A double-blind, placebo-controlled study of sertraline in the prevention of depression in stroke patients
Rasmussen A, Lunde M, Poulsen DL, Søresen K, Qvitzau S and Bech P;
Commented by , 26 May 2003
Background
Post-stroke depression (PSD) is common, with prevalence rates of 30-35%. PSD is associated with increased cognitive impairment, functional decline and mortality. While antidepressants have demonstrated efficacy in PSD, their role in PSD prophylaxis remains unclear.
Purpose
Evaluate the efficacy of sertraline in the prevention of PSD.
Methods
Consecutive stroke inpatients at 2 Danish university hospitals (May 1996 – May 1998) were screened within four weeks of acute stroke. Currently depressed and/or patients on antidepressants were excluded; please refer to the original paper for additional exclusion criteria.
Patients who met criteria were randomly assigned to 12 months of double-blind treatment with sertraline or placebo, starting at 50 mg/day with flexible increases to 150 mg/day. A comprehensive battery of assessments was completed at baseline (visit 0) and 11 postrandomization visits (~4-5 week intervals), which included the following outcome measures:
· Modified Ham-D17 (item 14, sexual behavior excluded) at visits 0, 3, 6 and 11
· 7-item clinician-rated Clinical Global Impression (CGI) severity and improvement scales at all visits
· The Udvalg for Kliniske Undersøgelser (UKU) Side Effect Rating Scale to evaluate tolerability
Kaplan-Meier survival analyses (p≤ 0.05 level of significance) were used, defining PSD as a score of >18 on the Ham-D17 or ≥ 9 on the Ham-D6, covering 6 core items of depression.
Results
137 patients were randomized: 70 to sertraline and 67 to placebo. Baseline demographic and clinical characteristics were similar between groups with 2 exceptions: the sertraline group was slightly older (72.0 vs 68.0 years), and had lower Ham-D17 scores (6.5 vs 7.6). 50% and 47.8% completed the 12-month study in the sertraline and placebo groups, respectively.
Kaplan-Meier analyses demonstrated the efficacy of sertraline for PSD prophylaxis to be significant. After 52 weeks of sertraline or placebo treatment, the rate of depression was 8.2% versus 22.8% (Ham-D17) and 11.5% versus 28.1% (Ham-D6), respectively. Using Last-observation-carried-forward analyses, there was a non-significant trend towards better global measures on the CGI for the sertraline group.
The mean daily dose of sertraline was 62.9 mg. Overall, sertraline was numerically better tolerated than placebo, at times reaching statistical significance; fewer patients experienced severe cardiovascular events on sertraline (p=0.02).
Discussion
This is the first study to demonstrate the prophylactic efficacy of antidepressants in PSD. Previous studies were limited by sample size (1), and low depression rates perhaps owing to the study’s active rehabilitation program (2). This latter study highlights the potential role of non-pharmacological treatments in PSD, which have demonstrated effectiveness in other medical populations (3,4), but bear further evaluation in PSD.
Using the current study’s 14.6% sparing effect (Ham-D17) with antidepressants, 6.8 is the number needed to treat (NNT) to prevent the occurrence of depression in one patient. Although a PSD is common and is associated with increased morbidity and mortality, is it reasonable to subject all stroke patients to antidepressants, whereby up to 65% of patients are unlikely to develop PSD?
Antidepressants are not innocuous, carrying risks of drug-drug interactions and other potential unresolved complications (5,6). Thus, future directions should target high-risk patient groups, most likely to benefit from prevention strategies.
The main study limitation is the large proportion of study non-completers limits the study’s validity; furthermore, with the exception of the non-significant CGI outcomes, it is unclear from the paper as to whether non-completers were included in the 10 outcome analyses (Ham-D17,6).
References
1. Narushima K, Kosier JT, Robinson RG. Preventing poststroke depression: a 12-week double-blind randomized treatment trial and 21-month follow-up. Journal of Nervous and Mental Disease 2002; 190; 296-303
2. Palomaki H, Kaste M, Berg A, Lonngqvist R, Lonngqvist J, Lehtihalmes M, Hares J. Prevention of poststroke depression: 1 year randomized placebo controlled double blind trial of mianserin with 6 month follow up after therapy. Journal of Neurology, Neurosurgery and Psychiatry 1999; 66; 490-494
3. Cowan MJ, Pike KC, Budzynski HK. Psychosocial nursing therapy following sudden cardiac arrest: impact on two-year survival. Nursing Research 2001; 50; 68-76
4. Markowitz JC, Kocsis JH, Fishman B, Spielman LA, Jacobsberg LB, Frances AJ, Klerman GL, Perry SW. Treatment of depressive symptoms in human immunodeficiency virus-positive patients. Archives of General Psychiatry. 1998; 55; 452-457.
5. Skop BP, Brown TM. Potential vascular and bleeding complications of treatment with selective serotonin reuptake inhibitors. Psychosomatics 1996; 37; 12-16
6. Liu B, Anderson G, Mittman N, To T, Axcell T, Shear N. Use of selective serotonin-reuptake inhibitors or tricyclic antidepressants and risk of hip fractures in elderly people. Lancet 1998; 351; 1303-1307