Patients with antidepressant-resistant depression may benefit from adjunct therapy with an atypical antipsychotic, even if given for a brief period, according to an article in the August issue of Neuropsychopharmacology AOP.

In the first large-scale study of its kind, the international trial tested two-drug therapy for 489 seriously ill patients who had failed to respond to selective serotonin reuptake inhibitors such as fluoxetine (one to three treatment failures) in the past.

At the start of the study, patients were treated open-label with citalopram, up to 60 milligrams per day for four to six weeks. Patients who did not have at least a 50 percent reduction in symptoms were offered the opportunity to proceed with open-label adjunct treatment with risperidone at up to 2 milligrams per day.

Almost 60 percent of people who had risperidone augmentation met criteria for remission from depression by the end of the open-label risperidone phase. At that point, individuals entered a four-week double-blind portion of the protocol where patients received risperidone or placebo.

In terms of numbers, 489 patients entered the initial, citalopram monotherapy phase, with 434 patients failing to achieve at least 50 percent improvement. Of the 386 nonresponders who entered open-label adjunct therapy, 243 achieved remission. Almost all of them (241) entered the double-blind adjunct therapy phase.
Median time to relapse was 102 for patients randomized to risperidone versus 85 days for placebo (rates of 56.1 and 54.6 percent, respectively).

The authors concluded that risperidone substantially improved the rate at which patients with antidepressant-resistant depression entered remission from symptoms, but longer-term benefits were not demonstrated.

Qualitatively, patients characterized as less severely ill only needed to take risperidone for a brief period of time to experience benefit. Patients who were characterized as more severely ill, however, needed to continue risperidone through the double-blind period to experience the same level of effectiveness.

“The implications of our research shows that a certain subset of individuals with chronic depression who don’t respond to standard treatment with antidepressant medication could benefit from a brief period of supplementary therapy,” said Mark H. Rapaport, MD, the study’s principal investigator.

“We are very encouraged by this research. Treatment-resistant depression is associated with the grave risk of increased morbidity and mortality and with a severely decreased quality of life. It is one of the most pressing public health needs that we face as a society,” Rapaport said. “We hope this study will stimulate other researchers to pursue investigating the need for continuation of supplemented therapies.”