Sertraline versus imipramine to prevent relapse in chronic depression

Abstract

Background: Chronic depressions are common, disabling and under-treated, and long-term treatment is little studied. We report the continuation phase results from a long-term treatment study. Methods: After 12 weeks of acute phase treatment in a double-blind, randomized, parallel-group, multi-center trial of sertraline or imipramine, patients with chronic depression (≥2 years in major depression, or major depression superimposed on dysthymia) continued study drug for 16 weeks. Initially, 635 patients were randomized to sertraline or imipramine in a 2:1 ratio. Nonresponders after 12 weeks entered a 12-week double-blind crossover trial of the alternate medication. Entry into continuation treatment required at least a satisfactory response (partial remission) to initial or crossover treatment. Results: Of 239 acute or crossover responders to sertraline, 60% entered continuation in full remission and 40% with a partial remission. These proportions were identical for imipramine patients (n=147). For both drug groups, over two-thirds of those entering in full remission retained it. For those entering in partial remission, over 40% achieved full remission. Patients requiring crossover treatment were less likely to maintain or improve their response during continuation treatment. The two drugs did not differ significantly in response distribution, drop out rates or discontinuation due to side effects during continuation treatment. Limitations: The absence of a placebo group constrains interpretation of our results, but chronic depressions have low placebo response rates. Conclusions: Most chronic depression patients who remit with 12 weeks of sertraline or imipramine treatment maintain remission during 16 weeks of continuation treatment. Most patients with a satisfactory therapeutic response (partial remission) after 12 weeks of treatment maintain it or further improve. Patients treated with imipramine experienced more side effects, but both drugs were well tolerated.

Introduction

Chronic depressions, defined as dysthymia, major depression lasting ≥2 years, or concurrent dysthymia and major depression concurrently (double depression), are common (Mueller et al., 1996, Weissman et al., 1988), disabling (Hays et al., 1995) and under-treated (Hirschfeld et al., 1997, Shelton et al., 1997). Although chronic depressions respond to short-term pharmacotherapy with tricyclic antidepressants (Bakish et al., 1993, Thase et al., 1996), selective serotonin reuptake inhibitors (Thase et al., 1996), serotonin type-2 receptor antagonists (Bakish et al., 1993), and a reversible MAO inhibitor (Versianai, 1994), little is known about longer term treatment.

Kocsis et al. (1996) reported that 86% of chronically depressed patients who achieved full remission during a 10-week trial of desipramine maintained this status during 16 weeks of continued treatment. During continuation treatment, 30% of patients entering with a partial remission achieved full remission. In an open-label study with a mean follow-up of 5 years, Haykal and Akiskal (1999) found promising results from long-term SSRI treatment of dysthymia.

We report the double-blind evaluation of continuation phase treatment of chronic major or double depression with sertraline or imipramine. This report addresses the following questions.

• Are sertraline and imipramine equally safe and effective in preventing relapse?

• Do patients who have improved without remitting after 12 weeks of treatment improve further?

• Do patients having either a satisfactory therapeutic response or remission after 12 weeks of treatment relapse despite continued treatment?

• Do patients requiring a crossover trial (12 weeks of the alternate medication) before responding have a worse outcome during continuation treatment?