Time course of response to antidepressants: Predictive value of early improvement and effect of additional psychotherapy

Abstract

Background The full response to antidepressant pharmacotherapy is evident only after several weeks, but considerable improvements may already be visible within the first two weeks. Little is known about the potential influence of additional psychotherapy on the speed of response to antidepressant treatment. We have analysed in more severely depressed inpatients treated with antidepressants i) the predictive value of early improvement for later response and ii) the impact of additional psychotherapy on the time course of response. Methods 124 patients with a major depression referred for hospitalized care were randomized to 5 weeks of sertraline (or amitriptyline as a second choice) plus either additional Interpersonal Psychotherapy modified for inpatients (IPT) or Clinical Management (CM). “Improvement” was defined as a decrease of ≥ 20% on the 17-item Hamilton Rating Scale for Depression (HAMD). “Onset of response” was defined as sustained improvement (without any subsequent increase in the HAMD) culminating in 50% decrease on the HAMD by week 5. Results Early improvement within two weeks was highly predictive of later stable response (≥ 50% decrease on the HAMD at weeks 4 and 5) or stable remission (HAMD score of ≤ 7 at weeks 4 and 5), irrespective of the type of medication or additional IPT or CM. Survival analysis of the ITT sample revealed that patients of the IPT group had a shorter time to “onset of response” than patients in the CM group (median: 12 vs. 30 days; p = 0.041, Log Rank). However, there was no significant difference in the time to onset of response, when more stringent conditions were used. Limitations Due to ethical restrictions a comparison with an untreated placebo group could not be performed. Conclusions Early improvement is highly predictive for later stable response or remission in more severely depressed inpatients. In combination therapy, the additional benefit of psychotherapy occurs at least as rapid as the response to antidepressants.