patients with bipolar disorder is fluoxetine plus olanzapine, now available as a combination drug.

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In the United Kingdom, the National Institute for Health and Care Excellence (NICE)9 made recommendations for the treatment of bipolar disorder after consulting with experts and agreed with the recommendation of the fluoxetine and olanzapine combination. NICE also recommends quetiapine as a good adjunct to the antidepressant prescribed.

Transitioning from acute to maintenance treatment

Transitioning patients from the acute treatment of bipolar disorder to long-term maintenance therapy requires careful management. The rates of relapse and suicide are higher among patients with bipolar disorder than among those with many other diseases and disorders. Manning10 provides a methodology to monitor adverse effects, symptom reduction, and signs of relapse. The author proposes the use of common rating scales to judge patient outcomes. These include the Patient Health Questionnaire 9 (PHQ-9) for symptoms of depression and the National Institute of Mental Health Life-Chart Method (NIMH-LCM) to track the long-term efficacy of bipolar disorder maintenance therapy. Manning10 proposes continuation of the medication(s) used for acute remission, with thorough monitoring of response levels.

Maintenance treatment of bipolar disorder

The FDA has approved 7 medications for the maintenance treatment of bipolar disorder: lithium, lamotrigine, aripiprazole, olanzapine, quetiapine (as an adjunct), ziprasidone (as an adjunct), and long-acting injectable (LAI) risperidone.11 Most patients with bipolar disorder demonstrate polarity, relapsing more frequently into either mania or depression. Patient polarity influences the choice of maintenance treatment (Table 6). Lamotrigine or quetiapine reduces depressive relapses in patients who have a depressive polarity. For patients with a mania polarity, the recommended therapies are lithium, aripiprazole, olanzapine, LAI risperidone, and either ziprasidone or quetiapine with mood stabilizers.10

Miura et al2 conducted research into the longer-term efficacy and tolerability of the medications used for the maintenance treatment of bipolar disorder. The authors analyzed 33 randomized, controlled trials to determine recommendations. The trials did not distinguish between subtypes of bipolar disorder. The authors concluded that lithium remains a good first-line option for maintenance treatment, but that olanzapine should be considered for patients with mania-dominant polarity and quetiapine for patients with depression-dominant polarity.