Long-Acting Injectable Antipsychotics May Delay Time to First Hospitalization in Early-Phase Schizophrenia

injection in arm
injection in arm
Compared with usual treatment, the use of long-acting injectable antipsychotics significantly increased the time to first hospitalization in patients with early-phase schizophrenia.

Long-acting injectable antipsychotics significantly increased time to first hospitalization in patients with early-phase schizophrenia, according to a study published in JAMA Psychiatry.

Many patients with schizophrenia struggle with relapse and hospitalization. One factor in this struggle may be treatment non-compliance. Long-acting injectable antipsychotics have the potential to increase compliance in patients with schizophrenia. However, many physicians are reluctant to prescribe LAIs until after patients with schizophrenia have experienced multiple hospitalizations and relapses. It may be beneficial to start long-acting injectable antipsychotics earlier in the course of schizophrenia, as patients are less responsive to the same treatment after a second episode of psychosis.

Randomized clinical trials have provided conflicting data on the beneficial effect of long-acting injectable antipsychotics in first episode and early-phase schizophrenia. The conflicting data may result from greater treatment adherence in patients enrolled in clinical trials than patients in the general population.

The Prevention of Relapse in Schizophrenia (PRELAPSE; ClinicalTrials.gov identifier NCT02360319) study used cluster randomization at the clinical level to more closely represent adherence in the general population of schizophrenia patients. Researchers collected data from 19 clinics that provided long-acting injectable antipsychotics treatment with long-acting aripiprazole monohydrate once monthly, and 20 clinics that provided antipsychotic medication treatment as usual. The inclusion criteria for participants (n=489; 75.3% men) included a schizophrenia diagnosis confirmed by the Structured Clinical Interview for DSM-5, Research Version (SCID-5), less than 5 years of lifetime antipsychotic use, age of 18 to 35, and ability to give consent. Patients were followed for 2 years, during which time data on hospitalizations and emergency department and crisis unit use was collected via monthly phone interviews and confirmed via hospital records or other sources.

Overall, treatment with long-acting aripiprazole monohydrate increased the time to first hospitalization and non-significantly reduced total number of hospitalizations compared to the standard antipsychotic treatment.

The mean survival time until first hospitalization was greater with long-acting aripiprazole monohydrate treatment (613.7 days; 95% CI, 582.3-645.1 days) than with standard care (530.6 days; 95% CI, 497.3-563.9 days). This difference indicated superiority of treatment with long-acting aripiprazole monohydrate (HR 0.56; 95% CI, 0.34-0.92; P =.02). The number needed to treat was 7 when comparing long-acting aripiprazole monohydrate with standard of care.

Limitations to the study included potential selection effects caused by the cluster randomization design and the use of only 1 formulation for comparison.

“Long-acting formulations are infrequently used in early-phase treatment, and the association between their use and decreased hospitalization risk can have implications for individual treatment decisions and public health efforts,” the researchers concluded.


Kane JM, Schooler NR, Marcy P, et al. Effect of long-acting injectable antipsychotics vs usual care on time to first hospitalization in early-phase schizophrenia: A randomized clinical trial [published online July 15, 2020]. JAMA Psychiatry. doi: 10.1001/jamapsychiatry.2020.2076