A randomized clinical trial comparing two two-phase treatment strategies for in-patients with severe depression

Acta Psychiatr Scand. 2017 Jul;136(1):118-128. doi: 10.1111/acps.12743. Epub 2017 May 6.

Abstract

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.

Keywords: imipramine; lithium; major depressive disorder; response; venlafaxine.

Publication types

  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Antidepressive Agents / administration & dosage
  • Antidepressive Agents / pharmacology*
  • Depressive Disorder, Major / drug therapy*
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Humans
  • Imipramine / administration & dosage
  • Imipramine / pharmacology*
  • Lithium Compounds / administration & dosage
  • Lithium Compounds / pharmacology*
  • Male
  • Middle Aged
  • Outcome Assessment, Health Care*
  • Severity of Illness Index
  • Venlafaxine Hydrochloride / administration & dosage
  • Venlafaxine Hydrochloride / pharmacology*

Substances

  • Antidepressive Agents
  • Lithium Compounds
  • Venlafaxine Hydrochloride
  • Imipramine

Associated data

  • ISRCTN/ISRCTN73221288