Difference in treatment outcome in outpatients with anxious versus nonanxious depression: a STAR*D report

Am J Psychiatry. 2008 Mar;165(3):342-51. doi: 10.1176/appi.ajp.2007.06111868. Epub 2008 Jan 2.


Objective: About half of outpatients with major depressive disorder also have clinically meaningful levels of anxiety. The authors conducted a secondary data analysis to compare antidepressant treatment outcomes for patients with anxious and nonanxious major depression in Levels 1 and 2 of the STAR*D study.

Method: A total of 2,876 adult outpatients with major depressive disorder, enrolled from 18 primary and 23 psychiatric care sites, received citalopram in Level 1 of STAR*D. In Level 2, a total of 1,292 patients who did not remit with or tolerate citalopram were randomly assigned either to switch to sustained-release bupropion (N=239), sertraline (N=238), or extended-release venlafaxine (N=250) or to continue taking citalopram and receive augmentation with sustained-release bupropion (N=279) or buspirone (N=286). Treatment could last up to 14 weeks in each level. Patients were designated as having anxious depression if their anxiety/somatization factor score from the 17-item Hamilton Depression Rating Scale (HAM-D) was 7 or higher at baseline. Rates of remission and response as well as times to remission and response were compared between patients with anxious depression and those with nonanxious depression.

Results: In Level 1 of STAR*D, 53.2% of patients had anxious depression. Remission was significantly less likely and took longer to occur in these patients than in those with nonanxious depression. Ratings of side effect frequency, intensity, and burden, as well as the number of serious adverse events, were significantly greater in the anxious depression group. Similarly, in Level 2, patients with anxious depression fared significantly worse in both the switching and augmentation options.

Conclusions: Anxious depression is associated with poorer acute outcomes than nonanxious depression following antidepressant treatment.

Publication types

  • Case Reports
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Ambulatory Care*
  • Antidepressive Agents / therapeutic use
  • Anxiety Disorders / diagnosis
  • Anxiety Disorders / drug therapy*
  • Anxiety Disorders / epidemiology
  • Citalopram / adverse effects
  • Citalopram / therapeutic use*
  • Comorbidity
  • Cyclohexanols / therapeutic use
  • Delayed-Action Preparations
  • Depressive Disorder, Major / diagnosis
  • Depressive Disorder, Major / drug therapy*
  • Depressive Disorder, Major / epidemiology
  • Drug Therapy, Combination
  • Female
  • Humans
  • Male
  • Middle Aged
  • Outcome Assessment, Health Care
  • Prospective Studies
  • Psychiatric Status Rating Scales / statistics & numerical data
  • Serotonin Uptake Inhibitors / adverse effects
  • Serotonin Uptake Inhibitors / therapeutic use*
  • Somatoform Disorders / diagnosis
  • Somatoform Disorders / drug therapy
  • Somatoform Disorders / epidemiology
  • Treatment Outcome
  • Venlafaxine Hydrochloride


  • Antidepressive Agents
  • Cyclohexanols
  • Delayed-Action Preparations
  • Serotonin Uptake Inhibitors
  • Citalopram
  • Venlafaxine Hydrochloride