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Following treatment of an acute episode, maintenance or preventive therapy is usually initiated. The goals of this stage of therapy include:

• Optimizing protection against recurrence of any episodes
• Maximizing patient functioning
• Minimizing the presence or occurrence of sub-clinical symptoms
• Minimizing side effects of medication
• Reducing the frequency of cycling

Treatments that may be utilized in maintenance therapy include:

• Medications
• Psychotherapy
• Electroconvulsive therapy

Medications

Mood Stabilizers

Lithium, divalproex and lamotrigine are most widely used either alone or in combination with other drugs.

Antipsychotics

Atypical (newer) antipsychotics (e.g. olanzapine, quetiapine, etc.) are increasingly being used for maintenance therapy. The combination of olanzapine and lithium or divalproex has also been shown to be effective for relapse prevention in maintenance treatment. The American Psychiatric Association suggests that, whenever possible, antipsychotics (especially typical antipsychotics) should be reduced or discontinued due to the risk of tardive dyskinesia.

Antidepressants

Use of antidepressants in bipolar disorder is controversial since they are associated with many side effects, including causing "switching" (inducing mania). SSRIs and bupropion are increasingly used while being combined with other drugs since they are well tolerated and effective in some circumstances.

According to the American Psychiatric Association (APA) Practice Guidelines of 2002, mood stabilizers are the cornerstone of prevention of relapse in bipolar disorder patients, either as monotherapies or combined with other drugs. Lamotrigine, carbamazepine or oxcarbazepine may be used as alternatives if the patient does not respond to the preferred medication or cannot tolerate the side effects.

The APA noted in the Guideline Watch published in 2005 that:

• Lamotrigine and lithium have "substantial utility" in the maintenance treatment for patients with bipolar disorder. Lamotrigine is more effective in preventing depressive episodes while lithium is more effective in preventing manic episodes.
• Olanzapine taken for manic or mixed episodes had a slightly shorter median time to onset of remission than divalproex but the rate of remission was the same for both medications. There were fewer side effects for divalproex.
• In a study comparing olanzapine and lithium for the prevention of relapse or recurrence of manic or mixed episode, olanzapine was superior when considering the rate of recurrence of mania or mixed episode but the rate of depression onset did not differ between the two drugs. Approximately 30% of patients on olanzapine relapsed into mania or depression compared to 39% of patients taking lithium. The APA noted that this is an insignificant difference.
• Combination therapy of olanzapine plus a mood stabilizer (lithium or valproate) is more effective for prevention of relapse than mood stabilizers alone. However, side effects from the combination therapy included somnolence, weight gain, and tremor.

Approximately 1 in 3 patients remain free of symptoms while taking mood stabilizers. Most other patients have a reduction in frequency and severity of subsequent episodes. As a general rule, the APA suggests that during the maintenance phase, the patient continue to take the medication that has been working up to that point and not to initiate new drugs.

It is easy for patients to become discouraged while on a preventive regimen because they may not see progress if they experience another episode or if they have mild symptoms. However, it is important for patients to remember that the change of frequency and intensity of episodes is the measure of success over the long-term.