How do antipsychotic agents affect glucose, lipid metabolism, and weight gain in patients with schizophrenia?

Updated: Mar 16, 2018
  • Author: Frances R Frankenburg, MD; Chief Editor: Glen L Xiong, MD  more...
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A Danish study of the risk for diabetes with antipsychotics compared nearly 346,000 individuals who purchased antipsychotics and nearly 1.5 million unexposed individuals and concluded that the rate ratio (RR) for risk with first-generation antipsychotics was 1.53, whereas the RR varied widely for second-generation antipsychotics (1.32; range, 1.17-1.57). [106]

Stroup et al studied 215 patients whose psychotic symptoms were stabilized on olanzapine, quetiapine, or risperidone. [107] After 24 weeks, those who switched to aripiprazole had improved cholesterol levels and other metabolic factors, and they lost more weight than those who stayed on their original medication. Relapse or worsening of psychotic symptoms occurred no more frequently in patients who switched medications than in those who stayed on their original medication. However, patients who switched to aripiprazole were more likely to discontinue the assigned medication: 43.9% of those who switched discontinued their medication, whereas 24.5% of those who stayed on their original medication discontinued it. They concluded patients experiencing cardiovascular or metabolic adverse effects of an antipsychotic medication may fare better if they switch to a different agent, provided they are closely monitored.

Weight gain is associated both with psychological problems (eg, decreased self-esteem) and with medical problems (eg, diabetes, coronary artery disease, and arthritis). Education about nutrition and exercise should be provided. Cognitive-behavioral therapy can be tried.

It is unclear whether weight-reducing drugs should be added to antipsychotic therapy. In one randomized, placebo-controlled study conducted in 72 patients with first-episode schizophrenia who gained more than 7% of their predrug weight, metformin (1000 mg/day) was effective and safe in attenuating antipsychotic-induced weight gain and insulin resistance. [108]

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