Weight change and metabolic effects of asenapine in patients with schizophrenia and bipolar disorder

J Clin Psychiatry. 2014 Mar;75(3):238-45. doi: 10.4088/JCP.12m08271.

Abstract

Objective: To describe weight changes and metabolic effects of asenapine compared with placebo and olanzapine in adults.

Method: Post hoc analyses were performed using data from 17 asenapine trials (13 schizophrenia and 4 bipolar mania trials) with placebo (5-10 mg twice daily; n = 1,748; 1-6 weeks) and/or olanzapine (5-20 mg, once daily; n = 3,430; 3-100 weeks). Data were pooled based on treatment into placebo-controlled and olanzapine-controlled trials. For trials with placebo and olanzapine treatment groups, the asenapine population was included in both pools. Changes from baseline for weight, body mass index, and fasting lipid and glucose levels were determined. The Medical Dictionary for Regulatory Activities was used to define metabolic adverse events.

Results: Mean (standard error [SE]) weight change was greater with asenapine than with placebo (1.2 [0.2] vs 0.14 [0.2] kg; P < .0001) and similar in schizophrenia and bipolar disorder. Mean changes differed for asenapine versus placebo in triglycerides (1.8 [6.3] vs -12.2 [5.9] mg/dL; P < .01) and fasting glucose (1.9 [1.7] vs -1.6 [1.5] mg/dL; P < .05). In the olanzapine-controlled trials, weight change was significantly lower with asenapine than with olanzapine (0.9 [0.1] vs 3.1 [0.2] kg; P < .0001). Changes associated with asenapine were lower than those with olanzapine in fasting glucose (2.0 vs 3.3 mg/dL), total cholesterol (-0.4 [1.1] vs 6.2 [1.2] mg/dL; P < .0001), low-density lipoprotein cholesterol (-0.3 [1.1] vs 3.1 [1.2] mg/dL; P < .01), and triglycerides (-0.9 [5.4] vs 24.3 [5.8] mg/dL; P < .0001).

Conclusions: Asenapine was associated with greater weight gain and glucose changes than placebo and not associated with a meaningful change in triglycerides or cholesterol levels. Asenapine was not significantly different from olanzapine in change in glucose levels and lower than olanzapine with respect to triglycerides, weight gain, and increased cholesterol.

Publication types

  • Comparative Study
  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antipsychotic Agents / adverse effects
  • Antipsychotic Agents / pharmacology*
  • Benzodiazepines / adverse effects
  • Benzodiazepines / pharmacology*
  • Bipolar Disorder / drug therapy*
  • Bipolar Disorder / metabolism
  • Blood Glucose / drug effects
  • Body Mass Index
  • Body Weight / drug effects
  • Cholesterol / blood
  • Cholesterol, LDL / blood
  • Cholesterol, LDL / drug effects
  • Controlled Clinical Trials as Topic
  • Dibenzocycloheptenes
  • Female
  • Hematologic Tests
  • Heterocyclic Compounds, 4 or More Rings / adverse effects
  • Heterocyclic Compounds, 4 or More Rings / pharmacology*
  • Humans
  • Male
  • Middle Aged
  • Olanzapine
  • Schizophrenia / drug therapy*
  • Schizophrenia / metabolism
  • Treatment Outcome
  • Triglycerides / blood
  • Weight Gain / drug effects*

Substances

  • Antipsychotic Agents
  • Blood Glucose
  • Cholesterol, LDL
  • Dibenzocycloheptenes
  • Heterocyclic Compounds, 4 or More Rings
  • Triglycerides
  • Benzodiazepines
  • Cholesterol
  • asenapine
  • Olanzapine