Relapse in patients with schizophrenia and amisulpride-induced hyperprolactinemia or olanzapine-induced metabolic disturbance after switching to other antipsychotics

•Antipsychotics with greater preventive efficacy (e.g. olanzapine and risperidone) may be a more suitable choice for patients with consistently normal metabolic profiles, while antipsychotics with moderate efficacy but limited metabolic side effects (e.g. amisulpride and blonanserin) would be an appropriate choice for patients who tend toward metabolic disturbance, as long as careful clinical monitoring for relapse prevention is applied.•Longer period of stable condition (>0.5 y) before changing the medication is a protective factor for relapse of schizophrenia.•Changing the medication regimen for schizophrenia patients not tolerating their original medication requires a comprehensive consideration, especially the substituted drugs and baseline clinical status. Hyperprolactinemia and metabolic disturbance are common side effects of antipsychotics that cause intolerance. Despite its potential influence on relapse, there are no established guidelines for antipsychotic switching. This naturalistic study explored the association between antipsychotic switching, baseline clinical status, metabolic changes, and relapse in patients with schizophrenia. In total, 177 patients with amisulpride-induced hyperprolactinemia and 274 with olanzapine-induced metabolic disturbance were enrolled. Relapse was determined by assessing changes in Positive and Negative Syndrome Scale (PANSS) total scores from baseline to 6 months (increased over 20% or 10% reaching 70). Metabolic indices were measured at baseline and 3 months. Patients with baseline PANSS >60 were more likely to relapse. Further, patients switching to aripiprazole had a higher risk of relapse regardless of their original medication. Participants who originally used amisulpride had reduced prolactin levels following medication change, while switching to olanzapine caused increased weight and blood glucose levels. In patients originally using olanzapine, only switching to aripiprazole reduced insulin resistance. Adverse effects on weight and lipid metabolism were observed in patients who switched to risperidone, while amisulpride improved lipid profiles. Changing schizophrenia treatment requires careful consideration of multiple variables, particularly the choice of substituted drug and the patient's baseline symptoms.