Non-neurological and metabolic side effects in the Cost Utility of the Latest Antipsychotics in Schizophrenia Randomised Controlled Trial (CUtLASS-1).

The impact of non-neurological and metabolic side effects (NNSEs) on the prescription of antipsychotics in real clinical practice remains unclear. We conducted an intention-to-treat, secondary analysis of data from a randomised, controlled trial (CUtLASS-1; n=227) to examine NNSEs emergent at 12 weeks and 52 weeks. A clinically significant difference was defined as double or half the symptoms in groups prescribed first- versus second-generation antipsychotics, represented by odds ratios greater than 2.0 (indicating advantage for first-generation drugs) or less than 0.5 (indicating advantage for the newer drugs). There were no differences between the treatment groups at baseline. At both 12 and 52 weeks follow-up, patients on second-generation drugs were more likely than their first-generation counterparts to experience cardiovascular problems and anticholinergic side effects, as well as increased sexual side effects in men. Objective weight gain was equivalent between the two groups at 12 weeks, but by one year fewer patients in the second-generation arm experienced weight gain and there was no significant difference with regard to percent change in BMI. These results suggest that there may be clinically significant increases in anticholinergic, cardiovascular, and sexual side effects for patients on second-generation drugs. The expected increased weight gain in the second-generation arm did not occur. This study provides evidence that clinicians should take a more nuanced approach toward expert antipsychotic prescription, rather than viewing the drugs as distinct classes.