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 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, “Pharmacological Treatment of Depression” (identifier: ISRCTN73221288).

Algorithm, ECT, Imipramine, Lithium, Major depressive disorder, Venlafaxine,
Progress in Neuro-Psychopharmacology & Biological Psychiatry
Department of Psychiatry

Vermeiden, M, Kamperman, A.M, Hoogendijk, W.J.G, van den Broek, W.W, & Birkenhäger, T.K. (2018). Outcome of a three-phase treatment algorithm for inpatients with melancholic depression. Progress in Neuro-Psychopharmacology & Biological Psychiatry, 84, 214–220. doi:10.1016/j.pnpbp.2018.03.002