Clinical Textbook of Addictive Disorders 3rd ed - R. Frances, S. Miller, A. Mack (Guilford, 2005) WW

10. Sedatives/Hypnotics and Benzodiazepines 229not dependent on liver functioning, so they are less likely to raise methadoneplasma levels or to build up plasma levels of the active benzodiazepine inpatients who have compromised liver functioning, including alcoholics and theelderly. The benzodiazepines metabolized by conjugation include lorazepam,oxazepam, and temazepam. Thus, because these are less “liked” by methadonemaintainedpatients and may be better choices for these patients and forpatients with compromised liver functioning, a benzodiazepine is to be used.Oxazepam is both a slow-onset and a conjugated benzodiazepine, making itperhaps the best choice for methadone-maintained patients who are treatedwith a benzodiazepine. On the other hand, oxazepam has a short eliminationhalf-life, which means it must be taken three or four times a day for continuoustherapeutic effects. Oxazepam is no less likely to produce physical dependence(including difficulties on discontinuation) than any other benzodiazepine.Oxazepam is a widely used benzodiazepine in Europe (but not in the UnitedStates, where it is commonly abused by drug addicts and alcoholics). Thus,whatever benefit oxazepam may possess for alcoholics and drug addicts comparedto other benzodiazepines is relative and not absolute (DuPont, 1988).PersistencePersistence of a benzodiazepine (or an active metabolite) in the body is importantclinically, because it governs the rapidity of onset of withdrawal symptomsafter the last dose for people who have used benzodiazepines for prolonged periods.The benzodiazepines with shorter elimination half-lives are more likely toproduce early and pronounced withdrawal symptoms on abrupt discontinuation,whereas those with longer elimination half-lives generally produce moredelayed and somewhat attenuated withdrawal symptoms. In general, alprazolam,lorazepam, and oxazepam are more rapidly eliminated than are clorazepate,diazepam, flurazepam, and prazepam. Thus, the benzodiazepines with shorterelimination half-lives are more likely to produce acute withdrawal on abruptcessation after prolonged use. Clonazepam has a longer elimination half-lifethan alprazolam or lorazepam, so it is less likely to produce interdose withdrawalsymptoms and is more appealing as a withdrawal agent (for the same reason,methadone and phenobarbital are attractive as agents in opiate withdrawal andsedative–hypnotic withdrawal).When discontinuing treatment with a benzodiazepine abruptly, the speedof onset and the severity of symptoms are greater for benzodiazepines withshorter elimination half-lives (e.g., alprazolam or lorazepam) than for thosewith a longer half-life (such as clonazepam). However, abrupt discontinuationis not an appropriate medical treatment for benzodiazepine discontinuationafter prolonged, everyday use. When short-acting benzodiazepines are withdrawngradually over several weeks or longer, they do not produce more symptomsof withdrawal than do longer acting benzodiazepines (Sellers et al., 1993).