Substance Use Disorder

1. Definition (DSM-V)1 • “A cluster of cognitive, behavioral and physiological symptoms indicating that the individual continues using the substance despite significant substance-related problems” • Diagnostic criteria • Impaired control over substance use • Social impairment due to use • Risky use (eg, while driving) • Pharmacological criteria (tolerance, withdrawal) Substance Use Disorder American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 5th ed. 2013.

2. BDZs and Z-drugs (zopiclone, zolpidem, and zaleplona) • Used by 9% of Canadians aged ≥15 years1 • Enhance GABA by binding to the alpha-1 subunit of GABAA receptors • Common adverse effects: daytime drowsiness, dizziness, agitation, hallucinations, sleepwalking Sedative Hypnotic Anxiolytic (SHA) Agents BDZ = benzodiazepine; GABA = gamma aminobutyric acid a Approved by Health Canada but no longer marketed Health Canada. Canadian Alcohol and Drug Use Monitoring Survey. 2011.

3. Results in clinically significant impairment or distress, and characterized by ≥2 of the following elements over a 12-month period: • Consumption in higher quantities and/or for longer duration than intended • Persistent urge or multiple attempts to reduce use • Time and effort devoted to the substance • Craving or strong desire to take the substance • Impairment of responsibilities and duties • Impairment in social situations or relationships • Avoidance or reduced time devoted to important activities • Use in physically dangerous situations • Consumption despite awareness of causing/worsening a health problem • Tolerance • Withdrawal signs and symptoms Summary of DSM-V Classification of SHA Use Disorder American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 5th ed. 2013.

4. SHAs account for <1% of all admissions for addiction treatment services1 • United States data: 0.3% in 12–17-year-olds; 0.2% in adults2 • Prevalence lowest in population ≥65 years old • Abuse/dependence associated with zolpidem and zopiclone significantly lower than with BDZs3 How Prevalent is SHA Use Disorder? Pirsi A; Centre for Addiction and Mental Health. CrossCurrents. 2011;14(3). American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 5th ed. 2013. Hajak G et al. Addiction. 2003;98(10):1371-1378.

5. Establish an open and accepting relationship • Conduct regular follow-up visits • Clarify target symptoms to be treated • Consider alternative/complementary management • Ask about family history of substance use disorder • Do a thorough history: medical, psychiatric, and alcohol/drug use • Assess psychosocial factors How Can I Safely Prescribe an SHA?

6. Perform a sleep history if insomnia is presenting complaint • Seek an organic cause for insomnia • Where possible, avoid: • Agents with a rapid entry into / more potent effect on central nervous system • Long-acting BDZs, especially in elderly • Stress that medication is intended for short-term use only and should be used as directed How Can I Safely Prescribe an SHA?cont.

7. Factors in not screening patients • Lack of information on how to support patients with substance use problems • Desire to avoid causing patients discomfort or embarrassment • Time • Stepped approach to screening • No concerns with patient: 1-2 questions • Clinically based concern: schedule follow-up • General screening tools for substance use disorder • NIDA-Modified ASSIST • CAGE questionnaire (Cut down, Annoyed, Guilty, Eye opener) • 5 A’s (Ask, Advise, Assess, Assist, Arrange) How Do I Screen for an SHA Use Disorder in One of My Patients?

8. Benzodiazepine Tapering Strategies: Outpatients • Switch to a longer-acting benzodiazepine • Convert to the equivalent dose of diazepam (max 80–100 mg/day) in divided doses, adjusting the initial dose according to symptoms • Tapering • Maximum 5 mg per week, or 5 mg every 3-4 days if the starting dose is >50 mg of diazepam equivalent • Adjust the rate of taper according to symptoms • Slow the rate of taper once the dose is <20 mg of diazepam equivalent (eg, 2–4 mg/week) • Depending on patient reliability, consider daily, biweekly, or weekly dispensing

9. Benzodiazepine Tapering Strategies: Inpatients • Start the taper at 1/2 to 1/3 the diazepam equivalent, administering in bid–tid doses • If the patient experiences significant withdrawal on this dose, increase the next day dose by 10–30 mg • The patient can be given 10–15 mg of diazepam for acute withdrawal symptoms during the taper • Hold diazepam and decrease the daily dose if the patient experiences sedation or drowsiness • Taper by 10–15 mg/day • Once the patient reaches a daily dose of <50 mg, treatment can be switched over to outpatient

10. Signs and Symptoms of SHA Withdrawal • Autonomic hyperactivity • eg, perspiration, tachycardia, hypertension • Increased hand tremor • Insomnia • Nausea or vomiting • Transient visual, tactile, or auditory illusions • Psychomotor agitation • Anxiety and panic attacks • Grand mal seizures • Delirium, psychosis, and cardiac abnormalities (select cases)

11. Alcohol • Alcohol reduces sleep-onset latency, but sleep is usually shallow and disrupted • Increases snoring, upper airway resistance, and apneic events, even if no apnea history1,2 • Sleep severely disturbed with chronic alcohol use3 • Prolonged sleep latency • Decreased SWS and REM sleep • Poor sleep efficiency • Greater sleep disruption • Sleep disruption in recovering alcoholics can be prolonged (up to 27 months)4 and increases risk of relapse SWS = slow-wave sleep; REM = rapid eye movement Scanlon MF et al. EurRespir J. 2000;16(5):909-913. Young T et al. Am J RespirCrit Care Med. 2002;165(9):1217-1239. Gillin JC et al. Am J Psychiatry. 1990;147(1):106-109. Cohn TJ et al. Addict Biol. 2003;8(4):455-462.

12. Over-the-counter Sleep Agents • First-generation antihistamines • Induce drowsiness by inhibiting histamine-1 receptor • Duration of action: 4–6 hours • Decrease sleep latency and nocturnal awakenings, increase sleep duration and quality1,2 • Potential adverse events: daytime sedation, impaired psychomotor performance, dizziness, and tinnitus • Caution with elderly patients due to possible cognitive impairment3 Kolla BP et al. Alcohol. 2011;46(5):578-585. Kudo Y and Kurihara M. J ClinPharmacol. 1990;30(11):1041-1048. Basu R et al. Am J Geriatr Psychiatry. 2003;11(2):205-213.

13. Over-the-counter Sleep Agents cont • Substance-related disorder can occur • Common pleasant effects: antianxiety, antidepressant, and euphoria/pleasure • Chronic users of high doses can experience significant withdrawal symptoms: dysphoria, agitation, nausea, and cravings • Withdrawal associated with nausea and anxiety; can last up to 10 days

14. Other Substances: Cannabis • Effect on sleep unclear • Subjective effect: induces relaxation and drowsiness • Objective effect: appears to decrease sleep latency and amount/density of REM sleep, and increases SWS1 • Chronic use: tolerance to effects on SWS and sleep latency, but effects on REM sleep persist2 • Higher doses may increase sleep latency3 • Acute discontinuation appears to cause rebound • Sleep disturbance cited as a reason for relapse4 Cousens K, DiMascio A. Psychopharmacologia. 1973;33(4):355-364. KaracanI et al. Ann N Y Acad Sci. 1976;282:348-374. Tassinari CA et al. In: Pharmacology of Marijuana. New York (NY). 1976. KouriEMand Pope HG Jr. ExpClinPsychopharmacol. 2000;8(4):483-492.

15. Other Substances: Opioids • Most commonly abused: codeine, morphine, hydromorphone, and oxycodone • Cause sedation, but reduce total and REM sleep time on first administration (drug-naïve) • Tolerance occurs quickly, requiring dose escalation to achieve effects (including sedation) • Sleep disrupted/suppressed during withdrawal; prolonged insomnia is a risk factor for relapse1 Gillin JC et al. In: Principles and Practice of Sleep Medicine, 4th ed. Philadelphia (PA): Elsevier Saunders; 2005:1345-1358.