Association of Central Nervous System–Affecting Medications With Occurrence and Short-Term Mortality of Traumatic Brain Injury

Abstract

BACKGROUND AND OBJECTIVES: The use of medications commonly prescribed after traumatic brain injury (TBI) has been little studied before TBI. This study examined the association between the use of medications that affect the central nervous system (CNS) and the occurrence and short-term mortality of TBI. METHODS: Mandatory Finnish registries were used to identify TBI admissions, fatal TBIs, and drug purchases during 2005–2018. Patients with TBI were 1:1 matched to nontrauma control patients to investigate the association between medications and the occurrence of TBI and 30-day mortality after TBI. Number needed to harm (NNH) was calculated for all medications. RESULTS: The cohort included 59 606 patients with TBI and a similar number of control patients. CNS-affecting drugs were more common in patients with TBI than in controls [odds ratio = 2.07 (2.02-2.13), P < .001)]. Benzodiazepines were the most common type of medications in patients with TBI (17%) and in controls (11%). The lowest NNH for the occurrence of TBI was associated with benzodiazepines (15.4), selective serotonin uptake inhibitors (18.5), and second-generation antipsychotics (25.8). Eight percent of the patients with TBI died within 30 days. The highest hazard ratios (HR) and lowest NNHs associated with short-term mortality were observed with strong opioids [HR = 1.41 (1.26-1.59), NNH = 33.1], second-generation antipsychotics [HR = 1.36 (1.23-1.50), NNH = 37.1], and atypical antidepressants [HR = 1.17 (1.04-1.31), NNH = 77.7]. CONCLUSION: Thirty-seven percent of patients with TBI used at least 1 CNS-affecting drug. This proportion was significantly higher than in the control population (24%). The highest risk and lowest NNH for short-term mortality were observed with strong opioids, second-generation antipsychotics, and atypical antidepressants. The current risks underscore the importance of weighing the benefits and risks before prescribing CNS-affecting drugs in patients at risk of head injury.