Imipramine is effective in preventing relapse in electroconvulsive therapy-responsive depressed inpatients with prior pharmacotherapy treatment failure: a randomized, placebo-controlled trial.
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.


METHODS
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 anti-depressant 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.
Department of Psychiatry, Erasmus Medical Centre, Rotterdam, the Netherlands. w.w.vandenbroek@erasmusmc.nl
Walter W
WW
van den Broek
Tom K
TK
Birkenhäger
Paul G H
PG
Mulder
Jan A
JA
Bruijn
Peter
P
Moleman
D000328:Adult; D000929:Antidepressive Agents, Tricyclic / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D003865:Major Depressive Disorder / Q000175:diagnosis / Q000188:drug therapy* / Q000628:therapy*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004351:Drug Resistance; D004359:Drug Therapy, Combination; D004565:Electroconvulsive Therapy; D005260:Female; D006760:Hospitalization; D006801:Humans; D007099:Imipramine / Q000627:therapeutic use*; D008094:Lithium / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D008996:Monoamine Oxidase Inhibitors / Q000627:therapeutic use; D017063:Outcome Assessment, Health Care; D010919:Placebos; D016016:Proportional Hazards Models; D011569:Psychiatric Status Rating Scales; D012307:Risk Factors; D055502:Secondary Prevention; D016896:Treatment Outcome
D000929:Antidepressive Agents, Tricyclic; D008996:Monoamine Oxidase Inhibitors; D010919:Placebos; D008094:Lithium; D007099:Imipramine