Efficacy and safety of minocycline in acute ischemic stroke: an updated systematic review and meta-analysis with trial sequential analysis of randomized controlled trials
6 affiliations
- 1King Faisal University
- 2King Fahad General Hospital
- 3School of Medicine, University College Dublin
- 4College of Medicine, King Khalid University
- 5University of Science and Technology College of Medicine
- 6Clinical Neurosciences department, King Faisal University
Abstract
Background Acute ischemic stroke (AIS) remains a leading cause of death and disability worldwide. Because neuroinflammation contributes substantially to ischemic brain injury, minocycline has been investigated as a potential adjunctive therapy owing to its anti-inflammatory and neuroprotective properties. Methods This systematic review and meta-analysis (PROSPERO: CRD420261340165) was conducted in accordance with PRISMA guidelines. We included randomized controlled trials (RCTs) enrolling adults with AIS that compared oral or intravenous minocycline plus standard care versus placebo plus standard care. The primary outcome was functional outcome assessed by the modified Rankin Scale (mRS) at 90 days. Random-effects meta-analysis with Hartung-Knapp adjustment was performed, and trial sequential analysis (TSA) was conducted for all-cause mortality. Results Five RCTs involving 2,073 patients were included. Minocycline did not significantly improve excellent functional outcome (mRS ≤1; RR 1.52, p=0.271), functional independence (mRS ≤2; RR 1.32, p=0.214), or moderate functional outcome (mRS ≤3; RR 1.05, p=0.282) at 90 days compared with placebo. Likewise, no significant differences were observed in early neurological improvement at day 7 (NIHSS; p=0.248) or functional independence at 90 days assessed by the Barthel Index (p=0.246). Minocycline was associated with lower all-cause mortality (RR 0.71, 95% CI 0.57–0.89; p=0.01); however, TSA indicated that the available evidence remains underpowered and insufficient for definitive conclusions. No significant differences were found in recurrent stroke or hemorrhagic transformation. Conclusion In conclusion, our findings suggest that minocycline is biologically credible, but it did not demonstrate a consistent benefit in functional or neurological outcomes after AIS (very low-to-low certainty evidence). Minocycline was associated with reduced all-cause mortality (moderate-certainty evidence), although trial sequential analysis indicates this finding remains inconclusive. With respect to the specific safety outcomes assessed—all-cause mortality, recurrent stroke, and hemorrhagic transformation—our findings do not raise safety concerns; however, safety was not comprehensively evaluated across the broader spectrum of known minocycline-associated adverse effects (e.g., hepatic toxicity, gastrointestinal intolerance, hypersensitivity reactions, vestibular symptoms), which were not systematically reported across the included trials. We therefore view minocycline as a promising adjunct that now needs better targeted, biomarker-informed, reperfusion-aware trials rather than immediate universal use in acute ischemic stroke.
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BibTeX
@article{altaha2026efficacy,
title = {{Efficacy and safety of minocycline in acute ischemic stroke: an updated systematic review and meta-analysis with trial sequential analysis of randomized controlled trials}},
author = {Mohammed B. Al-Taha and Asma Mohammed Abobaker and Muath Muhanna Almuhanna and Mohammed Ali Aljadani and Sharefa Mohammed Alshawi and Batool Ali Alshehab and Sukainah Ali Al Shehab and Zyad Abdulrahman Algolkhof and Mohammed Abdulrahman Al Jolkhof and Ayat Jassim Al Eid and Abdullah Faisal Albukhari and Afnan Khalid Alturki and Mohammed Al-Soufi and Saud A. Alnaim},
journal = {The Egyptian Journal of Neurology, Psychiatry and Neurosurgery},
year = {2026},
month = oct,
doi = {10.1186/s41983-026-01269-z},
url = {https://doi.org/10.1186/s41983-026-01269-z},
note = {CC BY},
}
RIS
TY - JOUR
TI - Efficacy and safety of minocycline in acute ischemic stroke: an updated systematic review and meta-analysis with trial sequential analysis of randomized controlled trials
AU - Mohammed B. Al-Taha
AU - Asma Mohammed Abobaker
AU - Muath Muhanna Almuhanna
AU - Mohammed Ali Aljadani
AU - Sharefa Mohammed Alshawi
AU - Batool Ali Alshehab
AU - Sukainah Ali Al Shehab
AU - Zyad Abdulrahman Algolkhof
AU - Mohammed Abdulrahman Al Jolkhof
AU - Ayat Jassim Al Eid
AU - Abdullah Faisal Albukhari
AU - Afnan Khalid Alturki
AU - Mohammed Al-Soufi
AU - Saud A. Alnaim
PY - 2026
DA - 2026/10/25
JO - The Egyptian Journal of Neurology, Psychiatry and Neurosurgery
DO - 10.1186/s41983-026-01269-z
UR - https://doi.org/10.1186/s41983-026-01269-z
AB - Background Acute ischemic stroke (AIS) remains a leading cause of death and disability worldwide. Because neuroinflammation contributes substantially to ischemic brain injury, minocycline has been investigated as a potential adjunctive therapy owing to its anti-inflammatory and neuroprotective properties. Methods This systematic review and meta-analysis (PROSPERO: CRD420261340165) was conducted in accordance with PRISMA guidelines. We included randomized controlled trials (RCTs) enrolling adults with AIS that compared oral or intravenous minocycline plus standard care versus placebo plus standard care. The primary outcome was functional outcome assessed by the modified Rankin Scale (mRS) at 90 days. Random-effects meta-analysis with Hartung-Knapp adjustment was performed, and trial sequential analysis (TSA) was conducted for all-cause mortality. Results Five RCTs involving 2,073 patients were included. Minocycline did not significantly improve excellent functional outcome (mRS ≤1; RR 1.52, p=0.271), functional independence (mRS ≤2; RR 1.32, p=0.214), or moderate functional outcome (mRS ≤3; RR 1.05, p=0.282) at 90 days compared with placebo. Likewise, no significant differences were observed in early neurological improvement at day 7 (NIHSS; p=0.248) or functional independence at 90 days assessed by the Barthel Index (p=0.246). Minocycline was associated with lower all-cause mortality (RR 0.71, 95% CI 0.57–0.89; p=0.01); however, TSA indicated that the available evidence remains underpowered and insufficient for definitive conclusions. No significant differences were found in recurrent stroke or hemorrhagic transformation. Conclusion In conclusion, our findings suggest that minocycline is biologically credible, but it did not demonstrate a consistent benefit in functional or neurological outcomes after AIS (very low-to-low certainty evidence). Minocycline was associated with reduced all-cause mortality (moderate-certainty evidence), although trial sequential analysis indicates this finding remains inconclusive. With respect to the specific safety outcomes assessed—all-cause mortality, recurrent stroke, and hemorrhagic transformation—our findings do not raise safety concerns; however, safety was not comprehensively evaluated across the broader spectrum of known minocycline-associated adverse effects (e.g., hepatic toxicity, gastrointestinal intolerance, hypersensitivity reactions, vestibular symptoms), which were not systematically reported across the included trials. We therefore view minocycline as a promising adjunct that now needs better targeted, biomarker-informed, reperfusion-aware trials rather than immediate universal use in acute ischemic stroke.
SN - 1687-8329
SN - 1110-1083
ER -