Long-Acting Injectable Antipsychotics May Benefit Patients With Severe Mental Illness

Long-acting injectable antipsychotics could reduce hospital time in unselected patient populations who maintain adherence, but may increase adverse events.

Unselected patient populations with severe mental illness may benefit from treatment with long-acting injectable antipsychotics (LAIs) with maintained adherence translating to less time hospitalized; however, the cost of this benefit is the occurrence of more adverse events over time and use of more antipsychotics, according to study findings published in Schizophrenia.

Among the major issues for patients with severe mental disorders is treatment adherence. Injectable LAIs may improve adherence and therefore long-term outcomes.

Investigators sought to compare use of psychotropic medications, adherence/attitude, psychopathology, hospitalization, and adverse events 1-year before and 1-year after a first injectable LAI in unselected patients with severe mental illness.

They conducted an observational mirror-image study (STAR Network Depot Study) that included 261 LAI-naive participants at least 18 years of age between 2015 and 2018.

LAI continuers spent less time hospitalized, but received more antipsychotics and suffered from more cumulative adverse events over time.

Participants (mean age 41.4±13.4 years, 41% women, 87.7% Italian) diagnosed with schizophrenia spectrum disorders (71.3%), bipolar disorders (21.8%), or personality disorders (6.9%), followed under real-world clinical practice. Psychotropic medications, adherence/attitude, psychopathology, hospitalization, and adverse events 1-year before and 1-year after a first LAI were compared. Overall, there were low levels of social support; 53% of participants lived with parents/relatives, 86% were unmarried, and 54% were unemployed. According to the study, 10% of participants had disease onset before 18 years of age, and 49% had onset between 18 and 30 years. The majority of participants received their diagnosis at least 6 years prior to recruitment.

The patients with obsessive-compulsive disorder, dementia, intellectual disability, substance-related psychosis, not LAI-naive, or lacking follow-up data were excluded. The participants were followed along clinical trajectories of LAI continuers (n=184) and LAI discontinuers (n=77). Among LAI discontinuers, 21 experienced adverse events, 19 were nonadherent, 19 switched to oral antipsychotics, 3 lacked clinical benefit, and 15 had missing information.

Overall, LAI discontinuers had lower adherence scores, lower attitude scores, and shorter illness duration at baseline. Among the 186 participants with schizophrenia spectrum disorders, 29.5% discontinued the LAI in less than 1 year (with about half discontinuing the treatment in the first trimester of follow-up).

The investigators noted that the LAI continuers had reduced hospital admissions in mirror-image analysis (P <.001) (mean number of admissions decreased from 0.86 [standard error {se}, 0.08 to 0.35 [se, 0.06]). LAI discontinuers had a nonsignificant reduction from 0.79 (se, 0.09) to 0.55 (se, 0.12; P =.059).

While LAI continuers spent fewer days hospitalized, they had more prescribed antipsychotics and suffered more adverse events; however, cumulative dose and overall cumulative dose for all psychotropic drugs remained nearly unchanged. LAI discontinuers saw significant decreases in the number of antipsychotics prescribed over time, cumulative dose, and overall cumulative dose for all psychotropic drugs. A stronger increase in cumulative medication-related adverse events was noted in continuers vs discontinuers, with a significant increase throughout follow-up only for continuers.

Sensitivity analysis, which included only participants with schizophrenia spectrum disorders (n=186), showed statistical significance for reduction in hospital admissions and days hospitalized for LAI continuers and discontinuers. It also showed no statistical differential change between continuers and discontinuers over time for hospital admissions and days hospitalized.

Study limitations include the observational design preventing establishment of causal link; the reduction of overall sample size by including only LAI-naive participants, thereby reducing statistical power; introduction of study population heterogeneity by including participants with various diagnoses; and an inability to determine the impact of adverse events on quality of life.

“LAI continuers spent less time hospitalized but received more antipsychotics and suffered from more cumulative adverse events over time,” the investigators concluded. They added, “This study shows that LAIs might be beneficial in unselected patient populations, provided that adherence is maintained.” They urged clinicians to carefully weigh the matter of initiating LAIs on a case-by-case basis.

Disclosure: One of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

This article originally appeared on Psychiatry Advisor


Ostuzzi G, Tedeschi F, Bertolini F, et al. Clinical trajectories of individuals with severe mental illness continuing and discontinuing long-acting antipsychotics: a 1-year mirror-image analysis from the STAR Network Depot study. Schizophrenia. Published online April 17, 2023. doi:10.1038/s41537-023-00342-3