Academic journal article Indian Journal of Psychiatry

Exploring New Frontiers in Neuropsychopharmacology: SSRIs for Stroke

Academic journal article Indian Journal of Psychiatry

Exploring New Frontiers in Neuropsychopharmacology: SSRIs for Stroke

Article excerpt

Byline: T. Sathyanarayana Rao, Chittaranjan. Andrade

Selective serotonin reuptake inhibitors (SSRIs) are approved treatments for a variety of indications: depression, obsessive-compulsive disorder, generalized anxiety disorder, panic disorder, social anxiety disorder, post-traumatic stress disorder, premenstrual dysphoric disorder, and others. [sup][1] SSRIs are experimental or off-label treatments for a variety of conditions ranging from premature ejaculation [sup][2] to alcoholism. [sup][3] A new frontier now appears to be opening for the use of SSRIs: stroke, a condition which commonly results in physical and cognitive impairments, functional dependence, caregiver burden, and poor quality of life. Importantly, the data for this indication have emerged from clinical trials that were independent of the pharmaceutical industry. What have been the findings?

Fluoxetine and Stroke

A meta-analysis [sup][4] of data from six randomized controlled trials (RCTs) with a pooled sample size of 385 patients suggested that in patients with recent stroke, fluoxetine may reduce the incidence of post-stroke depression [odds ratio (OR) 0.25; 95% confidence interval (CI) 0.11-0.56], promote the recovery of neurological functioning [weighted mean difference (WMD) 4.72; 95% CI 1.13-8.31], and improve independence in activities of daily living (WMD 8.04, 95% CI 2.68-3.40).

One of the fluoxetine RCTs [sup][5] provided interesting follow-up data. In the original study, 104 stroke patients were treated for 12 weeks with fluoxetine (up to 40 mg/day), nortriptyline (up to 100 mg/day), or placebo. At a 9-month follow-up, [sup][6] a third of patients were observed to have dropped out of each of the antidepressant arms relative to 14% dropout with placebo. A completer analysis performed on the combined antidepressant versus placebo groups showed that after adjusting for confounding variables such as age, intensity of rehabilitation therapy, baseline stroke severity, and baseline Hamilton Depression Rating Scale (HAM-D) score, patients who had received 3 months of treatment with antidepressant medication showed significantly greater improvement in modified Rankin Scale scores than those who had received placebo. Outcomes with fluoxetine and nortriptyline were similar, with each being superior to placebo. Activities of daily living, assessed using the Functional Independence Measure, showed a trend ( P =0.09) for superiority of antidepressant drugs over placebo. Outcomes in patients who received antidepressants for 6 months did not differ significantly from those in patients who received treatment for 3 months; however, these analyses were probably underpowered. A limitation of this completer analysis is that about half of the patients who did not complete the study dropped out because of medical deterioration or adverse effects; thus, an intent-to-treat analysis would almost certainly have found limited benefits with drugs. [sup][6]

Significantly, at a 9-year follow-up, 36 out of 53 (68%) patients who received full dose antidepressants were alive in contrast with only 10 out of 28 (36%) placebo-treated patients. After controlling for confounding variables such as age and coexisting diabetes, this long-term benefit of just 12 weeks of post-stroke antidepressant therapy was found to remain significant in patients who were depressed as well as in those who were not depressed at baseline. [sup][7]

Earlier this year, another fluoxetine RCT showed that in patients ( n =118) with stroke and moderate to severe hemiplegia or hemiparesis, fluoxetine (20 mg/day, started 5-10 days after stroke) combined with physiotherapy was associated with significantly better 3-month motor outcomes than placebo combined with physiotherapy. Gastrointestinal disturbances were commoner with fluoxetine than with placebo (25% vs. 11%, respectively); otherwise, common adverse effects differed little between groups. [sup][8]

One RCT found that fluoxetine, however, does not benefit the specific symptom of post-stroke fatigue. …

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