LAUSR

Abstract Background Very little is known about the effectiveness of pharmacotherapies for delusional disorders. Methods We aimed to study the comparative effectiveness of pharmacological agents for delusional disorder using Swedish national registries to observe a national cohort of patients with delusional disorder (n = 9,076). We studied the risk of hospitalization due to psychosis and work disability among all patients who had received a diagnosis of delusional disorder (ICD-10: F22, equates to DSM-V: 297.1) in Sweden during the years 2005 – 2016 in either inpatient or specialized outpatient care (N=9,076; 53.3% men, mean age 44.1 years [std 12.5 years], mean follow-up time 4.9 years) using prospectively gathered nationwide databases for specialized outpatient care, hospitalization, work disability (sickness absence and disability pension) and dispensed medications. Persons with previous diagnoses of schizophrenia, schizoaffective disorder or bipolar disorder (F20, F25, F30-31) were excluded and the follow-up censored if any study subject received any of these diagnoses during follow up. Individuals with a hospitalization due to psychosis during the follow-up period (n = 2074) were analyzed for rehospitalization risk. Patients not already on disability pension at start of follow-up (n = 5025) were analyzed for risk of work disability. The primary analysis was a within-individual Cox proportional hazards model in order to eliminate selection bias. Analyses were adjusted for the effects of time since cohort entry, order of treatments, and current use of other treatments. Long-acting injectables were pooled into a single therapeutic group. Results are reported as hazard ratios (HRs) with 95 % confidence intervals (95% CI). Results In comparison between use and no use among specific pharmacological agents reaching statistical significance, use of clozapine (HR 0.24, 95% CI 0.07–0.77, p = 0.016), any long-acting injectable (HR 0.28, 95% CI 0.16–0.49, p < 0.0001), olanzapine (HR 0.36, 95% CI 0.20–0.67, p = 0.001) or polytherapy with any two or more antipsychotics (0.53, 95% CI 0.34–0.83, p = 0.005) was associated with a reduced risk of hospitalization due to psychosis. Almost half (n= 4051, 45%) of the patients were already on disability pension at the time of cohort entry. Among those who were not, in comparison between use and no use among specific pharmacological agents reaching statistical significance, use of clozapine (HR 0.04, 95% CI 0.01–0.23, p = 0.0004), any LAI (HR 0.33, 95% CI 0.14–0.82, p = 0.017), antipsychotic polytherapy (HR 0.47, 95% CI 0.28–0.79, p = 0.004), aripiprazole (HR 0.49, 95% CI 0.29–0.83, p = 0.009) or risperidone (HR 0.55, 95% CI 0.36–0.86, p = 0.031) was associated with a decreased risk of work disability. Discussion Although delusional disorder has been thought to be a disorder affecting mainly the dopaminergic system, use of clozapine was associated with a reduced risk of hospitalization due to psychosis and work disability in this cohort of Swedish patients with delusional disorder. Also long-acting injectables were associated with a reduced risk of hospitalization due to psychosis, which might be due to better adherence and more regular follow ups required by the injectables being only administered by healthcare staff. Nevertheless, these results indicate that clozapine and long-acting injectables might be effective in the treatment of delusional disorder patients at high risk for work disability or hospitalization due to psychosis.