Background Contemporary data relating to antipsychotic prescribing in UK primary care for patients diagnosed with severe mental illness (SMI) are lacking. Aims To describe contemporary patterns of antipsychotic prescribing in UK primary care for patients diagnosed with SMI. Methods Cohort study of patients with an SMI diagnosis (i.e., schizophrenia, bipolar disorder, other non-organic psychoses) first recorded in primary care between 2000-2017 derived from Clinical Practice Research Datalink. Patients were considered exposed to antipsychotics if prescribed at least one antipsychotic in primary care between 2000-2019. We compared characteristics of patients prescribed and not prescribed antipsychotics; calculated annual prevalence rates for antipsychotic prescribing; and computed average daily antipsychotic doses stratified by patient characteristics. Results Of 309,378 patients first diagnosed with an SMI in primary care between 2000-2017, 212,618 (68.7%) were prescribed an antipsychotic between 2000-2019. Antipsychotic prescribing prevalence was 426 (95% CI, 420-433) per 1,000 patients in the year 2000, reaching a peak of 550 (547-553) in 2016, decreasing to 470 (468-473) in 2019. The proportion prescribed antipsychotics was higher amongst patients diagnosed with schizophrenia (81.0%) than with bipolar disorder (64.6%) and other non-organic psychoses (65.7%). Olanzapine, quetiapine, risperidone, and aripiprazole accounted for 78.8% of all prescriptions. Higher mean olanzapine equivalent total daily doses were prescribed to patients with the following characteristics: schizophrenia diagnosis, ethnic minority status, male sex, younger age, and greater deprivation. Conclusions Antipsychotic prescribing is dominated by olanzapine, quetiapine, risperidone, and aripiprazole. Two thirds of patients with diagnosed SMI were prescribed antipsychotics in primary care, but this proportion varied according to SMI diagnosis. There were disparities in both receipt and dose of antipsychotics across subgroups - further efforts are needed to understand why certain groups are prescribed higher doses and whether they require dose optimisation to minimise side effects.

JFH has received consultancy fees from Wellcome Trust and funding grants from juli Health. All other authors declare no potential competing interests.

ARB is funded by the Wellcome Trust through a PhD Fellowship in Mental Health Science. This research was funded in whole or in part by the Wellcome Trust. For the purpose of Open Access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript (AAM) version arising from this submission. KKCM reports grants from the CW Maplethorpe Fellowship, the European Union Horizon 2020, the UK National Institute of Health Research, the Hong Kong Research Grant Council, the Hong Kong Innovation and Technology Commission, and reports personal fees from IQVIA, unrelated to the current work. EB acknowledges the support of: Medical Research Council (G1100583, MR/W020238/1), National Institute of Health Research (NIHR200756), Mental Health Research UK - John Grace QC Scholarship 2018, Economic Social Research Councils Co-funded doctoral award, The British Medical Associations Margaret Temple Fellowship, Medical Research Council New Investigator and Centenary Awards (G0901310, G1100583), NIHR BRC at UCLH (Biomedical Research Centre at University College London Hospitals NHS Foundation Trust and University College London). DPJO is supported by the University College London Hospitals NIHR Biomedical Research Centre and the NIHR North Thames Applied Research Collaboration. This funder had no role in study design, data collection, data analysis, data interpretation, or writing of the report. The views expressed in this article are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health and Social Care. JFH is supported by UKRI grant MR/V023373/1, the University College London Hospitals NIHR Biomedical Research Centre and the NIHR ARC North Thames.

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

East Midlands - Derby Research Ethics Committee gave ethical approval for all procedures involving patients (reference: 21/EM/0265). This study was reviewed by the Independent Scientific Advisory Committee of CPRD (protocol no. 21_000729). All data sent by GP practices to CPRD are anonymised and therefore individual patient consent was not required.

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

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I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

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I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

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Data underlying this study were accessed via Clinical Practice Research Datalink (CPRD) under approved protocol no. 21_000729. Authors are not able to share the data directly, however data can be accessed directly from Clinical Practice Research Datalink (CPRD) following approval and licensing.

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