European Journal of Clinical Pharmacology

, Volume 74, Issue 11, pp 1485–1489 | Cite as

Weight changes associated with antiepileptic mood stabilizers in the treatment of bipolar disorder

  • Koen P. GrootensEmail author
  • Anna Meijer
  • Erwin G. Hartong
  • Bennard Doornbos
  • P. Roberto Bakker
  • Asmar Al Hadithy
  • Kirsten N. Hoogerheide
  • Frans Overmeire
  • Radboud M. Marijnissen
  • Henricus G. Ruhe
Pharmacoepidemiology and Prescription



To present up-to-date information and recommendations on the management of body weight changes during the use of antiepileptic mood stabilizers in bipolar disorder to help clinicians and patients make well-informed, practical decisions.

Data sources

Umbrella review. Systematic reviews and meta-analyses on the prevention, treatment, and monitoring of body weight changes as a side effect of the mood stabilizers valproate, lamotrigine, topiramate, and carbamazepine were identified in Embase (2010–2015, no language restrictions).

Study selection

The search yielded 18 relevant publications on antiepileptic mood stabilizers and weight changes in bipolar disorder.

Data extraction

Relevant scientific evidence was abstracted and put into a clinical perspective by a multidisciplinary expert panel of clinicians with expertise in the treatment of bipolar disorders across all age groups and a patient representative.


Valproate has been proven to be associated with weight gain in up to 50% of its users, and can be detected 2–3 months after initiation. Carbamazepine has been proven to have a low risk of weight gain. Lamotrigine and topiramate are associated with weight loss. Other option for this sentence = Weigth gain has been proven to be associated with valproate use in up to 50% of its users, and can be detected within 2-3 months after initiation.


Each antiepileptic mood stabilizer has specific effects on body weight and accordingly requires a discrete education, prevention, monitoring, and treatment strategy. Clinicians are recommended to adopt an active, anticipatory approach, educating patients about weight change as an important side effect in order to come to informed shared decisions about the most suitable mood stabilizer.


Bipolar disorder Weight gain Weight loss Anti-obesity agents Body weight changes Valproate Lamotrigine Topiramate Carbamazepine 



This study was funded by the Dutch network for quality development in mental health (Netwerk Kwaliteitsontwikkeling GGZ).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest.

Supplementary material

228_2018_2517_MOESM1_ESM.docx (23 kb)
Table 1 (DOCX 22 kb)
228_2018_2517_MOESM2_ESM.docx (56 kb)
Figure 1 (DOCX 56 kb)


  1. 1.
    Yatham LN, Kennedy SH, Parikh SV et al. Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) collaborative update of CANMAT guidelines for the management of patients with bipolar disorder: update 2013. Bipolar Disord 2013;15: 1–44Google Scholar
  2. 2.
    Bowden CL, Singh V (2005) Valproate in bipolar disorder: 2000 onwards. Acta Psychiatr Scand 111:13–20CrossRefGoogle Scholar
  3. 3.
    De Hert M, Correll CU, Bobes J et al (2011) Physical illness in patients with severe mental disorders. I. Prevalence, impact of medications and disparities in health care. World Psychiatry 10(1):52–77CrossRefGoogle Scholar
  4. 4.
    Chang HH, Yang YK, Gean PW, Huang HC, Chen PS, Lu RB (2010) The role of valproate in metabolic disturbances in bipolar disorder patients. J Affect Disord 124(3):319–323CrossRefGoogle Scholar
  5. 5.
    Zuo S, Fries BE, Szafara K, Regal R (2015) Valproic acid as a potentiator of metabolic syndrome in institutionalized residents on concomitant antipsychotics: fat chance, or slim to none? PT 40(2):126–132Google Scholar
  6. 6.
    Vancampfort D, Stubbs B, Mitchell AJ, De Hert M, Wampers M, Ward PB, Rosenbaum S, Correll CU (2015) Risk of metabolic syndrome and its components in people with schizophrenia and related psychotic disorders, bipolar disorder and major depressive disorder: a systematic review and meta-analysis. World Psychiatry 14(3):339–347CrossRefGoogle Scholar
  7. 7.
    National Collaborating Centre for Mental health bipolar disorder: the assessment and management of bipolar disorder in adults, children and young people in primary and secondary care; Updated edition 2014 National Institute for Health and Care Excellence (NICE)Google Scholar
  8. 8.
    Murru A, Popovic D, Pacchiarotti I, Hidalgo D, León-Caballero J, Vieta E et al (2015) Management of adverse effects of mood stabilizers. Curr Psychiatry Rep 17:66–76CrossRefGoogle Scholar
  9. 9.
    Nanau RM, Neuman MG (2013) Adverse drug reactions induced by valproic acid. Clin Biochem 46:1323–1338CrossRefGoogle Scholar
  10. 10.
    White W, Elmore L, Luthin DR, Cates ME (2013) Psychotropic-induced weight gain: a review of management strategies. Consultant 53(3):153–160Google Scholar
  11. 11.
    Nihalani N, Schwartz TL, Siddiqui UA, Megna JL (2012) Obesity and psychotropics. CNS Neurosci Ther 18:57–63CrossRefGoogle Scholar
  12. 12.
    Mago R, Borra D, Mahajan R (2014) Role of adverse effects in medication nonadherence in bipolar disorder. Harv Rev Psychiatry 22(6):363–366CrossRefGoogle Scholar
  13. 13.
    Domecq JP, Prutsky G, Leppin A, Sonbol MB, Altayar O, Undavalli C, Wang Z, Elraiyah T, Brito JP, Mauck KF, Lababidi MH, Prokop LJ, Asi N, Wei J, Fidahussein S, Montori VM, Murad MH (2015) Drugs commonly associated with weight change: a systematic review and meta-analysis. J Clin Endocrinol Metab 100(2):363–370CrossRefGoogle Scholar
  14. 14.
    Martınez-Ortega JM, Funes-Godoy S, Dıaz-Atienza F et al (2013) Weight gain and increase of body mass index among children and adolescents treated with antipsychotics: a critical review. Eur Child Adolesc Psychiatry 22:457–479CrossRefGoogle Scholar
  15. 15.
    Belcastro V, D’Egidio C, Striano P, Verrotti A (2013) Metabolic and endocrine effects of valproic acid chronic treatment. Epilepsy Res 107:1–8CrossRefGoogle Scholar
  16. 16.
    Verrotti A, D’Egidio C, Mohn A, Coppola G, Chiarelli F (2011) Weight gain following treatment with valproic acid: pathogenetic mechanisms and clinical implications. Obes Rev 12(5):32–43CrossRefGoogle Scholar
  17. 17.
    Hasnain M, Vieweg WVR (2013) Weight considerations in psychotropic drug prescribing and switching. Postgrad Med 125(5):117–129CrossRefGoogle Scholar
  18. 18.
    Seo HJ, Chiesa A, Lee SJ, Patkar AA, Han C, Masand PS, Serretti A, Pae CU (2011) Safety and tolerability of lamotrigine: results from 12 placebo-controlled clinical trials and clinical implications. Clin Neuropharmacol 34:39–47CrossRefGoogle Scholar
  19. 19.
    Dıaz-Caneja CM, Moreno C, Llorente C et al (2014) Practitioner review: long-term pharmacological treatment of pediatric bipolar disorder. J Child Psychol Psychiatry 55:959–980CrossRefGoogle Scholar
  20. 20.
    Srivastava S, Ketter TA (2011) Clinical relevance of treatments for acute bipolar disorder: balancing therapeutic and adverse effects. Clin Ther 33(12):4–43CrossRefGoogle Scholar
  21. 21.
    Deaton TL, Mauro LS (2014) Topiramate for migraine prophylaxis in pediatric patients. Ann Pharmacother 48(5):638–643CrossRefGoogle Scholar
  22. 22.
    Shamliyan TA, Kane RL, Ramakrishnan R, Taylor FR (2013) Episodic migraines in children: limited evidence on preventive pharmacological treatments. J Child Neurol 28(10):1320–1341CrossRefGoogle Scholar
  23. 23.
    Kushner SF, Khan A, Lane R, Olson WH (2006) Topiramate monotherapy in the management of acute mania: results of four double-blind placebo controlled trials. Bipolar Disord 8:15–27CrossRefGoogle Scholar
  24. 24.
    Pulman J, Jette N, Dykeman J, et al. Topiramate add-on for drug-resistant partial epilepsy. Cochrane Database 2014;25(2)
  25. 25.
    McIntyre RS, Alsuwaidan M, Goldstein BI, Taylor VH, Schaffer A, Beaulieu S, Kemp DE, Canadian Network for Mood and Anxiety Treatments (CANMAT) Task Force (2012) The Canadian Network for Mood and Anxiety Treatments (CANMAT) task force recommendations for the management of patients with mood disorders and comorbid metabolic disorders. Ann Clin Psychiatry 24(1):69–81PubMedGoogle Scholar
  26. 26.
    Maayan L, Vakhrusheva J, Correll CU (2010) Effectiveness of medications used to attenuate antipsychotic-related weight gain and metabolic abnormalities: a systematic review and meta-analysis. Neuropsychopharmacology 35(7):1520–1530CrossRefGoogle Scholar
  27. 27.
    Alvarez-Jiménez M, Hetrick SE, González-Blanch C, Gleeson JF, McGorry PD (2008) Non-pharmacological management of antipsychotic-induced weight gain: systematic review and meta-analysis of randomised controlled trials. Br J Psychiatry 193(2):101–107CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018
corrected publication September/2018

Authors and Affiliations

  • Koen P. Grootens
    • 1
    • 2
    Email author
  • Anna Meijer
    • 3
    • 4
  • Erwin G. Hartong
    • 5
  • Bennard Doornbos
    • 6
  • P. Roberto Bakker
    • 7
    • 8
  • Asmar Al Hadithy
    • 9
  • Kirsten N. Hoogerheide
    • 10
  • Frans Overmeire
    • 12
  • Radboud M. Marijnissen
    • 4
    • 11
  • Henricus G. Ruhe
    • 2
    • 4
  1. 1.Reinier van Arkel‘s-HertogenboschThe Netherlands
  2. 2.Radboud University Medical CentreNijmegenThe Netherlands
  3. 3.Department of Teacher Education, Faculty of Behavioural and Social SciencesUniversity of GroningenGroningenThe Netherlands
  4. 4.University Medical Centre GroningenGroningenThe Netherlands
  5. 5.Department of PsychiatryCanisius Wilhelmina Hospital NijmegenNijmegenThe Netherlands
  6. 6.GGZ DrentheAssenThe Netherlands
  7. 7.GGZ CentraalAmersfoortThe Netherlands
  8. 8.Maastricht UniversityMaastrichtThe Netherlands
  9. 9.Parnassia GroupThe HagueThe Netherlands
  10. 10.De JuttersThe HagueThe Netherlands
  11. 11.Pro PersonaWolfhezeThe Netherlands
  12. 12.VMDB (Dutch association of patients with bipolar disorder and their relatives)AmersfoortNetherlands

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