Frequently Asked Questions

Yes. In this hospital database analysis of patients with bipolar I disorder, long-acting injectable antipsychotics were associated with lower BD-Irelated rehospitalization rates than oral antipsychotics at 30 days (3.9% vs 5.0%; P=.033) and 60 days (5.9% vs 7.2%; P=.030). At 90 days, the BD-Irelated rehospitalization rate was also lower with LAIs (7.4% vs 8.5%), but that difference was not statistically significant (P=.064).

Yes. The second-generation LAI subgroup had lower BD-Irelated rehospitalization rates than the oral antipsychotic group at 30 days (3.6% vs 5.4%; P=.010), 60 days (5.2% vs 7.5%; P=.008), and 90 days (6.8% vs 9.1%; P=.015). For all-cause rehospitalization, second-generation LAIs were associated with significantly lower rates at 60 days (9.2% vs 11.4%; P=.036) and 90 days (11.4% vs 13.9%; P=.023), while the 30-day difference was numerically lower but not statistically significant (6.4% vs 7.9%; P=.094).

Patients discharged on LAIs had a lower adjusted risk of BD-Irelated rehospitalization than those discharged on oral antipsychotics within 30 days (HR 0.784; 95% CI, 0.6260.981) and 60 days (HR 0.818; 95% CI, 0.6800.984). The 90-day result also favored LAIs but was not statistically significant (HR 0.856; 95% CI, 0.7261.011).

The effect was stronger for second-generation LAIs, which were associated with lower BD-Irelated rehospitalization risk at 30 days (HR 0.653; 95% CI, 0.4690.909), 60 days (HR 0.692; 95% CI, 0.5260.911), and 90 days (HR 0.742; 95% CI, 0.5820.945).

Not for the overall LAI group. All-cause rehospitalization rates and risks were lower numerically for LAIs than for oral antipsychotics, but those differences were not statistically significant. In contrast, the second-generation LAI subgroup had significantly lower all-cause rehospitalization at 60 days (9.2% vs 11.4%; P=.036) and 90 days (11.4% vs 13.9%; P=.023), with a numerically lower but nonsignificant 30-day rate (6.4% vs 7.9%; P=.094).

The absolute benefit was modest. At 30 days, the absolute risk reduction for all LAIs was 1.1%, corresponding to an approximate number needed to treat of 91. For second-generation LAIs, the absolute risk reduction was 1.8% at 30 days, corresponding to an approximate number needed to treat of 56, and increased to 2.3% at 60 days, with an approximate number needed to treat of 43.

No clear difference was found. The average length of stay for BD-Irelated and all-cause rehospitalization within 30, 60, and 90 days was statistically similar between LAI, second-generation LAI, and oral antipsychotic groups.

For example, for BD-Irelated rehospitalization in the overall LAI versus oral antipsychotic groups, mean length of stay was 10.8 vs 11.0 days within 30 days, 10.1 vs 10.4 days within 60 days, and 9.9 vs 10.1 days within 90 days.

LAIs were used infrequently. Of 98,088 eligible hospitalized patients with bipolar I disorder, 76,608 (78.1%) received an oral antipsychotic at discharge, while only 2,334 (2.4%) received an LAI. In the same cohort, 9,105 (9.3%) received a mood stabilizer and 10,041 (10.2%) received none of these medication categories at discharge.

No. Among patients discharged on an oral antipsychotic at the index hospitalization, most remained on oral treatment at rehospitalization within 3090 days (84.4%86.4%). By contrast, only 38.9%41.4% of patients discharged on any LAI and 35.4%37.0% of those discharged on a second-generation LAI were maintained on an LAI at rehospitalization over the same time frame.

In exploratory analyses, patients who continued LAIs at first rehospitalization appeared to have lower rates of second rehospitalization than those who switched to oral antipsychotics. The authors noted, however, that most of these differences were not statistically significant, so this finding should be interpreted cautiously.

This was a retrospective cohort study using the Premier Hospital database from October 2020 through September 2023. Eligible patients were adults aged 18 years or older with a primary or admitting diagnosis of bipolar I disorder and at least 3 months of data before and after the index hospitalization.

To compare outcomes fairly, the investigators used 1:4 propensity-score matching and then assessed rehospitalization with adjusted Cox proportional hazards models. Because this was an observational database study rather than a randomized trial, the findings show association, not proof that LAIs caused the lower rehospitalization rates.

The main limitations were potential misdiagnosis of BD-I, treatment selection bias in routine practice, residual confounding despite propensity-score matching, and missing information on factors such as disease severity, prior treatment history, care received outside the same hospital, medication adherence, clinician practice patterns, and patient preferences. The authors also noted a possible exposure misclassification because the LAI group was defined by receiving an LAI during hospitalization, whereas the oral antipsychotic group was defined by treatment at discharge.

Additional limitations included the study period overlapping with the COVID-19 pandemic, lack of baseline information on LAI use in the prior 3 months, multiple comparisons without formal correction, and no separate analysis of first-generation LAIs. These issues mean the results should be interpreted with caution.