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CNS Drugs

, Volume 32, Issue 10, pp 905–916 | Cite as

Efficacy and Safety of Adjunctive Cannabidiol in Patients with Lennox–Gastaut Syndrome: A Systematic Review and Meta-Analysis

  • Simona Lattanzi
  • Francesco Brigo
  • Claudia Cagnetti
  • Eugen Trinka
  • Mauro Silvestrini
Systematic Review

Abstract

Background

Lennox–Gastaut syndrome (LGS) is a severe developmental epileptic encephalopathy, and available interventions fail to control seizures in most patients. Cannabidiol (CBD) is a major chemical of marijuana, which has anti-seizure properties and different mechanisms of action compared with other approved antiepileptic drugs (AEDs).

Objective

The aim was to evaluate the efficacy and safety of CBD as adjunctive treatment for seizures in patients with LGS using meta-analytical techniques.

Methods

Randomized, placebo-controlled, single- or double-blinded trials were identified. Main outcomes included the ≥ 50% reduction in baseline drop and non-drop seizure frequency, and the incidence of treatment withdrawal and adverse events (AEs). Risk ratios (RRs) with 95% confidence intervals (CIs) were estimated through the inverse variance method.

Results

Two trials were included involving 396 participants. Patients presenting ≥ 50% reduction in drop seizure frequency during the treatment were 40.0% with CBD and 19.3% with placebo [RR 2.12 (95% CI 1.48–3.03); p < 0.001]. The rate of non-drop seizure frequency was reduced by 50% or more in 49.4% of patients in the CBD and 30.4% in the placebo arms [RR 1.62 (95% CI 1.09–2.43); p = 0.018]. The RR for CBD withdrawal was 4.93 (95% CI 1.50–16.22; p = 0.009). The RR to develop any AE during CBD treatment was 1.24 (95% CI 1.11–1.38; p < 0.001). AEs significantly associated with CBD were somnolence, decreased appetite, diarrhea and increased serum aminotransferases.

Conclusions

Adjunctive CBD resulted in a greater reduction in seizure frequency and a higher rate of AEs than placebo in patients with LGS presenting seizures uncontrolled by concomitant AEDs.

Notes

Compliance with Ethical Standards

Funding

No funding was received to conduct this study.

Conflict of interest

Simona Lattanzi, Claudia Cagnetti and Mauro Silvestrini have no conflicts of interest directly relevant to the content of this study. Francesco Brigo acted as a consultant for Eisai. Eugen Trinka received speaker’s honoraria from UCB, Biogen, Gerot-Lannach, Bial, Eisai, Takeda, Newbridge, Sunovion Pharmaceuticals Inc., LivaNova and Novartis; consultancy funds from UCB, Biogen, Gerot-Lannach, Bial, Eisai, Takeda, Newbridge, GW Pharmaceuticals, Sunovion Pharmaceuticals Inc., and Novartis; and directorship funds from Neuroconsult GmbH. E. Trinka’s Institution received grants from Biogen, Red Bull, Merck, UCB, European Union, FWF Österreichischer Fond zur Wissenschaftsförderung, and Bundesministerium für Wissenschaft und Forschung.

Supplementary material

40263_2018_558_MOESM1_ESM.pdf (11 kb)
Supplementary material 1 (PDF 11 kb)

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Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  • Simona Lattanzi
    • 1
  • Francesco Brigo
    • 2
    • 3
  • Claudia Cagnetti
    • 1
  • Eugen Trinka
    • 4
    • 5
    • 6
  • Mauro Silvestrini
    • 1
  1. 1.Neurological Clinic, Department of Experimental and Clinical MedicineMarche Polytechnic UniversityAnconaItaly
  2. 2.Department of Neuroscience, Biomedicine and Movement ScienceUniversity of VeronaVeronaItaly
  3. 3.Division of Neurology“Franz Tappeiner” HospitalMeranoItaly
  4. 4.Department of Neurology, Christian Doppler KlinikParacelsus Medical UniversitySalzburgAustria
  5. 5.Center for Cognitive NeuroscienceSalzburgAustria
  6. 6.Public Health, Health Services Research and HTAUniversity for Health Sciences, Medical Informatics and TechnologyHall in TirolAustria

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