Abstract and Introduction
Background Despite the high prevalence of depression in people with neurological disorders, no previous study has sought to summarise existing evidence on the use of antidepressants in this population. A systematic review and meta-analysis was undertaken to determine whether antidepressants are more effective than placebo in the treatment of depression in neurological disorders, and whether any benefit is associated with improvement in function.
Methods Embase, Pubmed, Psycinfo and Cochrane trial registers were searched for randomised controlled trials (RCTs) comparing the efficacy of antidepressant and placebo in the treatment of depression in adults with a neurological disorder.
Findings 20 RCTs were included in the review, including patients with Parkinson's disease, multiple sclerosis, brain injury, epilepsy and stroke. Outcomes were analysed at four time points: 4–5 weeks, 6–8 weeks, 9–18 weeks and >18 weeks. The primary outcome was response to treatment at 6–8 weeks. The evidence favoured the use of antidepressants over placebo at all time points although pooled results were not statistically significant at all time points. At 6–8 weeks, antidepressant treatment was associated with a greater than twofold odds of remission (OR 2.23; 95% CI 1.54 to 3.23; number needed to treat=7). Fewer data were available for quality of life, and functional and cognitive outcomes, and there was little evidence of improvement with antidepressant treatment.
Interpretation Antidepressants are effective for the treatment of depression in patients with neurological disorders but the evidence for the efficacy of antidepressants in improving quality of life, and functional and cognitive outcomes is inconclusive.
Depression is common in patients with physical illness and prevalence studies have found high rates of depression in those with neurological disorders. Estimates of the prevalence of depression after stroke range from 20% to 72%; in Parkinson's disease, estimates are 40–50% and 19–54% for multiple sclerosis. In epilepsy, the prevalence is estimated at up to 55%.
Depression in patients with neurological disorders (and physical illness more generally) is associated with adverse outcomes, notably poorer quality of life; poorer compliance with medication or rehabilitation; lower quality relationships between patients and clinical staff; higher health service use; and—for some disorders—higher mortality.
Although systematic reviews have been published on antidepressant treatment of depression for individual neurological diagnoses, there have been no systematic reviews examining the efficacy of antidepressants for depression in neurological disorders as a category. Such a review could provide evidence as to whether antidepressants could be more broadly recommended for patients with depression in the context of a neurological disorder, and also whether the evidence in this population differs from the evidence for antidepressant use in other physically ill populations (where antidepressants have been found to be effective compared with placebo) and in general populations with depression.
We therefore conducted a systematic review of antidepressants for the treatment of depression in neurological disorders.
Review of Current Evidence
The evidence for antidepressants for the treatment of depression in neurological disorders is patchy. A review published in 2009 by the Cochrane Collaboration for the treatment of depression after stroke identified eight randomised placebo controlled trials. After examining the evidence, the authors tentatively supported antidepressant treatment but advised caution due to a risk of adverse events of antidepressant treatment in this population. A systematic review by the American Association of Neurologists in 2006, and in 2003 a Cochrane systematic review of depression in Parkinson's disease, found little evidence for the use of antidepressants in this population, although the use of tricyclic antidepressants was tentatively supported by the American Association of Neurologists. A 2005 review of the diagnosis and treatment of mood disorders in epilepsy noted that current recommendations for treatment were based on general treatment guidelines for patients without comorbid conditions due to lack of available trial evidence, and advised caution when using antidepressant therapies which might reduce seizure threshold.
Other authors have examined more broadly the evidence for antidepressants for patients with neurological disorders. One study found that treatment of depression in neurological disorders is under researched relative to the morbidity it causes, and a more recent paper identified a need for large controlled studies of pharmacological treatments in this area.
Our principal aim was to determine whether antidepressants are more effective than placebo in the treatment of depression (measured using standard depression rating scales at 6–8 weeks post randomisation) in patients with neurological disorders. Because we hypothesised that treating depression would improve neurological outcomes, we also examined quality of life, and functional and cognitive outcomes to determine whether antidepressants impact on these domains.
This study has been reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement.