Mining clinical data for novel medications to treat alcohol use disorder.

BACKGROUND: Alcohol use disorder (AUD) is a highly prevalent and often debilitating condition associated with high morbidity and mortality. Current AUD medications have limited efficacy and uptake. Alternative pharmacological options are needed. METHODS: We constructed a mechanistic tree of all US Food and Drug Administration approved medications and used a tree-based scan statistic, TreeScan, to identify medications associated with greater than expected improvements in alcohol consumption. Our cohort included all United States (US) Department of Veterans Affairs (VA) patients with a diagnosis of AUD between 10/1/1999 and 9/30/2019 with multiple Alcohol Use Disorders Identification Test-Consumption Module scores within the VA electronic health record data. RESULTS: Medications statistically associated with decreased alcohol consumption had, at large, minor effect sizes. Medications used in the treatment of chronic or life-threatening conditions like diabetes, chronic kidney disease, hepatitis C virus, or cancer produced larger effect sizes. Asenapine, an atypical antipsychotic, had a large effect with an observed to expected ratio of 1.78 (p = 0.003). Our findings were replicated in a propensity score matched population. CONCLUSION: Most medications significantly associated with decreased alcohol consumption in our analysis were either contraindicated with alcohol or likely attributable to patients abstaining from alcohol due to severe illness. However, the large effect of asenapine is notable, and a worthwhile candidate for more careful analysis.

Mining Clinical Data for Novel Posttraumatic Stress Disorder Medications.

BACKGROUND: Despite the prevalence and negative impact of posttraumatic stress disorder (PTSD), there are few medications approved by the U.S. Food and Drug Administration for treatment, and approved medications do not work well enough. We leveraged large-scale electronic health record data to identify existing medications that may be repurposed as PTSD treatments. METHODS: We constructed a mechanistic tree of all Food and Drug Administration-approved medications and used the tree-based scan statistic to identify medications associated with greater than expected levels of clinically meaningful improvement in PTSD symptoms using electronic health record data from the U.S. Department of Veterans Affairs. Our cohort included patients with a diagnosis of PTSD who had repeated symptom measurements using the PTSD Checklist over a 20-year period (N = 168,941). We calculated observed numbers based on patients taking each drug or mechanistically related class of drugs and the expected numbers based on the tree as a whole. RESULTS: Medications typically used to treat PTSD, such as the Food and Drug Administration-approved agent sertraline, were associated with improvement in PTSD symptoms, but the effects were small. Several, but not all, direct-acting antivirals used in the treatment of hepatitis C virus demonstrated a strong association with PTSD improvement. The finding was robust to a sensitivity analysis excluding patients who received established PTSD treatments, including trauma-focused psychotherapy, concurrent with hepatitis treatment. CONCLUSIONS: Our exploratory approach both demonstrated findings that are consistent with what is known about pharmacotherapy for PTSD and uncovered a novel class of medications that may improve PTSD symptoms.