Lithium or Valproate Adjunctive Therapy to Second-generation Antipsychotics and Metabolic Variables in Patients With Schizophrenia or Schizoaffective Disorder

J Psychiatr Pract. 2016 May;22(3):175-82. doi: 10.1097/PRA.0000000000000149.


Objective: People with schizophrenia are at greater risk for cardiovascular disease and their overall mortality rate is elevated compared to the general population. The metabolic side effects of antipsychotic medications have been widely studied; however, the effect of adding conventional mood stabilizers, such as lithium and valproate, to antipsychotic medication has not been assessed in terms of metabolic risk. The primary purpose of this secondary analysis was to examine whether treatment with lithium or valproate in addition to a second-generation antipsychotic is associated with poorer metabolic outcomes than treatment with a second-generation antipsychotic without lithium or depakote.

Methods: Baseline data from 3 studies, which included measurement of body mass index, waist circumference, fasting glucose, insulin, homeostatic model assessment of insulin resistance, insulin sensitivity index, glucose utilization, and acute insulin response to glucose, were included in the analysis.

Results: No differences were found between those taking lithium or valproate and those who were not in terms of fasting glucose, fasting insulin, and homeostatic model assessment of insulin resistance. Insulin sensitivity was lower among participants taking lithium or valproate. Participants taking lithium or valproate had a higher body mass index than those not taking conventional mood stabilizers, although the difference did not reach statistical significance.

Conclusions: These cross-sectional findings suggest it may be beneficial to monitor insulin sensitivity and body mass index in patients taking lithium or valproate in combination with a second-generation antipsychotic.

MeSH terms

  • Adult
  • Antimanic Agents / adverse effects*
  • Antipsychotic Agents / adverse effects*
  • Blood Glucose / drug effects*
  • Body Mass Index*
  • Cross-Sectional Studies
  • Drug Therapy, Combination
  • Female
  • Humans
  • Insulin / blood*
  • Lithium Compounds / adverse effects*
  • Male
  • Middle Aged
  • Psychotic Disorders / drug therapy*
  • Schizophrenia / drug therapy*
  • Valproic Acid / adverse effects*


  • Antimanic Agents
  • Antipsychotic Agents
  • Blood Glucose
  • Insulin
  • Lithium Compounds
  • Valproic Acid