Are There Guidelines for the Responsible Prescription of Benzodiazepines?

Nady el-Guebaly, MD, DPH, DPsych, FRCPC1; Jitender Sareen, MD, FRCPC2; Murray B Stein, MD, MPH, FRCPC3 Can J Psychiatry. 2010;55(11):709-714. The Prevalence of Prescriptions and Their Indications Benzodiazepines are reportedly the most frequently prescribed psychotropic medication. Among adults in the United States and Canada, 3% to 4% are using BDZs at any one time.1 About 100 million prescriptions are written per year. The European Study of the Epidemiology of Mental Disorders (commonly referred to as ESEMeD) investigated the use of ADs and BDZs in 2 1 425 respondents from 6 countries. In the nonhelp-seeking population, BDZs were used more commonly than ADs, while in the help-seeking population, with a 12-month prevalence of major depressive disorder or anxiety disorder, BDZs were used as commonly as ADs. In an Australian study/ 16% of the adults aged 65 years and older (n = 3970) had at least 1 BDZ prescription and the prescription prevalence increased with age. BDZs' sedative, hypnotic, and anxiolytic properties are used for various psychiatric and medical conditions including anxiety disorders, sleep disorders, seizure disorders, movement disorders, and muscle spasticity. They are used in anaesthesiology and for the symptomatic treatment of agitation associated with other psychiatric and neurological disorders including psychotic, mood, and cognitive disorders.4 In emergencies they are the preferred treatment of withdrawal from alcohol and sedative-hypnotics as well as agitation from stimulants. Tolerance to sedative effects usually develops among people receiving maintenance therapy with a stable dose of BDZs; by contrast, the memory-impairing effects can persist after several years of daily administration.5 Overdoses are almost never fatal unless occurring in combination with other sedative agents such as alcohol or opiates. The reinforcing effects of BDZs may not only be mediated through binding of the alpha 1 or lambda 2 subtypes of GABA receptors but also via an opioid mechanism. A partial mu receptor antagonist such as naltrexone may reduce anxiolytic and positive subjective effects of BDZs. This may explain the high level of co-occurrence of BDZs and opioid dependence. Of interest, BDZs are the only major class of drugs with abuse liability that decrease dopamine levels in the mesolimbic system.6 From Physiologic Dependence to Loss of Control The dose and duration of exposure to BDZs determines the development of physiological dependence. It is almost never seen in patients treated for less than 2 weeks but occurs in about 50% of patients treated daily for more than 4 months. Short- and long-acting BDZs produce comparable severity of withdrawal. The development of physiological dependence is reduced with intermittent, compared with continuous, exposure to BDZs. Among people exposed to BDZs, a small subset, likely among those who have abused other substances, will develop compulsive drug-seeking behaviour with loss of control and an inability to stop. The same may apply to people with a positive family history of drug or alcohol dependence, given that some of the risk may be hereditary.7 Most patients treated chronically with BDZs, who presumably may have physiological dependence, do not develop compulsive substance use,8 and some patients present with compulsive substance use without physiological dependence. The abuse potential of BDZs depends not only on the drug receptor selectivity but also on the characteristics of the individual and environmental circumstances. BDZs as a primary substance of abuse in people admitted for addiction treatment make up less than 1 % of all admissions. Most of these people report abuse of alcohol or opioids in addition to BDZs.9 The presence of another co-occurring psychiatric disorder (mood, anxiety, and Cluster C personality) occurs in up to 50% of these admissions. Among patients on methadone maintenance treatment, 40% to 50% abuse BDZs. …