Treatment of Benzodiazepine Dependence.

This paper reviews studies examining the pharmacological interactions and epidemiology of the combined use of opioids and benzodiazepines (BZDs). A search of English language publications from 1970 to 2012 was conducted using PubMed and PsycINFO(®). Our search found approximately 200 articles appropriate for inclusion in this paper. While numerous reports indicate that the co-abuse of opioids and BZDs is ubiquitous around the world, the reasons for the co-abuse of these medications are not entirely clear. Though the possibility remains that opioid abusers are using BZDs therapeutically to self-medicate anxiety, mania or insomnia, the data reviewed in this paper suggest that BZD use is primarily recreational. For example, co-users report seeking BZD prescriptions for the purpose of enhancing opioid intoxication or "high," and use doses that exceed the therapeutic range. Since there are few clinical studies investigating the pharmacological interaction and abuse liability of their combined use, this hypothesis has not been extensively evaluated in clinical settings. As such, our analysis encourages further systematic investigation of BZD abuse among opioid abusers. The co-abuse of BZDs and opioids is substantial and has negative consequences for general health, overdose lethality, and treatment outcome. Physicians should address this important and underappreciated problem with more cautious prescribing practices, and increased vigilance for abusive patterns of use.

Drug seeking and drug self-administration in both animals and humans can be triggered by drugs of abuse themselves or by stressful events. Here, we demonstrate that in vivo administration of drugs of abuse with different molecular mechanisms of action as well as acute stress both increase strength at excitatory synapses on midbrain dopamine neurons. Psychoactive drugs with minimal abuse potential do not cause this change. The synaptic effects of stress, but not of cocaine, are blocked by the glucocorticoid receptor antagonist RU486. These results suggest that plasticity at excitatory synapses on dopamine neurons may be a key neural adaptation contributing to addiction and its interactions with stress and thus may be an attractive therapeutic target for reducing the risk of addiction.

Because of the role of psychological factors in insomnia, the shortcomings of hypnotic medications, and patients' greater acceptance of nonpharmacological treatments for insomnia, the authors conducted a meta-analysis to examine the efficacy and durability of psychological treatments for the clinical management of chronic insomnia. A total of 59 treatment outcome studies, involving 2,102 patients, were selected for review on the basis of the following criteria: 1) the primary target problem was sleep-onset, maintenance, or mixed insomnia, 2) the treatment was nonpharmacological, 3) the study used a group design, and 4) the outcome measures included sleep-onset latency, time awake after sleep onset, number of nighttime awakenings, or total sleep time. Psychological interventions, averaging 5.0 hours of therapy time, produced reliable changes in two of the four sleep measures examined. The average effect sizes (i.e., z scores) were 0.88 for sleep latency and 0.65 for time awake after sleep onset. These results indicate that patients with insomnia were better off after treatment than 81% and 74% of untreated control subjects in terms of sleep induction and sleep maintenance, respectively. Stimulus control and sleep restriction were the most effective single therapy procedures, whereas sleep hygiene education was not effective when used alone. Clinical improvements seen at treatment completion were well maintained at follow-ups averaging 6 months in duration. The findings indicate that nonpharmacological interventions produce reliable and durable changes in the sleep patterns of patients with chronic insomnia.