Outcome of a three-phase treatment algorithm for inpatients with melancholic depression.

BACKGROUND: In patients suffering from major depressive disorder, non-response to initial antidepressant monotherapy is relatively common. The use of treatment algorithms may optimize and enhance treatment outcome. METHODS: A single-center 3-phase treatment algorithm was evaluated for inpatients with major depressive disorder, i.e. phase I (n = 85): 7 weeks optimal antidepressant monotherapy (imipramine or venlafaxine); phase II (n = 39): 4 weeks subsequent plasma level-targeted dose lithium addition in case of insufficient improvement of antidepressant monotherapy; and phase III (n = 8): subsequent electroconvulsive therapy in case of insufficient improvement of antidepressant­lithium treatment. Overall feasibility of the 3-phase algorithm was determined by the number of dropouts, and overall efficacy was evaluated using weekly scores on the 17-item Hamilton Rating Scale for Depression (HAM-D) during the treatment phases of the algorithm. This paper is based on an RCT comparing the two antidepressants in phase I and adding lithium in phase II. RESULTS: Of the 85 patients analyzed, overall dropout during the 3-phase treatment algorithm was 24 (28%) patients. When analyzing the 3-phase treatment algorithm on a modified intention-to-treat basis, 39 (46%) patients achieved complete remission (HAM-D score ≤ 7) by the end of the algorithm. Regarding response (HAM-D score reduction ≥50%): of the 85 patients, 60 (71%) were responders by the end of the algorithm. CONCLUSION: The favorable outcome of the 3-phase treatment algorithm emphasizes the importance of pursuing stepwise antidepressant treatment in patients who are nonresponsive to the first antidepressant. CLINICAL TRIAL REGISTRATION: This study protocol is registered at http://www.controlled-trials.com, "Pharmacological Treatment of Depression" (identifier: ISRCTN73221288).

Early improvement as a predictor of eventual antidepressant treatment response in severely depressed inpatients.

RATIONALE: Traditionally, the therapeutic effect of antidepressants is thought to take several weeks. However, several studies found evidence of early drug response occurring within the first 2 weeks of antidepressant treatment and that this early onset response may predict eventual treatment outcome. OBJECTIVE: This study aims to investigate the predictive value of early improvement in the course of treatment with imipramine or venlafaxine in an inpatient population with severe major depression. METHOD: A post hoc analysis was conducted after pooling data from two almost identical trials. The study included 149 patients with DSM-IV diagnosis major depression and a baseline score ≥17 on the 17-item Hamilton Rating Scale for Depression (HAM-D). Patients were randomized for double-blind treatment with either antidepressant. Early improvement (≥25 % reduction on HAM-D score) was evaluated after 2 weeks and response (≥50 % reduction on HAM-D score) after 6 weeks of acute treatment. RESULTS: Of 64 patients achieving early improvement, 38 (59 %) became responders, whereas of 85 patients not achieving early improvement, only 23 (27 %) became responders. There was a significant difference in time to response between patients achieving early improvement and patients not achieving early improvement. Early improvement is a modest sensitive predictor for eventual response. CONCLUSION: In the present study, although the sensitivity of early improvement was modest, based on the severity of clinical symptoms, a clinician treating a patient with severe major depression may seriously consider changing the treatment at an earlier stage than is presently customary.

A double-blind randomized study comparing plasma level-targeted dose imipramine and high-dose venlafaxine in depressed inpatients.

OBJECTIVE: To compare the efficacy of plasma level-targeted dose imipramine and high-dose venlafaxine in depressed inpatients in a randomized double-blind study. METHODS: The study included 85 patients with a diagnosis of major depressive episode according to the DSM IV criteria and a 17-item Hamilton Rating Scale for Depression (HAM-D) score ≥ 17. Patients were randomized to imipramine or venlafaxine. The dose of imipramine was adjusted for each patient to a predefined blood level of 200-300 ng/ml. The dose of venlafaxine was increased gradually to 300-375 mg/day. Efficacy was evaluated after 7 weeks of treatment. RESULTS: The mean age of the study group was 54.5 (range 29-82) years. There was no significant difference according to the primary outcome criterion of a ≥50% reduction on the HAM-D score: 17 of 43 (39.5%) patients on imipramine were responders compared to 21 of 42 (50%) patients on venlafaxine. When considering remission as outcome criterion (HAM-D score ≤ 7), 10 of 43 (23.3%) patients on imipramine were remitters compared to 15 of 42 (35.7%) patients on venlafaxine; again, no significant difference. When analysing a subpopulation of patients without psychotic features, with remission as outcome criterion, a significant difference was found: 5 of 34 (14.7%) patients on imipramine were remitters compared to 12 of 31 (38.7%) patients on venlafaxine. CONCLUSIONS: The present study used optimal doses in depressed inpatients and showed that venlafaxine is at least equal in efficacy to imipramine. The results in the subgroup without psychotic features indicate a possible superiority of venlafaxine.