Benzodiazepines is a class of medications frequently prescribed to patients with post-traumatic stress disorder. Patients with PTSD have a notable increased risk of suicide compared to the general population. These medications have been theorized to increase suicidality and pose a risk when used in this patient population. Previous research has found little utility of using benzodiazepines in the PTSD population. However, benzodiazepines are still commonly prescribed by some clinicians for their symptomatic benefit. This study aims to identify the comparative efficacy of commonly prescribed benzodiazepines including midazolam, lorazepam, alprazolam, clonazepam, diazepam and temazepam in relation to suicide-related behaviors (SRBs). A total of 38,807 patients who had an ICD9 or ICD10 diagnosis of PTSD from January 2004 to October 2019 were identified through an electronic medical record database. Inclusion criteria include patients that initiated one of the above benzodiazepines after PTSD diagnosis. Exclusion criteria include previous history of benzodiazepine usage or history of SRBs within the last year prior to enrollment. For patients enrolled in this study, other concomitant drugs were not limited. The primary outcome was onset of SRBs with each respective benzodiazepine. SRBs were identified as ideation, attempt, or death from suicide. We emulated clinical trials of head-to-head comparison between two drugs by pooled logistic regression methods with the Firth option adjusting for baseline characteristics and post-baseline confounders. A total of 5753 patients were eligible for this study, with an average follow up of 5.82 months. The overall incidence for SRB was 1.51% (87/5753). Head-to-head comparisons identified that patients who received alprazolam had fewer SRBs compared to clonazepam (p = 0.0351) and lorazepam (p = 0.0373), and patients taking midazolam experienced fewer relative incidences of SRBs when compared to lorazepam (p = 0.0021) and clonazepam (p = 0.0297). After adjusting for the false discovery rate (FDR), midazolam still had fewer SRBs compared to lorazepam (FDR-adjusted p value = 0.0315). Certain benzodiazepines may provide a reduced risk of development of SRBs, suggesting careful consideration when prescribing benzodiazepines to the PTSD population.

Post-traumatic stress disorder (PTSD) is a prevalent mental disorder marked by psychological and behavioral changes. Currently, there is no consensus of preferred antipsychotics to be used for the treatment of PTSD. We aim to discover whether certain antipsychotics have decreased suicide risk in the PTSD population, as these patients may be at higher risk. A total of 38,807 patients were identified with a diagnosis of PTSD through the ICD9 or ICD10 codes from January 2004 to October 2019. An emulation of randomized clinical trials was conducted to compare the outcomes of suicide-related events (SREs) among PTSD patients who ever used one of eight individual antipsychotics after the diagnosis of PTSD. Exclusion criteria included patients with a history of SREs and a previous history of antipsychotic use within one year before enrollment. Eligible individuals were assigned to a treatment group according to the antipsychotic initiated and followed until stopping current treatment, switching to another same class of drugs, death, or loss to follow up. The primary outcome was to identify the frequency of SREs associated with each antipsychotic. SREs were defined as ideation, attempts, and death by suicide. Pooled logistic regression methods with the Firth option were conducted to compare two drugs for their outcomes using SAS version 9.4 (SAS Institute, Cary, NC, USA). The results were adjusted for baseline characteristics and post-baseline, time-varying confounders. A total of 5294 patients were eligible for enrollment with an average follow up of 7.86 months. A total of 157 SREs were recorded throughout this study. Lurasidone showed a statistically significant decrease in SREs when compared head to head to almost all the other antipsychotics: aripiprazole, haloperidol, olanzapine, quetiapine, risperidone, and ziprasidone (p < 0.0001 and false discovery rate-adjusted p value < 0.0004). In addition, olanzapine was associated with higher SREs than quetiapine and risperidone, and ziprasidone was associated with higher SREs than risperidone. The results of this study suggest that certain antipsychotics may put individuals within the PTSD population at an increased risk of SREs, and that careful consideration may need to be taken when prescribed.

The purpose of this study is to identify medications with potentially beneficial effects on decreasing mortality in patients with acute kidney injury (AKI) while in the intensive care unit (ICU). We used logistic regression to investigate associations between medications received and ICU mortality in patients with AKI in the MIMIC III database. Drugs associated with reduced mortality were then validated using the eICU database. Propensity score matching (PSM) was used for matching the patients’ baseline severity of illness followed by a chi-square test to calculate the significance of drug use and mortality. Finally, we examined gene expression signatures to explore the drug’s molecular mechanism on AKI. While several drugs demonstrated potential beneficial effects on reducing mortality, most were used for potentially fatal illnesses (e.g. antibiotics, cardiac medications). One exception was found, ondansetron, a drug without previously identified life-saving effects, has correlation with lower mortality among AKI patients. This association was confirmed in a subsequent analysis using the eICU database. Based on the comparison of gene expression signatures, the presumed therapeutic effect of ondansetron may be elicited through the NF-KB pathway and JAK-STAT pathway. Our findings provide real-world evidence to support clinical trials of ondansetron for treatment of AKI.

The purpose of this study is to identify medications with potentially beneficial effects on decreasing mortality in patients with acute kidney injury (AKI) while in the intensive care unit (ICU). We used logistic regression to investigate associations between medications received and ICU mortality in patients with AKI in the MIMIC III database. Drugs associated with reduced mortality were then validated using the eICU database. Propensity score matching (PSM) was used for matching the patients’ baseline severity of illness followed by a chi-square test to calculate the significance of drug use and mortality. Finally, we examined gene expression signatures to explore the drug’s molecular mechanism on AKI. While several drugs demonstrated potential beneficial effects on reducing mortality, most were used for potentially fatal illnesses (e.g. antibiotics, cardiac medications). One exception was found, ondansetron, a drug without previously identified life-saving effects, has correlation with lower mortality among AKI patients. This association was confirmed in a subsequent analysis using the eICU database. Based on the comparison of gene expression signatures, the presumed therapeutic effect of ondansetron may be elicited through the NF-KB pathway and JAK-STAT pathway. Our findings provide real-world evidence to support clinical trials of ondansetron for treatment of AKI.