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Common Medications Which Lead to Unintended Alterations in Weight Gain or Organ Lipotoxicity

  • Nutrition and Obesity (SA McClave, Section Editor)
  • Published:
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Abstract

Obesity is one of the most common chronic conditions in the world. Its management is difficult, partly due to the multiple associated comorbidities including fatty liver, diabetes, hypertension, and hyperlipidemia. As a result, the choice of prescription medications in overweight and obese patients has important implications as some of them can actually worsen the fat accumulation and its associated metabolic complications. Several prescription medications are associated with weight gain with mechanisms that are often poorly understood and under-recognized. Even less data are available on the distribution of fat and lipotoxicity (the organ damage related to fat accumulation). The present review will discuss the drugs associated with weight gain, their mechanism of action, and the magnitude and timing of their effect.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. Ogden CL, Carroll MD, Kit BK, Flegal KM. Prevalence of childhood and adult obesity in the United States, 2011–2012. JAMA. 2014;311:806–14.

    Article  CAS  PubMed  Google Scholar 

  2. Malik S, Wong ND, Franklin SS, Kamath TV, L’Italien GJ, Pio JR, et al. Impact of the metabolic syndrome on mortality from coronary heart disease, cardiovascular disease, and all causes in United States adults. Circulation. 2004;110:1245–50.

    Article  PubMed  Google Scholar 

  3. Yusuf S, Hawken S, Ounpuu S, Dans T, Avezum A, Lanas F, et al. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case–control study. Lancet. 2004;364:937–52.

    Article  PubMed  Google Scholar 

  4. Knowles KM, Paiva LL, Sanchez SE, Revilla L, Lopez T, Yasuda MB, et al. Waist circumference, body mass index, and other measures of adiposity in predicting cardiovascular disease risk factors among Peruvian adults. Int J Hypertens. 2011;931402:1–10.

    Article  Google Scholar 

  5. Ghandehari H, Le V, Kamall-Bahal S, Bassin SL, Wong ND. Abdominal obesity and the spectrum of global cardiometabolic risks in US adults. Int J Obes. 2009;33(2):239–48.

    Article  CAS  Google Scholar 

  6. Amato MC, Guarnotta V, Giordano C. Body composition assessment for the definition of cardiometabolic risk. J Endocrinol Investig. 2013;36:537–43.

    CAS  Google Scholar 

  7. MCClain CJ, Barve S, Deaciuc I. Good fat/bad fat. Hepatology. 2007;45:1343–6.

    Article  CAS  PubMed  Google Scholar 

  8. Cave MC, Hurt RT, Frazier TH, Matheson PJ, Garrison RN, McClain CJ, et al. Obesity, inflammation, and the potential application of pharmaconutrition. Nutr Clin Pract. 2008;23:16–34.

    Article  PubMed  Google Scholar 

  9. Yki-Jarvinen H. Thiazolidinediones. N Engl J Med. 2004;351:1106–18.

    Article  PubMed  Google Scholar 

  10. Zangeneh F, Kudva YC, Basu A. Insulin sensitizers. Mayo Clin Proc. 2003;78:471–9.

    Article  CAS  PubMed  Google Scholar 

  11. Petersen KF, Krssak M, Inzucchi S, Cline GW, Dufour S, Shulman GI. Mechanism of troglitazone action in type 2. Diabetes. 2000;49:827.

    Article  CAS  PubMed  Google Scholar 

  12. Akazawa S, Sun F, Ito M, Kawasaki E, Eguchi K. Efficacy of troglitazone on body fat distribution in type 2 diabetes. Diabetes Care. 2000;23:1067.

    Article  CAS  PubMed  Google Scholar 

  13. Sanyal AJ, Chalasani N, Kowdley KV, McCullough A, Diehl AM, Bass NM, et al. Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis. N Engl J Med. 2010;362:1675–85.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  14. Aronoff S, Rosenblatt S, Braithwaite S, Egan JW, Mathisen AL, Schneider R. Pioglitazone hydrochloride monotherapy improves glycemic control in the treatment of patients with type 2 diabetes: a 6-month randomized placebo-controlled dose–response study. The pioglitazone 001 study group. Diabetes Care. 2000;23:1605–11.

    Article  CAS  PubMed  Google Scholar 

  15. Fonseca V, Rosenstock J, Patwardhan R, Salzman A. Effect if metformin and rosiglitazone combination therapy in patients with type 2 diabetes mellitus: a randomized controlled trial. JAMA. 2000;283:1695–702.

    Article  CAS  PubMed  Google Scholar 

  16. Bressler R, Johnson DG. Pharmacological regulation of blood glucose levels in non-insulin-dependent diabetes mellitus. Arch Int Med. 1997;157:836–48.

    Article  CAS  Google Scholar 

  17. Hemmingsen B, Schroll JB, Wetterslev J, Gluud C, Vaag A, Sonne DP, et al. Sulfonylurea versus metformin monotherapy in patients with type 2 diabetes: a Cochrane systematic review and meta-analysis of randomized clinical trials and trial sequential analysis. CMAJ Open. 2014;2:E162–75.

    Article  PubMed Central  PubMed  Google Scholar 

  18. Inzucchi SE. Oral antihyperglycemic therapy for type 2 diabetes: scientific review. JAMA. 2002;287:360–72.

    Article  CAS  PubMed  Google Scholar 

  19. Nathan DM, Roussell A, Godine JE. Glyburide or insulin for metabolic control in non-insulin dependent diabetes. Ann Intern Med. 1998;108:334–40.

    Article  Google Scholar 

  20. Johnston PS, Lebovitz HE, Coniff RF, Simonson DC, Raskin P, Munera CL. Advantages of alpha-glocoside inhibition as monotherapy in elderly type 2 diabetic patients. J Clin Endocrinol Metab. 1998;83:1515–22.

    CAS  PubMed  Google Scholar 

  21. Maffioli P, Fogari E, D’Angelo A, Perrone T, Derosa G. Ultrasonography modifications of visceral and subcutaneous adipose tissue after pioglitazone or glibenclamide therapy combined with rosuvastatin in type 2 diabetic patients not well controlled by metformin. Eur J Gastroenterol Hepatol. 2013;25:1113–22.

    Article  PubMed  Google Scholar 

  22. Kodama N, Tahara N, Tahara A, Honda A, Nitta Y, Mizoguchi M, et al. Effects of pioglitazone on visceral fat metabolic activity in impaired glucose tolerance or type 2 diabetes mellitus. J Clin Endocrinol Metab. 2013;98:4438–45. This paper demonstrates the effects of pioglitazone or glibenclamide on glucose metabolism of visceral and subcutaneous adipose tissue using (18)F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) and computed tomography imaging.

    Article  CAS  PubMed  Google Scholar 

  23. Furlong NJ, Hulme SA, O’Brien SV, Hardy KJ. Repaglinide versus metformin in combination with bedtime NPH insulin in patients with type 2 diabetes established on insulin/metformin combination therapy. Diabetes Care. 2002;25:1685–90.

    Article  CAS  PubMed  Google Scholar 

  24. Rosenstock J, Hassman DR, Madder RD, Brazinsky SA, Farrell J, Khutoryansky N, et al. Repaglinide versus nateglinide monotherapy: a randomized, multicenter study. Diabetes Care. 2004;27:1265–70.

    Article  CAS  PubMed  Google Scholar 

  25. The DCCT Research Group. Weight gain associated with intensive therapy in the diabetes control and complications trial. Diabetes Care. 1988;11:567–73.

    Article  Google Scholar 

  26. UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet. 1998;352:837–53.

    Article  Google Scholar 

  27. Shah PK, Mudaliar S, Chang AR, Aroda V, Andre M, Burke P, et al. Effects of intensive insulin therapy alone and in combination with pioglitazone on body weight, composition, distribution and liver fat content in patients with type 2 diabetes. Diabetes Obes Metab. 2011;13:505–10.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  28. Jacob AN, Salinas K, Adams-Huet B, Raskin P. Weight gain in type 2 diabetes mellitus. Diabetes Obes Metab. 2007;9:386–93.

    Article  CAS  PubMed  Google Scholar 

  29. Domecq JP, Prutsky G, Leppin A, Sonbol MB, Altayar O, Undavalli C, et al. MH.J clinical review: drugs commonly associated with weight change: a systematic review and meta-analysis. Clin Endocrinol Metab. 2015;100:363–70.

    Article  CAS  Google Scholar 

  30. Kent ST, Shimbo D, Huang L, Diaz KM, Kilgore ML, Oparil S, et al. Antihypertensive medication classes used among medicare beneficiaries initiating treatment in 2007–2010. PLoS One. 2014;9:e105888.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  31. Rössner S, Taylor CL, Byington RP, Furberg CD. Long term propranolol treatment and changes in body weight after myocardial infarction. BMJ. 1990;300:902–3.

    Article  PubMed Central  PubMed  Google Scholar 

  32. Messerli FH, Bell DS, Fonseca V, Katholi RE, McGill JB, Phillips RA, et al. Body weight changes with beta-blocker use: results from GEMINI. Am J Med. 2007;120:610–5.

    Article  CAS  PubMed  Google Scholar 

  33. Sharma AM, Pischon T, Hardt S, Kunz I, Luft FC. Hypothesis: beta-adrenergic receptor blockers and weight gain: a systematic analysis. Hypertension. 2001;37:250–4.

    Article  CAS  PubMed  Google Scholar 

  34. Welle S, Schwartz RG, Statt M. Reduced metabolic rate during beta-adrenergic blockade in humans. Metabolism. 1991;40:619–22.

    Article  CAS  PubMed  Google Scholar 

  35. Kunz I, Schorr U, Klaus S, Sharma AM. Resting metabolic rate and substrate use in obesity hypertension. Hypertension. 2000;36:26–32.

    Article  CAS  PubMed  Google Scholar 

  36. Astrup A, Simonsen L, Bulow J, Madsen J, Christensen NJ. Epinephrine mediates facultative carbohydrate-induced thermogenesis in human skeletal muscle. Am J Physiol. 1989;257(3 Pt 1):E340–5.

    CAS  PubMed  Google Scholar 

  37. Koch G, Franz IW, Lohmann FW. Effects of short-term and long-term treatment with cardio-selective and non-selective beta-receptor blockade on carbohydrate and lipid metabolism and on plasma catecholamines at rest and during exercise. Clin Sci (Lond). 1981;61 suppl 7:433s–5.

    Article  CAS  Google Scholar 

  38. Wolfe RR, Herndon DN, Peters EJ, Jahoor F, Desai MH, Holland OB. Regulation of lipolysis in severely burned children. Ann Surg. 1987;206:214–21.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  39. Hryniewicz K, Androne AS, Hudraihed A, Katz SD. Partial reversal of cachexia by β-adrenergic receptor blocker therapy in patients with chronic heart failure. J Card Fail. 2003;9:464–8.

    Article  CAS  PubMed  Google Scholar 

  40. Boxall BW, Clark AL. Beta-blockers and weight change in patients with chronic heart failure. J Card Fail. 2012;18:233–7.

    Article  CAS  PubMed  Google Scholar 

  41. Hayden MR, Sowers JR. Treating hypertension while protecting the vulnerable islet in the cardiometabolic syndrome. J Am Soc Hypertens: JASH. 2008;2:239–66.

    Article  PubMed Central  PubMed  Google Scholar 

  42. Karnes JH, Cooper-DeHoff RM. Antihypertensive medications: benefits of blood pressure lowering and hazards of metabolic effects. Expert Rev Cardiovasc Ther. 2009;7:689–702.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  43. Bakris GL, Fonseca V, Katholi RE, McGill JB, Messerli FH, Phillips RA, et al. Metabolic effects of carvedilol vs metoprolol in patients with type 2 diabetes mellitus and hypertension: a randomized controlled trial. JAMA. 2004;292:2227–36.

    Article  CAS  PubMed  Google Scholar 

  44. Pollare T, Lithell H, Selinus I, Berne C. Sensitivity to insulin during treatment with atenolol and metoprolol: a randomised, double blind study of effects on carbohydrate and lipoprotein metabolism in hypertensive patients. BMJ. 1989;298:1152–7.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  45. Harper R, Ennis CN, Sheridan B, Atkinson AB, Johnston GD, Bell PM. Effects of low dose versus conventional dose thiazide diuretic on insulin action in essential hypertension. BMJ. 1994;309:226–30.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  46. Elliott WJ, Meyer PM. Incident diabetes in clinical trials of antihypertensive drugs: a network meta-analysis. Lancet. 2007;369:201–7.

    Article  CAS  PubMed  Google Scholar 

  47. Sugimoto K, Qi NR, Kazdová L, Pravenec M, Ogihara T, Kurtz TW. Telmisartan but not valsartan increases caloric expenditure and protects against weight gain and hepatic steatosis. Hypertension. 2006;47:1003–9.

    Article  CAS  PubMed  Google Scholar 

  48. de Kloet AD, Krause EG, Kim DH, Sakai RR, Seeley RJ, Woods SC. The effect of angiotensin-converting enzyme inhibition using captopril on energy balance and glucose homeostasis. Endocrinology. 2009;150:4114–23.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  49. Sever P. New hypertension guidelines from the national institute for health and clinical excellence and the British hypertension society. J Renin Angiotensin Aldosterone Syst. 2006;7:61–3.

    Article  PubMed  Google Scholar 

  50. Barrow RE, Wolfe RR, Dasu MR, Barrow LN, Herndon DN. The use of beta-adrenergic blockade in preventing trauma-induced hepatomegaly. Ann Surg. 2006;243:115–20.

    Article  PubMed Central  PubMed  Google Scholar 

  51. James PA, Oparil S, Carter BL, Cushman WC, Dennison-Himmelfarb C, Handler J, et al. 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA. 2014;311:507–20.

    Article  CAS  PubMed  Google Scholar 

  52. Babatin M, Lee SS, Pollak PT. Amiodarone hepatotoxicity. Curr Vasc Pharmacol. 2008;6:228–36.

    Article  CAS  PubMed  Google Scholar 

  53. Mattar W, Juliar B, Gradus-Pizlo I, Kwo PY. Amiodarone hepatotoxicity in the context of the metabolic syndrome and right-sided heart failure. J Gastrointest Liver Dis. 2009;18:419–23.

    Google Scholar 

  54. Szalowska E, van der Burg B, Man HY, Hendriksen PJ, Peijnenburg AA. Model steatogenic compounds (amiodarone, valproic acid, and tetracycline) alter lipid metabolism by different mechanisms in mouse liver slices. PLoS One. 2014;9:e86795. This paper indicates the possible mechanisms related to induction of steatosis after use of amiodarone, valproic acid, and tetracycline. Mechanisms include impairment of the peroxisome proliferator activated-receptor (PPAR) signaling.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  55. Anthérieu S, Rogue A, Fromenty B, Guillouzo A, Robin MA. Induction of vesicular steatosis by amiodarone and tetracycline is associated with up-regulation of lipogenic genes in HepaRG cells. Hepatology. 2011;53:1895–905.

    Article  PubMed  CAS  Google Scholar 

  56. Christ-Crain M, Kola B, Lolli F, Fekete C, Seboek D, Wittmann G, et al. AMP-activated protein kinase mediates glucocorticoid-induced metabolic changes: a novel mechanism in Cushing’s syndrome. FASEB J. 2008;22:1672–83.

    Article  CAS  PubMed  Google Scholar 

  57. Wung PK, Anderson T, Fontaine KR, Hoffman GS, Specks U, Merkel PA, et al. Effects of glucocorticoids on weight change during the treatment of Wegener’s granulomatosis. Arthritis Rheum. 2008;59:746–53.

    Article  PubMed Central  PubMed  Google Scholar 

  58. Bruera E, Roca E, Cedaro L, Carraro S, Chacon R. Action of oral methylprednisolone in terminal cancer patients: a prospective randomized double-blind study. Cancer Treat Rev. 1985;69:751–4.

    CAS  Google Scholar 

  59. Chong PK, Jung RT, Scrimgeour CM, Rennie MJ. The effect of pharmacological dosages of glucocorticoids on free living total energy expenditure in man. Clin Endocrinol. 1994;40:577–81.

    Article  CAS  Google Scholar 

  60. Loprinzi CL, Kugler JW, Sloan JA, Mailliard JA, Krook JE, Wilwerding MB, et al. Randomized comparison of megestrol acetate versus dexamethasone versus fluoxymesterone for the treatment of cancer anorexia/cachexia. J Clin Oncol. 1999;17:3299–306.

    CAS  PubMed  Google Scholar 

  61. Mattox TW. Treatment of unintentional weight loss in patients with cancer. Nutr Clin Pract. 2005;20:400–10.

    Article  PubMed  Google Scholar 

  62. Petrovic G, Ristic V, Vrbaski S, Ristic M, Suzic S. The effect of long-term ingestion of glucocorticoids on liver and serum plasma in rats. Physiol Res. 1993;42:45–7.

    CAS  PubMed  Google Scholar 

  63. Itoh S, Igarashi M, Tsukada Y, Ichinoe A. Nonalcoholic fatty liver with alcoholic hyaline after long-term glucocorticoid therapy. Acta Hepato-Gastroenterol. 1977;24:415–8.

    CAS  Google Scholar 

  64. Vanina Y, Podolskaya A, Sedky K, Shahab H, Siddiqui A, Munshi F, et al. Body weight changes associated with psychopharmacology. Psychiatr Serv. 2002;53:842–7.

    Article  PubMed  Google Scholar 

  65. Raeder MB, Ferno J, Vik-Mo AO, Steen VM. SREBP activation by antipsychotic- and antidepressant drugs in cultured human liver cells: relevance for metabolic side-effects? Mol Cell Biochem. 2006;289:167–73.

    Article  CAS  PubMed  Google Scholar 

  66. Pande AC, Birkett M, Fechner-Bates S, Haskett RF, Greden JF. Fluoxetine versus phenelzine in atypical depression. Biol Psychiatry. 1996;40:1017–20.

    Article  CAS  PubMed  Google Scholar 

  67. Fava M. Weight gain and anti depressants. J Clin Psychiatry. 2000;61 Suppl 11:37–41.

    CAS  PubMed  Google Scholar 

  68. Bernstein JG. Induction of obesity by psychotropic drugs. Ann NY Acad Sci. 1987;499:203–15.

    Article  CAS  PubMed  Google Scholar 

  69. Michelson D, Amsterdam JD, Quitkin FM, Reimherr FW, Rosenbaum JF, Zajecka J, et al. Changes in weight during 1-year trial of fluoxetine. Am J Psychiatry. 1999;156:1770–6.

    Google Scholar 

  70. Fava M, Judge R, Hoog SL, Nilsson ME, Koke SC. Fluoxetine versus sertraline and paroxetine in major depressive disorder: changes in weight with long-term treatment. J Clin Psychiatry. 2000;61:863–7.

    Article  CAS  PubMed  Google Scholar 

  71. Harvey B, Bouwer C. Neuropharmacology of paradoxic weight gain with selective serotonin reuptake inhibitors. Clin Neuropharmacol. 2000;23:90–7.

    Article  CAS  PubMed  Google Scholar 

  72. Lustman PJ, Freedland KE, Griffith LS, Clouse RE. Fluoxetine for depression in diabetes: a randomized double-blind placebo-controlled trial. Diabetes Care. 2000;23:618–23.

    Article  CAS  PubMed  Google Scholar 

  73. Andersohn F, Schade R, Suissa S, Garbe E. Long-term use of antidepressants for depressive disorders and the risk of diabetes mellitus. Am J Psychiatry. 2009;166:591.

    Article  PubMed  Google Scholar 

  74. Isaac R, Boura-Halfon S, Gurevitch D, Shainskaya A, Levkovitz Y, Zick Y. Selective serotonin reuptake inhibitors (SSRIs) inhibit insulin secretion and action in pancreatic β-cells. J Biol Chem. 2013;288:5682–93. This paper demonstrates the mechanisms underlying the development of insulin resistance after SSRIs use. The mechanisms include inhibition of insulin secretion; induction of the unfolded protein response; activation of apoptotic process, and triggering of β cell death.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  75. Watanabe N, Omori IM, Nakagawa A, Cipriani A, Barbui C, Churchill R. Mirtazapine versus other antidepressive agents for depression. Cochrane Database Syst Rev. 2011;12:CD006528.

    PubMed  Google Scholar 

  76. Versiani M, Moreno R, Ramakers-van Moorsel CJ, Schutte AJ. Comparative efficacy antidepressants study group. Comparison of the effects of mirtazapine and fluoxetine in severely depressed patients. CNS Drugs. 2005;19:137–46.

    Article  CAS  PubMed  Google Scholar 

  77. Khoza S, Barner JC. Glucose dysregulation associated with antidepressant agents: an analysis of 17 published case reports. Int J Clin Pharm. 2011;33:484–92.

    Article  CAS  PubMed  Google Scholar 

  78. Baptista T, De Mendoza S, Beaulieu S, Bermúdez A, Martinez M. The metabolic syndrome during atypical antipsychotic drug treatment: mechanisms and management. Metab Syndr Relat Disord. 2004;2:290–307.

    Article  CAS  PubMed  Google Scholar 

  79. Adams CE, Award GA, Rathbone J, Thornley B, Soares-Weiser K. Chlorpromazine versus placebo for schizophrenia. Cochrane Database Syst Rev. 2014;1:CD000284.

    PubMed  Google Scholar 

  80. Dossenbach M, Treuer T, Kryzhanovskaya L, Saylan M, Dominguez S, Huang X, et al. Olanzapine versus chlorpromazine in the treatment of schizophrenia: a pooled analysis of four 6-week, randomized, open-label studies in the Middle East and North Africa. J Clin Psychopharmacol. 2007;27(4):329–37.

    Article  CAS  PubMed  Google Scholar 

  81. Meyer JM, Koro CE. The effects of antipsychotic therapy on serum lipids: a comprehensive review. Schizophr Res. 2004;70:1.

    Article  PubMed  Google Scholar 

  82. Allison DB, Mentore JL, Heo M, Chandler LP, Cappelleri JC, Infante MC, et al. Antipsychotic-induced weight gain: a comprehensive research synthesis. Am J Psychiatry. 1999;156:1686–96.

    CAS  PubMed  Google Scholar 

  83. Thonnard-Neumann E. Phenothiazine and diabetes in hospitalized women. Am J Psychiatry. 1968;124:978–82.

    Article  CAS  PubMed  Google Scholar 

  84. Cookson JC. Side effects during long-term treatment with depot antipsychotic medications. Clin Neuropharmacol. 1991;14 Suppl 2:S24.

    PubMed  Google Scholar 

  85. Brambilla F, Guastalla A, Guerrini A, Riggi F, Rovere C, Zanoboni A, et al. Glucose-insulin metabolism in chronic schizophrenia. Dis Nerv Syst. 1976;37(2):98–103.

    CAS  PubMed  Google Scholar 

  86. Vidarsdottir S, de Leeuw van Weenen JE, Frölich M, Roelfsema F, Romijn JA, et al. Effects of olanzapine and haloperidol on the metabolic status of healthy men. J Clin Endocrinol Metab. 2010;95(1):118–25.

    Article  CAS  PubMed  Google Scholar 

  87. Saddichha S, Manjunatha N, Ameen S, Akhtar S. Metabolic syndrome in first episode schizophrenia—a randomized double-blind controlled, short-term prospective study. Schizophr Res. 2008;101:266–72.

    Article  PubMed  Google Scholar 

  88. Musil R, Obermeier M, Russ P, Hamerle M. Weight gain and antipsychotics: a drug safety review. Expert Opin Drug Saf. 2015;1:73–96.

    Article  CAS  Google Scholar 

  89. Bak M, Fransen A, Janssen J, van Os J, Drukker M. Almost all antipsychotics result in weight gain: a meta-analysis. PLoS One. 2014;9:94112.

    Article  Google Scholar 

  90. Krill RA, Kumra S. Metabolic consequences of second-generation antipsychotics in youth: appropriate monitoring and clinical management. Adolesc Health Med Ther. 2014;5:171–82.

    PubMed Central  PubMed  Google Scholar 

  91. Montelone P, Fabrazzo M, Tortorella A, La Pia S, Maj M. Pronounced early increase in circulating leptin predicts lower weight gain during clozapine treatment. J Clin Psychopharmacol. 2002;22:424–6.

    Article  Google Scholar 

  92. Zai CC, Tiwari AK, Chowdhury NI, Brandl EJ, Shaikh SA, Freeman N. Association study of GABAA alpha2 receptor subunit gene variants in antipsychotic-associated weight gain. J Clin Psychopharmacol. 2015;35:7–12.

    Article  CAS  PubMed  Google Scholar 

  93. Cheskin LJ, Bartlett SJ, Zayas R, Twilley CH, Allison DB, Contoreggi C. Prescription medications: a modifiable contributor to obesity. South Med J. 1999;92:898–904.

    Article  CAS  PubMed  Google Scholar 

  94. Lieberman JA, Phillips M, Gu H, Stroup S, Zhang P, Kong L, et al. Atypical and conventional antipsychotic drugs in treatment-naïve first-episode schizophrenia: a 52-week randomized trial of clozapine vs chlorpromazine. Neuropsychopharmacology. 2003;28:995–1003.

    CAS  PubMed  Google Scholar 

  95. Lieberman JA, Stroup TS, McEvoy JP, Swartz MS, Rosenheck RA, Perkins DO. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N Engl J Med. 2005;353:1209–23.

    Article  CAS  PubMed  Google Scholar 

  96. Brown S, Inskip H, Barraclough B. Causes of the excess mortality of schizophrenia. Br J Psychiatry. 2000;177:212–7.

    Article  CAS  PubMed  Google Scholar 

  97. Ferno J, Vik-Mo AO, Jassim G, Håvik B, Berge K, Skrede S. Acute clozapine exposure in vivo induces lipid accumulation and marked sequential changes in the expression of SREBP, PPAR, and LXR target genes in rat liver. Psychopharmacology. 2009;203:73–84.

    Article  PubMed  CAS  Google Scholar 

  98. Ader M, Kim SP, Catalano KJ, Ionut V, Hucking K, Richey JM, 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;54:862–71.

    Article  CAS  PubMed  Google Scholar 

  99. Sechter D, Peuskens J, Fleurot O, Rein W, Lecrubier Y, Amisulpride Study Group. Amisulpride vs. risperidone in chronic schizophrenia: results of a 6-month double-blind study. Neuropsychopharmacology. 2002;27(6):1071–81.

    Article  CAS  PubMed  Google Scholar 

  100. Fukui H, Murai T. Severe weight gain induced by combination treatment with risperidone and paroxetine. Clin Neuropharmacol. 2002;25(5):269–71.

    Article  CAS  PubMed  Google Scholar 

  101. Holtmann M, Kopf D, Mayer M, Bechtinger E, Schmidt MH. Risperidone-associated steatohepatitis and excessive weight-gain. Pharmacopsychiatry. 2003;36:206–7.

    Article  CAS  PubMed  Google Scholar 

  102. Auger F, Duriez P, Martin-Nizard F, Durieux N, Bordet R, Pétrault O. Long-term risperidone treatment induces visceral adiposity associated with hepatic steatosis in mice: a magnetic resonance approach. Schizophr Res Treat. 2014;2014:429291. This paper demonstrates how risperidone can worsen visceral adiposity and hepatic steatosis and studied fatty acid composition and fat accumulation in tissues using MR spectroscopy.

    Google Scholar 

  103. Lauressergues E, Martin F, Helleboid A, Bouchaert E, Cussac D, Bordet R, et al. Overweight induced by chronic risperidone exposure is correlated with overexpression of the SREBP-1c and FAS genes in mouse liver. Naunyn Schmiedeberg’s Arch Pharmacol. 2011;383:423–36.

    Article  CAS  Google Scholar 

  104. Kirino E. Profile of aripiprazole in the treatment of bipolar disorder in children and adolescents. Adolesc Health Ther. 2014;5:211–21.

    Article  CAS  Google Scholar 

  105. Fraguas D, Correll CU, Merchan-Naranjo J. Efficacy and safety of second-generation antipsychotics in children and adolescents with psychotic and bipolar spectrum disorders: comprehensive review of prospective head-to-head and placebo-controlled comparisons. Eur Neuropsychopharmacol. 2011;21:621–45.

    Article  CAS  PubMed  Google Scholar 

  106. Keck Jr PE, Calabrese JR, McQuade RD, Carson WH, Carlson BX, Rollin LM, et al. A randomized, double-blind, placebo-controlled 26-week trial of aripiprazole in recently manic patients with bipolar I disorder. J Clin Psychiatry. 2006;67:626–37.

    Article  CAS  PubMed  Google Scholar 

  107. Citrome L, Kalsekar I, Baker RA, Hebden T. A review of real-world data on the effects of aripiprazole on weight and metabolic outcomes in adults. Curr Med Res Opin. 2014;30:1629–41.

    Article  CAS  PubMed  Google Scholar 

  108. McKnight RF, Adida M, Budge K, Stockton S, Goodwin GM, Geddes JR. Lithium toxicity profile: a systematic review and meta-analysis. Lancet. 2012;379:721–8.

    Article  CAS  PubMed  Google Scholar 

  109. Goodwin FK, Jamison KR. Maintenance medical treatment. Manic-depressive illness. New York: Oxford University Press. 1990; 665–724 and 746–62.

  110. Vestergaard P, Poulstrup I, Schou M. Prospective studies on a lithium cohort. 3. Tremor, weight gain, diarrhea, psychological complaints. Acta Psychiatr Scand. 1988;78:434–41.

    Article  CAS  PubMed  Google Scholar 

  111. Sachs GS, Guille C. Weight gain associated with the use of psychotropic medications. J Clin Psychiatry. 1999;60 Suppl 21:16–9.

    PubMed  Google Scholar 

  112. Chen Y, Silverstone T. Lithium and weight gain. Int Clin Psychopharmacol. 1990;5:217–25.

    Article  CAS  PubMed  Google Scholar 

  113. Atmaca M, Kuloglu M, Texcan E, Ustundag B. Weight gain and serum leptin levels in patients on lithium treatment. Neuropshychobiology. 2002;46:67–9.

    Article  CAS  Google Scholar 

  114. Soeiro-de-Souza MG, Gold PW, Brunoni AR, de Sousa RT, Zanetti MV, Carvalho AF, et al. Lithium decreases plasma adiponectin levels in bipolar depression. Neurosci Lett. 2014;564:111–4.

    Article  CAS  PubMed  Google Scholar 

  115. Chengappa KN, Chalasani L, Brar JS, Parepally H. 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;24:1576–84.

    Article  CAS  PubMed  Google Scholar 

  116. Gitlin MJ, Cochran SD, Jamison KR. Maintenance lithium treatment: side effects and compliance. J Clin Psychiatry. 1989;50:127–31.

    CAS  PubMed  Google Scholar 

  117. Verrotti A, D’Egidio C, Mohn A, Coppola G, Chiarelli F. Weight gain following treatment with valproic acid: pathogenetic mechanisms and clinical implications. Obes Rev. 2011;12:e32–43.

    Article  CAS  PubMed  Google Scholar 

  118. Jallon P, Picard F. Bodyweight gain and anticonvulsants: a comparative review. Drug Saf. 2001;24:969–78.

    Article  CAS  PubMed  Google Scholar 

  119. Mikkonen K, Knip M, Pakarinen AJ, Lanning P, Isojärvi JIT, Vainionpää LK. Growth and lipid metabolism in girls and young women with epilepsy during pubertal maturation. Epilepsia. 2005;46:1114–20.

    Article  PubMed  Google Scholar 

  120. Hamed SA, Fida NM, Hamed EA. States of serum leptin and insulin in children with epilepsy: risk predictors of weight gain. Eur J Paediatr Neurol. 2009;13:261–8.

    Article  PubMed  Google Scholar 

  121. Morrell MJ, Isojärvi J, Taylor AE, Dam M, Ayala R, Gomez G, et al. Higher androgens and weight gain with valproate compared to lamotrigine for epilepsy. Epilepsy Res. 2003;54:189–99.

    Article  CAS  PubMed  Google Scholar 

  122. Verrotti A, Agostinelli S, Parisi P, Chiarelli F, Coppola G. Nonalcoholic fatty liver disease in adolescents receiving valproic acid. Epilepsy Behav. 2011;20:382–5.

    Article  PubMed  Google Scholar 

  123. Luef G, Rauchenzauner M, Waldmann M, Sturm W, Sandhofer A, Seppi K. Non-alcoholic fatty liver disease (NAFLD), insulin resistance and lipid profile in antiepileptic drug treatment. Epilepsy Res. 2009;86:42–7.

    Article  CAS  PubMed  Google Scholar 

  124. Kanemura H, Sano F, Maeda Y, Sugita K, Aihara M. Valproate sodium enhances body weight gain in patients with childhood epilepsy: a pathogenic mechanisms and open-label clinical trial of behavior therapy. Seizure. 2012;21:496–500. This paper shows that valproate treatment for epilepsy was associated with increased serum insulin level and insulin/glucose ratio, and increased appetite.

    Article  PubMed  Google Scholar 

  125. Tokgoz H, Aydin K, Oran B, Kiyici A. Plasma leptin, neuropeptide Y, ghrelin, and adiponectin levels and carotid artery intima media thickness in epileptic children treated with valproate. Childs Nerv Syst. 2012;28:1049–53.

    Article  PubMed  Google Scholar 

  126. Qiao L, Schaack J, Shao J. Suppression of adiponectin gene expression by histone deacetylase inhibitor valproic acid. Endocrinology. 2006;147:865–74.

    Article  CAS  PubMed  Google Scholar 

  127. Lampl Y, Eshel Y, Rapaport A, Sarova-Pinhas I. Weight gain, increased appetite, and excessive food intake induced by carbamazepine. Clin Neuropharmacol. 1991;14:251–5.

    Article  CAS  PubMed  Google Scholar 

  128. Turpin E, Muscat A, Vatier C, Chetrite G, Corruble E, Moldes M, et al. Carbamazepine directly inhibits adipocyte differentiation through activation of the ERK1/2 pathway. Br J Pharmacol. 2013;168:139–50. This paper elucidates the possible mechanism involved in adipose tissue deposition during the use of carbamazepine. In particular, carbamazepine alters adipose tissue development and metabolism by activating the ERK1/2 pathway.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  129. DeToledo JC, Toledo C, DeCerce J, Ramsey RE. Changes in body weight with chronic, high-dose gabapentin therapy. Ther Drug Monit. 1997;19:394–6.

    Article  CAS  PubMed  Google Scholar 

  130. Baulac M, Cavalcanti D, Semah F, Arzimanoglou A, Portal JJ. Gabapentin add-on therapy with adaptable dosages in 610 patients with partial epilepsy: an open, observational study. The French gabapentin collaborative group. Seizure. 1998;7:55–62.

    Article  CAS  PubMed  Google Scholar 

  131. Cordeira JW, Felsted JA, Teillon S, Daftary S, Panessiti M, Wirth J, et al. Hypothalamic dysfunction of the thrombospondin receptor α2δ-1 underlies the overeating and obesity triggered by brain-derived neurotrophic factor deficiency. J Neurosci. 2014;34:554–65.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  132. Gallo MF, Lopez LM, Grimes DA, Carayon F, Schulz KF, Helmerhorst FM. Combination contraceptives: effects on weight. Cochrane Database Syst Rev. 2014;1:CD003987.

    PubMed  Google Scholar 

  133. Warholm L, Petersen KR, Ravn P. Combined oral contraceptives’ influence on weight, body composition, height, and bone mineral density in girls younger than 18 years: a systematic review. Eur J Contracept Reprod Health Care. 2012;17:245–53.

    Article  PubMed  Google Scholar 

  134. Mayeda ER, Torgal AH, Westhoff CL. Weight and body composition changes during oral contraceptive use in obese and normal weight women. J Women’s Health (Larchmt). 2014;23:38–43.

    Article  Google Scholar 

  135. Lopez LM, Edelman A, Chen M, Otterness C, Trussell J, Helmerhorst FM. Progestin-only contraceptives: effects on weight. Cochrane Database Syst Rev. 2013;7:CD008815.

    PubMed Central  PubMed  Google Scholar 

  136. Liu SH, Lazo M, Koteish A, Kao WH, Shih MH, Bonekamp S, et al. Oral contraceptive pill use is associated with reduced odds of nonalcoholic fatty liver disease in menstruating women: results from NHANES III. J Gastroenterol. 2013;48:1151–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  137. Vickery Z, Madden T, Zhao Q, Secura GM, Allsworth JE, Peipert JF. Weight change at 12 months in users of three progestin-only contraceptive methods. Contraception. 2013;88:503–8.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Internal Medicine, Division of Gastroenterology and Hepatology, University of California Davis, 4150 V Street, Sacramento, CA, 95816, USA

    Valentina Medici

  2. Department of Medicine, Division of Gastroenterology, Hepatology, and Nutrition, University of Louisville School of Medicine, 550 South Jackson Street, Louisville, KY, 40202, USA

    Stephen A. McClave

  3. Department of Surgery, University of Louisville, ACB 2nd Floor, 550 South Jackson Street, Louisville, KY, 40202, USA

    Keith R. Miller

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  1. Valentina Medici
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  3. Keith R. Miller
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Valentina Medici, Keith R. Miller, and Stephen A. McClave declare that they have no conflicts of interest.

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Medici, V., McClave, S.A. & Miller, K.R. Common Medications Which Lead to Unintended Alterations in Weight Gain or Organ Lipotoxicity. Curr Gastroenterol Rep 18, 2 (2016). https://doi.org/10.1007/s11894-015-0479-4

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