AbstractBackgroundData remain scarce for the first‐line antipsychotic choice in treating delusional infestation (DI).ObjectivesWe evaluated the treatment responses associated with different antipsychotics in DI patients.MethodsWe undertook a multicentre, retrospective observational study using anonymised electronic patient records from two hospitals in the United Kingdom from 1 January 2011 to 1 January 2023. Eligible participants were adults (≥18 years) diagnosed with DI treated with an antipsychotic, and had both an assigned baseline and follow‐up Clinical Global Impression Scale (CGI‐S) score. The CGI‐S is a validated psychiatric research tool. Participants were excluded if they had known limited or non‐adherence to an antipsychotic, or if no CGI‐S scores were present at follow‐up. First clinic visits before the initiation of an antipsychotic were assigned as the baseline CGI‐S score. The last available CGI‐S score before the patient either changed antipsychotic or left the clinic for any reason was used to assign follow‐up CGI‐S scores. The primary outcome was the response to each individual antipsychotic treatment, measured by the difference in the baseline and last available follow‐up CGI‐S scores. Differences in CGI‐S changes between antipsychotic episodes were tested by analysis of variance (ANOVA).ResultsIn total, 414 patient records were analysed, and data were extracted. The mean age was 61.8 years (SD 14.1). One hundred seventy (41%) of 414 patients were men and 244 (59%) were women. In total, 156 (38%) of 414 patients were eligible, yielding a total of 315 antipsychotic prescribing episodes. The ANOVA, ranking in order of treatment response, showed that the highest mean score (expressing highest treatment response) was observed in amisulpride (31 [67%] of 46) and risperidone (95 [57%] of 167), followed by some distance by quetiapine (9 [36%] of 25), aripiprazole (13 [28%] of 46) and olanzapine (7 [25%] of 28).ConclusionsAmisulpride and risperidone were associated with a higher treatment response than quetiapine, aripiprazole and olanzapine. Amisulpride and risperidone should therefore be considered the first‐line treatment options in DI patients.