Study Identifies Homelessness as a Predictor Against Clozapine Use

Kathleen Shangraw, MD

Credit: University of Utah

For the first time, a study identified homelessness as a predictor against clozapine use. The research also saw, like previous studies, that minority status impacted clozapine prescription patterns, with Black individuals having greater clozapine prescriptions.¹

“To our knowledge, housing status has not been previously described as a predictor against clozapine initiation, which raises important ethical and clinical considerations,” wrote investigators, led by Kathleen Shangraw, MD, from the department of psychiatry at the University of Utah. “Prescribers may be less likely to prescribe clozapine to homeless patients due to anticipated medication non‐adherence or loss to follow‐up.”

The team added how severe, non-treated mental illness increases the likelihood of homelessness, and clozapine treatment could help ease psychiatric symptoms which can help individuals function and potentially improve financially.

“In this sense, consideration of early clozapine initiation in eligible patients is particularly important in this patient population,” investigators continued.

Clozapine, although effective for treatment-resistant schizophrenia spectrum disorders and considered a gold-standard therapy, remains underutilized. Investigators sought to identify factors impacting clozapine prescription patterns among patients with treatment-resistant schizophrenia and schizoaffective disorder. They examined demographic, socioeconomic, medical, and psychiatric characteristics to determine predictors for starting clozapine.

The retrospective combined cohort and case-control study included individuals who participated in ≥ 2 prior antipsychotic trials and were admitted to a University of Utah inpatient psychiatric facility from January 2014 – March 2021. The team compared patients who did and did not receive clozapine during the index hospitalization. In total, 12% received clozapine during the index admission.

Black patients were twice as likely to receive clozapine than White or Hispanic patients (odds ratio [OR], 2.18; 95% confidence interval [CI], 1.20 – 3.97; P = .008). This finding contradicts early studies which had shown minority groups have underutilization of clozapine.²

“The reason for this is unclear, though confounding by medical comorbidity may play a role,” investigators wrote.¹ “A greater incidence of benign ethnic neutropenia (BEN), cardiovascular and metabolic comorbidities have been proposed as contributors to underutilization among Black and African‐American patients It is worth noting that no analyses accounted for BEN in the aforementioned systematic review studies.”

The team noted they did not specifically control for these potential confounders, but post-hoc analyses showed no difference in contraindication to clozapine between racial groups for the history of neutropenia, diabetes, and cardiovascular disease.

The study showed no relationship between starting clozapine and a history of suicide attempts, violent behavior, or substance use. The team was surprised by this since clozapine is FDA-approved for reducing suicidal behavior in schizophrenia-spectrum disorders.

Furthermore, the case-control analysis demonstrated patients with more psychiatric admissions (OR, 1.4; P = .079) and antipsychotic trials (OR, 1.40; P = .038) had greater odds of receiving clozapine.

“These findings are important to emphasize since patients who receive clozapine earlier in the disease course are more likely to respond,” investigators wrote.

Moreover, clozapine recipients and non-recipients had similar rates of homelessness based on the EMR flagging system (15% vs 21.28%; P = .45). However, a manual review of charts revealed a substantially lower rate of homelessness in the clozapine recipients compared to the non-receipts group (5% vs. 21%; P = .0016). The study ultimately identified homelessness as a predictor against clozapine use (OR, 2.77; 95% confidence interval [CI], 1.24 – 6.19; P = .014).

“Our findings… identify differential clozapine prescribing patterns in minority and homeless patients, introducing potential areas of intervention for clinical practice and healthcare policies,” investigators concluded.

References

1. ^{Shangraw K, Schmutz C, Dowdle T, Kelley R, Porter C, Reynolds M, Schwartz Z, Sutton O, Kious B. Medical, Psychiatric, and Sociodemographic Predictors of Clozapine Initiation at an Academic Medical Center. Psychiatr Res Clin Pract. 2024 Jun 28;6(3):104-111. doi: 10.1176/appi.prcp.20240056. PMID: 39568504; PMCID: PMC11574452.}
2. ^{Williams JC, Harowitz J, Glover J, Tek C, Srihari V. Systematic review of racial disparities in clozapine prescribing. Schizophr Res. 2020 Oct;224:11-18. doi: 10.1016/j.schres.2020.07.023. Epub 2020 Nov 10. PMID: 33183948.}