The goal of treatment of bipolar disorder is to prevent both manic and depressive episodes, controlling the extreme highs and lows to create a stable mood. The core treatment is mood-stabilizing medications.

Lithium (Lithobid) was the first medication to be approved for treating mania, and it remains the mainstay of bipolar disorder treatment today. (Blood levels of lithium are measured regularly to ensure adequate doses and to avoid the dangerous effects of toxic levels.) Because lithium can take more than a week to have an effect, a neuroleptic (an antipsychotic drug) or a benzodiazepine (an antianxiety drug) may be added to treat symptoms of acute mania. Benzodiazepines should be used with caution, however, because of the risk of dependency and abuse. They can also disinhibit some manic patients, escalating inappropriate behavior.

Other Mood-Stabilizing Drugs

Instead of lithium, doctors may choose to use other mood-stabilizing medications—carbamazepine (Equetro), valproic acid (Depakene, Depakote), or lamotrigine (Lamictal)—in combination with one another or with neuroleptics or benzodiazepines to treat acute mania. The neuroleptic drugs aripiprazole (Abilify, generics), olanzapine (Zyprexa), quetiapine (Seroquel), risperidone (Risperdal), and ziprasidone (Geodon) have also been approved for treating manic episodes. Valproic acid and neuroleptics are also good options for people who have mixed episodes—simultaneous symptoms of mania and depression.

In December 2014, the FDA warned that this medication may be associated with a rare, but serious skin reaction that may affect other areas of the body. This reaction, which is called drug reaction with eosinophilia and systemic symptoms (DRESS), causes high levels of certain white blood cells (eosinophils) and can be fatal. Symptoms include rash that spreads, fever, swollen lymph nodes, and organ inflammation.

A neuroleptic drug is prescribed in combination with a mood-stabilizing drug when manic episodes are severe or involve hallucinations or delusional ideas. Neuroleptics are usually taken only for short periods because of their neurological side effects, which include repetitive, involuntary, purposeless movements or twitches (known as tardive dyskinesia or tardive dystonia) that may not go away even if medication is stopped. These side effects occur less often with some newer (or atypical) neuroleptics, such as Zyprexa and Risperdal. These drugs are also linked with a condition called neuroleptic malignant syndrome, which includes symptoms such as muscle stiffness or spasms, high fever, and confusion or disorientation.

Medications to Treat Depressive Episodes

A new episode of mild or moderate depression in people with bipolar disorder is typically treated with a mood stabilizer such as lithium. If the depression is severe, only then would an antidepressant drug be added to the mood stabilizer. (Lithium has been shown to be effective in preventing suicide, and antidepressants must be used with caution in people with bipolar disorder.) If the depression involves psychotic symptoms, the person may need to take neuroleptic medication in addition to the mood stabilizer and antidepressant.

The reason antidepressants must be used with extreme care in people with bipolar disorder is that they can stimulate a manic episode or cause rapid cycling between depression and mania. This is particularly true for tricyclic antidepressants. A recent study in The New England Journal of Medicine suggests that they offered no clear benefit but were also associated with no significant increase in manic symptoms when prescribed in combination with a mood-stabilizing medication during the 26 weeks of the study. Despite the presumed risk and lack of proven benefit, it’s estimated that 50 to 70 percent of people with bipolar disorder are prescribed antidepressants. Each individual’s situation must be assessed, since some clinical situations—such as prominent coexisting anxiety symptoms—may be the reason for including an antidepressant in the treatment.

SSRIs and other relatively new antidepressants, such as Wellbutrin or Effexor, are the most likely drugs to be used. In addition, Symbyax—a combination of an atypical neuroleptic (olanzapine) and an SSRI (fluoxetine) —has been approved by the FDA to treat depressive episodes in people with bipolar disorder.

Despite the risk of mania, according to a study in The American Journal of Psychiatry, people with bipolar disorder whose depression responded to treatment with antidepressant medication (in addition to their other medications) had a low incidence of relapse into depression or mania during the first year after the depression eased if they remained on antidepressant medication during that time.

Updated by Remedy Health Media

Publication Review By: Karen L. Swartz, M.D.

Published: 03 Mar 2011

Last Modified: 01 May 2015