Objective: To compare the efficacy of two antidepressant treatment strategies in severely depressed in-patients, that is, imipramine vs. venlafaxine, both with subsequent lithium addition in non-responders. Method: In-patients (n = 88) with major depressive disorder were randomized to 7-week treatment with imipramine or venlafaxine (phase I). All non-responders (n = 44) received 4-week plasma level-targeted dose lithium addition (phase II). Efficacy was evaluated after 11 weeks of treatment. Results: Analyzing phases I and II combined, non-inferiority was established and the difference in the proportion of responders (HAM-D score reduction ≥50%) by the end of phase II demonstrated the venlafaxine-lithium treatment strategy to be significantly superior to the imipramine-lithium treatment strategy (77% vs. 52%) (χ2(1) = 6.03; P = 0.01). Regarding remission (HAM-D score ≤ 7), 15 of 44 (34%) patients in the imipramine-lithium treatment group were remitters compared to 22 of 44 (50%) patients in the venlafaxine-lithium treatment group, a non-significant difference. Patients in the venlafaxine-lithium treatment group had a non-significant larger mean HAM-D score reduction compared with patients in the imipramine-lithium treatment group (16.1 vs. 13.5 points, respectively; Cohen's d = 0.30). Conclusion: The venlafaxine-lithium treatment strategy can be considered a valuable alternative for the imipramine-lithium treatment strategy in the treatment of severely depressed in-patients.

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Keywords imipramine, lithium, major depressive disorder, response, venlafaxine
Persistent URL dx.doi.org/10.1111/acps.12743, hdl.handle.net/1765/108477
Journal Acta Psychiatrica Scandinavica
Vermeiden, M, Kamperman, A.M, Hoogendijk, W.J.G, van den Broek, W.W, & Birkenhäger, T.K. (2017). A randomized clinical trial comparing two two-phase treatment strategies for in-patients with severe depression. Acta Psychiatrica Scandinavica, 136(1), 118–128. doi:10.1111/acps.12743