Current Psychiatry Reports

, Volume 9, Issue 6, pp 521–528 | Cite as

Weight gain and metabolic issues of medicines used for bipolar disorder



Patients with bipolar disorder are at high risk of gaining weight and developing metabolic illnesses, and pharmacologic treatment for the disorder may significantly increase this risk. This paper reviews the literature on the metabolic consequences of the medications used in bipolar disorder and describes the possible strategies to prevent, monitor, and treat the common metabolic illnesses that patients with bipolar disorder may develop during treatment.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References and Recommended Reading

  1. 1.
    Kupfer DJ: The increasing medical burden in bipolar disorder. JAMA 2005, 293:2528–2530.PubMedCrossRefGoogle Scholar
  2. 2.
    Fagiolini A, Kupfer DJ, Houck PR, et al.: Obesity as a correlate of outcome in patients with bipolar I disorder. Am J Psychiatry 2003, 160:112–117.PubMedCrossRefGoogle Scholar
  3. 3.
    Fagiolini A, Frank E, Scott JA, et al.: Metabolic syndrome in bipolar disorder: findings from the Bipolar Disorder Center for Pennsylvanians. Bipolar Disord 2005, 7:424–430.PubMedCrossRefGoogle Scholar
  4. 4.
    Fagiolini A, Kupfer DJ, Rucci P, et al.: Suicide attempts and ideation in patients with bipolar I disorder. J Clin Psychiatry 2004, 65:509–514.PubMedGoogle Scholar
  5. 5.
    Kilbourne AM, Cornelius JR, Han X, et al.: Burden of general medical conditions among individuals with bipolar disorder. Bipolar Disord 2004, 6:368–373.PubMedCrossRefGoogle Scholar
  6. 6.
    McElroy SL, Frye MA, Suppes T, et al.: Correlates of overweight and obesity in 644 patients with bipolar disorder. J Clin Psychiatry 2002, 63:207–213.PubMedGoogle Scholar
  7. 7.
    Basu R, Brar JS, Chengappa KN, et al.: The prevalence of the metabolic syndrome in patients with schizoaffective disorder — bipolar subtype. Bipolar Disord 2004, 6:314–318.PubMedCrossRefGoogle Scholar
  8. 8.
    Aronne LJ, Segal KR: Weight gain in the treatment of mood disorders. J Clin Psychiatry 2003, 64(Suppl 8):22–29.PubMedGoogle Scholar
  9. 9.
    Baptista T, Teneud L, Contreras Q, et al.: Lithium and body weight gain. Pharmacopsychiatry 1995, 28:35–44.PubMedCrossRefGoogle Scholar
  10. 10.
    Chengappa KN, Chalasani L, Brar JS, et al.: Changes in body weight and body mass index among psychiatric patients receiving lithium, valproate, or topiramate: an open-label, nonrandomized chart review. Clin Ther 2002, 24:1576–1584.PubMedCrossRefGoogle Scholar
  11. 11.
    Vestergaard P, Amdisen A, Schou M: Clinically significant side-effects of lithium treatment. A survey of 237 patients in long-term treatment. Acta Psychiatr Scand 1980, 62:193–200.PubMedCrossRefGoogle Scholar
  12. 12.
    Mellerup ET, Grondlund Thompson H, Bjorum N, et al.: Lithium, weight gain and serum insulin in manic-depressive patients. Acta Psychiatr Scand 1972, 48:332–336.PubMedCrossRefGoogle Scholar
  13. 13.
    Birnbaumer L, Pohl SL, Rodbell M: Adenyl cyclase in fat cells. 1. Properties and the effects of adrenocorticotropin and fluoride. J Biol Chem 1969, 244:3468–3476.PubMedGoogle Scholar
  14. 14.
    Himmerich H, Koethe D, Schuld A, et al.: Plasma levels of leptin and endogenous immune modulators during treatment with carbamazepine or lithium. Psychopharmacology (Berl) 2005, 179:447–451.CrossRefGoogle Scholar
  15. 15.
    Okosieme OE, Campbell A, Patton K, et al.: Transient diabetes associated with withdrawal of lithium therapy. Diabetes Care 2006, 29:1181.PubMedCrossRefGoogle Scholar
  16. 16.
    Bergmann T, Hahn EG, Harsch IA, et al.: Lithium—a role in hyperlipidemia? Metabolism 2007, 56:583–585.PubMedCrossRefGoogle Scholar
  17. 17.
    Livingstone C, Rampes H: Lithium: a review of its metabolic adverse effects. J Psychopharmacol 2006, 20:347–355.PubMedCrossRefGoogle Scholar
  18. 18.
    Kleiner J, Altshuler L, Hendrick V, et al.: Lithium-induced subclinical hypothyroidism: review of the literature and guidelines for treatment. J Clin Psychiatry 1999, 60:249–255.PubMedCrossRefGoogle Scholar
  19. 19.
    Gidal BE, Anderson GD, Spencer NW, et al.: Valproate-associated weight gain: potential relation to energy expenditure and metabolism in patients with epilepsy. J Epilepsy 1996, 9:234–241.CrossRefGoogle Scholar
  20. 20.
    Jallon P, Picard F: Bodyweight gain and anticonvulsants: a comparative review. Drug Saf 2001, 24:969–978.PubMedCrossRefGoogle Scholar
  21. 21.
    El-Khatib F, Rauchenzuner M, Lechleitner M, et al.: Valproate, weight gain and carbohydrate craving: a gender study. Seizure 2007, 16:226–232.PubMedCrossRefGoogle Scholar
  22. 22.
    Pylvänen V, Pakarinen A, Knip M, et al.: Characterization of insulin secretion in valproate-treated patients with epilepsy. Epilepsia 2006, 47:1460–1464.PubMedCrossRefGoogle Scholar
  23. 23.
    Pylvänen V, Pakarinen A, Knip M, et al.: Insulin-related metabolic changes during treatment with valproate in patients with epilepsy. Epilepsy Behav 2006, 8:643–648.PubMedCrossRefGoogle Scholar
  24. 24.
    Dunaif A: Insulin resistance and the polycystic ovary syndrome: mechanism and implications for pathogenesis. Endocr Rev 1997, 18:774–800.PubMedCrossRefGoogle Scholar
  25. 25.
    Akdeniz F, Taneli F, Noyan A, et al.: Valproate-associated reproductive and metabolic abnormalities: are epileptic women at greater risk than bipolar women? Prog Neuropsychopharmacol Biol Psychiatry 2003, 27:115–121.PubMedCrossRefGoogle Scholar
  26. 26.
    Joffe H, Cohen L, Suppes T, et al.: Valproate is associated with new-onset oligoamenorrhea with hyperandrogenism in women with bipolar disorder. Biol Psychiatry 2006, 59:1078–1086.PubMedCrossRefGoogle Scholar
  27. 27.
    Rasgon N: The relationship between polycystic ovary syndrome and antiepileptic drugs: a review of the evidence. J Clin Psychopharmacol 2004, 24:322–340.PubMedCrossRefGoogle Scholar
  28. 28.
    Coxhead N, Silverstone T, Cookson J: Carbamazepine versus lithium in the prophylaxis of bipolar affective disorder. Acta Psychiatr Scand 1992, 85:114–118.PubMedCrossRefGoogle Scholar
  29. 29.
    Weisler H, Keck PE, Swann AC, et al.: Extended-release carbamazepine capsules as monotherapy for acute mania in bipolar disorder: a multicenter, randomized, double-blind placebo-controlled trial. J Clin Psychiatry 2005, 66:323–330.PubMedGoogle Scholar
  30. 30.
    Ketter TA, Kalali AH, Weisler RH, et al.: A 6-month, multicenter, open-label evaluation of beaded extended-release carbamazepine capsule monotherapy in bipolar disorder patients with manic or mixed episodes. J Clin Psychiatry 2004, 65:668–673.PubMedCrossRefGoogle Scholar
  31. 31.
    Brämswig S, Kerksiek A, Sudhop T: Carbamazepine increases atherogenic lipoproteins: mechanism of action in male adults. Am J Physiol Heart Circ Physiol 2002, 282:H704–H716.PubMedGoogle Scholar
  32. 32.
    Devinsky O, Vuong A, Hammer A, et al.: Stable weight during lamotrigine therapy: a review of 32 studies. Neurology 2000, 54:973–975.PubMedGoogle Scholar
  33. 33.
    Sachs G, Bowden C, Calabrese JR, et al.: Effects of lamotrigine and lithium on body weight during maintenance treatment of bipolar I disorder. Bipolar Disord 2006, 8:175–181.PubMedCrossRefGoogle Scholar
  34. 34.
    Kushner SF, Khan A, Lane R, et al.: Topiramate monotherapy in the management of acute mania: results of four double-blind placebo-controlled trials. Bipolar Disord 2006, 8:15–27.PubMedCrossRefGoogle Scholar
  35. 35.
    Chengappa KN, Schwarzman L, Hulihan JF, et al.: Adjunctive topiramate therapy in patients receiving a mood stabilizer for bipolar I disorder: a randomized, placebo-controlled trial. J Clin Psychiatry 2006, 67:1698–1706.Google Scholar
  36. 36.
    Kishi T, Horiguchi J: Psychiatric disorders and neural mechanisms underlying energy intake and expenditure: a review. Nihon Shinkei Seishin Yakurigaku Zasshi 2003, 23:197–203.PubMedGoogle Scholar
  37. 37.
    Reynolds GP, Zhang ZJ, Zhang XB: Association of antipsychotic drug-induced weight gain with a 5-HT2C receptor gene polymorphism. Lancet 2002, 359:2086–2087.PubMedCrossRefGoogle Scholar
  38. 38.
    Masand PS: Relative weight gain among antipsychotics. J Clin Psychiatry 2001, 60:706–708.CrossRefGoogle Scholar
  39. 39.
    Dunner DL: Safety and tolerability of emerging pharmacological treatments for bipolar disorder. Bipolar Disord 2005, 7:307–325.PubMedCrossRefGoogle Scholar
  40. 40.
    Koro CE, Fedder DO, L’Italien GJ, et al.: An assessment of the independent effects of olanzapine and risperidone exposure on the risk of hyperlipidemia in schizophrenic patients. Arch Gen Psychiatry 2002, 59:1021–1026.PubMedCrossRefGoogle Scholar
  41. 41.
    Koller EA, Doraiswamy PM: Olanzapine-associated diabetes mellitus. Pharmacotherapy 2002, 22:841–852.PubMedCrossRefGoogle Scholar
  42. 42.
    Newcomer JW, Haupt DW, Fucetola R, et al.: Abnormalities in glucose regulation during antipsychotic treatment of schizophrenia. Arch Gen Psychiatry 2002, 59:337–345.PubMedCrossRefGoogle Scholar
  43. 43.
    Koro CE, Fedder DO, L’Italien GJ, et al.: Assessment of independent effect of olanzapine and risperidone on risk of diabetes among patients with schizophrenia: population based nested case-control study. BMJ 2002, 325:243.PubMedCrossRefGoogle Scholar
  44. 44.
    Sowell MO, Mukhopadhyay N, Cavazzoni P, et al.: Hyperglycemic clamp assessment of insulin secretory responses in normal subjects treated with olanzapine, risperidone or placebo. J Clin Endocrinol Metab 2002, 87:2918–2923.PubMedCrossRefGoogle Scholar
  45. 45.
    Ader M, Kim SP, Catalano KJ, et al.: Metabolic dysregulation with atypical antipsychotics occurs in the absence of underlying disease: a placebo-controlled study of olanzapine and risperidone in dogs. Diabetes 2005, 54:862–871.PubMedCrossRefGoogle Scholar
  46. 46.
    Melkersson KI, Dahl ML: Relationship between levels of insulin or triglycerides and serum concentrations of the atypical antipsychotics clozapine and olanzapine in patients on treatment with therapeutic doses. Psychopharmacology (Berl) 2003, 170:157–166.CrossRefGoogle Scholar
  47. 47.
    Koller EA, Cross JT, Doraiswamy PM, et al.: Risperidone-associated diabetes mellitus: a pharmacovigilance study. Pharmacotherapy 2003, 23:735–744.PubMedCrossRefGoogle Scholar
  48. 48.
    Potkin SG, Saha AR, Kukawa MJ, et al.: Aripiprazole, an antipsychotic with a novel mechanism of action, and risperidone vs placebo in patients with schizophrenia and schizoaffective disorder. Arch Gen Psychiatry 2003, 60:681–690.PubMedCrossRefGoogle Scholar
  49. 49.
    Gianfrancesco F, White R, Wang RH, et al.: Antipsychotic-induced type 2 diabetes: evidence from a large health plan database. J Clin Psychopharmacol 2003, 23:328–335.PubMedCrossRefGoogle Scholar
  50. 50.
    Shaw JA, Lewis JE, Pascal S, et al.: A study of quetiapine: efficacy and tolerability in psychotic adolescents. J Child Adolesc Psychopharmacol 2001, 11:415–442.PubMedCrossRefGoogle Scholar
  51. 51.
    Atmaca M, Kuloglu M, Tezcan E, et al.: Weight gain, serum leptin and triglyceride levels in patients with schizophrenia on antipsychotic treatment with quetiapine, olanzapine and haloperidol. Schizophr Res 2003, 60:99–100.PubMedCrossRefGoogle Scholar
  52. 52.
    Atmaca M, Kuloglu M, Tezcan E, et al.: Serum leptin and triglyceride levels in patients on treatment with atypical antipsychotics. J Clin Psychiatry 2003, 64:598–604.PubMedGoogle Scholar
  53. 53.
    Meyer JM: Novel antipsychotics and severe hyperlipidemia. J Clin Psychopharmacol 2001, 21:369–374.PubMedCrossRefGoogle Scholar
  54. 54.
    Domon SE, Cargile CS: Quetiapine-associated hyperglycemia and hypertriglyceridemia. J Am Acad Child Adolesc Psychiatry 2002, 41:495–496.PubMedCrossRefGoogle Scholar
  55. 55.
    Seroquel [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals, LP; 2007.Google Scholar
  56. 56.
    American Diabetes Association, American Psychiatric Association, American Association of Clinical Endocrinologists, North American Association for the Study of Obesity: Consensus development conference on antipsychotic drugs and obesity and diabetes. Diabetes Care 2004, 27:596–601.CrossRefGoogle Scholar
  57. 57.
    McQuade RD, Marcus R, Sanchez R, et al.: Aripiprazole versus placebo in acute mania: safety and tolerability pooled analysis. Poster presented at the 5th International Conference on Bipolar Disorder. Pittsburgh, PA; June 12–14, 2003.Google Scholar
  58. 58.
    Keck PE, Jr, Calabrese JR, McQuade RD, et al.: A placebo-controlled 26-week trial of aripiprazole in recently manic patients with bipolar I disorder. J Clin Psychiatry 2006, 67:626–637.PubMedCrossRefGoogle Scholar
  59. 59.
    Casey DE, Carson WH, Saha AR, et al.: Switching patients to aripiprazole from other antipsychotic agents: a multicenter randomized study. Psychopharmacology (Berl) 2003, 166:391–399.Google Scholar
  60. 60.
    Stimmel GL, Gutierrez MA, Lee V: Ziprasidone: an atypical antipsychotic drug for the treatment of schizophrenia. Clin Ther 2002, 24:21–37.PubMedCrossRefGoogle Scholar
  61. 61.
    Lieberman JA, Stroup ST, McEvoy JP, et al.: Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N Engl J Med 2005, 353:1209–1223.PubMedCrossRefGoogle Scholar
  62. 62.
    Weiden PJ, Simpson GM, Potkin SG, et al.: Effectiveness of switching to ziprasidone for stable but symptomatic outpatients with schizophrenia. J Clin Psychiatry 2003, 64:580–588.PubMedCrossRefGoogle Scholar
  63. 63.
    Molitch ME: Disorders of prolactin secretion. Endocrinol Metab Clin North Am 2001, 30:585–610.PubMedCrossRefGoogle Scholar
  64. 64.
    Molitch ME: Medication-induced hyperprolactinemia. Mayo Clin Proc 2005, 80:1050–1057.PubMedGoogle Scholar
  65. 65.
    Wolf J, Fiedler U: Hyperprolactinemia and amenorrhea associated with olanzapine normalized after addition of aripiprazole. J Clin Pharm Ther 2007, 32:197–198.PubMedCrossRefGoogle Scholar

Copyright information

© Current Medicine Group LLC 2007

Authors and Affiliations

  1. 1.Western Psychiatric Institute and ClinicUniversity of Pittsburgh Medical CenterPittsburghUSA

Personalised recommendations