Metabolic disturbances and renal stone promotion on treatment with topiramate: a systematic review

Br J Clin Pharmacol. 2014 Jun;77(6):958-64. doi: 10.1111/bcp.12283.


Aims: The use of topiramate, which is prescribed for the management of epilepsy, for migraine headache prophylaxis and as a weight-loss agent, has been associated with the development of metabolic acidosis, hypokalaemia and renal stone disease. We systematically reviewed all the literature.

Methods: The systematic review of the literature was realized using the principles underlying the UK Economic and Social Research Council guidance on the conduct of narrative synthesis and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement.

Results: Fourty-seven reports published between 1996 and 2013 were retained for the final analysis. Five case-control studies and six longitudinal studies addressed the effect of topiramate on acid-base and potassium balance. A significant tendency towards mild-to-moderate hyperchloraemic metabolic acidosis (with bicarbonate ≤21.0 mmol l(-1) in approximately every third case) and mild hypokalaemia (with potassium ≤3.5 mmol l(-1) in 10% of the cases) was noted on treatment with topiramate, which was similar in children and adults. A single study observed that topiramate causes mild hyperuricaemia in male adults. A tendency towards hypocitraturia, a recognized promoter of renal stone formation, was noted in all patients on topiramate.

Conclusions: Increasing evidence supports the use of topiramate. Topiramate is generally well tolerated, and serious adverse events are rare. Nonetheless, the present systematic review of the literature indicates that its use is linked with the development of acidosis, hypokalaemia, hyperuricaemia and hypocitraturia.

Keywords: Acidosis; citraturia; hyperuricaemia; hypokalaemia; renal stone promotion; topiramate.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Acidosis / chemically induced*
  • Female
  • Fructose / adverse effects
  • Fructose / analogs & derivatives*
  • Humans
  • Hypokalemia / chemically induced*
  • Kidney Calculi / chemically induced*
  • Kidney Calculi / epidemiology
  • Male
  • Topiramate


  • Topiramate
  • Fructose