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Pharmaceutical Drugs
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Wilkinson, C. J. (1998). The abuse potential of zolpidem, administered alone and with alcohol. Pharmacology, Biochemistry and Behavior, 60, 193-202.
The abuse potential of zolpidem, alone and in combination with alcohol, was examined in healthy volunteers with a history of social use of alcohol and drugs. Zolpidem, a short-acting imidazopyridine hypnotic with selectivity for a benzodiazepine receptor subtype (BZ1 or omega1), was administered double blind at 0, 10, or 15 mg with alcohol (0.75 g ethanol/kg b.wt.) or with placebo beverage in a randomized, six-way crossover design. Outcome measures included the Drug Effect Questionnaire (DEQ), the Addiction Research Center Inventory (ARCI-40), and the Profile of Mood States (POMS). Blood alcohol concentrations (BACs) were not significantly modified by zolpidem. Relative to placebo, zolpidem and alcohol significantly (p < 0.05) increased drug strength perception, drug-liking, and drug-disliking scores on the DEQ. On the ARCI-40, zolpidem and alcohol significantly increased sedation/intoxication and dysphoria/fear scores, but did not significantly change euphoria/well-being scores. Zolpidem and alcohol were rated more unfavorably than placebo on the POMS. Alcohol did not have additive effects on the subjective ratings for zolpidem. It is concluded that, for this population and at the doses tested, the abuse potential of zolpidem appears to be modest and not increased by alcohol
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Wilkinson, C. J. (1995). The acute effects of zolpidem, administered alone and with alcohol, on cognitive and psychomotor function. Journal of Clinical Psychiatry, 56, 309-318.
BACKGROUND: Skills performance impairment after acute doses of zolpidem (a short-acting, nonbenzodiazepine hypnotic), alone and with alcohol, was evaluated in 24 subjects. The study was designed to test whether the effects of zolpidem and alcohol are simply additive or reflect potentiation. METHOD: Healthy male volunteers participated in a randomized, six-way crossover study of placebo, zolpidem 10 mg, or zolpidem 15 mg in combination with a placebo beverage or an alcohol dose selected to attain a peak blood alcohol concentration of 0.08% (drug administered double-blind; beverages administered single-blind). A laboratory test battery of four tasks measured concurrent information processing ability (divided attention task), information processing rate (visual backward masking task), immediate memory (Sternberg task), and sustained attention (vigilance task). The battery was repeated three times to measure peak (+45 minutes), postpeak (+130 minutes), and residual (+230 minutes) treatment effects after each dosing. RESULTS: Performance on each test-battery task was significantly impaired (p < .05) by both alcohol and zolpidem (combined and each given alone) during the peak-effect assessment. Residual effects were not observed, with the exception of significant alcohol and drug effects on divided attention performance (p < .05). Analysis of variance tests revealed significant main effects of alcohol and zolpidem, but no significant alcohol-by-drug interactions were found for any measure of skills performance. In general, additive effects of alcohol were detected with zolpidem 10 mg but not with zolpidem 15 mg. CONCLUSION: Although some additive effects of alcohol on performance skills were seen with the lower 10-mg dose of zolpidem, no nonadditive effects were found. That is, alcohol does not appear to potentiate the effects of zolpidem on the various performance skills tested in this population and at the doses and times evaluated. With the exception of persisting deficits (at 4 hours postdose) on the more demanding divided attention task, all other findings were consistent with evidence that zolpidem is a short-acting hypnotic drug.
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Moskowitz, H. A., Linnoila, M., & Roehrs, T. (1990). Psychomotor performance in chronic insomniacs during 14-day use of flurazepam and midazolam. Journal of Clinical Psychopharmacology, 4(Suppl.), 44S-55S.
Four skills performance (psychomotor) tasks, including simple and choice reaction time, divided attention, and vigilance, were given to 99 chronic insomniacs to determine whether the use of midazolam 15 mg, or of flurazepam 15 or 30 mg, compared with placebo would produce next-day impairment throughout a 14-day treatment period. Tests were administered during 2 baseline days and on treatment days 1 and 2 (early interval), 7 (middle interval) and 13 and 14 (late interval). Compared with placebo, performance on all four tasks was impaired by flurazepam 30 mg. The deficits associated with flurazepam 15 mg were roughly half the magnitude of those produced by flurazepam 30 mg, but these changes did not reach statistical significance for single response measures at single time intervals. Midazolam showed no consistent pattern of performance effects; however, for divided attention tracking error, there was a significant decrement. The placebo group showed flat performance curves or improved performance as a result of learning (practice effect).
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Moskowitz, H. A., & Burns, M. M. (1988). The effects on performance of two antidepressants, alone and in combination with diazepam. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 12, 783-792.
1. Ninety healthy adult men participated in a study of the effects on performance of 60 mg fluoxetine, 50 mg amitriptyline or placebo, alone and in combination with 5 mg diazepam or placebo. 2. In a 2X3 factorial design study, groups of 15 Ss received one of six possible treatment combinations. 3. Ss were tested with a battery of laboratory tests at two post-dosing times. 4. Amitriptyline impaired the performance of all tasks. When diazepam was added to the amitriptyline treatment, the impairment of three tasks increased. Diazepam alone produced impairment on two measures. 5. Fluoxetine alone impaired no task; some impairment occurred with the fluoxetine-diazepam combination.
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Moskowitz, H. A., & Burns, M. M. (1988). Effects of terfenadine, diphenhydramine, and placebo on skills performance. Cutis, 1988; 42(4A), 14-18.
The behavioral effects of the antihistamines terfenadine and diphenhydramine were compared in a placebo-controlled, double-blind crossover study. Performance of skills deemed important in safe man-machine interactions was objectively assessed one, three, and five hours after administration of test substances. The results indicate that diphenhydramine use resulted in various degrees of impairment of the ability to perform a visual-search task, a tracking task, a divided-attention task, and a vigilance task. Terfenadine users performed as well as or better than placebo-treated subjects. No differences between terfenadine and placebo were found on a subjective evaluation scale. Diphenhydramine users consistently reported feelings of impairment.
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Smiley, A., & Moskowitz, H. A. (1986). Effects of long-term administration of buspirone and diazepam on driver steering control. American Journal of Medicine, 80(3B), 22-29.
The effects of buspirone, diazepam, and placebo on tracking control were investigated over a nine-day period, using three groups of subjects, each with eight females and eight males. Subjects were tested using an interactive, computer-based driving simulator on days one, eight, and nine of the treatment period. On day nine, subjects received alcohol with their drug treatment. Measures of steering control were derived from car-driver transfer functions. Tracking performance was also measured. Diazepam was found to adversely affect steering control measures in comparison with placebo. This was true both after doses on the first as well as the eighth day of treatment. Thus, there was no evidence of behavioral tolerance to diazepam. In contrast, buspirone was not found to have any adverse effects on steering control; in fact, some evidence of improved tracking control was found. When alcohol was added to each treatment on the ninth day, differences between the drug treatment groups were less pronounced but in the same direction as on the first and eighth days.
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Moskowitz, H. A., & Burns, M. M. (1986). Cognitive performance in geriatric subjects after acute treatment with antidepressants. Neuropsychobiology, 15(Suppl.1), 38-43.
The effects of amitriptyline, trazodone and placebo on cognitive skills performance were examined in a group of 15 normal volunteers with a minimum age of 60. Each subject was behaviorally tested after single, acute treatments at weekly sessions using a battery of tasks measuring visual search, division of attention, tracking, critical tracking, rate of information processing, and vigilance. Amitriptyline, 50 mg, produced impairment on the vigilance task, the divided attention task and the critical tracking task. In addition, episodes of extended insensitivity to external stimuli similar to short-term sleep occurred. In contrast, trazodone exhibited impairment only on the critical tracking task. This study indicates that trazodone is less likely than amitriptyline to produce impairment of skills performance aspects of cognition.
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Burns, M. M., Moskowitz, H. A., & Jaffe, J. (1986). A comparison of the effects of trazodone and amitriptyline on skills performance by geriatric subjects. Journal of Clinical Psychiatry, 47(5), 252-254.
Fifteen healthy adults, aged 60 years and older, participated in a double-blind, crossover study of trazodone in comparison with amitriptyline and placebo. A battery of laboratory tests was used to measure drug effects on information processing, attention, and visual-motor skills. Amitriptyline 50 mg impaired vigilance and tracking performance and increased drowsiness. Trazodone 100 mg impaired only the most difficult tracking task. This study demonstrates that cognition and performance are less adversely affected in geriatric subjects by trazodone than by amitriptyline beginning 90 minutes after a single-dosage trial.
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Wilkinson, C. J. (1985). Effects of diazepam (Valium) and trait anxiety on human physical aggression and emotional state. Journal of Behavioral Medicine, 8, 101-114.
The effects of diazepam (10 mg orally) and trait anxiety on the aggressive behavior of normal male undergraduates were studied in a competitive reaction time task paradigm which entails shock setting with an increasingly provocative "opponent." Diazepam produced an aggression-enhancing effect which was specifically shown only by the low-trait anxious group under low provocation and generally shown by all groups under conditions of higher provocation. Reductions in state anxiety following diazepam ingestion were seen most clearly in the high- and, somewhat, the moderate-trait anxious groups. In contrast, the low-trait anxious group evidenced an increase in depression but little change in anxiety. The results are consistent with reports of the ability of antianxiety drugs to disinhibit suppressed behaviors. Moreover, trait anxiety appears to mediate the effects of diazepam on both mood states and aggressive behavior.
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Moskowitz, H. A. (1984). Attention tasks as skills performance measures of drug effects. British Journal of Clinical Pharmacology, 18(Suppl.1), 51S-61S.
Both empirical epidemiological data on the causes of traffic accidents and conceptual models of skilled human performance stress the central role of perception and cognition. This paper examines the effects of drugs on two major components of cognitive perceptual performance, namely, concentrated attention or vigilance and divided attention. It is demonstrated that these two types of attention tasks are differentially affected by various drugs, so that sometimes one and sometimes another of these tasks is impaired. Various experimental paradigms to investigate these two attention functions are presented. It is demonstrated that attention tasks are frequently highly sensitive to drug effects, suggesting the importance of examining these functions when investigating the effects of drugs on skills performance.
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Moskowitz, H. A., & Smiley, A. (1982). Effects of chronically administered buspirone and diazepam on driving-related skills performance. Journal of Clinical Psychiatry, 43(12), 45-55.
The effects on driving skills of buspirone and diazepam, singly and in combination with alcohol, were examined. Three groups of 16 subjects each (8 men and 8 women) received either 20 mg of buspirone, 15 mg of diazepam, or placebo daily for 9 days. On day 9, they also received alcohol (men, 0.85 g/kg; women, 0.72 g/kg). On days 1, 8, and 9, subjects were tested on a driving simulator and given four sessions of divided attention tasks examining tracking and visual search performance. Extensive evidence of performance impairment associated with diazepam contrasted with improved performance under chronic buspirone treatment. Alcohol effects were additive.
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