Frequently Asked Questions

Yes. In this study, patients who started a long-acting injectable (LAI) antipsychotic within 1 year of schizophrenia diagnosis had fewer psychiatric hospitalization days during continuous LAI treatment than patients who started more than 5 years after diagnosis. In the full cohort of 6,380 patients, initiation at >5 years was associated with a higher hospitalization-day ratio than initiation within 1 year (β=0.024, t=2.87, P=.004). Within the >5-year group, longer delay to LAI initiation was also associated with greater hospitalization burden (β=3.69×10−5, t=2.53, P=.011).

Later LAI initiation was associated with lower risk of LAI treatment discontinuation than initiation within the first year. Compared with patients who started within 1 year of diagnosis, the hazard ratios for discontinuation were lower at 2–3 years (HR=0.774; 95% CI, 0.692–0.866; P<.001), 3–4 years (HR=0.768; 95% CI, 0.682–0.864; P<.001), 4–5 years (HR=0.698; 95% CI, 0.613–0.794; P<.001), and >5 years (HR=0.657; 95% CI, 0.586–0.736; P<.001). The authors interpreted this as indicating higher discontinuation risk among those who began LAIs within the first year.

Among patients who had psychiatric hospitalization during LAI treatment, earlier initiation was associated with lower hospitalization burden. In this subgroup (N=2,109), compared with starting within 1 year, starting at 1–2 years (β=0.039, t=2.06, P=.039), 3–4 years (β=0.057, t=2.57, P=.010), and >5 years (β=0.162, t=7.71, P<.001) was associated with higher hospitalization-day ratios.

Within-group analyses also showed that longer delay to LAI initiation was associated with greater hospitalization burden in the <1-year group (β=2.02×10−4, t=2.12, P=.034), the 4–5-year group (β=3.45×10−4, t=2.22, P=.028), and the >5-year group (β=1.87×10−4, t=4.96, P<.001).

Yes. The mean time from schizophrenia diagnosis to LAI initiation fell markedly over the study period, from 1,980.8 days in 2011 to 133.4 days in 2020. This indicates a clear temporal shift toward earlier LAI use in routine practice. Over the same period, mean continuous LAI treatment duration before discontinuation declined from 646.1 days to 246.4 days.

Early initiation was still relatively uncommon: 30.5% of the 6,380 patients started LAI treatment within the first year after diagnosis. The cohort included patients with incident schizophrenia who went on to receive continuous LAI treatment, defined as at least 7 consecutive LAI prescriptions with no gap longer than the expected injection interval plus a 28-day grace period.

Paliperidone palmitate 1-month formulation (PP1M) was the most commonly prescribed LAI throughout the study period. It accounted for 76.9% of initial LAI prescriptions in 2011 and 65.2% in 2020. Aripiprazole monohydrate increased from 19.8% in 2011 to 43.5% in 2017, then declined to 33.8% in 2020; haloperidol decanoate, risperidone microspheres, and paliperidone 3-month formulation were used infrequently.

The main hospitalization outcome was the proportion of psychiatric hospitalization days during the continuous LAI treatment period. The authors reconstructed hospitalization episodes from monthly claims using an episode-of-care approach, applied a 1-day clean period to separate consecutive admissions, and treated psychiatric readmissions within 30 days as continuation of the previous hospitalization episode. Total psychiatric hospitalization days were then divided by the duration of the LAI treatment period to calculate the hospitalization-day ratio.

The results come from administrative claims data and show associations, not proof that earlier LAI initiation directly caused better outcomes. The database lacked key clinical variables such as symptom severity, functional status, and patient insight; continuous treatment was inferred from prescription patterns rather than confirmed medication receipt; and unmeasured confounding may remain despite adjustment for age, sex, and year of diagnosis.

Additional limitations were that concurrent oral psychotropic use could have influenced outcomes, analyses were not stratified by LAI type, the study focused on hospitalization during continuous LAI use rather than intermittent use or post-discontinuation effects, and some patients classified as incident schizophrenia may have had prior psychotic episodes before study registration.