Title: Psychotropic medications and Glioma: an international pharmacoepidemiological study
Funder: Cancer Research UK

Abstract: Background Glioma causes significant morbidity and mortality worldwide and treatment options remain limited. Pre-clinical evidence suggests psychotropic medications, which penetrate the blood brain barrier, may exert antineoplastic effects in glioma. Previous studies suggest psychotropics, including antidepressants may reduce glioma risk, however, statistical precision was limited. Therefore, further investigations utilizing data from multiple sources is needed. Furthermore, little is known about the use of these medications in patients with glioma. Aims We aim to set up an international multicenter study from the UK, Denmark, Sweden, Norway and the USA, to 1. Investigate the association between antidepressant use and glioma risk 2. Investigate the use of psychotropic medications among glioma patients. Methods This study will utilize population-based data from Wales (SAIL databank) and Scotland (National Prescribing Information System), as well as Danish, Swedish and Norwegian registries and Kaiser Permanente Northern California. From cancer registries we will identify approximately 23,466 patients with a primary diagnosis of glioma from 1998-2018. Each case will be matched to 20 population controls on sex and age. Antidepressant medication use will be ascertained using electronic prescribing or dispensing records. Using conditional logistic regression models, we will calculate adjusted odds ratios (ORs) and 95% confidence intervals for glioma associated with use of tricyclic antidepressants. Additional analyses will investigate dose response relations, and associations for individual tricyclic antidepressants, SSRIs and by histological subtype. Site-specific estimates will be pooled using DerSimonian and Laird random effects models. Utilizing the primary cases of glioma and matched controls outlined previously, we will evaluate the utilization of psychotropic medications in glioma patients, and controls as a cancer-free comparison cohort. Psychotropic medications will include antidepressant, antipsychotics, anxiolytics, anti-epileptics, hypnotics and sedatives, psychostimulants and antihistamines. Rates of new drug treatment and total drug use will be calculated and the use of new and prevalent drugs before and after diagnosis examined, including by histological subtypes. How the results of this research will be used This study would provide information on the aetiology of glioma and how this interacts with medications. Additionally it may potentially identify chemopreventive drugs, which hold promise for glioma treatment, and merit further study in observational and clinical trial settings. Drug utilization evaluation will provide important guidance for clinical practice and optimizing care for patients. This would also be a vital step in informing future studies from this international collaboration, to investigate the potential use of psychotropics in glioma patients to improve survival outcomes.


Research activity codes: 2.2 FACTORS RELATING TO PHYSICAL ENVIRONMENT;3.3 NUTRITION AND CHEMOPREVENTION
Health categories: CANCER AND NEOPLASMS