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SSRIs may improve motor function, disability, QOL after stroke

Roshini Claire Anthony
05 Sep 2017

Selective serotonin reuptake inhibitors (SSRIs) may improve gross motor function, disability, and quality of life (QOL) among patients recovering from stroke, according to a systematic review and meta-analysis.

Researchers looked at 44 randomized controlled trials (RCTs) published between 1986 and 2016 which compared the outcomes of antidepressants, anti-Alzheimer drugs, anti-Parkinson drugs, central nervous system (CNS) stimulants, or piracetam vs placebo or no treatment on gross motor function, cognition, disability, dependency, and QOL of patients (n=2,658) aged 48–80 years who had been diagnosed with stroke.

SSRIs appeared to improve gross motor function (three studies; standardized mean difference [SMD], 0.54), in particular fluoxetine (SMD, 0.64), while there was no gross motor function benefit observed with dexamphetamine or levodopa-carbidopa. [Clin Drug Investig 2017;doi:10.1007/s40261-017-0558-4]

“[The benefit of] SSRIs, in particular fluoxetine, [on] gross motor function … may be attributed to the facilitation of motor output by the brain serotoninergic system,” said the researchers led by Dr Yau Wai-Ping from the Department of Pharmacy, National University of Singapore.

Based on analysis of five studies, SSRIs had no significant impact on cognition (SMD, 0.23), though one study pointed to a positive cognitive benefit rendered by citalopram (SMD, 0.63).

An analysis of 14 studies highlighted the benefit of SSRIs on disability (SMD, 0.49), specifically paroxetine (SMD, 1.05), fluoxetine (SMD, 0.41), and citalopram (SMD, 0.51). Individual studies also pointed to a potential benefit on disability conferred by the serotonin-norepinephrine reuptake inhibitor duloxetine and the monoamine oxidase inhibitor selegiline (SMD, 1.22 and 0.74, respectively).

The impact of SSRIs on disability was restricted to longer treatment duration (≥4 weeks; SMD, 0.42–0.66) compared with short-term treatment (2 weeks, SMD, 0.03), and among Chinese participants (SMD, 0.56) and not Caucasian ones (SMD, 0.29). The disability benefit was also restricted to the use of antidepressants with low anticholinergic activity.

“It is … likely that the benefit of SSRIs on improving stroke disability may not depend on the inhibition of serotonin reuptake that occurs soon after drug administration, but rather on the downstream cascades, where time is required for the modification of serotonergic receptors and increased production of neuroprotective proteins … in response to the initial increase in synaptic serotonin,” said Yau and co-authors.

“[The] lack of improvement in disability post-stroke with antidepressants with higher degrees of anticholinergic effects implied that the deleterious effects of increasing levels of anticholinergic activity may overpower the possible benefits,” they said, referring to previous research that demonstrated an association between dementia, delirium, and cognitive impairment with anticholinergic medications.

SSRIs also had a positive impact on overall QOL (two studies; mean difference [MD], 6.46), specifically duloxetine, fluoxetine, and sertraline (three studies; MD, 6.25), while one RCT demonstrated that treatment with fluoxetine resulted in a reduction in dependency among stroke patients.

There was little evidence to support the use of anti-Alzheimer drugs, anti-Parkinson drugs, CNS stimulants, and piracetam in aiding recovery in patients with stroke.

“[T]he choice of SSRI should be individualized for every patient, taking into consideration patient characteristics and the potential adverse effects of the drugs,” said the researchers.

The researchers acknowledged that the small number of studies for subgroup analysis may have impacted the findings, and that the findings may not be applicable to all stroke patients as most patients in the included studies had mild to moderate stroke, thus necessitating larger studies to verify the findings. Further investigation into the interactions between genetic and environmental factors may elucidate how variations in ethnicity may influence treatment response, they said. 

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