Time to clozapine initiation in treatment-resistant schizophrenia in the United Arab Emirates: retrospective cohort study with international benchmarking

Abstract

Background Clozapine is the only antipsychotic with demonstrated efficacy in treatment-resistant schizophrenia, but remains underutilised worldwide, with limited data from the Middle East and North Africa. Aims We examined clozapine initiation, delays and outcomes in a large United Arab Emirates (UAE) cohort. Method We conducted a retrospective cohort study of patients prescribed antipsychotics at a tertiary psychiatric hospital in the UAE (2018–2025). Treatment resistance was defined as two or more distinct sequential adequate antipsychotic trials, each for at least 6 weeks and at a drug-specific therapeutic dose (defined daily dose method). Outcomes were clozapine initiation, time to initiation, guideline concordance (within 3 months) and hospital admissions. Results Of 6256 patients with schizophrenia spectrum diagnoses prescribed antipsychotics, 1738 (27.8%) met treatment-resistance criteria. Clozapine was initiated in 129 (7.4%; 95% CI 6.3–8.8%), comparably between expatriates and nationals (7.7 v. 7.1%; p = 0.72). Among 76 delayed initiators, median delay was 13.2 months (interquartile range 2.2–32.5) and 26.3% were guideline-concordant. The number of adequate trials most strongly predicted initiation (adjusted odds ratio 1.98, 95% CI 1.70–2.30; p < 0.001). Delayed initiation was associated with higher hospital admission rates (adjusted incidence rate ratios 2.5–2.6 for delays up to 24 months; p < 0.05), although an exploratory propensity-weighted analysis was underpowered (β = −2.57; p = 0.12). Conclusions Clozapine remains underutilised in this setting, with fewer than 1 in 12 treatment-resistant patients receiving it and only a quarter of delayed initiators achieving guideline-concordant timing. These findings highlight an evidence-to-practice gap and support strategies for earlier clozapine access.