Adverse performance effects of acute lorazepam administration in elderly long-term users: Pharmacokinetic and clinical predictors

Abstract

Background The benzodiazepine lorazepam is widely utilized in the treatment of elderly individuals with anxiety disorders and related conditions. Negative effects of acute lorazepam administration on cognitive performance, especially memory, have been reported in both previously untreated elderly and in individuals who have received short term (up to three weeks) treatment with therapeutic doses. However, it remains unclear if these adverse cognitive effects also persist after long-term use, which is frequently found in clinical practice. Methods Cognitively intact elderly individuals (n=37) on long-term (at least three months) daily treatment with lorazepam were studied using a double-blind placebo-controlled cross-over study design. Subjects were administered their highest daily unit dose of lorazepam (0.25 – 3.00 mg) orplacebo on different days, approximately 1 week apart in a random order, and were assessed on memory, psychomotor speed, and subjective mood states Results Subjects had significantly poorer recall and slowed psychomotor performance following acute lorazepam administration. There were no significant effects on self-ratings of mood, sedation, or anxiety in the whole group, but secondary analyses suggested a differential response in subjects with Generalized Anxiety Disorder. Conclusions The reduced recall and psychomotor slowing that we observed, along with an absence of significant therapeutic benefits, following acute lorazepam administration in elderly long-term users reinforces the importance of cognitive toxicity as a clinical factor in benzodiazepine use, especially in this population.

Influence of Long-Term Benzodiazepine use on Neurocognitive Skills Related to Driving Performance in Patient Populations: A Review

“…Ten studies compared neurocognitive and/or driving performance of long-term users to other patient groups [22][23][24], to healthy controls [25][26][27], or to both [28][29][30][31]. Three studies assessed the influence of acute benzodiazepine administration on neurocognitive and/or driving performance of long-term users in comparison to the acute effects of a benzodiazepine in treatment naïve controls [32], placebo [33], or both [34]. Most studies included patients that had been using benzodiazepines for a number of years.…”

“…Review Thieme after zopiclone administration, but this effect was not observed in chronic users. Pomara et al [33] examined the effects of a single dose of lorazepam in elderly long-term users of lorazepam. The lorazepam dose was calibrated for each individual participant and based on the highest daily dose of lorazepam.…”

Effect of Diazepam on 24-Hour Blood Pressure and Heart Rate in Healthy Young Volunteers

“…Of course this observation would not be of clinical relevance if diazepam was used for a short time, as indicated for all benzodiazepines, but actually a number of surveys suggest that their use is more extensive; in particular, from 13 to 25% of subjects with more than 65 years chronically take them as hypnotic agents [31, 32]. Therefore, it is of great interest to know their cardiovascular effects particularly in subjects bearing a major risk of cardiovascular events such as diabetic, hypertensive and elderly patients as well as in those with cardiac diseases, as compared to healthy subjects.…”

Association Between Opioid and Benzodiazepine Use and Clinical Deterioration in Ward Patients

“…Opioids can cause central and obstructive sleep apneas (19–21), and benzodiazepines contribute to respiratory depression and airway relaxation (22). Benzodiazepines also impair psychomotor function and recall (23), which could mediate the recognized risk for delirium and falls in the hospital (24, 25). These findings suggest pathways by which these medications might contribute to clinical deterioration.…”