Isolating the impact of antipsychotic medication on metabolic health: Secondary analysis of a randomized controlled trial of antipsychotic medication versus placebo in antipsychotic medication naïve first-episode psychosis (the STAGES study)

Brian O'Donoghue, Kelly Allott, Susy Harrigan, Franco Scalzo, Janine Ward, Sumudu Mallawaarachchi, Sarah Whitson, Lara Baldwin, Jessica Graham, Edward Mullen, Craig MacNeil, Stephen J. Wood, Michael Berk, Mario Alvarez-Jimenez, Andrew Thompson, Alex Fornito, Hok Pan Yuen, Barnaby Nelson, Shona M. Francey, Patrick McGorry

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Background: Cardiovascular and metabolic diseases are the leading contributors to the early mortality associated with psychotic disorders. To date, it has not been possible to disentangle the effect of medication and non-medication factors on the physical health of people with a first episode of psychosis (FEP). This study aimed to isolate the effects of antipsychotic medication on anthropometric measurements, fasting glucose and lipids. Methods: This study utilized data from a triple-blind randomized placebo-controlled trial comparing two groups of antipsychotic-naïve young people with a FEP who were randomized to receive a second-generation antipsychotic medication (FEP-medication group) or placebo (FEP-placebo group) for 6 months. Twenty-seven control participants were also recruited. Results: Eighty-one participants commenced the trial; 69.1% completed at least 3 months of the intervention and 33.3% completed the full 6 months. The FEP-placebo group gained a mean of 2.4 kg (±4.9) compared to 1.1 kg (±4.9) in the control participants (t = 0.76, p =.45). After controlling for multiple analyses, there was no difference in blood pressure, waist circumference or heart rate between the FEP-placebo group and controls. After 6 months, the FEP medication group had gained 4.1 kg (±4.5), higher than those receiving placebo but not statistically significant (t = 0.8, p =.44). There were no differences in fasting glucose or lipids between the FEP groups after 3 months. Conclusions: While limited by small numbers and high attrition, these findings indicate that some of the metabolic complications observed in psychotic disorders could be attributable to factors other than medication. This emphasizes the need to deliver physical health interventions early in the course of FEP.

Original languageEnglish
Number of pages11
JournalEarly Intervention in Psychiatry
Publication statusAccepted/In press - 2022


  • antipsychotic medication
  • metabolic syndrome
  • obesity
  • psychosis
  • schizophrenia

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