Relative Incidence of New-Onset Substance Use Disorders Following Traumatic Brain Injury: A Global Retrospective...

Background: Traumatic brain injury (TBI) imposes a substantial public health burden through long-term physical, cognitive, and psychiatric effects. This includes substance use disorders (SUDs) for which TBI is a demonstrated risk factor; however, prior studies have not comprehensively compared relative incidences of SUD subtypes post-TBI or differences between intracranial hemorrhage (ICH) and non-ICH TBI in patients without prior SUD history. This global retrospective analysis using the TriNetX database aims to quantify new-onset SUD incidence post-TBI in the largest cohort of patients evaluated to date, with cohorts stratified by SUD subtype and ICH versus non-ICH TBI, to highlight opportunities for post-injury care models to mitigate SUD risk. Methods: De-identified data from the TriNetX Research Network were used to select patients with TBI (n = 1,889,112) and define distinct cohorts based upon the presence (n = 420,868) or absence (n = 1,471,592) of ICH. Patients with previously diagnosed SUD before the date of TBI were excluded. Patient demographics and medical comorbidities were calculated for each group. The incidence of new SUD diagnosis over the lifetime and at 1-, 3-, and 5-years post-TBI were calculated and compared. Subtypes of SUD were defined and calculated based on the specific substance used. Propensity scores were calculated to create balanced matched ICH and non-ICH cohorts (n = 331,812 each) were used for comparisons of 5-year SUD incidence. Results: In the full TBI cohort, 5-year new SUD incidence was 4.2% overall, with nicotine (2.4%) and alcohol (1.1%) predominating, followed by cannabis (0.9%) and opioids (0.4%). Rates of SUDs increased over time, but attenuated beyond 5 years, with approximately 50% of those who would ultimately be diagnosed with SUD manifesting (lifetime) by 3 years post-TBI. After propensity matching, non-ICH TBI showed higher 5-year risk for any SUD (4.2% vs. 3.6%; risk difference -0.65%, p < 0.0001) and all subtypes (p < 0.05) except inhalants (p = 0.53). Conclusions: This largest-to-date analysis of new-onset SUD post-TBI demonstrates significantly higher rates of SUD in TBI patients; rates of nicotine, alcohol, cannabis, and opioid use disorders were most common. Non-ICH TBI patients demonstrated greater rates of SUD after injury than patients with ICH-associated TBI. Of patients suffering from TBI without ICH who would eventually be diagnosed with SUD, approximately 50% had obtained that diagnosis within 3 years of the injury. Taken together, these findings demonstrate the clinical need for routine SUD screening in post-TBI care, especially for 3 years post-injury. Such an intervention has the potential to significantly alleviate the public health burden and associated cost of care for TBI-associated substance use disorder patients.