THE IMPACT OF PHYSIOTHERAPY INTERVENTIONS COMBINED WITH PHARMACOLOGICAL MANAGEMENT ON FUNCTIONAL RECOVERY IN POST-STROKE PATIENTS: A SYSTEMATIC REVIEW

Abstract Background: Rehabilitation pharmacology aims to augment post-stroke neuroplasticity when paired with task-specific training, but no drug is currently approved to enhance motor recovery after stroke. Objective: To synthesize randomized trials of pharmacologic agents given with rehabilitation to improve functional outcomes after stroke. Methods: We narratively synthesized six pre-specified randomized, double-blind trials: levodopa+physiotherapy (2001), dextroamphetamine+physiotherapy (STARS, 2006), methylphenidate and levodopa+physiotherapy (2011), and three large pragmatic trials of fluoxetine for 6 months (FOCUS, 2019; AFFINITY, 2020; EFFECTS, 2020). Primary functional endpoints (eg, Rivermead Motor Assessment, Fugl-Meyer, mRS) and safety were extracted as reported. Results: Levodopa 100 mg given before therapy for 3 weeks improved Rivermead Motor Assessment versus placebo, with gains persisting at 6 weeks (8.2 vs 5.7 points; p=0.020). Dextroamphetamine+physiotherapy showed no overall benefit on Fugl-Meyer; an apparent advantage in moderate deficits was confounded by baseline imbalance. A factorial methylphenidate/levodopa trial found small advantages on Barthel Index and NIHSS at 6 months without robust motor superiority; tolerability was acceptable. The fluoxetine megatrials were neutral for mRS shift and reported more adverse events (fractures, hyponatremia, seizures) with fluoxetine. Conclusions: Timing levodopa immediately before therapy shows promising but unconfirmed benefits; routine SSRI use to “boost” recovery is not supported and may increase harm. Current guidelines emphasize comprehensive, adequately dosed, team-based rehabilitation and individualized decisions.