Skip to main content
SpringerLink
Log in

Bodyweight Gain and Anticonvulsants

A Comparative Review

  • Review Article
  • Published:
Drug Safety Aims and scope Submit manuscript

Abstract

Bodyweight gain is a common and frequent undesirable effect associated with the use of anticonvulsant drugs. This has been observed for many years with valproic acid (sodium valproate) and carbamazepine, and also, more recently, with some of the newer anticonvulsants such as vigabatrin and gabapentin.

Very often bodyweight gain in children, adolescents and adults with epilepsy taking such anticonvulsants results in cosmetic adverse effects. On the other hand, bodyweight gain is disturbing to general health, with a possible increase in the risk of diabetes mellitus or heart disease. Other potential adverse effects, such as the association of obesity with polycystic ovaries, have been reported with the use of valproic acid.

Potential mechanisms of anticonvulsant-associated bodyweight gain are not yet clear and differ between drugs used. The involvement of lowered blood glucose level, which may stimulate eating through an effect on the hypothalamus, constitutes one of the possible mechanisms. Lowered blood glucose levels may result from a competition between the binding of the drug and long chain fatty acids. An increased availability of the latter stimulates insulin production and lowers the serum glucose levels. Another possible explanation for lowered blood glucose may be a deficiency in carnitine directly caused by the drug, that would result in a reduction of fatty acid metabolism and an increase in glucose consumption. An enhancing effect of γ-aminobutyric acid-mediated neurotransmission may increase appetite for carbohydrates and reduce energy expenditure. An antidiuretic hormone-like effect or effects on norepinephrine (noradrenaline) or serotonin-mediated neurotransmission are more rarely considered. Many studies on anticonvulsant-associated bodyweight gain illustrate how we could better define the risk factors for the development of anticonvulsant-induced bodyweight gain and uncover the mechanisms behind it.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Table I

Similar content being viewed by others

References

  1. Corman CL, Leung NM, Guberman AH. Weight gain in epileptic patients during treatment with valproic acid: a retrospective study. Can J Neurol Sci 1997 Aug; 24(3): 240–4

    PubMed  CAS  Google Scholar 

  2. Easter D, O’Bryan-Tear CG, Verity C. Weight gain with valproate or carbamazepine — a reappraisal. Seizure 1997; 6: 121–5

    Article  PubMed  CAS  Google Scholar 

  3. Völzke E, Doose H. Dipropylacetate (Depakine, Ergenyl) in the treatment of epilepsy. Epilepsia 1973; 14: 185–93

    Article  PubMed  Google Scholar 

  4. Hassan MN, Laljee HCK, Parsonage MJ. Sodium Valproate in the treatment of resistant epilepsy. Acta Neurol Scand 1976; 54: 209–18

    Article  PubMed  CAS  Google Scholar 

  5. Covanis A, Gupta AK, Jeavons PM. Sodium valproate: monotherapy and polytherapy. Epilepsia 1982: 693–720

    Google Scholar 

  6. Feuerstein J, Revol M, Roger J, et al. La monothérapie par le valproate de sodium dans les épilepsies généralisées primaires. Actualités Psychiatriques 1981; 5: 126–39

    Google Scholar 

  7. Schmidt D. Adverse effects of valproate. Epilepsia 1984; 25Suppl. 1: S44–9

    Article  PubMed  Google Scholar 

  8. Laljee HCK, Parsonage MJ. Unwanted effects of sodium valproate in the treatment of epilepsy: the place of sodium valproate in the treatment of epilepsy. In: Parsonage MJ, Chadwick D, editors. The place of sodium valproate in the treatment of epilepsy. International Congress and Symposium Series. London: Academic Press Inc. and the Royal Society of Medicine Services, 1980: 141–58

    Google Scholar 

  9. Egger J, Brett EM. Effects of sodium valproate in 100 children with special reference to weight. BMJ 1981; 283: 577–81

    Article  PubMed  CAS  Google Scholar 

  10. Dinesen H, Gram L, Andersen T, et al. Weight gain during treatment with valproate. Acta Neurol Scand 1984; 69: 65–9

    Article  Google Scholar 

  11. Bourgeois B, Beaumanoir A, Blajev B, et al. Monotherapy with valproate in primary generalised epilepsies. Epilepsia 1987; 28Suppl. 2: S8–11

    Article  PubMed  Google Scholar 

  12. Mattson RH, Cramer JA, Collins JF, et al. A comparison of valproate with carbamazepine for the treatment of complex partial seizures and secondarily generalized tonic-clonic seizures in adults. N Engl J Med 1992; 327: 765–71

    Article  PubMed  CAS  Google Scholar 

  13. Richens A, Davidson DLW, Cartlidge NEF, et al., on behalf of the Adult EPITEG Collaborative Group. A multicenter comparative trial of sodium valproate and carbamazepine in adult-onset epilepsy. J Neurol Neurosurg Psychiatry 1994; 57: 682–7

    Article  PubMed  CAS  Google Scholar 

  14. Isojärvi JIT, Laatikainen TJ, Knip M, et al. Obesity and endocrine disorders in women taking valproate for epilepsy. Ann Neurol 1996; 39: 579–84

    Article  PubMed  Google Scholar 

  15. Novak GP, Maytal J, Alshansky A, et al. Risk of excessive weight gain in epileptic children treated with valproate. J Child Neurol 1999 Aug; 14(8): 490–5

    Article  PubMed  CAS  Google Scholar 

  16. Verrotti A, Basciani F, Morresi S, et al. Serum leptin changes in epileptic patients who gain weight after therapy with valproic acid. Neurology 1999; 53: 230–2

    Article  PubMed  CAS  Google Scholar 

  17. Bauer J, Jarre A, Klingmüller D, et al. Polycystic ovary syndrome in patients with focal epilepsy: a study in 93 women. Epilepsy Res 2000; 41: 163–7

    Article  PubMed  CAS  Google Scholar 

  18. Dam M, Gram L. Weight changes in epileptic patients treated with valproate. In: Dam M, Gram L, Pedersen B, et al. editors. Valproate in the treatment of seizures. Copenhagen: Danish Epilepsy Society, 1981: 83–5

    Google Scholar 

  19. Perucca E, Garratt A, Hebdige S, et al. Water intoxication in epileptic patients receiving carbamazepine. J Neurol Neurosurg Psychiatry 1978; 41: 713–8

    Article  PubMed  CAS  Google Scholar 

  20. Henry DA, Lawson DH, Reavey P, et al. Hyponatremia during carbamazepine treatment. BMJ 1977; 1: 83–4

    Article  PubMed  CAS  Google Scholar 

  21. Isojärvi JIT, Laatikainen TJ, Pakarinen AJ, et al. Polycystic ovaries and hyperandrogenism in women taking valproate for epilepsy. N Engl J Med 1993; 329: 1383–8

    Article  PubMed  Google Scholar 

  22. Lampl Y, Eshel Y, Rapaport A, et al. Weight gain, increased appetite, and excessive food intake induced by carbamazepine. Clin Neuropharmacol 1991; 14(3): 251–5

    Article  PubMed  CAS  Google Scholar 

  23. Hogan RE, Bertrand ME, Deaton RL, et al. Total percentage body weight changes during add-on therapy with tiagabine, carbamazepine and phenytoin. Epilepsy Res 2000; 41: 23–8

    Article  PubMed  CAS  Google Scholar 

  24. Eke T, Talbot JF, Lawden MC. Severe persistent visual field constriction associated with vigabatrin. BMJ 1997; 314: 180–1

    Article  PubMed  CAS  Google Scholar 

  25. Remy C, Beaumont D. Efficacy and safety of vigabatrin in the long-term treatment of the refractory epilepsy. Br J Clin Pharmacol 1989; 27Suppl. 1: S125–9

    Article  Google Scholar 

  26. Tartara A, Manni R, Galimberti CA, et al. Six-year follow-up study on the efficacy and safety of vigabatrin in patients with epilepsy. Acta Neurol Scand 1992; 86: 247–51

    Article  PubMed  CAS  Google Scholar 

  27. Chadwick D. Safety and efficacy of vigabatrin and carbamazepine in newly diagnosed epilepsy: a multicentre randomised double-blind study. Vigabatrin European Monotherapy Study Group. Lancet 1999 Jul 3; 354(9172): 13–9

    Article  PubMed  CAS  Google Scholar 

  28. Guberman A, Bruni J. Long-term open multicentre, add-on trial of vigabatrin in adult resistant partial epilepsy. The Canadian Vigabatrin Study Group. Seizure 2000 Mar; 9(2): 112–8

    Article  PubMed  CAS  Google Scholar 

  29. Chadwick DW, Anhut H, Greiner MJ, et al. A double blind trial of gabapentin monotherapy for newly diagnosed partial seizures. Neurology 1998; 51: 1282–8

    Article  PubMed  CAS  Google Scholar 

  30. Beydoun A, Fisher J, Labar DR, et al. Gabapentin monotherapy: II. A26—week, double blind, dose controlled, multicenter study of conversion from polytherapy in outpatients with refractory complex partial or secondarily generalized seizures. Neurology 1997; 49: 746–52

    Article  PubMed  CAS  Google Scholar 

  31. Baulac M, Calvacanti D, Semah F, et al. Gabapentin add-on therapy with adaptable dosages in 610 patients with partial epilepsy: an open, observational study. Seizure 1998; 7: 55–62

    Article  PubMed  CAS  Google Scholar 

  32. De Toledo JC, Toledo C, De Cerce J, et al. Changes in body weight with chronic, high dose gabapentin therapy. Ther Drug Monit 1997; 19: 394–6

    Article  PubMed  Google Scholar 

  33. Greenwood RS. Adverse effects of antiepileptic drugs. Epilepsia 2000; 41: S42–52

    Article  PubMed  CAS  Google Scholar 

  34. Carmel PW. Vegetative dysfunctions of the hypothalamus. Acta Neurochir (Wien) 1985; 75: 113–21

    Article  CAS  Google Scholar 

  35. Pijl H, Meinders AE. Bodyweight change as an adverse effect of drug treatment: mechanisms and management. Drug Saf 1996; 14: 329–42

    Article  PubMed  CAS  Google Scholar 

  36. Leibowitz SF. Neurochemical-neuroendocrine systems in the brain controlling macronutrient intake and metabolism. Trends Neurosci 1992; 15: 491–7

    Article  PubMed  CAS  Google Scholar 

  37. Leibowitz SF, Weiss GF, Walsh UA, et al. Medial hypothalamic serotonin: role in circadian patterns of feeding and macronutrient selection. Brain Res 1989; 503: 132–40

    Article  PubMed  CAS  Google Scholar 

  38. Goldman CK, Marino L, Leibowitz SF. Postsynaptic α2-noradrenergic receptors mediate feeding induced by paraventricular nucleus injection of norepinephrine and clonidine. Eur J Pharmacol 1985; 115: 11–91

    Article  PubMed  CAS  Google Scholar 

  39. Angel I. Central receptors and recognition sites mediating the effects of monoamines and anorectic drugs on feeding behavior. Clin Neuropharmacol 1990; 13: 361–91

    Article  PubMed  CAS  Google Scholar 

  40. Tritos NA, Mantzoros CS. Leptin: its role in obesity and beyond. Diabetologia 1997; 40: 1371–9

    Article  PubMed  CAS  Google Scholar 

  41. Arch JRS, Stock MJ, Trayhurn P. Leptin resistance in obese humans: does it exist and what does it mean? Int J Obes 1998; 22: 1159–63

    Article  CAS  Google Scholar 

  42. Jansky L. Humoral thermogenesis and its role in maintaining energy balance. Physiol Rev 1995; 75: 237–59

    PubMed  CAS  Google Scholar 

  43. Brodersen R, Jorgensen N, Vorum H, et al. Valproate and palmitate binding to human serum albumin: an hypothesis on obesity. Mol Pharmacol 1990; 37: 704–9

    PubMed  CAS  Google Scholar 

  44. Vorum H, Gram L, Honore B. Valproate and palmitate binding to serum albumin in valproate-treated patients. Relation to obesity. Epilepsy Res 1993; 16: 55–64

    Article  PubMed  CAS  Google Scholar 

  45. Isojärvi JIT, Rättyä J, Myllylä VV, et al. Valproate, lamotrigine, and insulin-mediated risks in women with epilepsy. Ann Neurol 1998; 43: 446–51

    Article  PubMed  Google Scholar 

  46. Rattya J, Vainionpaa L, Knip M, et al. The effects of valproate, carbamazepine, and oxcarbazepine on growth and sexual maturation in girls with epilepsy. Pediatrics 1999; 103: 588–93

    Article  PubMed  CAS  Google Scholar 

  47. Breum L, Astrup A, Gram L, et al. Metabolic changes during treatment with valproate in humans: implications for untoward weight gain. Metabolism 1992; 41: 666–70

    Article  PubMed  CAS  Google Scholar 

  48. Kimura T, Matsui K, Sato T, et al. Mechanism of carbamazepine (Tegretol) induced antidiuresis: evidence for release of antidiuretic hormone and impaired excretion of a water load. J Clin Endocrinol Metab 1974; 38: 356–62

    Article  PubMed  CAS  Google Scholar 

  49. Russ MJ, Ackerman SH. Antidepressants and weight gain. Appetite 1988; 10: 103–17

    Article  PubMed  CAS  Google Scholar 

  50. Rall TW, Schleifer LS. Drugs effective in the therapy of the epilepsies. In: Gilman AG, Rall TW, Nies AS, et al., editors. The pharmacological basis of therapeutics. New York: Pergamon Press, 1990: 436–62

    Google Scholar 

  51. Murialdo G, Galimberti CA, Magri F, et al. Menstrual cycle and ovary alterations in women with epilepsy on antiepileptic drugs. J Endocrinol Invest 1997; 20: 519–26

    PubMed  CAS  Google Scholar 

  52. Murialdo G, Galimberti CA, Gianelli MV, et al. Effects of valproate, phenobarbital and carbamazepine on sex steroid setup in women with epilepsy. Clin Neuropharmacol 1998; 21: 52–8

    PubMed  CAS  Google Scholar 

  53. Genton P, Bauer J, Ducan S, et al. On the association between valproate and polycystic ovary syndrome. Epilepsia 2001; 42: 295–304

    Article  PubMed  CAS  Google Scholar 

  54. Isojärvi JIT, Tauboll E, Tapanainen JS, et al. On the association between valproate and polycystic ovary syndrome: a response and an alternative view. Epilepsia 2001; 42: 305–10

    Article  PubMed  Google Scholar 

  55. Herzog AG, Schachter S. Valproate and the polycystic ovarian syndrome: final thoughts. Epilepsia 2001; 42: 311–5

    Article  PubMed  CAS  Google Scholar 

  56. Devinsky O, Vuong A, Hammer A, et al. Stable weight during lamotrigine therapy: a review of 32 studies. Neurology 2000; 54: 973–5

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Epilepsy Unit, Hôpital Cantonal, 1211, Geneva 14, Switzerland

    Pierre Jallon & Fabienne Picard

Authors
  1. Pierre Jallon
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Fabienne Picard
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Pierre Jallon.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Jallon, P., Picard, F. Bodyweight Gain and Anticonvulsants. Drug-Safety 24, 969–978 (2001). https://doi.org/10.2165/00002018-200124130-00004

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00002018-200124130-00004

Keywords

Search

Navigation