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      Patient with Delayed, Persistent Initial Response To Mirtazapine May Benefit the Most from Continued Therapy

      A DGReview of :"Placebo-Controlled Continuation Treatment with Mirtazapine: Acute Pattern of Response Predicts Relapse"
      Neuropsychopharmacology

      04/05/2004
      By Keely S. Solomon, Ph.D.


      Patients who show a delayed and persistent response to mirtazapine therapy for depression may be more likely to benefit from continued therapy than those who show a rapid and fluctuating initial response, say researchers.

      Previous studies have suggested that a delayed and persistent initial response to antidepressant therapy may be more common among patients whose improvement is due to the drug (true-drug initial response pattern), whereas a rapid and fluctuating response may be more characteristic of improvement due to a placebo effect. However, most studies investigating this relationship have been performed with fluoxetine, and it was previously unknown whether this pattern could be generalised to other antidepressants.

      To address this concern, Andrew A. Nierenberg, MD, of Harvard Medical School, Boston, Massachusetts, United States, and colleagues performed a trial investigating the relationship between acute patterns of response and subsequent placebo-controlled continuation of treatment with the antidepressant, mirtazapine.

      Depressed patients were included in the study after an initial screening with criteria from the Hamilton Rating Scale for Depression. Patients were treated with mirtazapine (15-45 mg/day) for a period of 8 to 12 weeks, and depressive symptoms were evaluated at multiple time points. Those showing symptom remission for at least 2 weeks at the end of this period were permitted to enter a 40-week double-blind treatment continuation phase. Among the 156 participants in the continuation phase, 76 continued taking mirtazapine and 81 were randomly chosen to switch to placebo treatment.

      During the initial treatment phase, 75 patients (49.1%; mean age, 39.7; 47% female) were classified as placebo responders and 81 (50.9%; mean age, 41.1; 54% female) were classified as true-drug initial responders. Patients with a true-drug initial response pattern switched to placebo had a significantly higher relapse rate (56%) than those continued on the drug (25%, P = .009). In contrast, no significant difference was detected between patients with an initial placebo response pattern switched to placebo (30%) and those continued on the drug (14%, P = .14). The researchers also note that true-drug initial response patients switched to placebo had a significantly greater relapse rate than placebo initial responders switched to placebo (P = .03).

      Based on their findings, the researchers conclude that, "patients with 'true-drug initial response pattern' are at greatest risk of relapse if drug is prematurely withdrawn and may benefit the most from continuation pharmacotherapy." However, they caution that pattern analysis is only one parameter, and should be considered in the context of all relevant clinical variables.


      Neuropsychopharmacology 2004 Mar 3;[Epub ahead of print]. "Placebo-Controlled Continuation Treatment with Mirtazapine: Acute Pattern of Response Predicts Relapse"

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