Fewer Than 1 in 5 Young Patients With First-Episode Psychosis Adhere to Antipsychotics

Fewer than 1 in 5 adolescents and young adults who start antipsychotic treatment after a first episode of psychosis (FEP) remain adherent over the following year, according to a recent retrospective cohort study. Adherence was associated with more behavioral health outpatient visits and fewer emergency department (ED) visits.¹

This is especially important as evidence shows that adolescents and young adults with FEP had a 6.92-fold higher hazard of all-cause mortality than those in the general outpatient population.²

About the Study

Investigators analyzed administrative claims from the Merative MarketScan commercial insurance database from January 1, 2013, to December 31, 2021. Of 27,592 individuals aged 15 to 40 years identified with FEP, 11,889 (43.1%) went on to fill a first antipsychotic prescription and made up the analytic cohort. Participants had a mean (SD) age of 22.7 (6.8) years, and 6708 (56.4%) were male. Adherence was measured over the 365 days following the index antipsychotic prescription using the proportion of days covered (PDC), with a PDC of 0.8 or greater defined as adherent. Schizophrenia spectrum disorders accounted for 43.0% of the cohort, mood disorders with psychotic features for 42.5%, and other psychotic spectrum disorders for 14.5%.

On average, participants had antipsychotic coverage for 43.3% of days, or 158 of 365 days, in the year after initiation. Overall, 2270 of 11,889 individuals (19.1%) met the adherence threshold.

Adherence Varies by Diagnosis

Adherence varied by diagnosis: 23.1% (1181 of 5111) of patients with schizophrenia spectrum disorder, 16.9% (857 of 5058) with mood disorders with psychotic features, and 13.5% (232 of 1720) with other psychotic spectrum disorders were adherent. In multivariable log-binomial regression, adherence was more prevalent among those with schizophrenia spectrum disorders (prevalence ratio [PR], 1.78; 95% CI, 1.57-2.04; P < .001) and mood disorders with psychotic features (PR, 1.21; 95% CI, 1.06-1.39; P = .005) compared with individuals with other psychotic spectrum disorders. No significant differences were found by sex, Charlson Comorbidity Index score, autism spectrum disorder, or posttraumatic stress disorder.

The investigators noted prior studies using the same PDC measure reported adherence of 35.4% to 52.5% in chronic schizophrenia populations drawn from Medicare and Medicaid data, where mean ages ranged from 42.9 to 55 years. They suggested younger patients may have limited insight into illness severity, uncertainty about long-term treatment, and concerns about adverse effects such as weight gain, sexual adverse effects, and sedation. Patients newly entering care may have fewer established connections with mental health services. A sensitivity analysis that counted antipsychotics, antidepressants, and mood stabilizers together raised the adherence rate to 32.7% (3891 of 11,889), suggesting that low antipsychotic adherence does not always reflect complete disengagement from medication treatment.

Fewer ED Visits for Adherent Patients

In negative binomial models, adherent patients had fewer ED visits (incidence rate ratio [IRR], 0.85; 95% CI, 0.81-0.90; P < .001), more behavioral health outpatient visits (IRR, 1.53; 95% CI, 1.47-1.59; P < .001), and more general outpatient visits (IRR, 1.07; 95% CI, 1.02-1.13; P = .003). Adherence was not significantly associated with psychiatric hospitalization (IRR, 0.99; 95% CI, 0.83-1.17; P = .88) or general hospitalization (IRR, 0.96; 95% CI, 0.88-1.05; P = .39). The authors described nonadherence as associated with a shift in the site of care from outpatient services toward acute settings, which may fragment treatment and limit continuity with outpatient clinicians.

LAI Use Still Rare

Long-acting injectable (LAI) antipsychotics were uncommon at treatment initiation. Of the patient cohort, 95.4% received oral antipsychotics exclusively, 0.5% received LAIs exclusively, and 3.9% used both formulations. The investigators wrote that, given evidence linking LAIs to improved adherence and reduced relapse, this underuse points to a potential gap in early treatment strategies, and greater consideration of LAIs during the initial treatment phase may reduce reliance on acute care.

Limitations include reliance on claims data, which cannot capture medications administered during hospitalization or whether filled prescriptions were taken. The authors concluded that low adherence may be a hurdle for initiatives aiming to improve psychosis outcomes, and that improving adherence and outpatient continuity during early psychosis may help reduce acute care use. They called for future research characterizing longitudinal medication trajectories during early psychosis.

References

1. Chi E, Sridhar S, Montesano V, et al. Treatment adherence and health care utilization after a first episode of psychosis. JAMA Netw Open. 2026;9(9):e2635805.

2. Simon GE, Stewart C, Yarborough BJ, et al. Mortality rates after the first diagnosis of psychotic disorder in adolescents and young adults. JAMA Psychiatry. 2018;75(3):254-260.