Benzodiazepines dependence liability

Reynaud M, Petit G, Potard D, et al Six deaths linked to concomitant use of buprenor-phine and benzodiazepines. Addiction 93 1383-1392, 1998 Richards JG, Martin JR Binding profiles and physical dependence liabilities of selected benzodiazepine receptor ligands. Brain Res Bull 43 381-387, 1998... 

Eszopiclone Bind selectively to a subgroup of GABAa receptors, acting like benzodiazepines to enhance membrane hyperpolarization Rapid onset of hypnosis with few amnestic effects or day-after psychomotor depression or somnolence Sleep disorders, especially those characterized by difficulty in falling asleep Oral activity short half-lives CYP substrates Toxicity Extensions of CNS depressant effects dependence liability Interactions Additive CNS depression with ethanol and many other drugs... 

Because all benzodiazepines have abuse and dependence liability, patients cannot be switched from one benzodiazepine to another in hopes of decreasing a pattern of drug abuse or dependence behavior. Zolpidem, a nonbenzodiazepine nonbarbiturate sedative, has been suggested to have little liability for physical dependence, but tolerance and withdrawal have been reported in association with its use as well."... 

Three of the drugs listed are effective in absence seizures. Ethosuximide and valproic acid are not sedating, and tolerance does not develop to their antiseizure activity. Clonazepam is effective but exerts troublesome CNS depressant effects, and tolerance develops with chronic use. At high doses, the drug has a dependence liability like most benzodiazepines. The answer is (A). 

Anxiety disorders are common in the population of opioid-addicted individuals however, treatment studies are lacking. It is uncertain whether the frequency of anxiety disorders contributes to high rates of illicit use of benzodiazepines, which is common in methadone maintenance programs (Ross and Darke 2000). Increased toxicity has been observed when benzodiazepines are co-administered with some opioids (Borron et al. 2002 Caplehorn and Drummer 2002). Although there is an interesting report of clonazepam maintenance treatment for methadone maintenance patients who abuse benzodiazepines, further studies are needed (Bleich et al. 2002). Unfortunately, buspirone, which has low abuse liability, was not effective in an anxiety treatment study in opioid-dependent subjects (McRae et al. 2004). Current clinical practice is to prescribe SSRIs or other antidepressants that have antianxiety actions for these patients. Carefully controlled benzodiazepine prescribing is advocated by some practitioners. 

Williams H, Oyefeso A, Ghodse AH Benzodiazepine misuse and dependence among opiate addicts in treatment. It J Psychol Med 13 62-64, 1996 Wiseman SM, Spencer-Peet J Prescribing for alcoholics a survey of drugs taken prior to admission to an alcoholism unit. Practitioner 229 88—89, 1985 Wolf B, Grohmann R, Biber D, et al Benzodiazepine abuse and dependence in psychiatric inpatients. Pharmacopsychiatry 22 54—60, 1989 Wood MR, Kim JJ, Han W, et al Benzodiazepines as potent and selective bradykinin B1 antagonists. J Med Chem 46 1803—1806, 2003 Zawertailo LA, Busto UE, Kaplan HL, et al Comparative abuse liability and pharmacological effects of meprobamate, triazolam, and butabarbital. J Clin Psycho-pharmacol 23 269-280, 2003... 

Many CNS depressants have some liability for dependence. This is typically greater with barbiturates, but lesser with benzodiazepines, and perhaps nonexistent in many antiseizure medications. CNS depressants produce tolerance when administered chronically, where increasingly larger doses are required to sustain the same level of effect. Further, a cross-tolerance often develops, where the tolerance is generalized to other CNS depressants. For example, a person with an ethanol tolerance will also display some tolerance to barbiturates. The therapeutic index tends to decrease as tolerance increases, so that the difference between an effective and toxic dose diminishes. Thus, tolerance to CNS depressants is accompanied by a smaller safety margin. 

Azapirones. Though several azapirones have been developed and tested in the laboratory setting, only one, bnspirone (Bnspar), is currently on the market. Buspirone is the first nonsedating, nonbenzodiazepine anxiolytic, other than the antidepressants described earlier. It has no dependence or addictive liability and is not lethal in overdose. Buspirone is also devoid of many of the problems of the benzodiazepines such as sedation, motor impairment, addiction, physical dependence, or withdrawal. Yet, doubts remain in the minds of many practitioners regarding the effectiveness of buspirone. This will be discussed in more detail later in this chapter. 

Drug abuse and dependence In a study of abuse liability conducted in individuals with known histories of benzodiazepine abuse, doses of eszopiclone 6 and 12 mg produced euphoric effects similar to those of diazepam 20 mg. 

Uhlenhuth EH, Balter MB, Ban TA, et al. International study of expert judgment on therapeutic use of benzodiazepines and other psychotherapeutic medications IV. Therapeutic dose dependence and abuse liability of benzodiazepines in the long-term treatment of anxiety disorders. J Clin Psychopharmacol 1999 19(suppl 2) 23S-29S. 

From the published clinical studies, it would appear that the partial agonists bretazenil and abercamil are less likely to cause physiological dependence, have lower reinforcing effects and a lower incidence of subjective effects associated with abuse liability than the conventional 1,4-benzodiazepine sedative-hypnotics. It is presently unclear whether the full agonists for the GABA-A receptor, zolpidem and zopiclone, offer a real advance in the treatment of insomnia although their adverse effect profiles and abuse liability may be lower than that of the conventional benzodiazepines. 

An additional psychotropic medication that may be worth considering specifically for GAD is buspirone. One major benefit of buspirone can be found in the virtual absence of dependence and abuse liability. Although it is not effective for the acute relief of anxiety or panic disorders (anxiolytic effects may take up to a week to be established), buspirone may be indicated for patients with a history of alcohol abuse or among those who fear physiologic and psychological dependence with benzodiazepines. 

Answer B. Buspirone has selective anxiolytic activity that is slow in onset The drug has no abuse liability and will not suppress withdrawal symptoms in patients who have become physically dependent on barbiturates, benzodiazepines, or ethanol. Bupropion is an antidepressant, also approved for management of dependence on nicotine. Baclofen is a spinal cord muscle relaxant that activates GABAfi receptors. Buprenorphine is a long-acting opioid analgesic with no effectiveness in GAD, and butabarbital is a barbiturate that may cause dependence. 

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