Treatment of unipolar psychotic depression: a randomized, double-blind study comparing imipramine, venlafaxine, and venlafaxine plus quetiapine

Acta Psychiatr Scand. 2010 Mar;121(3):190-200. doi: 10.1111/j.1600-0447.2009.01464.x. Epub 2009 Aug 19.


Objective: It remains unclear whether unipolar psychotic depression should be treated with an antidepressant and an antipsychotic or with an antidepressant alone.

Method: In a multi-center RCT, 122 patients (18-65 years) with DSM-IV-TR psychotic major depression and HAM-D-17 > or = 18 were randomized to 7 weeks imipramine (plasma-levels 200-300 microg/l), venlafaxine (375 mg/day) or venlafaxine-quetiapine (375 mg/day, 600 mg/day). Primary outcome was response on HAM-D-17. Secondary outcomes were response on CGI and remission (HAM-D-17).

Results: Venlafaxine-quetiapine was more effective than venlafaxine with no significant differences between venlafaxine-quetiapine and imipramine, or between imipramine and venlafaxine. Secondary outcomes followed the same pattern.

Conclusion: That unipolar psychotic depression should be treated with a combination of an antidepressant and an antipsychotic and not with an antidepressant alone, can be considered evidence based with regard to venlafaxine-quetiapine vs. venlafaxine monotherapy. Whether this is also the case for imipramine monotherapy is likely, but cannot be concluded from the data.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Affective Disorders, Psychotic / drug therapy*
  • Aged
  • Antidepressive Agents, Tricyclic / therapeutic use
  • Antipsychotic Agents / therapeutic use
  • Cyclohexanols / therapeutic use*
  • Depressive Disorder / drug therapy*
  • Dibenzothiazepines / therapeutic use*
  • Double-Blind Method
  • Drug Administration Schedule
  • Drug Dosage Calculations
  • Drug Therapy, Combination
  • Female
  • Humans
  • Imipramine / therapeutic use*
  • Male
  • Middle Aged
  • Quetiapine Fumarate
  • Remission Induction
  • Selective Serotonin Reuptake Inhibitors / therapeutic use
  • Severity of Illness Index
  • Treatment Outcome
  • Venlafaxine Hydrochloride
  • Young Adult


  • Antidepressive Agents, Tricyclic
  • Antipsychotic Agents
  • Cyclohexanols
  • Dibenzothiazepines
  • Serotonin Uptake Inhibitors
  • Quetiapine Fumarate
  • Venlafaxine Hydrochloride
  • Imipramine