Melatonin and Benzodiazepine/Z-Drug Abuse

Abstract

A temporal relationship between the nocturnal rise in melatonin secretion and the increase in sleep propensity at the beginning of the night, coupled with the sleep-promoting effects of exogenous melatonin, supports the view that melatonin is involved in the regulation of sleep. Both meta-analyses and consensus agreements give credibility to the therapeutic use of melatonin in sleep disorders. Administration of melatonin will cue the circadian phase of sleep/wake cycles in a variety of disorders including jet lag problems, shift work maladaptation, advanced and delayed sleep phase disorders, major affective disorder, seasonal affective disorder, and disrupted rhythms in attention deficit hyperactivity disorder, autism, and schizophrenia. This action is attributed to MT1 and MT2 melatonin receptors present in the hypothalamic suprachiasmatic nucleus (SCN) and in other brain areas. Almost every single neuron in the SCN contains GABA, and many results in animals point out to a melatonin interaction with GABA-containing neurons. In addition, central-type benzodiazepine (BZD) antagonism that obliterates GABAA receptor function blunted melatonin behavioral effects including sleep. The sleep-promoting activity of melatonin is relevant because the BZD and type Z-drugs usually prescribed as sleep promoters have many adverse effects, such as next-day hangover, dependence, and impairment of memory. This chapter discusses available data on the efficacy of melatonin to curtail chronic BZD/Z-drug use in insomnia patients.