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Treating Unmet Needs in Psychiatry (TUNE-UP): A Targeted Service Increases Outpatient Initiations of Clozapine

Ahmad Khan, Z.; Varvari, I.; Mancini, V.; Zita Zauchenberger, C.; Kantor, S.; Fanshawe, J.; Musiiwa, S.; Pledge, A.; Pearce, B.; de la Motte, S.; Quested, D.; Maughan, D.; McGuire, P.; Howes, O.; Pillinger, T.; McCutcheon, R.

2025-04-04 psychiatry and clinical psychology
10.1101/2025.04.04.25325236 medRxiv
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BackgroundUp to one-third of patients with schizophrenia do not benefit from standard antipsychotic treatment - termed treatment-resistant schizophrenia (TRS). Clozapine is the only licensed treatment in TRS and is associated with better outcomes. However, it is underused, as its initiation is often limited by the need for inpatient admission, which is costly and unattractive to patients. Community clozapine titration services may address this. AimsTo describe a targeted outpatient clinic (TUNE-UP) for TRS management and assess its impact on clozapine initiation rates. MethodWe reviewed clozapine titrations for patients under four community mental health teams in the United Kingdom from September 2021 to January 2025, noting whether titration occurred in inpatient or outpatient settings. The TUNE-UP clozapine clinic operated for 12 months (September 2023 to September 2024). Initiation rates during the TUNE-UP period were compared with rates when the service was unavailable using Poisson regression. Clinical outcomes were assessed using scales such as the Positive and Negative Syndrome Scale (PANSS) for symptom severity and the Social and Occupational Functioning Assessment Scale (SOFAS) for functioning. Results61 individuals were commenced on clozapine. During the TUNE-UP clinics operation, community initiation rates increased to 11.0 per year (up from 1.33 per year when the service was unavailable), while inpatient initiations were similar (11.0 per year vs. 11.67 per year). Increases in total initiations (p = 0.048) and community initiations (p = 0.0003) were statistically significant. Patients seen by TUNE-UP had improvements in PANSS (mean baseline 63.3 (SD 18.3); mean improvement 20.5 (SD 12.2; p = 0.009)), and SOFAS (mean baseline 48.3 (SD 7.5); mean improvement 8.8 (SD 7.1, p = 0.028)). ConclusionA specialist community service was associated with a significant increase in clozapine initiations alongside improved clinical outcomes. This approach offers a clinically and cost-effective strategy to enhance treatment for TRS.

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