Metformin for the Prevention of Weight Gain due to Atypical Antipsychotics

Abstract

Excessive weight gain, hyperglycemia, type 2 diabetes and hyperlipidemia are significant clinical adverse effects that appear as a result of the treatment with second generation atypical antipsychotic drugs. These drugs possibly cause weight gain by stimulating appetite and increasing insulin resistance. Amantadine, nizatidine, ranitidine, famotidine, topiramate, reboxetine and metformin are notified as the effective drugs which were used in order to prevent the weight gain due to atypical antipsychotic drugs. As an antidiabetic agent, metformin draws attention due to reducing weight gain and correcting insulin resistance. The aim of this paper was to evaluate studies searching fort he effect of metformin on weight-gain due to atypical antipsychotics.

Keywords

• atypical antipsychotic drugs, metformin, weight gain

Atipik Antipsikotiklere Bağlı Kilo Artışının Önlenmesinde Metformin Kullanımı

Öz

Aşırı kilo artışı, hiperglisemi, tip 2 diyabet ve hiperlipidemi ikinci kuşak atipik antipsikotik ilaçlarla tedavi sonucu ortaya çıkan önemli klinik yan etkilerdir. Bu ilaçların iştahı uyararak ve insülin direncini artırarak kilo artışına neden oldukları ileri sürülmektedir. Amantadin, nizatidin, ranitidin, famotidin, topiramat, reboksetin ve metforminin atipik antipsikotik ilaçlara bağlı kilo artışını önlemede kullanılmış ve etkili olduğu bildirilen ilaçlardan bazılarıdır. Antidiyabetik bir ajan olan metformin, insülin direncini düzeltmesi ve kilo artışını azaltması nedeniyle özellikle dikkati çekmektedir. Bu çalışmada atipik antipsikotiklerin kilo artışının kontrolünde metforminin etkisini araştıran çalışmalar değerlendirilmiştir.

Anahtar Kelimeler

• atipik antipsikotik ilaçlar, metformin, kilo artışı

Kaynakça

1. Kelleher JP, Centorrino F, Albert MJ, Baldessarini RJ. Advances in atypical antipsychotics for the treatment of schizophrenia: New formulations and new agents. CNS Drugs 2002; 16:249-261.
2. Bergman RN, Ader M. Atypical antipsychotics and glucose homeostasis. J Clin Psychiatry 2005; 66:504-514.
3. Jin H, Meyer JM, Jeste DV. Atypical antipsychotics and glucose dysregulation: A systematic review. Schizophr Res 2004;71(2-3):195-212.
4. Çelik GG, Tahiroğlu AY, Avcı A. Çocuk ve ergenlerde atipik antipsikotik ilaçların metabolik ve endokrin yan etkileri. Psikiyatride Güncel Yaklaşımlar 2011; 3:232-250.
5. Dixon L, Perkins D, Calmes C. Guideline Watch (September 2009): Practice guideline for treatment of patients with schizophrenia. Washinton D.C., American Psychiatric Association, 2009.
6. Savaş HA, Yumru M, Savaş E. Psikofarmakoterapinin yol açtığı kilo alımına karşı ilâçla tedavi yaklaşımları. Yeni Symposium 2007; 45:35-40.
7. Mario AJ, Cesar GB, Jose VB, Rocio PI, Obdulia MG,Teresa PP et al. Attenuation of antipsychotic-induced weight gain with early behavioral intervention in drug-naive first-episode psychosis patients:a randomized controlled trial. J Clin Psychiatry 2006; 67:1253-1260.
8. Hagg S, Joelsson L, Mjorndal T. Prevalence of diabetes and impaired glucose tolerance in patients treated with clozapine compared with patients treated with conventional depot neuroleptic medications. J Clin Psychiatry 1998; 59:294-299.

9. Wu RR, Zhao JP, Guo XF, He YQ, Fang MS, Guo WB et al. Metformin addition attenuates olanzapine-induced weight gain in drug-naive first-episode schizophrenia patients: A double-blind, placebo-controlled study. Am J Psychiatry 2008; 165:352- 358.
10. Faulkner G, Cohn T, Remington G. Interventions to reduce weight gain in schizophrenia. Cochrane Database Syst Rev 2007; 1:CD005148.
11. 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; 156:1686-1696.
12. Lean ME, Pajonk FG. Patients on atypical antipsychotic drugs: Another high-risk group for type 2 diabetes. Diabetes Care 2003; 26:1597-1605.
13. Stahl SM, Mignon L, Meyer JM. Which comes first: atypical antipsychotic treatment or cardiometabolic risk? Acta Psychiatr Scand 2009; 119:171-179.
14. Stahl SM. Neuropharmacology of obesity:my receptors make me eat. J Clin Psychiatry 1998; 59:447-448.
15. 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; 54:862-871.
16. Kraus T, Haack M, Schuld A, Hinze-Selch D, Kühn M, Uhr M et al. Body weight and leptin plasma levels during treatment with antipsychotic drugs. Am J Psychiatry 1999; 156:312-314.
17. Melkersson KI, Hulting AL, Brismar KE. Elevated levels of insulin, leptin, and blood lipids in olanzapine-treated patients with schizophrenia or related psychoses. J Clin Psychiatry 2000; 61:742-749.
18. Thakore JH, Mann JN, Vlahos I, Martin A, Reznek R. Increased fat distribution in drug-naive and drug-free patients with schizophrenia. Int J Obes Relat Metab Disord 2002; 26:137-141.
19. Reynolds GP, Kirk SL. Metabolic side effects of antipsychotic drug treatment: Pharmacological mechanisms. Pharmacol Ther 2010; 125:169-179.
20. Şengül C, Herken H. Antipsikotiklere bağlı kilo alımının farmakogenetiği. Klinik Psikofarmakoloji Bülteni 2009; 19:297-303.
21. Yazıcı K, Yazıcı A. Antipsikotik ilaçların yol açtığı kilo artışı: Genlerin payı ne? Klinik Psikofarmakoloji Bülteni 2008; 18:59-70.
22. Henderson DC, Cagliero E, Copeland PM, Borba CP, Evins E, Hayden D et al. Glucose metabolism in patients with schizophrenia treated with atypical antipsychotic agents: A frequently sampled intravenous glucose tolerance test and minimal modal analysis. Arch Gen Psychiatry 2005; 62:19-28.
23. Lieberman JA, Stroup TS, McEvoy JP, Swartz MS, Rosenheck RA, Perkins DO et al. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N Engl J Med 2005; 353:1209-1223.
24. Baptista T, Kin NM, Beaulie S, Baptista EA. Obesity and related metabolic abnormalities during antipsychotic drug adminitration: Mechanism, management and research perspectives. Pharmacopsychiatry 2002; 35:205-219.
25. Weterling T. Bodyweight gain with atypical antipsychotics:comparative review. Drug Saf 2001; 24:59-73.
26. Kinon BJ, Basson MS, Gilmore LM. Long term olanzapine treatment, weight change and weight-related health factors in schizophrenia. J Clin Psychiatry 1993; 54:272- 276.
27. Miller LJ, Pharm D. Management of atypical antipsychotic drug-induced weight gain: Focus on metformin. Pharmacotherapy 2009; 29:725-735.
28. Hummer M, Kemler G, Kurz M, Kurzthaler I, Oberbauer H, Fleischhacker WW. Weight gain induced by clozapine. Eur Neuropsychopharmacol 1995; 5:437-440.
29. Wu RR, Zhao JP, Jin H, Shao P, Fang MS, Guo XF et al. Lifestyle intervention and metformin for treatment of antipsychotic induced weight gain: A randomized controlled trial. JAMA 2008; 299:185-193.
30. Wadden TA, Berkowitz RI, Womble LG, Sarwer DB, Phelan S, Cato RK et al. Randomized trial of lifestyle modification and pharmacotherapy for obesity. N Engl J Med 2005; 353:2111-2120.
31. Özenoğlu A, Uğurlu S, Can G, Eker E, Elmacıoğlu F. Psikiyatrik tedavilerle gelişen metabolik bozukluklar ve tedavisinde diyetetik yaklaşımın önemi. Nobel Medicus 2009; 5(Ek 1):36-44
32. Bergman LB, Asplund AB, Lindh JD. Metformin for weight in non-diabetic patients on antipsychotic drugs: A systematic review and meta-analysis. J Psychopharmacology 2010;doi:10.1177/0269881109353461.
33. Seufert J, Lubben G, Dietrich K, Bates PC. A comparison of the effects of thiazolidinediones and metformin on metabolic control in patients with type 2 diabetes mellitus. Clin Ther 2004; 26:805-818.
34. Morrison JA, Cottingham EM, Barton BA. Metformin for weight loss in pediatric patients taking psychotropic drugs. Am J Psychiatry 2002; 159:655-657.
35. Klein DJ, Cottingham EM, Sorter M, Barton BA, Morrison JA. A randomized, double-blind, placebo-controlled trial of metformin treatment of weight gain associated with initiation of atypical antipsychotic therapy in children and adolescent. Am J Psychiatry 2006; 163:2072-2079.
36. Arman S, Sadramely MR, Nadi M, Koleini N. A randomized, placebo controlled, double-blind trial of metformin for weight gain associated with initiation of risperidone in children and adolescents. Saudi Med J 2008; 29:1130-1134.
37. Baptista T, Martínez J, Lacruz A, Rangel N, Beaulieu S, Serrano A et al. Metformin for prevention of weight gain and insulin resistance with olanzapine: A double-blind placebo-controlled trial. Can J Psychiatry 2006; 51:192-196.
38. Baptista T, Rangel N, Frenández V, Carrizo E, Fakih YE, Uzcátegui E et al. Metformin as an adjunctive treatment to control body weight and metabolic dysfunction during olanzapine administration: A multicentric, double-blind, placebo- controlled trial. Schizophr Res 2007; 93:99-108.
39. Baptista T, Uzcátegui M, Rangel N, Fakih YE, Galeazzi T, Beaulieu S et al. Metformin plus sibutramine for olanzapine-associated weight gain and metabolic dysfunction in schizophrenia: A 12-week double-blind, placebo-controlled pilot study. Psychiatry Res 2008; 159:250-253.
40. Chen CH, Chiu CC, Huang MC, Wu TH, Liu HC, Lu ML. Metformin for metabolic dysregulation in schizophrenic patients treated with olanzapine. Prog Neuropsychopharmacol Biol Psychiatry 2008; 32:925-931.
41. Carrizo E, Frenández V, Connell L, Sandia I, Prieto D, Mogollón J et al. Extended release metformin for metabolic control assistance during prolonged clozapine administration: A 14 week, double-blind, paralel group, placebo-controlled study. Schizophr Res 2009; 113:19-26.