Imipramine Is Effective in Preventing Relapse in Electroconvulsive Therapy-Responsive Depressed Inpatients With Prior Pharmacotherapy Treatment Failure: A Randomized, Placebo-Controlled Trial

Walter W. van den Broek, M.D., Ph.D.; Tom K. Birkenhäger, M.D., Ph.D.; Paul G. H. Mulder, Ph.D.; Jan A. Bruijn, M.D., Ph.D.;and Peter Moleman, Ph.D.

Objective: To compare the efficacy of imipramine versus placebo in preventing relapse after successful electroconvulsive therapy (ECT) in depressive inpatients with pharmacotherapy treatment failure prior to ECT.

Method: During a 6-month period, the incidence of relapse was assessed. Two centers, both inpatient units for treatment of depressed patients, participated in this trial. Patients with DSM-IV-diagnosed major depressive disorder resistant to an antidepressant and subsequent lithium addition and/or a monoamine oxidase inhibitor were included. Patients were randomly assigned to double-blind treatment with imipramine with adequate plasma levels (N = 12) or placebo (N = 15) after successful ECT. The mean imipramine dosage was 209 mg/day (standard deviation: 91.7, range: 75 - 325 mg/day). The main outcome measure was relapse defined as at least "moderately worse" compared with baseline score on the Clinical Global Impressions-Improvement scale. Treatments were compared with survival analysis using the Cox proportional hazards model, including psychotic features and the score on the Hamilton Rating Scale for Depression (HAM-D) at baseline as prespecified covariables. Patients were enrolled in the study from April 1997 to July 2001.

Results: In the placebo group, 80% (12/15) of the patients relapsed compared with 18% (2/11) in the imipramine group. The Cox regression analysis showed a significant reduction in the risk of relapse of 85.6% with imipramine compared to placebo (p = .007; 95% confidence interval [CI] = 24.6% to 97.2%) adjusted for the covariables. There was an 18% increase in the relapse rate (p = .032; 95% CI = 2% to 36%) per unit increase in HAM-D score before the start of the trial; psychotic features had no significant effect (p = .794).

Conclusions: Depressed patients with pharmacotherapy treatment failure may benefit from the prophylactic effect of the same class of drug during maintenance therapy after response to ECT.

(J Clin Psychiatry 2006;67:263-268)

Received May 26, 2005; accepted Aug. 15, 2005. From the Departments of Psychiatry (Drs. van den Broek, Birkenhäger, and Bruijn) and Biostatistics and Epidemiology (Dr. Mulder), Erasmus Medical Centre, Rotterdam; and Moleman Psychopharmacology, Amerongen (Dr. Moleman), the Netherlands.

This study was supported by an unconditional grant from Psychiatric Hospital Parnassia, The Hague, the Netherlands.

Dr. Moleman has been an employee of Eli Lilly and Wyeth; has served as a consultant to Pfizer and Solvay Duphar; has received grant/research support from Lundbeck and AstraZeneca; has received honoraria from Boehringer Ingelheim and Bristol-Myers Squibb; has served on the speakers or advisory boards of GlaxoSmithKline and ICN; is a stock shareholder of Janssen and Synthon; and has received other material support from Organon. Drs. van den Broek, Birkenhäger, Mulder, and Bruijn report no other significant commercial relationships relevant to the study.

We thank the pharmacy department of the Erasmus Medical Centre for the preparation of the medication, determination of the plasma levels, and assistance in dosing the antidepressants.

Corresponding author and reprints: Walter W. van den Broek, M.D., P.O. Box 2040, 3000 CA Rotterdam, the Netherlands (e-mail: w.w.vandenbroek@erasmusmc.nl).