Montelukast and neuropsychiatric events - a sequence symmetry analysis.

OBJECTIVES: Neuropsychiatric events (NEs) reported with montelukast during post-marketing surveillance by the US Food & Drug Administration resulted in a 2008 safety alert and a black box warning in 2020. Our objective was to evaluate montelukast exposure and NEs risk using sequence symmetry analysis. METHODS: National Veterans Health Administration (VHA) administrative data were used to identify 11 840 patients prescribed incident montelukast during fiscal year 2014. Incident prescribing of neuropsychiatric medication was used as a proxy marker for incident NEs and included antidepressants, benzodiazepines, hypnotics, antipsychotics, mood stabilizers, and buspirone. Symmetry ratios were calculated as the ratio of patients with an incident neuropsychiatric event in the year following montelukast initiation to the year preceding initiation. Exposure counterfactual analyses were used to examine the relationship between potential therapeutic alternatives to montelukast and risk for NEs. RESULTS: Incident NEs were observed in 2305 patients following montelukast initiation and 2734 patients preceding montelukast initiation (SR 0.84, 95% CI 0.80-0.89). Sensitivity analyses examining each of the 6 sub-types of psychiatric medications also failed to show increased risk of NEs following montelukast initiation. Therapeutic alternatives to montelukast, such as inhaled corticosteroids, were also not associated increased NE risk. CONCLUSIONS: Initiation of montelukast was not associated with increased risk of a variety of NEs in this sequence symmetry analysis involving adult patients in the VHA. Our findings do not support the hypothesis that NEs are associated with montelukast initiation.

Prazosin Outcomes in Older Veterans With Posttraumatic Stress Disorder.

Even at relatively high dosages, prazosin was well tolerated and significantly improved posttraumatic stress disorder severity and related nightmares in an older patient population.

Prazosin initiation and dose titration in a patient with posttraumatic stress disorder on concurrent carvedilol.

One mechanism involved in the pathophysiology of posttraumatic stress disorder (PTSD) is increased noradrenergic stimulation. Prazosin, a commonly utilized treatment for PTSD nightmares, works to block noradrenergic stimulation of the alpha-1 adrenoreceptor. Dual antagonism of this receptor would be expected to increase risk of adverse effects. Carvedilol has both alpha-1 adrenergic and nonselective beta-adrenoreceptor antagonist activity. To our knowledge, there is no clinical guidance on use of prazosin in patients concomitantly prescribed carvedilol for hypertension. This case describes the successful titration of prazosin for PTSD symptoms in a 49-year-old male concurrently prescribed carvedilol for hypertension. This patient had a previous unsuccessful prazosin trial due to adverse effects. His second trial of prazosin was efficacious and well tolerated using individualized titration with close monitoring by mental health clinical pharmacy specialists in the pharmacist-managed prazosin titration clinic. This case details the importance of utilizing caution and close follow-up in prazosin dose titration in patients prescribed concomitant alpha-1 antagonists. This appears to be the first case report describing the successful dose titration of prazosin for PTSD in a patient on a concurrent alpha-1 antagonist antihypertensive agent.

Assessment of Guideline Discordance With Antimicrobial Prophylaxis Best Practices for Common Urologic Procedures.

Importance: The American Urological Association guidelines recommend 24 or fewer hours of antimicrobial prophylaxis for most urologic procedures. Continuing antimicrobial therapy beyond 24 hours may carry more risks than advantages. Objectives: To assess guideline discordance of antimicrobial prophylaxis for common urologic endoscopic procedures, and to identify opportunities for improving antimicrobial prescribing through future stewardship interventions. Design, Setting, and Participants: This multicenter cohort study conducted manual audits of medical records of 375 patients who underwent 1 of 3 urologic procedures (transurethral resection of bladder tumor [TURBT], transurethral resection of the prostate [TURP], and ureteroscopy [URS]) at 5 Veterans Health Administration facilities from January 1, 2016, to June 30, 2017. Antimicrobial prescribing practices across the national Veterans Health Administration system were assessed using the administrative data for 29 530 records. Main Outcomes and Measures: Guideline discordance was assessed in the medical record review. Excessive postprocedural antimicrobial use was measured in the national administrative data analysis. Results: The medical records of a total of 375 patients were manually reviewed. Among the 375 patients, 366 (97.6%) were male and 9 (2.4%) were female, with a mean (SD) age of 64.2 (10.9) years and a predominantly white race/ethnicity (289 [77.1%]). In addition, 29 530 patient records in the national administrative database were assessed. Among the patient records, 28 938 (98.0%) were male and 592 (2.0%) were female with a mean (SD) age of 69.1 (10.2) years and a predominantly white race/ethnicity (23 297 [78.9%]). Among the manually reviewed medical records, periprocedural or postprocedural antimicrobial prescribing was guideline discordant in 217 patients (57.9%). Postprocedural antimicrobial agents were continued beyond 24 hours in 211 patients (56.3%) and were guideline discordant in 177 patients (83.9%), with a median (interquartile range) duration of 3 (3-5) days of unnecessary antimicrobial therapy. In the analysis of national administrative data, excessive postprocedural antimicrobial agents were prescribed in 10 988 of 29 350 patient records (37.2%), with a median (interquartile range) of 3 (2-6) excess days. For any given facility, a statistically significant correlation was observed in the frequency of postprocedural antimicrobial prescribing between any 2 procedures, indicating that facilities with higher rates of excessive use for 1 procedure also had higher rates for another procedure: TURP and TURBT (ρ = 0.719; 95% CI, 0.603-0.803; P < .001), TURP and URS (ρ = 0.629; 95% CI, 0.476-0.741; P < .001), and TURBT and URS (ρ = 0.813; 95% CI, 0.724-0.873; P < .001). Conclusions and Relevance: In this study of patients who underwent common urologic procedures, the rate of guideline-discordant antimicrobial use was high mostly because of overprescribing of postprocedural antimicrobial agents; future antimicrobial stewardship interventions should target the postprocedural period.