Escitalopram and problem-solving therapy for prevention of poststroke depression: a randomized controlled trial

Abstract

Context: Depression occurs in more than half of patients who have experienced a stroke. Poststroke depression has been shown in numerous studies to be associated with both impaired recovery in activities of daily living and increased mortality. Prevention of depression thus represents a potentially important goal.

Objective: To determine whether treatment with escitalopram or problem-solving therapy over the first year following acute stroke will decrease the number of depression cases that develop compared with placebo medication.

Design, setting, and participants: A multisite randomized controlled trial for prevention of depression among 176 nondepressed patients was conducted within 3 months following acute stroke from July 9, 2003, to October 1, 2007. The 12-month trial included 3 groups: a double-blind placebo-controlled comparison of escitalopram (n = 59) with placebo (n = 58), and a nonblinded problem-solving therapy group (n = 59).

Main outcome measures: The main outcome measure was the development of major or minor poststroke depression based on symptoms elicited by the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) (DSM-IV) and the diagnostic criteria from DSM-IV for depression due to stroke with major depressive-like episode or minor depression (ie, research criteria).

Results: Patients who received placebo were significantly more likely to develop depression than individuals who received escitalopram (11 major and 2 minor cases of depression [22.4%] vs 3 major and 2 minor cases of depression [8.5%], adjusted hazard ratio [HR], 4.5; 95% confidence interval [CI], 2.4-8.2; P < .001) and also more likely than individuals who received problem-solving therapy (5 major and 2 minor cases of depression [11.9%], adjusted HR, 2.2; 95% CI, 1.4-3.5; P < .001). These results were adjusted for history of mood disorders and remained significant after considering possible confounders such as age, sex, treatment site, and severity of impairment in the model. Using an intention-to-treat conservative method of analyzing the data, which assumed that all 27 patients who did not start randomized treatment would have developed depression, and controlling for prior history of mood disorders, escitalopram was superior to placebo (23.1% vs 34.5%; adjusted HR, 2.2; 95% CI, 1.2-3.9; P = .007), while problem-solving therapy was not significantly better than placebo (30.5% vs 34.5%; adjusted HR, 1.1; 95% CI, 0.8-1.5; P = .51). Adverse events, including all-cause hospitalizations, nausea, and adverse effects associated with escitalopram were not significantly different between the 3 groups.

Conclusions: In this study of nondepressed patients with recent stroke, the use of escitalopram or problem-solving therapy resulted in a significantly lower incidence of depression over 12 months of treatment compared with placebo, but problem-solving therapy did not achieve significant results over placebo using the intention-to-treat conservative method of analysis.

Trial registration: clinicaltrials.gov Identifier: NCT00071643.

Figure 1

Patients Assessed and Randomized to Receive Escitalopram, Problem-Solving Therapy, or Placebo PST indicates problem-solving therapy. Of 149 patients who received at least 1 dose of escitalopram or 1 session of PST, 89.9% reached the study end points. ^aStudy participation was not allowed at skilled nursing facilities.

Figure 2

Risk Comparison of Depression Onset for Patients Receiving Escitalopram, Problem-Solving Therapy (PST), or Placebo Over 1 Year After adjusting for previous history of mood disorders, participants who received placebo were 4.5 times more likely to develop depression than participants who received escitalopram (adjusted hazard ratio, 4.5; 95% confidence interval, 2.4–8.2; P<.001) and 2.2 times more likely than participants who received problem-solving therapy (adjusted hazard ratio, 2.2; 95% confidence interval, 1.4–3.5; P<.001).