Escitalopram and Problem-Solving Therapy for Prevention of Post stroke Depression

Background:  Approximately 37% of stroke survivors develop depression after the acute stroke period.  Considering that the annual incidence of stroke in the United States exceeds 700,000 cases, the number of survivors that develop depression is quite striking.  Investigators have previously attempted to prevent the development of post stroke depression to no avail.

Objective:  To assess the efficacy of escitalopram or psychological problem-solving therapy in the prevention of post stroke depression.

Methods:  Investigators conducted a multisite, parallel, controlled trial in which 176 post stroke victims were randomized to receive escitalopram (n=59), placebo (n=58), or problem-solving therapy (n=59) for one year.  Inclusion criteria consisted of age 50-90 years and with either hemispheric, brain stem, or cerebellar stroke within the last 3 months.  Exclusion criteria included major or minor depressive disorder, severe comprehension deficits, and patients with impaired decision-making capacity.  Occurrence of stroke secondary to complications from an intracranial aneurysm, arterial-venous malformation, intracranial tumor or neoplastic process, stroke during the course of myocardial infarction, aortic dissection, or revascularization surgery were all excluded from the study.  Other exclusion criteria included life-threatening heart or respiratory failure, renal or hepatic failure, severely disabling musculoskeletal disorder, cancer, neurodegenerative disorders, and alcohol or substance abuse or dependence within the past 12 months.  Patients randomized to the escitalopram group received 10mg every day if they were less than 65 years old and 5mg/day if they were less than 65.  Patients in the problem-solving therapy group received 6 treatment sessions over the first 12 weeks and 6 reinforcement sessions within the year.  Primary outcome measures were the incidence of depression due to stroke with major depressive-like episode and the incidence minor depression.  Secondary outcome measures included an assessment of activities of daily living and further neuropsychological assessment such as hemispatial neglect and impaired ability to follow oral instructions.  Researchers predicted a power of 0.80, and intention-to-treat was used in the analysis.

Results:  Overall, 53 patients in the placebo group completed the study, and 52 and 56 patients in the escitalopram and problem-solving therapy groups completed the study respectively.  Of the patients who received placebo, 13 cases (11 major, 2 minor, 22.4%) of depression were reported.  Of the patients receiving escitalopram, 5 cases (3 major, 2 minor, 8.5%) of depression were reported, and of the patients receiving problem-solving therapy, 7 cases (5 major, 2 minor, 11.9%) of depression were reported.  Patients who received placebo were 4.5 times more likely to develop depression than patients receiving escitalopram (adjusted HR, 4.5; 95% CI, 2.4-8.2; p<.001) and 2.2 times more likely than patients receiving problem-solving therapy (adjusted HR, 2.2; 95% CI, 1.4-3.5; p<.001).  Patients with a history of mood disorders were 5.2 times more likely to develop depression in the course of a year than patients without a previous history (adjusted HR, 5.2; 95%CI, 3.3-8.1, p<.001).  All three groups improved in activities of daily living over time, scores on the functional independence measure and social functioning over time. 
            The authors concluded that their study successfully demonstrated prevention of post-stroke depression.  They also concluded that depression can be significantly decreased in frequency by preventive use of escitalopram compared with placebo over the first year following an acute stroke. 

Strengths:  An appropriate study design is a strength of the study, as well as the calculated power.  Primary and secondary outcomes were easily and objectively measured.  The authors also reported drop-outs in great detail. 
           
Weaknesses:  The inclusion and exclusion criteria of the study were extremely narrow and specific.  There is a possibility that the study results do not apply to most stroke victims.  The study sample size and the prevalence of depression within the groups were relatively small, which are major limitations of the study. 

Conclusion:  The inclusion/exclusion criteria of this study greatly limit the population for which the data can be extrapolated.  One key finding was the higher instance of depression among patients that had previously suffered from a mental illness.  This information is more clinically useful than the data that supports starting all poststroke patients on an antidepressant to prevent depression.  Further research needs to be conducted to determine long-term effects of the drug and the necessary duration of therapy to prevent depression. 

Robinson RG, Ricardo EF, Moser DJ, Acion L, Solodkin A, Small SL, et al. Escitalopram and problem-solving therapy for prevention of poststroke depression.  JAMA. 2008; 229(20): 2391-2400.

Dana Stone, Doctor of Pharmacy Candidate