Behavioral effects of alprazolam in humans

Kelly, Thomas C.; Rw, Foltin; Serpick, E; Mw, Fischman

doi:10.1097/00008877-199702000-00005

Cited by 13 publications

(7 citation statements)

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“…The target dose range for clinical indications of alprazolam XR is 3–6 mg/day. That sedation and performance decrements were observed at a sub-therapeutic dose might be considered surprising, although other studies have demonstrated similar effects at lower doses (e.g., Kaplan et al, 1998; Kelly et al, 1997). Tolerance to the effects of benzodiazepines, such as sedation and performance impairment, is frequently observed with repeated use (e.g., Seidel et al, 1985; Stoops and Rush, 2003).…”

Section: Discussionmentioning

confidence: 84%

Physiological and subjective effects of acute intranasal methamphetamine during extended-release alprazolam maintenance

Lile

Stoops

Glaser

et al. 2011

Drug and Alcohol Dependence

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Background Medications development for methamphetamine dependence is ongoing, but no widely accepted, effective pharmacotherapy has been identified. Previous studies have demonstrated neurobiological perturbations to central GABAA activity following chronic stimulant use, and that positive modulation of GABAA receptors attenuates the neurochemical and behavioral response to stimulant drugs such as methamphetamine. Therefore, GABAA modulators could be useful as pharmacotherapies for stimulant-use disorders. Methods This study tested the hypothesis that intranasal methamphetamine would be safe and well tolerated during maintenance on extended-release alprazolam (XR), and that the effects of methamphetamine would be attenuated. Eight non-treatment-seeking, stimulant-dependent individuals completed an inpatient experiment in which ascending doses of intranasal methamphetamine (0, 5, 10, 20 and 30 mg) were administered after four days of alprazolam XR maintenance (0 and 1 mg/day). Results Intranasal methamphetamine produced prototypical effects (e.g., increased positive subjective ratings and elevated cardiovascular signs). The combination of intranasal methamphetamine and alprazolam XR was safe and well tolerated. Alprazolam XR produced small, but orderly, reductions in some of the subjective effects of methamphetamine, and performance impairment. Conclusions The present results demonstrate that methamphetamine use during alprazolam XR treatment would not pose a significant safety risk. Given the potential of GABAA positive modulators to manage certain aspects of stimulant abuse and dependence (i.e., drug-induced seizures, anxiety and stress), but the relatively small impact on the acute abuse-related effects of methamphetamine observed here, additional research with GABAA positive modulators is warranted, but should consider their use as an adjunct component of combination behavioral and/or drug treatment.

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Section: Discussionmentioning

confidence: 84%

Physiological and subjective effects of acute intranasal methamphetamine during extended-release alprazolam maintenance

Lile

Stoops

Glaser

et al. 2011

Drug and Alcohol Dependence

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“…The literature search yielded 56 different studies using 16 different benzodiazepines, published since 1966 [14–67]. There were 173 different tests used, on average 3.1 tests per study.…”

Section: Resultsmentioning

confidence: 99%

Biomarkers for the effects of benzodiazepines in healthy volunteers

Visser

Post

Waal

et al. 2003

Brit J Clinical Pharma

103

135

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Studies of novel centrally acting drugs in healthy volunteers are traditionally concerned with kinetics and tolerability, but useful information may also be obtained from biomarkers of clinical endpoints. A useful biomarker should meet the following requirements: a consistent response across studies and drugs; a clear response of the biomarker to a therapeutic dose; a dose-response relationship; a plausible relationship between biomarker, pharmacology and pathogenesis. In the current review, all individual tests found in studies of benzodiazepine agonists registered for anxiety in healthy volunteers since 1966 were progressively evaluated for compliance with these requirements. A MedLine search yielded 56 different studies, investigating the effects of 16 different benzodiazepines on 73 different (variants of ) neuropsychological tests, which could be clustered into seven neuropsychological domains. Subjective and objective measures of alertness were most sensitive to benzodiazepines. The most consistent effects were observed on saccadic peak velocity (SPV) and visual analogue scores ( VAS) of alertness, where 100% and 79% of all studies respectively showed statistically significant effects. A dose-response relationship could be constructed for temazepam and SPV, which was used to determine dose equivalencies relative to temazepam, for seven different benzodiazepines. These dose equivalencies correlated with the lowest recommended daily maintenance dose ( r 2 = 0.737, P < 0.05). This relationship between SPV reduction and clinical efficacy could reflect the clinical practice of aiming for maximum tolerated levels, or it could represent a common basis behind SPV reduction and anxiolytic activity for benzodiazepines (probably sedation). The number of tests used in human psychopharmacology appears to be excessive and their sensitivity and reproducibility low.

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“…Previous research had established as well that the performance battery required only a brief amount of time to complete and was sensitive to manipulations, such as drug administration and changes in nutrition, known to affect human behavior (e.g., Foltin et al, 1990;Kelly, Foltin, & Fischman, 1993;Kelly, Foltin, Rolls, & Fischman, 1994;Kelly, Foltin, Serpick, & Fischman, 1997;Ward, Kelly, Foltin, & Fischman, 1997). During each test session, the tasks were presented in the following order:…”

Section: Task Batterymentioning

confidence: 99%

Crewmember Performance Before, During, and After Spaceflight

Kelly

Hienz

Zarcone

et al. 2005

Journal of the Experimental Analysis of Behavior

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The development of technologies for monitoring the welfare of crewmembers is a critical requirement for extended spaceflight. Behavior analytic methodologies provide a framework for studying the performance of individuals and groups, and brief computerized tests have been used successfully to examine the impairing effects of sleep, drug, and nutrition manipulations on human behavior. The purpose of the present study was to evaluate the feasibility and sensitivity of repeated performance testing during spaceflight. Four National Aeronautics and Space Administration crewmembers were trained to complete computerized questionnaires and performance tasks at repeated regular intervals before and after a 10-day shuttle mission and at times that interfered minimally with other mission activities during spaceflight. Two types of performance, Digit-Symbol Substitution trial completion rates and response times during the most complex Number Recognition trials, were altered slightly during spaceflight. All other dimensions of the performance tasks remained essentially unchanged over the course of the study. Verbal ratings of Fatigue increased slightly during spaceflight and decreased during the postflight test sessions. Arousal ratings increased during spaceflight and decreased postflight. No other consistent changes in rating-scale measures were observed over the course of the study. Crewmembers completed all mission requirements in an efficient manner with no indication of clinically significant behavioral impairment during the 10-day spaceflight. These results support the feasibility and utility of computerized task performances and questionnaire rating scales for repeated measurement of behavior during spaceflight.

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Behavioral effects of alprazolam in humans

Cited by 13 publications

References 0 publications

Physiological and subjective effects of acute intranasal methamphetamine during extended-release alprazolam maintenance

Physiological and subjective effects of acute intranasal methamphetamine during extended-release alprazolam maintenance

Biomarkers for the effects of benzodiazepines in healthy volunteers

Crewmember Performance Before, During, and After Spaceflight

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