Abstract Background The U.S. Food and Drug Administration (FDA) recently linked antiepileptic drug (AED) exposure to suicide-related behaviors based on meta-analysis of randomized clinical trials. We examined the relationship between suicide-related behaviors and different AEDs in older veterans receiving new AED monotherapy from the Veterans Health Administration (VA), controlling for potential confounders. Methods VA and Medicare databases were used to identify veterans 66 years and older, who received a) care from the VA between 1999 and 2004, and b) an incident AED (monotherapy) prescription. Previously validated ICD-9-CM codes were used to identify suicidal ideation or behavior (suicide-related behaviors cases), epilepsy, and other conditions previously associated with suicide-related behaviors. Each case was matched to controls based on prior history of suicide-related behaviors, year of AED prescription, and epilepsy status. Results The strongest predictor of suicide-related behaviors (N = 64; Controls N = 768) based on conditional logistic regression analysis was affective disorder (depression, anxiety, or post-traumatic stress disorder (PTSD); Odds Ratio 4.42, 95% CI 2.30 to 8.49) diagnosed before AED treatment. Increased suicide-related behaviors were not associated with individual AEDs, including the most commonly prescribed AED in the US - phenytoin. Conclusion Our extensive diagnostic and treatment data demonstrated that the strongest predictor of suicide-related behaviors for older patients newly treated with AED monotherapy was a previous diagnosis of affective disorder. Additional, research using a larger sample is needed to clearly determine the risk of suicide-related behaviors among less commonly used AEDs.

Mild traumatic brain injury in the Veteran population is frequently comorbid with pain, post-traumatic stress disorder, and/or depression. However, not everyone exposed to mild traumatic brain injury experiences these comorbidities and it is unclear what factors contribute to this variability. The objective of this study was to identify comorbidity phenotypes among Post-9/11 deployed Veterans with no or mild traumatic brain injury and examine the association of comorbidity phenotypes with adverse outcomes. We found that Veterans with mild traumatic brain injury (n = 93,003) and no brain injury (n = 434,378) were mean age of 32.0 (SD 9.21) on entering Department of Veterans Health Administration care, were predominantly Caucasian non-Hispanic (64.69%), and served in the Army (61.31%). Latent class analysis revealed five phenotypes in each subcohort; Moderately Healthy and Mental Health phenotypes were common to both. The Healthy phenotype was found only in no brain injury. Unique phenotypes in mild traumatic brain injury included Moderately Healthy+Decline, Polytrauma, and Polytrauma+Improvement. There was substantial variation in adverse outcomes. The Polytrauma+Improvement phenotype had the lowest likelihood of adverse outcomes. There were no differences between Moderately Healthy+Decline and Polytrauma phenotypes. Phenotypes of comorbidity vary significantly by traumatic brain injury status including divergence in phenotypes (and outcomes) over time in the mild traumatic brain injury subcohort. Understanding risk factors for the divergence between Polytrauma vs. Polytrauma+Improvement and Moderately Healthy vs. Moderately Healthy+Decline, will improve our ability to proactively mitigate risk, better understand the early patterns of comorbidity that are associated with neurodegenerative sequelae following mild traumatic brain injury, and plan more patient-centered care.