Orlistat for the Treatment of Antipsychotic-induced Weight Gain: an Eight-week Multicenter, Randomized, Placebo-controlled, Double-blind Trial

Overview

Journal Lipids Health Dis

Publisher Biomed Central

Specialties Biochemistry
Endocrinology

Date 2024 Jul 25

PMID 39049073

Authors

Peng Xie

Tiannan Shao

Yujun Long

WeiWei Xie

Yangjun Liu

Ye Yang

Yuyan Huang

Renrong Wu

Qijian Deng

Hui Tang

Affiliations

Soon will be listed here.

Abstract

Background: Weight gain and metabolic disorders are commonly induced by antipsychotics. Orlistat is a lipase inhibitor used for weight control. The effect of orlistat on weight gain and metabolic disturbances in people (especially women) treated with antipsychotics has not been sufficiently studied. This study aimed to investigate the efficacy of orlistat in mitigating antipsychotic-induced weight gain and abnormal glycolipid metabolism.

Methods: Patients with schizophrenia or bipolar disorder with a weight gain ≥ 7% after taking antipsychotics were recruited. Participants were randomly allocated to two groups: one received eight weeks of orlistat (360 mg/day) and the other received a placebo. Anthropometric and fasting serum biochemical parameters were measured at baseline, week 4 and week 8.

Results: Sixty individuals (orlistat:placebo = 32:28) participated in the study. After controlling for the study center, the eight-week changes in body mass index (BMI), cholesterol (CHOL), high-density lipoprotein cholesterol (HDL-CH) and low-density lipoprotein cholesterol (LDL-CH) were significantly different between the groups. According to the mixed linear models, CHOL and LDL-CH were significantly lower in the orlistat group than in the control group at week 8. The week 0-to-8 slopes of BMI, CHOL and LDL-CH were also significantly lower in the orlistat group.

Conclusions: These findings suggested that orlistat is an effective intervention for attenuating weight gain and serum lipid disturbances in antipsychotic-treated patients.

Trial Registration: ClinicalTrials.gov NCT03451734.

References

Ingimarsson O, MacCabe J, Haraldsson M, Jonsdottir H, Sigurdsson E . Risk of diabetes and dyslipidemia during clozapine and other antipsychotic drug treatment of schizophrenia in Iceland. Nord J Psychiatry. 2017; 71(7):496-502. DOI: 10.1080/08039488.2017.1334821. View

Kopelman P, Groot G, Rissanen A, Rossner S, Toubro S, Palmer R . Weight loss, HbA1c reduction, and tolerability of cetilistat in a randomized, placebo-controlled phase 2 trial in obese diabetics: comparison with orlistat (Xenical). Obesity (Silver Spring). 2009; 18(1):108-15. DOI: 10.1038/oby.2009.155. View

Miyakoshi T, Ishikawa S, Okubo R, Hashimoto N, Sato N, Kusumi I . Risk factors for abnormal glucose metabolism during antipsychotic treatment: A prospective cohort study. J Psychiatr Res. 2023; 168:149-156. DOI: 10.1016/j.jpsychires.2023.10.055. View

Kim K, Suh H, Hwang I, Ko K . Influence of eating behaviors on short-term weight loss by orlistat and anorectic agent. Eat Behav. 2014; 15(1):87-90. DOI: 10.1016/j.eatbeh.2013.10.019. View

Lemstra M, Bird Y, Nwankwo C, Rogers M, Moraros J . Weight loss intervention adherence and factors promoting adherence: a meta-analysis. Patient Prefer Adherence. 2016; 10:1547-59. PMC: 4990387. DOI: 10.2147/PPA.S103649. View

Chadda R, Ramshankar P, Deb K, Sood M . Metabolic syndrome in schizophrenia: Differences between antipsychotic-naïve and treated patients. J Pharmacol Pharmacother. 2013; 4(3):176-86. PMC: 3746300. DOI: 10.4103/0976-500X.114596. View

Olszanecka-Glinianowicz M, Dabrowski P, Kocelak P, Janowska J, Smertka M, Jonderko K . Long-term inhibition of intestinal lipase by orlistat improves release of gut hormones increasing satiety in obese women. Pharmacol Rep. 2013; 65(3):666-71. DOI: 10.1016/s1734-1140(13)71044-2. View

Cho L, Kilpatrick E, Keevil B, Coady A, Atkin S . Effect of metformin, orlistat and pioglitazone treatment on mean insulin resistance and its biological variability in polycystic ovary syndrome. Clin Endocrinol (Oxf). 2008; 70(2):233-7. DOI: 10.1111/j.1365-2265.2008.03309.x. View

Lieberman J, Stroup T, McEvoy J, Swartz M, Rosenheck R, Perkins D . Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N Engl J Med. 2005; 353(12):1209-23. DOI: 10.1056/NEJMoa051688. View

10.

Heck A, Yanovski J, Calis K . Orlistat, a new lipase inhibitor for the management of obesity. Pharmacotherapy. 2000; 20(3):270-9. PMC: 6145169. DOI: 10.1592/phco.20.4.270.34882. View

11.

Hollander P, Elbein S, Hirsch I, Kelley D, McGill J, Taylor T . Role of orlistat in the treatment of obese patients with type 2 diabetes. A 1-year randomized double-blind study. Diabetes Care. 1998; 21(8):1288-94. DOI: 10.2337/diacare.21.8.1288. View

12.

Hauptman J, Lucas C, Boldrin M, Collins H, Segal K . Orlistat in the long-term treatment of obesity in primary care settings. Arch Fam Med. 2000; 9(2):160-7. DOI: 10.1001/archfami.9.2.160. View

13.

Derosa G, Maffioli P, Salvadeo S, Ferrari I, Gravina A, Mereu R . Comparison of orlistat treatment and placebo in obese type 2 diabetic patients. Expert Opin Pharmacother. 2010; 11(12):1971-82. DOI: 10.1517/14656566.2010.493557. View

14.

McKnight R, Adida M, Budge K, Stockton S, Goodwin G, Geddes J . Lithium toxicity profile: a systematic review and meta-analysis. Lancet. 2012; 379(9817):721-8. DOI: 10.1016/S0140-6736(11)61516-X. View

15.

Zeng Q, Li N, Pan X, Chen L, Pan A . Clinical management and treatment of obesity in China. Lancet Diabetes Endocrinol. 2021; 9(6):393-405. DOI: 10.1016/S2213-8587(21)00047-4. View

16.

Afzal M, Siddiqi N, Ahmad B, Afsheen N, Aslam F, Ali A . Prevalence of Overweight and Obesity in People With Severe Mental Illness: Systematic Review and Meta-Analysis. Front Endocrinol (Lausanne). 2021; 12:769309. PMC: 8656226. DOI: 10.3389/fendo.2021.769309. View

17.

Aldekhail N, Logue J, McLoone P, Morrison D . Effect of orlistat on glycaemic control in overweight and obese patients with type 2 diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials. Obes Rev. 2015; 16(12):1071-80. DOI: 10.1111/obr.12318. View

18.

Hogan S, Fleury A, Hadvary P, Lengsfeld H, Meier M, Triscari J . Studies on the antiobesity activity of tetrahydrolipstatin, a potent and selective inhibitor of pancreatic lipase. Int J Obes. 1987; 11 Suppl 3:35-42. View

19.

Woldekidan N, Mohammed A, Degu A, Tadiwos Y . Prevalence of metabolic syndrome and associated factors among psychiatric patients at University of Gondar Comprehensive Specialized Hospital, Northwest Ethiopia. PLoS One. 2021; 16(8):e0256195. PMC: 8389454. DOI: 10.1371/journal.pone.0256195. View

20.

Alanazi J, Unnisa A, Ahmad S, Itumalla R, Alanazi M, Alharby T . Significance of Orlistat in management of dyslipidemia, systolic blood pressure and body mass index. Eur Rev Med Pharmacol Sci. 2022; 26(22):8326-8332. DOI: 10.26355/eurrev_202211_30365. View