Journal of Neurology

, Volume 265, Issue 8, pp 1871–1879 | Cite as

Minocycline for acute stroke treatment: a systematic review and meta-analysis of randomized clinical trials

  • Konark Malhotra
  • Jason J. Chang
  • Arjun Khunger
  • David Blacker
  • Jeffrey A. Switzer
  • Nitin Goyal
  • Adrian V. Hernandez
  • Vinay Pasupuleti
  • Andrei V. Alexandrov
  • Georgios Tsivgoulis
Original Communication



Various randomized-controlled clinical trials (RCTs) have investigated the neuroprotective role of minocycline in acute ischemic stroke (AIS) or acute intracerebral hemorrhage (ICH) patients. We sought to consolidate and investigate the efficacy and safety of minocycline in patients with acute stroke.


Literature search spanned through November 30, 2017 across major databases to identify all RCTs that reported following efficacy outcomes among acute stroke patients treated with minocycline vs. placebo: National Institute of Health Stroke Scale (NIHSS), Barthel Index (BI), and modified Rankin Scale (mRS) scores. Additional safety, neuroimaging and biochemical endpoints were extracted. We pooled mean differences (MD) and risk ratios (RR) from RCTs using random-effects models.


We identified 7 RCTs comprising a total of 426 patients. Of these, additional unpublished data was obtained on contacting corresponding authors of 5 RCTs. In pooled analysis, minocycline demonstrated a favorable trend towards 3-month functional independence (mRS-scores of 0–2) (RR = 1.31; 95% CI 0.98–1.74, p = 0.06) and 3-month BI (MD = 6.92; 95% CI − 0.92, 14.75; p = 0.08). In AIS subgroup, minocycline was associated with higher rates of 3-month mRS-scores of 0–2 (RR = 1.59; 95% CI 1.19–2.12, p = 0.002; I2 = 58%) and 3-month BI (MD = 12.37; 95% CI 5.60, 19.14, p = 0.0003; I2 = 47%), whereas reduced the 3-month NIHSS (MD − 2.84; 95% CI − 5.55, − 0.13; p = 0.04; I2 = 86%). Minocycline administration was not associated with an increased risk of mortality, recurrent stroke, myocardial infarction and hemorrhagic conversion.


Although data is limited, minocycline demonstrated efficacy and seems a promising neuroprotective agent in acute stroke patients, especially in AIS subgroup. Further RCTs are needed to evaluate the efficacy and safety of minocycline among ICH patients.


Minocycline Ischemic stroke Intracerebral hemorrhage Recovery 


Author contributions

KM: Study concept and design, acquisition of data, analysis and interpretation, critical revision of the manuscript for important intellectual content. JJC: Acquisition and interpretation of data, critical revision of the manuscript for important intellectual content. AK: Analysis and interpretation, critical revision of the manuscript for important intellectual content. DB: Acquisition and interpretation of data, critical revision of the manuscript for important intellectual content. JAS: Acquisition and interpretation of data, critical revision of the manuscript for important intellectual content. NG: Acquisition and interpretation of data, critical revision of the manuscript for important intellectual content. AVH: Analysis and interpretation, critical revision of the manuscript for important intellectual content. VP: Analysis and interpretation, critical revision of the manuscript for important intellectual content. AVA: Acquisition and interpretation of data, critical revision of the manuscript for important intellectual content. GT: Study concept and design, study supervision, critical revision of the manuscript for important intellectual content.


This study received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.

Compliance with ethical standards

Conflicts of interest

Dr. Malhotra reports no disclosures. Dr. Chang reports no disclosures. Dr. Khunger reports no disclosures. Dr. Blacker reports no disclosures. Dr. Switzer reports no disclosures. Dr. Goyal reports no disclosures. Dr. Hernandez reports no disclosures. Dr. Pasupuleti reports no disclosures. Dr. Alexandrov reports no disclosures. Dr. Tsivgoulis reports no disclosures.

Supplementary material

415_2018_8935_MOESM1_ESM.doc (844 kb)
Supplementary material 1 (DOC 844 KB)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Konark Malhotra
    • 1
  • Jason J. Chang
    • 2
  • Arjun Khunger
    • 3
  • David Blacker
    • 4
  • Jeffrey A. Switzer
    • 5
  • Nitin Goyal
    • 6
  • Adrian V. Hernandez
    • 7
    • 8
  • Vinay Pasupuleti
    • 9
  • Andrei V. Alexandrov
    • 6
  • Georgios Tsivgoulis
    • 6
    • 10
  1. 1.Department of Neurology, Charleston Area Medical CenterWest Virginia University-Charleston DivisionCharlestonUSA
  2. 2.Department of Critical Care MedicineMedStar Washington Hospital CenterWashington, DCUSA
  3. 3.Department of Hematology and Oncology, Cleveland Clinic FoundationClevelandUSA
  4. 4.Department of Neurology and Clinical NeurophysiologySir Charles Gairdner HospitalNedlandsAustralia
  5. 5.Department of NeurologyMedical College of Georgia at Augusta UniversityGeorgiaUSA
  6. 6.Department of NeurologyUniversity of Tennessee Health Science CenterMemphisUSA
  7. 7.University of Connecticut/Hartford Hospital Evidence-based Practice CenterHartfordUSA
  8. 8.School of MedicineUniversidad Peruana de Ciencias Aplicadas (UPC)LimaPeru
  9. 9.ProEd Communications Inc.ClevelandUSA
  10. 10.Second Department of NeurologyNational and Kapodistrian University of Athens, “Attikon” University HospitalAthensGreece

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