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Combination Therapy for Bipolar Disorder

When a single drug does not work, experts recommend trying other mood stabilizers. If several medications are tried with no improvement, trying a combination of mood stabilizers is the next step. This approach is called combination therapy. Two mood stabilizers together may be more effective in relieving symptoms than one alone.

Sometimes, a mood stabilizer is used in combination with medication to relieve behavioral symptoms (hyperactivity or physical expression of distress, such as restlessness, pacing and hypersensitivity to surroundings), psychosis, anxiety or insomnia. These drugs are called adjunctive medications.

Adjunctive medications include benzodiazepines, a type of sedative that is prescribed for behavioral agitation or verbal excitement. For instance, lorazepam (Ativan®) can calm a hostile or aggressive manic patient. Antidepressants may be prescribed for depressed bipolar patients to improve their mood, but careful monitoring is necessary to avoid pushing the mood into mania or hypomania (which is less severe than full-blown mania). The choice of antidepressant is influenced by patient tolerance, potential drug interactions and side effects. For example, a patient who gained weight on lithium would be prescribed an antidepressant associated with less weight gain such as bupropion (Wellbutrin®).

Sometimes, patients with extreme manic episodes can develop psychotic symptoms, such as paranoia, hallucinations and delusions. When psychotic symptoms occur during mania, supplementing the mood stabilizer with an antipsychotic drug can be helpful. Antipsychotic medications are administered during acute treatment and usually can be tapered before continuation treatment begins. However, some patients experience the best results by staying on an antipsychotic drug. A newer class of antipsychotic medications used in the management of manic patients is risperidone (Risperdal®), haloperidol (Haldol®), quetiapine (Seroquel®) and olanzapine (Zyprexa®).

Combination Therapy for Bipolar Disorder

Jim Haggerty, M.D.

APA Reference
Haggerty, J. (2016). Combination Therapy for Bipolar Disorder. Psych Central. Retrieved on December 12, 2018, from


Scientifically Reviewed
Last updated: 17 Jul 2016
Last reviewed: By John M. Grohol, Psy.D. on 17 Jul 2016
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