CNS Drugs

, Volume 29, Issue 2, pp 163–169 | Cite as

Weight Regain after Discontinuation of Topiramate Treatment in Patients with Migraine: a Prospective Observational Study

  • Alberto Verrotti
  • Pasquale Parisi
  • Sergio Agostinelli
  • Giulia Loiacono
  • Francesca Marra
  • Giangennaro Coppola
  • Laura Rosa Pisani
  • Gaetano Gorgone
  • Pasquale Striano
  • Francesco Pisani
  • Vincenzo Belcastro
Short Communication

Abstract

Purpose

To monitor weight regain after therapy discontinuation in patients with migraine experiencing weight loss during topiramate (TPM) treatment.

Methods

Patients with migraine without aura were enrolled in this observational prospective study. Weight, body mass index (BMI), waist circumference, systolic and diastolic blood pressure, plasma levels of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, leptin, and ghrelin, and homeostatic model assessment of insulin resistance (HOMA-IR) were evaluated before starting TPM (T1), at 3 (T2) and 6 (T3) months of treatment and 6 months after withdrawal of TPM (T4). Weight loss/regain was considered as a change of </>5 % of pre-TPM body weight.

Results

A total of 241 patients were analyzed. Of these, 87 (36 %) patients experienced weight loss on TPM medication. During TPM therapy significant reductions in mean values of weight (p < 0.001), BMI (p < 0.001), waist circumference (p < 0.01), HOMA-IR (p < 0.01), and leptin (p < 0.01) were observed. After TPM discontinuation, all of these parameters showed a clear trend to increase at T4, achieving pre-TPM values in 27 patients. Among potential predictors, only HOMA-IR before starting TPM (parameter estimate = 1.36, effect size = 0.75; p = 0.006) was significantly associated with weight regain after therapy discontinuation.

Conclusions

Loss of body weight is a reversible effect, which at 6 months after TPM discontinuation shows a clear trend to return to baseline values. HOMA-IR is the only predictive factor of weight regain.

Notes

Disclosures

Alberto Verrotti, Pasquale Parisi, Sergio Agostinelli, Giulia Loiacono, Francesca Marra, Giangennaro Coppola, Laura Rosa Pisani, Gaetano Gorgone, Pasquale Striano, Francesco Pisani, and Vincenzo Belcastro have nothing to disclose and report no conflicts of interest. This manuscript received no funding.

References

  1. 1.
    Maryanoff BE. Pharmaceutical “gold” from neurostabilizing agents: topiramate and successor molecules. J Med Chem. 2009;52:3431–40.CrossRefPubMedGoogle Scholar
  2. 2.
    Silberstein SD, Holland S, Freitag F, et al. Evidence-based guideline update: pharmacologic treatment for episodic migraine prevention in adults: report of the Quality Standards Subcommittee of the American Academy of Neurology and the American Headache Society. Neurology. 2012;78:1337–45.CrossRefPubMedCentralPubMedGoogle Scholar
  3. 3.
    Scozzafava A, Supuran CT, Carta F. Antiobesity carbonic anhydrase inhibitors: a literature and patent review. Expert Opin Ther Pat. 2013;23:725–35.CrossRefPubMedGoogle Scholar
  4. 4.
    Okuyaz C, Kursel O, Komur M, et al. Evaluation of appetite-stimulating hormones in prepubertal children with epilepsy during topiramate treatment. Pediatr Neurol. 2012;47:423–36.CrossRefPubMedGoogle Scholar
  5. 5.
    Pickrell WO, Lacey AS, Thomas RH, et al. Weight change associated with antiepileptic drugs. J Neurol Neurosurg Psychiatry. 2013;84:796–9.CrossRefPubMedGoogle Scholar
  6. 6.
    Klein KM, Theisen F, Knake S, et al. Topiramate, nutrition and weight change: a prospective study. J Neurol Neurosurg Psychiatry. 2008;79:590–3.CrossRefPubMedGoogle Scholar
  7. 7.
    McElroy SL, Guerdjikova AI, Martens B, et al. Role of antiepileptic drugs in the management of eating disorders. CNS Drugs. 2009;23:139–56.CrossRefPubMedGoogle Scholar
  8. 8.
    Wilding J, Van Gaal L, Rissanen A, Vercruysse F, Fitchet M, OBES-002 Study Group. A randomized double-blind placebo-controlled study of the long-term efficacy and safety of topiramate in the treatment of obese subjects. Obes Relat Metab Disord. 2004;28(11):1399–410.CrossRefGoogle Scholar
  9. 9.
    Theisen FM, Beyenburg S, Gebhardt S, Kluge M, Blum WF, Remschmidt H, Elger CE, Hebebrand J. A prospective study of body weight and serum leptin levels in patients treated with topiramate. Clin Neuropharmacol. 2008;31(4):226–30.CrossRefPubMedGoogle Scholar
  10. 10.
    Wing RR, Phelan S. Long-term weight loss maintenance. Am J Clin Nutr. 2005;82:222S–5S.PubMedGoogle Scholar
  11. 11.
    Verrotti A, Chiarelli F, Tumini S, et al. Seasonal variations of glycosylated haemoglobin in diabetic children. Eur J Pediatr. 1989;149:146–7.CrossRefPubMedGoogle Scholar
  12. 12.
    Keskin M, Kurtoglu S, Kendirci M, et al. Homeostasis model assessment is more reliable than the fasting glucose/insulin ratio and quantitative insulin sensitivity check index for assessing insulin resistance among obese children and adolescents. Pediatrics. 2005;115:500–3.CrossRefGoogle Scholar
  13. 13.
    Cacciari E, Milani S, Balsamo A, et al. Italian cross-sectional growth charts for height, weight and BMI (6–20 y). Eur J Clin Nutr. 2002;56:171–80.CrossRefPubMedGoogle Scholar
  14. 14.
    Cook S, Weitzman M, Auinger P, et al. Prevalence of a metabolic syndrome phenotype in adolescents: findings from the Third National Health and Nutrition Examination Survey, 1988–1994. Arch Pediatr Adolesc Med. 2003;157:821–7.CrossRefPubMedGoogle Scholar
  15. 15.
    Arroyo S, Dodson WE, Privitera MD, et al. Randomized dose-controlled study of topiramate as first-line therapy in epilepsy. Acta Neurol Scand. 2005;112:214–22.CrossRefPubMedGoogle Scholar
  16. 16.
    Ben-Menachem E, Axelsen M, Johanson EH, et al. Predictors of weight loss in adults with topiramate-treated epilepsy. Obesity Res. 2003;11:556–62.CrossRefGoogle Scholar
  17. 17.
    Guerrini R, Carpay J, Groselj J, et al. Topiramate monotherapy as broad-spectrum antiepileptic drug in a naturalistic clinical setting. Seizure. 2005;14:371–80.CrossRefPubMedGoogle Scholar
  18. 18.
    Aribi AM, Stringer JL. Effects of antiepileptic drugs on extracellular pH regulation in the hippocampal CA1 region in vivo. Epilepsy Res. 2002;49:143–51.CrossRefPubMedGoogle Scholar
  19. 19.
    Stringer JL. A comparison of topiramate and acetazolamide on seizure duration and paired pulse inhibition in the dentate gyrus of the rat. Epilepsy Res. 2000;40:147–53.CrossRefPubMedGoogle Scholar
  20. 20.
    Casini A, Antel J, Abbate F, et al. Carbonic anhydrase inhibitors: SAR and X-ray crystallographic study for the interaction of sugar sulfamates/sulfamides with isozymes I, II and IV. Bioorg Med Chem Lett. 2003;13:841–5.CrossRefPubMedGoogle Scholar
  21. 21.
    Vitale RM, Pedone C, Amodeo P, et al. Molecular modeling study for the binding of zonisamide and topiramate to the human mitochondrial carbonic anhydrase isoform VA. Bioorg Med Chem. 2007;15:4152–8.CrossRefPubMedGoogle Scholar
  22. 22.
    De Simone G, Supuran CT. Antiobesity carbonic anhydrase inhibitors. Curr Top Med Chem. 2007;7:879–84.CrossRefPubMedGoogle Scholar
  23. 23.
    Supuran CT, Di Fiore A, De Simone G. Carbonic anhydrase inhibitors as emerging drugs for the treatment of obesity. Expert Opin Emerg Drugs. 2008;13:383–92.CrossRefPubMedGoogle Scholar
  24. 24.
    Verrotti A, Scaparrotta A, Agostinelli S, et al. Topiramate-induced weight loss: a review. Epilepsy Res. 2011;95:189–99.CrossRefPubMedGoogle Scholar
  25. 25.
    Franzoni E, Verrotti A, Sarajlija J, et al. Topiramate: effects on serum lipids and lipoproteins levels in children. Eur J Neurol. 2007;14:1334–7.CrossRefPubMedGoogle Scholar
  26. 26.
    Li HF, Zou Y, Xia ZZ, et al. Effects of topiramate on weight and metabolism in children with epilepsy. Acta Paediatr. 2009;98:1521–5.CrossRefPubMedGoogle Scholar
  27. 27.
    Chai N, Bond D, Moghekar A, et al. Obesity and headache. Part II: potential mechanism and treatment considerations. Headache. 2014;54:459–71.CrossRefPubMedCentralGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  • Alberto Verrotti
    • 1
  • Pasquale Parisi
    • 2
  • Sergio Agostinelli
    • 3
  • Giulia Loiacono
    • 4
  • Francesca Marra
    • 2
  • Giangennaro Coppola
    • 5
  • Laura Rosa Pisani
    • 6
  • Gaetano Gorgone
    • 7
  • Pasquale Striano
    • 8
  • Francesco Pisani
    • 9
  • Vincenzo Belcastro
    • 10
  1. 1.Department of PediatricsUniversity of PerugiaPerugiaItaly
  2. 2.Child Neurology and Pediatric Headache Center, Chair of Pediatrics, NESMOS Department, Faculty of Medicine and Psychology c/o ‘S. Andrea’ HospitalUniversity of Rome ‘Sapienza’RomeItaly
  3. 3.Pediatric UnitOspedale Madonna del SoccorsoSan Benedetto del TrontoItaly
  4. 4.Department of PediatricsUniversity of ChietiChietiItaly
  5. 5.Child and Adolescent Neuropsychiatry, Medical SchoolUniversity of SalernoSalernoItaly
  6. 6.IRCCS Centro Neurolesi ‘Bonino-Pulejo’MessinaItaly
  7. 7.Neurology UnitTreviglio-Caravaggio HospitalTreviglioItaly
  8. 8.Pediatric Neurology and Muscular Diseases Unit, Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health‘G. Gaslini’ Institute, University of GenoaGenoaItaly
  9. 9.Department of NeurosciencesUniversity Hospital of MessinaMessinaItaly
  10. 10.Neurology Unit, Department of MedicineS. Anna HospitalComoItaly

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