Psychopharmacology

, Volume 186, Issue 4, pp 572–578 | Cite as

Effects of typical and atypical antipsychotics on glucose–insulin homeostasis and lipid metabolism in first-episode schizophrenia

  • Ren-Rong Wu
  • Jing-Ping Zhao
  • Zhe-Ning Liu
  • Jin-Guo Zhai
  • Xiao-Feng Guo
  • Wen-Bing Guo
  • Jing-Song Tang
Original Investigation

Abstract

Rationale

Glucose and lipid metabolism dysfunction is a significant side effect associated with antipsychotics. Although there are many studies about the linkages between drugs and metabolic dysfunction, most of these studies have compared the effects of two antipsychotics on only one metabolic measure: either glucose or lipid metabolism.

Objectives

The present study aimed to investigate the effects of clozapine, olanzapine, risperidone, and sulpiride on glucose and lipid metabolism in first-episode schizophrenia.

Materials and methods

One hundred twelve schizophrenics were assigned randomly to receive clozapine, olanzapine, risperidone, or sulpiride for 8 weeks. Planned assessments included body mass index (BMI), waist-to-hip ratio, fasting glucose, insulin, C-peptide, insulin resistance index (IRI), cholesterol, and triglyceride. All measures were collected at baseline and at the end of the 8-week treatment.

Results

After treatment, insulin, C-peptide, and IRI were significantly increased in the four groups, but not fasting glucose levels. Cholesterol and triglyceride levels were significantly increased in the clozapine and olanzapine groups. Patients treated with clozapine and olanzapine had higher fasting insulin, C-peptide, and IRI levels than those treated with risperidone and sulpiride. Among the four antipsychotics, the increases of mean BMI from high to low were as follows: clozapine, olanzapine, sulpiride, and risperidone.

Conclusions

This study confirmed that the four antipsychotic drugs were associated with an increase of insulin, C-peptide, and IRI. It was found that clozapine and olanzapine were associated with an increase in cholesterol and triglyceride levels. The effects of clozapine and olanzapine on the glucose and lipid metabolism outweighed those of risperidone and sulpiride.

Keywords

Antipsychotic Clozapine Olanzapine Risperidone Sulpiride Metabolism Glucose Lipid 

Notes

Acknowledgement

The research was supported by National Key Technologies R&D Program in the 10th Five-year-plan grant 2004BA720A22 from the Ministry of Science and Technology of the People’s Republic of China.

References

  1. Allison DB, Mentore JL, Heo M, Chandler LP, Cappelleri JC, Infante MC, Weiden PJ (1999) Antipsychotic-induced weight gain: a comprehensive research synthesis. Am J Psychiatry 156:1686–1696PubMedGoogle Scholar
  2. Aquila R, Emanuel M (2000) Interventions for weight gain in adults treated with novel antipsychotics. Prim Care Companion J Clin Psychiatry 2:20–23PubMedGoogle Scholar
  3. Bergman RN, Ader M (2005) Atypical antipsychotics and glucose homeostasis. J Clin Psychiatry 66:504–512PubMedCrossRefGoogle Scholar
  4. Bernstein JG (1987) Induction of obesity by psychotropic drugs. Ann N Y Acad Sci 499:203–215PubMedCrossRefGoogle Scholar
  5. Best L, Yates AP, Reynolds GP (2005) Actions of antipsychotic drugs on pancreatic beta-cell function: contrasting effects of clozapine and haloperidol. J Psychopharmacol 19:597–601CrossRefPubMedGoogle Scholar
  6. Citrome IL (2004) The increase in risk of diabetes mellitus from exposure to second-generation antipsychotic agents. Drugs Today 40:445–464CrossRefPubMedGoogle Scholar
  7. Citrome LL (2005) Antipsychotic medication and diabetes mellitus. J Clin Psychiatry 66:395PubMedGoogle Scholar
  8. Dunlop BW, Sternberg M, Phillips LS, Andersen J, Duncan E (2003) Disturbed glucose metabolism among patients taking olanzapine and typical antipsychotics. Psychopharmacol Bull 37:99–117PubMedGoogle Scholar
  9. Haffner SM, Miettinen H, Stern MP (1997) The homeostasis model in the San Antonio Heart Study. Diabetes Care 20:1087–1092PubMedCrossRefGoogle Scholar
  10. Ha Ya A-, Stensland MD , Kinon BJ, Tollefson GD (2005) Long-term improvement in insulin sensitivity by changing lifestyles of people with impaired glucose tolerance. J Psychopharmacol 19:110–117CrossRefPubMedGoogle Scholar
  11. Howes OD, Gaughran FP, Amiel SA, Murray RM, Pilowsky LS (2004) The effect of clozapine on factors controlling glucose homeostasis. J Clin Psychiatry 65:1352–1355PubMedGoogle Scholar
  12. Kamran A, Doraiswamy PM, Jane JL, Hammett EB, Dunn L (1994) Severe hyperglycemia associated with high doses of clozapine. Am J Psychiatry 151(9):1395PubMedGoogle Scholar
  13. Kuan-Pin S, Po-Lun W, Carmine MP (2005) A crossover study on lipid and weight changes associated with olanzapine and risperidone. Psychopharmacology 183:383–386CrossRefPubMedGoogle Scholar
  14. Lieberman JA, Stroup TS, McEvoy JP, Swartz MS, Rosenheck RA, Perkins DO, Keefe RS, Davis SM, Davis CE, Lebowitz BD, Severe J, Hsiao JK (2005) Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N Engl J Med 353:1209–1223CrossRefPubMedGoogle Scholar
  15. Liese A, Mayer-Davis E, Haffner S (1998) Development of the multiple metabolic syndrome: an epidemiologic perspective. Epidemiol Rev 20(2):157–172PubMedGoogle Scholar
  16. Lindenmayer JP, Czobor P, Volavka J (2003) Changes in glucose and cholesterol levels in patients with schizophrenia treated with typical or atypical antipsychotics. Am J Psychiatry 160:290–296CrossRefPubMedGoogle Scholar
  17. Melkersson K (2004) Clozapine and olanzapine, but not conventional antipsychotics, increase insulin release in vitro. Eur Neuropsychopharmacol 14:115–119CrossRefPubMedGoogle Scholar
  18. Melkersson KI, Hulting AL, Brismar KE (2000) Elevated levels of insulin, leptin, and blood lipids in olanzapine-treated patients with schizophrenia or related psychoses. J Clin Psychiatry 61:742–749PubMedGoogle Scholar
  19. Melkersson KI, Dahl ML, Hulting AL (2004) Guidelines for prevention and treatment of adverse effects of antipsychotic drugs on glucose–insulin homeostasis and lipid metabolism. Psychopharmacology 175:1–6CrossRefPubMedGoogle Scholar
  20. Meyer JM (2000) A retrospective comparison of lipid, glucose, and weight changes at one year between olanzapine and risperidone treated inpatients. In: Proceedings of the 39th Annual Meeting of the American College of Neuropsychopharmacology. Nashville, Tenn, ACNPGoogle Scholar
  21. Nasrallah HA, Newcomer JW (2004) Atypical antipsychotics and metabolic dysregulation: evaluating the risk/benefit equation and improving the standard of care. J Clin Psychopharmacol 24:7–14CrossRefGoogle Scholar
  22. Newcomer JW, Haupt DW, Fucetola R, Melson AK, Schweiger JA, Cooper BP, Selke G (2002) Abnormalities in glucose regulation during antipsychotic treatment of schizophrenia. Arch Gen Psychiatry 59:337–345CrossRefPubMedGoogle Scholar
  23. Palik E, Birkas KD, Faludi G, Karadi I, Cseh K (2005) Correlation of serum ghrelin levels with body mass index and carbohydrate metabolism in patients treated with atypical antipsychotics. Diabetes Res Clin Pract 68:60–64CrossRefGoogle Scholar
  24. Poyurovsky M, Pashinian A, Gil-Ad I, Maayan R, Schneidman M, Fuchs C, Weizman A (2002) Olanzapine-induced weight gain in patients with first-episode schizophrenia:a double-blind, placebo-controlled study of fluoxetine addition. Am J Psychiatry 159:1058–1060CrossRefPubMedGoogle Scholar
  25. Ried LD, Renner BT, Bengtson MA, Wilcox BM, Acholonu WW Jr (2003) Weight change after an atypical antipsychotic switch. Ann Pharmacother 37:1381–1385CrossRefPubMedGoogle Scholar
  26. Simpson GM, Glick ID, Weiden PJ, Romano SJ, Siu CO (2004) Randomized, controlled, double-blind multicenter comparison of the efficacy and tolerability of ziprasidone and olanzapine in acutely ill inpatients with schizophrenia or schizoaffective disorder. Am J Psychiatry 161:1837–1847CrossRefPubMedGoogle Scholar
  27. Smith RC, Lindenmayer JP, Khandat A, Wahab M, Bodala P, Rosenberger J (2001) A prospective study of glucose and lipid metabolism with atypical and conventional antipsychotics (poster). In: Proceedings of the 14th Annual Research Conference of the New York State Office of Mental Health. Albany, New York State Office of Mental HealthGoogle Scholar
  28. Smith RC, Lindenmayer JP, Bark N, Warner-Cohen J, Vaidhyanathaswamy S, Khandat A (2005) Clozapine, risperidone, olanzapine, and conventional antipsychotic drug effects on glucose, lipids, and leptin in schizophrenia patients. Int J Neuropsychopharmacol 8:183–194CrossRefPubMedGoogle Scholar
  29. Su KP, Wu PL, Pariante CM (2005) A crossover study on lipid and weight changes associated with olanzapine and risperidone. Psychopharmacology 21:1–4Google Scholar
  30. Wozniak KM, Linnoila M (1991) Hyperglycemic properties of serotonin receptor antagonists. Life Sci 49:101–109CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Ren-Rong Wu
    • 1
  • Jing-Ping Zhao
    • 1
  • Zhe-Ning Liu
    • 1
  • Jin-Guo Zhai
    • 1
  • Xiao-Feng Guo
    • 1
  • Wen-Bing Guo
    • 1
  • Jing-Song Tang
    • 1
  1. 1.Institute of Mental Health of The Second Xiangya HospitalCentral South UniversityChangshaChina

Personalised recommendations