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Relative Abuse Liability of Hypnotic Drugs: A Conceptual Framework and Algorithm for Differentiating Among Compounds.

Roland R. Griffiths, PhD and Matthew W. Johnson, PhD

Published: November 15, 2005

Article Abstract

Hypnotic drugs, including benzodiazepine receptor ligands, barbiturates, antihistamines, and melatoninreceptor ligands, are useful in treating insomnia, but clinicians should consider the relativeabuse liability of these drugs when prescribing them. Two types of problematic hypnotic self-administrationare distinguished. First, recreational abuse occurs when medications are used purposefullyfor the subjective “high.” This type of abuse usually occurs in polydrug abusers, who are mostoften young and male. Second, chronic quasi-therapeutic abuse is a problematic use of hypnotic drugsin which patients continue long-term use despite medical recommendations to the contrary. Relativeabuse liability is defined as an interaction between the relative reinforcing effects (i.e., the capacity tomaintain drug self-administration behavior, thereby increasing the likelihood of nonmedical problematicuse) and the relative toxicity (i.e., adverse effects having the capacity to harm the individualand/or society). An algorithm is provided that differentiates relative likelihood of abuse and relativetoxicity of 19 hypnotic compounds: pentobarbital, methaqualone, diazepam, flunitrazepam, lorazepam,GHB (γ-hydroxybutyrate, also known as sodium oxybate), temazepam, zaleplon, eszopiclone,triazolam, zopiclone, flurazepam, zolpidem, oxazepam, estazolam, diphenhydramine, quazepam, trazodone,and ramelteon. Factors in the analysis include preclinical and clinical assessment of reinforcingeffects, preclinical and clinical assessment of withdrawal, actual abuse, acute sedation/memoryimpairment, and overdose lethality. The analysis shows that both the likelihood of abuse and the toxicityvary from high to none across these compounds. The primary clinical implication of the range ofdifferences in abuse liability is that concern about recreational abuse, inappropriate long-term use, oradverse effects should not deter physicians from prescribing hypnotics when clinically indicated.

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