Electroconvulsive therapy (ECT) has a high response rate in patients with medication-resistant major depressive disorder. However, relapse rates are also high—more than 50 percent in the year following ECT. This rate is highest in patients who are untreated following ECT. Sackeim and associates conducted this randomized, double-blind, placebo-controlled trial to determine if relapse following ECT could be prevented if patients were given antidepressant pharmacotherapy after the ECT. This study sought to correct some of the flaws that exist in previous studies of this question.

Patients meeting the diagnostic criteria of major depressive disorder were included if they had a pre–ECT score of at least 21 on the Hamilton Rating Scale for Depression. Patients with other psychiatric illnesses, severe medical illnesses or substance abuse were excluded. Patients who received at least five ECT treatments were allowed into the continuation phase of the trial if they had a 60 percent or greater reduction in the Hamilton Rating Scale for Depression score compared with their own baseline score, and a score of no more than 10 at a two- and four- to eight-day follow-up assessment. Symptoms were also reviewed, because severity of symptoms is predictive of relapse after treatment for depression. Those whose symptoms had remitted were randomized to one of three groups: 29 received placebo, 27 received 50 mg of nortriptyline and 28 received 50 mg of nortriptyline plus 600 mg of lithium. Dosages were adjusted so that adequate steady-state levels were achieved. Plasma levels were obtained 10 times during the 24-week trial; clinical ratings and adverse events were also recorded during the study period. The main outcome measure was time to relapse. Relapse was defined as a mean Hamilton score of 16 and an increase of at least 10 points over two consecutive visits. It is this magnitude of score change that would generally cause a physician to change the treatment plan for a patient.

Slightly more than one half (54.8 percent) of the 290 patients who had ECT continued in the study as remitters. In the placebo group, 84 percent of the patients relapsed, compared to 60 percent of those in the nortriptyline group and 39.1 percent in the nortriptyline-lithium group. In the first two groups, relapse rates continued to rise during the 24-week study period. In the nortriptyline-lithium group, only one patient relapsed after five weeks of medication.

Without treatment, almost all patients who respond to ECT will have a relapse within six months of ECT. The authors conclude that post–ECT treatment with nortriptyline plus lithium is associated with lower relapse rates than post–ECT treatment with nortriptyline alone or placebo.