Frequently Asked Questions

In the EPINET sample, 23.7% of participants received a long-acting injectable antipsychotic and 5.6% received clozapine at some point in treatment. Specifically, among 5,324 participants with medication data, 1,261 received an LAI and 297 received clozapine.

Prescribing varied markedly across both hubs and clinics. Across the 8 EPINET hubs, LAI use ranged from 5.0% to 37.5% and clozapine use ranged from 1.7% to 9.0%. Across 113 clinics, the proportion receiving LAIs ranged from 0.024 to 0.60 and the proportion receiving clozapine ranged from 0.005 to 0.33.

No. Clinic-level variation in LAI and clozapine prescribing remained significant after adjustment for biological sex, ethnicity, and racial background. Hub-level LAI variability also remained significant after adjustment for ethnicity and race, but not after adjustment for biological sex (P=.07); unadjusted hub-level variation in clozapine prescribing was not significant (P=.12) and was only marginally significant after adjustment for race (P=.042).

Yes. Men were more likely than women to be prescribed both medication types. For LAIs, males had higher utilization than females (logOdds=1.11, SE=0.099, P<.00001), and for clozapine, males also had higher utilization (logOdds=0.83, SE=0.17, P<.00001).

Yes for LAIs, but not clearly for clozapine. African American participants had higher LAI prescribing rates than White participants (logOdds=0.47, SE=0.079, P<.000001), while the difference for clozapine was not statistically significant (logOdds=-0.29, SE=0.16, P=.067). There were no significant differences between Hispanic and non-Hispanic participants for LAIs (logOdds=0.14, SE=0.098, P=.14) or clozapine (logOdds=0.37, SE=0.20, P=.059).

An LAI trial can help clarify whether persistent symptoms reflect nonadherence or true inadequate response because LAIs provide a more conclusive assessment of whether medication is actually being taken. The article cites TRIPP Working Group guidelines recommending a trial of an LAI before confirming treatment-resistant schizophrenia, and notes that in one report, one-third of patients referred to a treatment-resistant schizophrenia program had subtherapeutic or nondetectable antipsychotic blood levels.

The article suggests that large site-level differences in clozapine use may reflect the logistical burden of prescribing clozapine, including mandatory hematologic monitoring, intensive side-effect management, clinic resources, and prescriber expertise. The authors also discuss broader contributors to variability such as clinician attitudes and training, administrative barriers, support services, leadership support, and insurance or policy issues.

This was an observational analysis of EPINET coordinated specialty care data rather than a randomized treatment trial. The dataset included 16,847 Core Assessment Battery assessments from 5,324 participants across 113 clinical sites associated with 8 hubs, using the most recent cumulative consolidated dataset dated June 18, 2024. Participants were counted as receiving clozapine or an LAI if they received those agents at any point in treatment.

• The data came from 8 hubs and 113 clinics, and the smaller number of hubs may have limited the ability to detect hub-level differences in clozapine rates.
• EPINET clinics may not fully represent all coordinated specialty care clinics in the United States or first-episode programs outside the United States.
• Medication data reflect prescriptions recorded at Core Assessment Battery time points, so medications prescribed between assessments were not captured.
• The dataset did not include information on patient, clinician, or family treatment preferences in shared decision-making.
• The authors could not determine the extent of clozapine underutilization because they did not have cohort-specific data on how many patients met indications for clozapine.
• Missing data may have limited generalizability.

The findings suggest that use of evidence-based medications in coordinated specialty care is inconsistent and that very large differences between clinics are unlikely to be explained only by patient demographics. The authors state that the variability strongly suggests underutilization at some clinics and argue that implementation strategies at the clinic and hub level, including staff education, training, practice facilitation, and organizational support, may be needed to improve appropriate use of LAIs and clozapine.