JMIR Publications

ABSTRACT

Background:

The relationship between cancer and central nervous system disorders has received increasing attention recently. Consequently, antipsychotics and antidepressants, commonly prescribed for conditions such as depression, bipolar disorder, and schizophrenia, have emerged as potential modulators of subsequent cancer risk. Previous studies have suggested that the use of these medications is associated with a decreased risk of cancer incidence and mortality, making them suitable candidates for drug repurposing. However, the potential therapeutic benefits do not extend to all cancer types, as some data suggest an increased risk for specific tumors.

Objective:

This study aims to evaluate whether exposure to antipsychotic or antidepressant drugs alters the risk of cancer using available evidence from systematic reviews of observational and experimental studies.

Methods:

To provide a clear overview of this review, we have designed and registered the study protocol. Specifically, we will include systematic reviews and meta-analyses that examine the relationship between previous antipsychotic or antidepressant treatments and the subsequent cancer risk. The primary outcome will be the risk of cancer incidence and mortality (all malignant neoplasms) associated with exposure to psychopharmacological medications. Furthermore, secondary outcomes will include site-specific cancer incidence and mortality (for example, lung cancer). Literature searches will be conducted in multiple electronic databases (from their inception onwards), including PubMed/MEDLINE, EMBASE, and the Cochrane Database of Systematic Reviews. Three researchers will independently screen all citations, abstracts, and full-text articles. We will perform parallel search, selection, and extraction tasks using a Large Language Model (GPT4-o). Thus, we will verify whether this type of tool can accelerate or even perform the tasks involved in a systematic review. The risk of bias and the quality of individual studies will be evaluated using appropriate tools. Subsequently, we will calculate the association measures and their associated 95% confidence intervals. Where sufficient data are available, subgroup analyses of specific classes of medications will be performed. Finally, potential sources of heterogeneity will be explored.

Results:

Data collection was completed by May 2025 with a final sample size of 21 articles. Results are expected to be published in 2025.

Conclusions:

This overview of systematic review and meta-analysis will provide an updated synthesis of the cancer risk associated with antipsychotic and antidepressant drugs. Furthermore, this study will examine factors that may explain potential study variations. Ultimately, these findings will be published in a peer-reviewed journal. Clinical Trial: Open Science Framework [https://doi.org/10.17605/OSF.IO/5ACWH]