Relapse from antidepressant medication may be lack of response to medication in the first place

A new study by Rhode Island Hospital researchers indicates that a relapse during antidepressant continuation treatment may be due to a relapse in patients who were not true drug responders.

The loss of drug response may be due to loss of placebo response (a positive medical response to taking a placebo as if it were an active medication.). The study was published in the August issue of the Journal of Clinical Psychiatry.

Historically, the treatment of depression is divided into three phases initial/acute, continuation and maintenance. During the initial phase, the goal is to reduce symptoms and psychosocial impairment. During the continuation phase, usually six months to one year after initial treatment response, the goal is to maintain the gains and prevent a relapse. In the maintenance phase, which occurs after a sustained period of improvement, the goal is to further maintain the gains and prevent recurrence of the disorder.

Mark Zimmerman, MD, director of outpatient psychiatry at Rhode Island Hospital and associate professor of psychiatry and human behavior at the Warren Alpert School of Medicine at Brown University, is the paper's lead author. Zimmerman, along with his colleague Tavi Thongy, MD, also of Rhode Island Hospital and Brown University, conducted a meta-analysis of continuation studies of new generation antidepressants that began as placebo-controlled acute phase studies. Treatment studies of depression have found that approximately 50 to 65 percent of patients respond to medication and that approximately 25 to 35 percent respond to placebo.

Past studies have indicated that a number of patients who respond to treatment in the initial phase experience a relapse or recurrence despite ongoing pharmacotherapy during the two latter phases of treatment. This return of symptoms is often interpreted as a loss of efficacy of antidepressant activity, and is referred to as tachyphylaxis or the poop-out effect.

Zimmerman says, "When a patient improves after being prescribed an antidepressant medication you do not know if they got better because of the medication or because they had a placebo response."

The researchers used formulas developed by Quitkin and colleagues more than a decade ago to calculate the relapse rate attributable to relapse in presumptive placebo responders. "Our study suggests that the return of symptoms despite ongoing treatment during the continuation and maintenance phases of treatment may not represent a loss of drug effect because the patient may not have experienced a true drug response in the first place."

Zimmerman also notes, "While our conclusion is limited to the continuation phase of treatment, our results suggest that these findings probably also apply to the maintenance phase of treatment."

The researchers note that these findings are not inconsistent with conclusions that continuation and maintenance studies of antidepressants have clearly established the benefit of ongoing treatment beyond the acute phase.

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