LAUSR

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): 7weeks optimal antidepressant monotherapy (imipramine or venlafaxine); phase II (n=39): 4weeks 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 antidepressant lithium 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). HIGHLIGHTSIn the completers, the favorable outcome of the algorithm is shown by a 93% response rate and a 64% remission rate.Feasibility of the algorithm was reasonable, with an overall dropout rate of 28%.Both an index episode less than one year, and not having received previous adequate treatment predicted a greater chance of achieving remission.