Summary of clinical evidence on individual SSRIs for post-stroke recovery.
| SSRI | Study [Ref] | SD/SAM/SS | ToI | D&D | Primary endpoint | FU | Main efficacy findings | Safety findings | Interpretation | Level of evidence |
|---|---|---|---|---|---|---|---|---|---|---|
| FLX | FLAME [24] | RCT; n = 118; moderate-severe ischemic stroke | Subacute phase (~5–10 days post-stroke) | 20 mg/day for 3 months | FMMS | 90 days | Improved motor recovery; higher proportion with mRS 0–2 | Generally well tolerated; no major safety signal reported | Early evidence of motor improvement in selected patients | Moderate |
| Smaller RCTs [25–29] | Small RCTs, mechanistic studies; n < 100 per study; mainly ischemic stroke | Early or very early post-stroke | Short-term (days–weeks) | NIHSS, motor learning, neurophysiology | Short-term | Improved motor/executive function; enhanced cortical plasticity markers | Limited reporting; generally mild adverse events | Suggests neuroplastic effects but low-certainty evidence | Low | |
| AFFINITY [30], EFFECTS [31], FOCUS [32] | Multicenter RCTs; n > 5,000 total; ischemic and hemorrhagic stroke | Early post-stroke (initiation within 2–15 days post-stroke) | 20 mg/day for 6 months | mRS (6–12 months) | 6–12 months | No improvement in global functional outcome (mRS) | Increased fractures, falls, seizures, and hyponatremia | No improvement on global disability; consistent adverse effects | High | |
| CTP | TALOS [33] | RCT; n = 642; ischemic stroke | Early subacute phase | 20 mg/day for 6 months | mRS, cognition, stroke recurrence | 6 months | No improvement in global disability, cognition, or recurrence | No major safety concerns reported | No evidence of improvement in global outcomes | High |
| Smaller RCTs [19, 34, 35] | Small clinical and mechanistic studies; n = 172 (pooled); ischemic stroke | Early or single-dose administration | Short-term/variable | Motor performance, cortical excitability | Short-term | Improved dexterity and motor cortex modulation | Limited safety reporting | Possible neurophysiological effects; low-quality evidence | Low | |
| ESC | Jorge et al. [36] | RCT; small to moderate sample (n = 104); post-stroke patients | Early post-stroke | Short-term administration | Cognitive function scales | Short–medium term | Improved global cognitive performance independent of mood | No significant adverse safety signal | Potential cognitive improvement | Moderate |
| Cao et al. [37], EMOTION trial [38] | RCTs; n ≈ 450 pooled; acute ischemic stroke | Early post-stroke (within days to weeks) | ESC 10–20 mg/day; up to 3–6 months | Emotional symptoms, neurological outcomes, stress-related biomarkers | 3–6 months | Reduced post-stroke depressive/emotional symptoms; improvement in selected neurological outcomes and lower plasma copeptin levels | Generally well tolerated; no major safety concerns reported | Potential benefits on emotional recovery and selected neurological/stress-related outcomes | Moderate | |
| Others (SRT & FLV) | No RCTs evaluating stroke are available | Not applicable | Not applicable | Not applicable | Not applicable | Not applicable | Not applicable | Not applicable | Evidence insufficient for recommendation | Not applicable |
SSRIs: selective serotonin reuptake inhibitors; SD/SAM/SS: study design/sample/stroke subtype; ToI: timing of initiation; D&D: dose & duration; FU: follow-up; FLX: fluoxetine; CTP: citalopram; ESC: escitalopram; SRT: sertraline; FLV: fluvoxamine; FLAME: FLX for Motor Recovery After Acute Ischemic Stroke; RCT: randomized controlled trial; FMMS: Fugl-Meyer Motor Scale; mRS: modified Rankin Scale; NIHSS: National Institutes of Health Stroke Scale.