Lack of Preference for Diazepam in Anxious Volunteers

Wit, Harriet de; Uhlenhuth, E. H.; Hedeker, Don; McCracken, Stanley G.; Johanson, Chris E.

doi:10.1001/archpsyc.1986.01800060023004

Cited by 72 publications

(27 citation statements)

References 20 publications

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“…In fact, only a few studies have examined the reinforcing effects of psychoactive drugs in individuals who receive them for clinical purposes. For example, the reinforcing effects of diazepam and alprazolam-sedatives which have clearly demonstrated abuse potential in non-clinical samples (Gomez et al 2002;Juergens 1991;Woods and Winger 1995)-have been examined in individuals diagnosed with varying levels of clinically significant anxiety (McCracken et al 1990;Roache et al 1997;deWit et al 1986). In one study, volunteers with either generalized anxiety disorder or panic disorder preferred alprazolam significantly more than placebo under free-choice, double-blind conditions, which by definition suggested reinforcing effects.…”

Section: Introductionmentioning

confidence: 99%

Assessing methylphenidate preference in ADHD patients using a choice procedure

Fredericks

Kollins

2004

Psychopharmacology

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Despite higher preference of MPH than placebo in this clinical sample, other measures of abuse potential were not elevated, and MPH choosers were more symptomatic than non-choosers. As such, MPH preference in ADHD populations likely reflects therapeutic efficacy rather than abuse potential. Future work should examine MPH choice in diagnosed and non-diagnosed populations to further explore the role of clinical efficacy in the preference of this stimulant drug.

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Section: Introductionmentioning

confidence: 99%

Assessing methylphenidate preference in ADHD patients using a choice procedure

Fredericks

Kollins

2004

Psychopharmacology

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“…The large majority of patients suffering from anxiety and panic disorder use benzodiazepines appropriately. Studies suggest that these patients find benzodiazepines to be highly effective and do not report the type of preference/drug-liking that has been associated with risk of abuse [42,43]. Consistent with this, the long-term therapeutic use of benzodiazepines is not associated with dose escalation or patterns of recreational use typical of drugs of abuse [42,44].…”

Section: Tolerability and Safety Considerationsmentioning

confidence: 95%

“…These findings are consistent with previous research. Despite the public perception that abuse of benzodiazepines is a widespread problem, studies suggest that benzodiazepines that are prescribed for anxiety and/or panic disorder are rarely abused [41][42][43][44]60,61]. The subgroup with the highest abuse liability appear to be polydrug users who typically resort to benzodiazepines when their drug of choice is unavailable or if they need to self-medicate to control the stimulatory and/or withdrawal effects of their preferred drug of abuse.…”

Section: Effect Of Alprazolam-xr Pharmacokinetic Profile On Abuse Liamentioning

confidence: 99%

Alprazolam extended-release in panic disorder

Rickels¹

2004

Expert Opinion on Pharmacotherapy

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Alprazolam-XR is an extended-release formulation of alprazolam designed to deliver sustained therapeutic concentrations for 24 h after once-daily dosing. Plasma concentrations gradually decline as the time for the next dose approaches, but still remain above therapeutic minimum levels. The anti-panic efficacy of alprazolam-XR appears to be comparable to the original formulation of alprazolam. The main advantage of the new extended-release formulation appears to be its greater tolerability and safety. The speed with which high-potency benzodiazepines are absorbed, and rise to peak concentrations is correlated with both abuse potential and with the incidence and severity of common adverse events, such as sedation and cognitive and psychomotor impairment. Alprazolam-XR does not exhibit the sudden increases in plasma concentration characteristic of the original formulation of alprazolam. This pharmacokinetic difference appears to translate into a reduced liability of abuse and a reduced incidence of sedation and cognitive and psychomotor impairment during acute therapy. This would appear to give alprazolam-XR a more favourable benefit:risk profile than the original formulation of alprazolam. In addition, the once-daily dosing (as opposed to three or four times per day) reduces clock-watching, increases compliance and it eliminates the penalty of breakthrough anxiety and panic that many patients experience if they inadvertently miss a dose. It should be noted that long-term therapy with alprazolam-XR carries the same risk of dependence and withdrawal during discontinuation as the original formulation of alprazolam.

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“…Similar results have been obtained from a preclinical study investigating the S R and S D effects of benzodiazepines (Ator 2002). Additionally, consideration of the individual characteristics of each subject can affect the interpretation of group data regarding any relationship between subjective (i.e., S D ) and S R effects (see Evans and Griffiths 1992; de Wit et al 1986a, b). Uhlenhuth et al (1981) demonstrated that the baseline subjective state of subjects but not drug-induced subjective effects determined drug preference.…”

Section: Introductionmentioning

confidence: 99%

A within-subject assessment of the discriminative stimulus and reinforcing effects of self-administered cocaine in rhesus monkeys

Martelle

Nader

2008

Psychopharmacology

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Rationale Drug discrimination (DD) and drug self-administration (SA) are frequently used preclinical assays. All preclinical studies with cocaine have examined the discriminative stimulus (S D ) and reinforcing (S R ) effects in separate groups of subjects. Objective The objective of the study is to train drug-naïve rhesus macaques to discriminate self-administered cocaine from saline and to assess S D and S R effects using a withinsubjects design. Materials and methods Adult male rhesus monkeys (n=4) were trained to self-administer cocaine (0.1 mg/kg per injection) under a progressive-ratio (PR) reinforcement schedule. Next, they were trained to discriminate selfadministered cocaine (0.45 or 0.56 mg/kg) or saline under a fixed-ratio (FR) 50 schedule of food presentation. The final schedule combined DD and SA into a multiple [chained FR 50 SA (cocaine or saline), food-reinforced DD] and PR SA schedule. Results Each subject acquired SA under a PR schedule with significant differences in breakpoint between saline and cocaine evident by session 5. Self-administered cocaine was established as an S D , such that 80% of responding before delivery of the first reinforcer and 90% of all responding occurred on the injection-appropriate lever. In all monkeys, there was at least one cocaine dose that did not engender cocaine-appropriate responding during DD (i.e., <20% cocaine-appropriate responding) yet functioned as a reinforcer during PR SA, suggesting that cocaine-like S D effects are not necessary for cocaine reinforcement. Conclusions This within-subject model may provide new information related to the behavioral mechanisms of action leading to the high abuse potential of cocaine; such information may lead to novel pharmacological treatment strategies for addiction.

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Lack of Preference for Diazepam in Anxious Volunteers

Cited by 72 publications

References 20 publications

Assessing methylphenidate preference in ADHD patients using a choice procedure

Assessing methylphenidate preference in ADHD patients using a choice procedure

Alprazolam extended-release in panic disorder

A within-subject assessment of the discriminative stimulus and reinforcing effects of self-administered cocaine in rhesus monkeys

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