Continued Prescription of Antidepressant Drugs for Relapse Prevention in Depression

A topic in Clinical Evidence 1 summarizes the results of a systematic review on continuation treatment with antidepressant drugs in patients who had responded to treatment over the previous 1 month to 3 years. There were 31 RCTs with a total of 4410 people. Continuing antidepressant drugs reduced the proportion of people who relapsed compared to placebo (18% vs 41%, OR 0.30, 95% CI 0.22 to 0.38). For patients who had responded after 2 months' treatment, the NNT to prevent one additional relapse over 6 months was 6 (95% CI 5 to 8), over 12 months 5 (95% CI 4 to 6), and over 24-36 months 4 (95% CI 3 to 7). More patients on continuous antidepressants withdrew from the trials compared to placebo (18% vs 15%, OR 1.30, 95% CI 1.07 t0 1.59). 5/767 people continuing maprotiline and 1/185 continuing sertraline compared with 1 person taking placebo committed suicide (OR 5.96, 95% CI 0.72 to 49.47).

A systematic review 1 including 27 studies with a total of 3,037 subjects was abstracted in DARE. Patients whose antidepressants were discontinued showed much higher relapse rates than those whose treatments were continued (6.24% versus 1.85%, p<0.001). Those whose treatment was discontinued also showed shorter time to 50% relapse (14.2 months vs 48.0 months, p<0.001) and higher 12-month relapse rate (44.8% vs 19.4%). Longer prior treatment did not yield lower postdiscontinuation relapse risk. Relapsess off versus on antidepressants fall markedly with longer follow-up.

Another systematic review 2 including 4 RCTs with a total of 788 subjects was abstracted in DARE. In addition, the guidelines of the American Psychiatric Association and the AHCPR were evaluated in the discussion. In the first study, differences were non-significant between lithium and amitriptyline, but statistically significant between drug and placebo (p=0.025). In the second study, imipramine and lithium were better than placebo. In the third study, imipramine was better than lithium in patients with severe illness, and the combination regimen offered no advantages. In the fourth study, imipramine with or without IPT-M was found to be the best maintanance treatment consistently over the 3 years of follow-up.

The following decision support rules contain links to this evidence summary:

• Duration of antidepressive drug therapy http://www.ebmeds.org/ebmeds/ebmeds_home.asp?mode=scripts&submode=view&id=scr00475&country=UK

References

• Viguera AC, Baldessarini RJ, Friedberg J. Discontinuing antidepressant treatment in major depression. Harv Rev Psychiatry 1998 Mar-Apr;5(6):293-306. [PubMed] [DARE]
• Blacker D. Maintenance treatment of major depression: a review of the literature. Harv Rev Psychiatry 1996 May-Jun;4(1):1-9. [PubMed][DARE]