MIRTAZAPINE VERSUS AMITRIPTYLINE IN THE LONG-TERM TREATMENT OF DEPRESSION - A DOUBLE-BLIND PLACEBO-CONTROLLED STUDY

Of 580 patients randomly assigned to short-term, double-blind treatmen t with either mirtazapine, amitriptyline or placebo, a total of 217 pa tients clinically judged to be responders subsequently continued on th e same medication for up to 2 years in the long-term treatment study ( mirtazapine, n = 74; amitriptyline, n = 86 and placebo, n = 57). The e fficacy of mirtazapine in relapse prevention was seen in an analysis o f the first 20 weeks data. Significantly fewer patients relapsed durin g treatment with mirtazapine compared with placebo (p < 0.05), and a s ignificantly longer time to relapse was shown on the survival analysis . There was a significant advantage for amitriptyline compared with pl acebo in the first 20 weeks, with fewer patients relapsing. There was a significant advantage for mirtazapine compared with amitriptyline at 20 weeks seen on the survival analysis (p < 0.05). The significant ad vantage for mirtazapine compared with placebo was also seen in the pro phylactic phase of treatment after 20 weeks. At the endpoint there wer e significantly more patients in the placebo group with a return of sy mptoms and significantly fewer showing sustained response. Amitriptyli ne was better than placebo with fewer patients suffering a recurrence of symptoms, but there was no difference from placebo in the proportio n of patients with sustained response. Mirtazapine was well tolerated with a side-effect profile similar to that of placebo. The only advers e event reported significantly more frequently on mirtazapine than on placebo was weight gain. Objectively measured weight gain was more fre quent with amitriptyline (22% of patients) compared with mirtazapine ( 13% of patients). Amitriptyline was associated with significantly more adverse events than either mirtazapine or placebo, in particular seda tive and anticholinergic side effects. The efficacy of mirtazapine in reducing the risk of relapse and the recurrence of depression, which o n some measures showed an advantage compared with amitriptyline, coupl ed with its improved side-effect profile, commends this antidepressant for the long-term treatment of depression. (C) 1998 Rapid Science Ltd .