Relative Abuse Liability of Hypnotic Drugs: A Conceptual Framework and Algorithm for Differentiating Among Compounds.
J Clin Psychiatry 2005;66(suppl 9):31-41
© Copyright 2015 Physicians Postgraduate Press, Inc.
Hypnotic drugs, including benzodiazepine receptor ligands, barbiturates, antihistamines, and melatonin
receptor ligands, are useful in treating insomnia, but clinicians should consider the relative
abuse liability of these drugs when prescribing them. Two types of problematic hypnotic self-administration
are distinguished. First, recreational abuse occurs when medications are used purposefully
for the subjective "high." This type of abuse usually occurs in polydrug abusers, who are most
often young and male. Second, chronic quasi-therapeutic abuse is a problematic use of hypnotic drugs
in which patients continue long-term use despite medical recommendations to the contrary. Relative
abuse liability is defined as an interaction between the relative reinforcing effects (i.e., the capacity to
maintain drug self-administration behavior, thereby increasing the likelihood of nonmedical problematic
use) and the relative toxicity (i.e., adverse effects having the capacity to harm the individual
and/or society). An algorithm is provided that differentiates relative likelihood of abuse and relative
toxicity 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 reinforcing
effects, preclinical and clinical assessment of withdrawal, actual abuse, acute sedation/memory
impairment, and overdose lethality. The analysis shows that both the likelihood of abuse and the toxicity
vary from high to none across these compounds. The primary clinical implication of the range of
differences in abuse liability is that concern about recreational abuse, inappropriate long-term use, or
adverse effects should not deter physicians from prescribing hypnotics when clinically indicated.