Quetiapine adjunct to selective serotonin reuptake inhibitors or venlafaxine in patients with major depression, comorbid anxiety, and residual depressive symptoms: a randomized, placebo-controlled pilot study

Depress Anxiety. 2007;24(7):487-94. doi: 10.1002/da.20275.


This double-blind, placebo-controlled study examined the efficacy and tolerability of quetiapine in combination with selective serotonin reuptake inhibitors (SSRIs)/venlafaxine in 58 patients with major depressive disorder, comorbid anxiety symptoms (HAM-A-14 score > or =14), and residual depressive symptoms (HAM-D-17 score > or =18, CGI-S score > or =4). Patients had received an SSRI/venlafaxine (at a predefined therapeutic dose) for > or =6 weeks. Overall, 62% (18/29) of quetiapine- and 55% (16/29) of placebo-treated patients completed the study. The mean change in HAM-D and HAM-A total scores from baseline to Week 8 (primary endpoint) was significantly greater with quetiapine (mean dose 182 mg/day) than placebo: -11.2 vs. -5.5 (P=.008) and -12.5 vs. -5.9 (P=.002), respectively. The onset of quetiapine efficacy (HAM-D/HAM-A/CGI-I) was rapid (by Week 1) and continued through to Week 8. Significant differences (P<.05) from baseline to Week 8 were observed between groups in 7/17 HAM-D (including feelings of guilt, suicide) and 6/14 HAM-A items (including tension, cardiovascular symptoms). Response (> or =50% decrease in total score) was higher for quetiapine than placebo: HAM-D, 48% vs. 28% (not significant, NS); HAM-A, 62% vs. 28% (P=.02). Remission (total score < or =7) was higher for quetiapine than placebo: HAM-D, 31% vs. 17% (NS); HAM-A, 41% vs. 17% (NS). CGI-S, CGI-I, and the Global Assessment Scale showed that quetiapine was significantly more effective than placebo. For quetiapine, adverse events (AEs) were similar to those previously observed; sedation/somnolence/lethargy was the most commonly reported. Here quetiapine was shown to be effective as augmentation of SSRI/venlafaxine therapy in patients with major depression, comorbid anxiety, and residual depressive symptoms, with no unexpected tolerability issues. Further studies are warranted.

Publication types

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

MeSH terms

  • Adult
  • Antidepressive Agents, Second-Generation / administration & dosage*
  • Antidepressive Agents, Second-Generation / adverse effects
  • Antipsychotic Agents / administration & dosage*
  • Antipsychotic Agents / adverse effects
  • Anxiety Disorders / diagnosis
  • Anxiety Disorders / drug therapy
  • Anxiety Disorders / psychology
  • Comorbidity
  • Cyclohexanols / administration & dosage*
  • Cyclohexanols / adverse effects
  • Depressive Disorder, Major / drug therapy*
  • Dibenzothiazepines / administration & dosage*
  • Dibenzothiazepines / adverse effects
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Humans
  • Male
  • Middle Aged
  • Personality Inventory
  • Quetiapine Fumarate
  • Selective Serotonin Reuptake Inhibitors / administration & dosage*
  • Selective Serotonin Reuptake Inhibitors / adverse effects
  • Venlafaxine Hydrochloride


  • Antidepressive Agents, Second-Generation
  • Antipsychotic Agents
  • Cyclohexanols
  • Dibenzothiazepines
  • Serotonin Uptake Inhibitors
  • Quetiapine Fumarate
  • Venlafaxine Hydrochloride