The Effects of Antipsychotic Dose Reduction on Movement Disorders and Cardiometabolic Indices in Patients Remitted from a First Episode of Psychosis

Background and Hypothesis: The extent to which tapering antipsychotic (AP) attenuates AP-related movement disorders and cardiometabolic dysfunction remains unclear. We aim to investigate the long-term effects of AP-dose reduction on these adverse effects in patients remitted from a first episode of psychosis (FEP). Study Methods: We included 293 FEP participants from the HAMLETT trial. Movement disorders were assessed using the St. Hans Rating Scale (SHRS) and Barnes Akathisia Rating Scale. Cardiometabolic indices included body mass index (BMI), waist circumference, blood pressure (BP), glucose, triglycerides, and cholesterol. Linear mixed-effects models assessed longitudinal relationships between AP-dose reduction, movement disorders and cardiometabolic indices. Study Results: Over an average 29-month follow-up (SD = 19), a 1 mg olanzapine equivalent dose reduction from baseline was associated with a 0.013-point decrease in Parkinsonism (95% CI, −0.019, −0.006), a potential 0.003-point decrease in tardive dyskinesia (95% CI, −0.006, −0.000) on SHRS (range 0-6), and decreases of 0.037 (0.15%) kg/m² in BMI (95% CI, −0.059, −0.015), 0.153 (0.17%) cm in waist circumference (95% CI, −0.265, −0.037), 0.023 (0.47%) mmol/L in total cholesterol (95% CI, −0.039, −0.007), 0.018 (0.60%) mmol/L in low-density lipoprotein cholesterol (95% CI, −0.032, −0.003), and 0.021 (0.58%) mmol/L in nonhigh-density lipoprotein cholesterol (95% CI, −0.037, −0.005). We found no evidence for an association with tardive dystonia, akathisia, BP, glucose, or triglycerides. Conclusions: AP-dose reduction modestly benefits AP-related Parkinsonism, weight gain, cholesterol levels and potentially tardive dyskinesia in patients after FEP over time. These benefits should be carefully weighed against the risks of relapse and suicide.