Should you take an antipsychotic drug to treat depression?

These powerful medications pose risks, and may only help some people feel better

Published: November 2011

Although antipsychotics were developed to treat schizophrenia, newer ones are sometimes used to treat depression that has not been relieved by antidepressants or other treatments.

Depression is a common health problem in the U.S., with some 14.8 million adults suffering from the condition in any given year. Psychotherapy and antidepressant medication, if necessary, can often help relieve depression. But the majority of people with the condition--60 to 70 percent--don't get adequate treatment, and antidepressants are ineffective for up to 40 percent of those who try them.

Nine newer antipsychotics, called atypical antipsychotics, are used as "augmentation therapy," or add-ons to treat depression that hasn't responded to antidepressants or other treatments. This is known as "treatment resistant" depression. They are aripiprazole (Abilify), asenapine (Saphris), clozapine (Clozaril and generics), iloperidone (Fanapt), olanzapine (Zyprexa), paliperidone (Invega), quetiapine (Seroquel, Seroquel XR), risperidone (Risperdal and generics), and ziprasidone (Geodon). Three--Abilify, Seroquel XR, and Zyprexa--and a combination pill--Symbyax--that contains olanzapine (Zyprexa) plus the antidepressant fluoxetine (Prozac)--are approved by the Food and Drug Administration for this use, but other antipsychotics are used "off-label" for this purpose.

However, the available evidence indicates that antipsychotics aren't very effective at treating "resistant" depression and aren't the best choice for this use for most people. Other options, such as increasing the dose of your antidepressant or switching to a different one, are at least as effective and are safer. Combining two antidepressants may also be an option. And it remains unclear whether antipsychotics are any better than a placebo at preventing a relapse or return of depression over the long-term. Antipsychotics can also cause serious side effects, such as involuntary movements of the tongue, lips, face, trunk, arms, or legs (tardive dyskinesia), significant weight gain, and an increased risk of type 2 diabetes, heart disease, and stroke. In addition, they are very expensive, with some costing more than $1,000 a month.

For those reasons, the atypical antipsychotics aren't good first choices as add-ons to antidepressants, especially if you are overweight or have heart disease or diabetes. Our medical consultants recommend they be used cautiously and only after first trying the strategies listed above. In this report, we do not choose any as Best Buy selections. Instead, we evaluate how well the medications actually work at relieving resistant depression and the risk of side effects.

If your depression hasn't responded to an antidepressant after four to eight weeks, you should first rule out that you don't have other medical or mental-health conditions that could make your depression more difficult to treat, such as bipolar disorder or post-traumatic stress disorder.

If you've tried all those strategies, then your next option is to talk with your doctor about the treatment options that make sense for your situation. In addition to antipsychotics, other medications used include lithium, thyroid hormone, low doses of stimulants, anticonvulsants, and other classes of antidepressants, such as tricyclic antidepressants and monoamine oxidase inhibitors (MAOIs). Nonmedication options include electroconvulsive therapy, transcranial magnetic stimulation, and vagus nerve stimulation. If you decide to try an antipsychotic, our medical advisers suggest that you consult a psychiatrist to help manage the side effects.

Editor's Note:

These materials are made possible by a grant from the state Attorney General Consumer and Prescriber Education Grant Program, which is funded by the multi-state settlement of consumer-fraud claims regarding the marketing of the prescription drug Neurontin (gabapentin).

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