The article titled All-cause mortality risk in long-acting injectable versus oral antipsychotics in schizophrenia: a systematic review and meta-analysis by Claudia Aymerich and colleagues explores the mortality risks associated with two forms of antipsychotic treatments—long-acting injectable (LAI) and oral medications—in patients with schizophrenia. Schizophrenia is a chronic and severe mental disorder that is associated with a significantly reduced life expectancy, primarily due to cardiovascular disease, poor lifestyle habits, and limited access to healthcare services. Antipsychotic treatment plays a crucial role in reducing the risk of death, but patient adherence to medication is a persistent challenge, with many individuals discontinuing their oral antipsychotic medications.

Long-acting injectable antipsychotics were developed to improve adherence, offering consistent medication levels and reducing the risk of relapse and hospitalization. Despite their introduction, there remains uncertainty regarding their impact on mortality compared to oral antipsychotics. This study aims to clarify the differences in mortality risks—both all-cause and specific types, including suicidal and non-suicidal mortality—between patients treated with LAI antipsychotics and those on oral formulations.

To address this, the authors conducted a comprehensive systematic review and meta-analysis, analyzing data from 17 studies involving over 12,000 patients with schizophrenia. These studies compared mortality rates between those using LAI antipsychotics and those taking oral antipsychotics. The analysis included randomized controlled trials as well as observational studies, and patients from both first-episode psychosis (FEP) and chronic schizophrenia were included. Additionally, the study examined the effects of various factors such as age, gender, dosage, and race on mortality outcomes.

The results of the meta-analysis indicated that patients receiving LAI antipsychotics had a significantly lower risk of all-cause mortality compared to those using oral antipsychotics. This protective effect was particularly pronounced in patients with first-episode psychosis, suggesting that introducing LAI treatment early in the disease course could be beneficial in reducing mortality risks. Interestingly, while the study did not find a significant difference in suicidal mortality between the two treatment groups, non-suicidal mortality was notably lower among those receiving LAI antipsychotics. The authors suggest that this reduction in non-suicidal mortality may be due to better adherence to medication, as well as more frequent contact with healthcare services. Patients on LAI antipsychotics are required to visit healthcare providers regularly for their injections, allowing for early intervention in case of emerging health issues.

These findings have important implications for the treatment of schizophrenia, particularly in clinical settings where medication adherence is a significant concern. The study supports the idea that long-acting injectable antipsychotics may offer a safer and more effective long-term treatment option, particularly for patients who struggle with adherence to oral medications. The authors recommend that, whenever possible, LAI antipsychotics should be considered, especially during the early stages of treatment, such as in first-episode psychosis, where the risks of relapse and deterioration are highest.

The study also highlights the need for further research to examine the specific contributions of different antipsychotic formulations to these outcomes. While this meta-analysis provides strong evidence for the overall benefits of LAI antipsychotics in reducing non-suicidal mortality, more research is needed to explore how different drugs within the LAI category may vary in their impact on mortality risks. Additionally, long-term studies with larger sample sizes could help clarify whether these benefits persist over time and across diverse patient populations.

In conclusion, this research provides valuable insights into the mortality risks associated with antipsychotic treatment in schizophrenia, emphasizing the potential of long-acting injectable antipsychotics to improve patient outcomes. For practitioners working in the field of schizophrenia treatment, this study reinforces the importance of considering LAI antipsychotics as a key component of treatment strategies, particularly for improving adherence and reducing non-suicidal mortality.

Reference:

Aymerich, C et al. Mol Psychiatry (2024). Epub ahead of print. Abstract