Atypical antipsychotic drugs — which are now commonly prescribed as an add-on therapy for the treatment of depression — offer few benefits and risk significant side effects, according to a new study.

The side effects of these drugs include extreme sleepiness and weight gain.

“It’s become pretty clear that antipsychotics are being used at an increased rate for depression over the last few years, so we wanted to see if the evidence supported that practice,” said Glen Spielmans, Ph.D., a researcher and associate professor of psychology at Metropolitan State University in St. Paul.

Only one-third of patients with depression responds to antidepressant medications — one of the main reasons that physicians are prescribing additional antipsychotics.

In fact, the practice of using antipsychotics as an adjunct therapy has nearly doubled from the mid-1990s to the late 2000s.

For the study, researchers reviewed 14 previous randomized clinical trials in which the combined use of an antidepressant and an antipsychotic medication were compared to the use of an antidepressant with a placebo.

The medications investigated in the studies were aripiprazole (Abilify), olanzapine/fluoxetine (Symbyax), quetiapine (Seroquel) and risperidone (Risperdal).

The results showed a small benefit with antipsychotic use on relieving the symptoms of depression. But when the researchers looked for a more meaningful outcome — whether the patients’ quality of life had improved — no benefit was found.

“In terms of quality of life and how well people were functioning, there was really not much evidence that these drugs did anything,” said Spielmans.

Antipsychotic medications were associated, however, with more negative side effects, including weight gain, akathisia (a feeling of restlessness), sleepiness and abnormal results from cholesterol and other metabolic-related laboratory tests.

“Taken together,” wrote Spielmans and his study’s co-authors, “our meta-analysis found evidence of (1) some improvement in clinician-assessed depressive symptoms, (2) little evidence of substantial benefit in overall well-being, and (3) abundant evidence of potential treatment-related harm.”

In another study, British researchers found strong evidence that engaging in talk therapy was an effective add-on to antidepressants.

The findings showed that antidepressant-resistant patients who received cognitive behavioral therapy in addition to an antidepressant experienced both a significant reduction in their depression and a significant improvement in their quality of life.

If the results from that study hold, said Spielmans, cognitive behavioral therapy “may be a better choice for more people than taking an antipsychotic.”

Spielmans recommends that patients with depression use caution before taking antipsychotics as an adjunct to antidepressants. “Look at whatever research is available, and encourage your doctor to do the same,” he said.

Source: PLOS Medicine