Caffeine and seizures: A systematic review and quantitative analysis

Epilepsy Behav. 2018 Mar;80:37-47. doi: 10.1016/j.yebeh.2017.11.003. Epub 2018 Feb 3.


Purpose: Caffeine is the most commonly used central nervous system (CNS) stimulant. The relationship between caffeine, seizures, epilepsy, and antiepileptic drugs (AEDs) is complex and not fully understood. Case reports suggest that caffeine triggers seizures in susceptible people. Our systematic review reports on the relationship between caffeine, seizures, and drugs in animal and human studies. Quantitative analyses were also done on animal studies regarding the effects of caffeine on AEDs.

Methods: PubMed was searched for studies assessing the effects of caffeine on seizure susceptibility, epilepsy, and drug interactions in people and in animal models. To quantify the interaction between AEDs and caffeine, the data of six animal studies were pooled and analyzed using a general linear model univariate analysis or One-way Analysis of Variance (ANOVA).

Results: In total, 442 items were identified from which we included 105 studies. Caffeine can increase seizure susceptibility and protect from seizures, depending on the dose, administration type (chronic or acute), and the developmental stage at which caffeine exposure started. In animal studies, caffeine decreased the antiepileptic potency of some drugs; this effect was strongest in topiramate.

Conclusion: Preclinical studies suggest that caffeine increases seizure susceptibility. In some cases, chronic use of caffeine may protect against seizures. Caffeine lowers the efficacy of several drugs, especially topiramate. It is unclear how these findings in models can be translated to the clinical condition. Until clinical studies suggest otherwise, caffeine intake should be considered as a factor in achieving and maintaining seizure control in epilepsy.

Keywords: Animal model; Antiepileptic drugs; Cortical excitability; Energy drink; Epilepsy.

Publication types

  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Animals
  • Anticonvulsants / pharmacology*
  • Caffeine / administration & dosage
  • Caffeine / pharmacology*
  • Central Nervous System Stimulants / administration & dosage
  • Central Nervous System Stimulants / pharmacology*
  • Drug Interactions
  • Epilepsy / drug therapy*
  • Humans
  • Seizures / prevention & control*


  • Anticonvulsants
  • Central Nervous System Stimulants
  • Caffeine