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Chapter 140 Medication and Substance Abuse Timothy Roehrs; Thomas Roth Chapter Highlights • Most psychoactive drugs with abuse • Some of the drugs of abuse are legal and widely liability have effects on sleep and used socially and may be the cause of patients’ wakefulness. sleep or alertness complaints. • The mechanisms underlying substance abuse • Other drugs with abuse liability are drugs are known, but the role of the drug’s sleep-wake indicated in the treatment of sleep disorders. state–altering effects in substance abuse is • This chapter provides guidelines for sleep not fully known, although it is likely to be disorders clinicians to differentiate drug-seeking important. behavior from therapy-seeking behavior. Various legal medications and all illegal central nervous system criteria is important for referral decisions. Substance abuse (CNS)–acting drugs have a high abuse liability, that is, the and dependence are common, as 18% of the U.S. population likelihood for development of physiologic or behavioral will experience a substance abuse disorder during their life- dependence on these substances is heightened. The various time, and about 20% of patients in general medical practice terms often used in discussing substance abuse are confusing, and 35% of psychiatric patients present with substance abuse are controversial, and need clarification. Physiologic depen- disorders. dence is a state induced by repeated drug use that results in a Virtually all drugs with a high abuse liability have pro- withdrawal syndrome when the drug is discontinued or an found effects on sleep and wake. For this reason, sleep disor- antagonist is administered. Many legal medications and illegal ders clinicians should assess all the drug-taking behavior of drugs can produce physiologic dependence, although the syn- their patients, including prescribed and over-the-counter drome intensity, relation to dose, and necessary duration of drugs, recreational drugs, tobacco and caffeine, health foods, use vary among different drugs. The fact that a drug produces steroids, botanicals, and natural substances. This chapter physiologic dependence, meaning that a withdrawal syndrome reviews the sleep-wake alterations produced by administration appears when the drug is discontinued, does not necessarily and discontinuation of various drug classes associated with imply substance abuse. abuse. Also discussed is the way that the state-altering char- In the sleep field, a phenomenon suggestive of the presence acteristics (i.e., their disruptive effects on sleep or daytime of physiologic dependence on a drug is rapid eye movement alertness) of these drugs contribute to their dependence liabil- (REM) sleep rebound. When drugs that suppress REM sleep ity. Finally, what is known about the neurobiologic and behav- are discontinued, a REM rebound (i.e., increased REM pres- ioral mechanisms that underlie these drugs’ abuse liability and sure) is seen, which is manifested by reduced REM sleep their state-altering effects is discussed. latency, by increased REM sleep time and REM density, and Some drugs of abuse have no legal therapeutic indications subjectively with reports of nightmares. Most of the antide- (i.e., various inhalants, LSD); others have narrowly defined pressant medications at therapeutic doses suppress REM therapeutic indications (i.e., amphetamine, methylphenidate), sleep, and a REM sleep rebound occurs when the drug is and some have broader therapeutic indications (i.e., benzodi- discontinued. However, a REM sleep rebound after antide- azepine receptor agonists). Other drugs of abuse have wide pressant use does not lead to resumption of antidepressant use. use as social drugs (i.e., alcohol and caffeine). Marijuana occu- On the other hand, a reduced REM latency (e.g., one sign of pies a unique position as it remains illegal federally but as of REM pressure and an underlying REM sleep disturbance) in 2014 is legal in 20-plus states for specific therapeutic indica- abstinent alcoholics is predictive of alcoholic relapse. tions and in a few states for recreational and social use. For Physiologic dependence may be a component of but is these various reasons, guidelines are provided for sleep disor- neither a necessary nor a sufficient condition for behavioral ders clinicians that will help them differentiate drug-seeking dependence. Behavioral dependence is a pattern of behavior behavior from therapy-seeking behavior. In drug-seeking characterized by repetitive and compulsive drug seeking and behavior, the drug and its effects are the focus of the drug use, consumption, despite considerable substance-related prob- whereas in therapy-seeking behavior, the medications’ ability lems. The formal diagnostic criteria according to theDiagnos - to reverse the signs and symptoms of the disease is the focus tic and Statistical Manual of Mental Disorders, fifth edition of the drug use. This distinction is important because many of (DSM-5) are discussed later. Whereas the sleep disorders the drugs used by sleep disorders clinicians are used chroni- clinician will not make formal diagnoses, awareness of the cally, and hence it is important to differentiate long-term use 1380 Downloaded for Rohul Amin ([email protected]) at Uniformed Services Univ of the Health Sciences from ClinicalKey.com by Elsevier on September 29, 2018. For personal use only. No other uses without permission. Copyright ©2018. Elsevier Inc. All rights reserved. Chapter 140 Medication and Substance Abuse 1381 from abuse. Many of these medications also have scientifically state, such as a withdrawal syndrome, insomnia, or excessive documented efficacy and are hence indicated for specific sleep sleepiness-fatigue. The two processes, positive and negative disorders; some of these drugs also are abused and, impor- drug reinforcement, are not necessarily mutually exclusive and tantly, may be the cause of a sleep disorder. may operate concurrently or at the different stages in a drug abuse cycle (i.e., its initiation, maintenance, or relapse). These DIAGNOSIS OF SUBSTANCE-RELATED two reinforcement processes lead to the initiation and main- DISORDERS tenance of excessive and hazardous drug use. How the sleep- wake state–altering consequences of the drugs addressed in The generally accepted diagnostic classification system for this chapter may function as positive or negative reinforcers substance-related disorders is DSM-5. DSM-5 reflects a can be illustrated. major departure from DSM-IV and DSM-IV-TR. Substance- The alerting effects of stimulants are reinforcing for indi- related disorders are divided into two major classes: (1) sub- viduals who are sleepy, fatigued, and having difficulty in stance use and (2) substance-induced disorders. Substance use functioning to their desired level. Healthy normals will self- disorders, formerly termed substance abuse and substance administer a stimulant when they are sleepy but not when dependence (DSM-IV-TR), are characterized by behaviors alert.1 That self-administration does not necessarily imply and consequences (a total of 11 criteria are listed) in groupings abuse. In substance abuse, however, the sleepiness may be that show impaired control, social impairment, risky use, and present as part of a withdrawal syndrome due to abstinence pharmacologic consequences (i.e., tolerance, withdrawal) associ- following chronic nonmedical use of a stimulant. It has been ated with use of 10 classes of substances. Rather than distin- hypothesized that continued substance use, difficulty in reduc- guishing abuse and dependence as in DSM-IV-TR, DSM-5 ing use, or relapse may reflect “self-medication” to reverse the rates the severity of the disorder by the number of symptoms excessive sleepiness of the abstinence. For example, in chronic present: mild, two or three; moderate, four or five; and severe, caffeine or nicotine dependence, the 8-hour sleep period is six or more. Substance-induced disorders are characterized by functionally an enforced abstinence, and given the pharmaco- symptoms reflecting the presence of intoxication, withdrawal, kinetics of these drugs, the 8-hour abstinence during the sleep or a mental disorder. As this category name implies, the dis- period is followed by enhanced sleepiness in the morning and, order has to be associated with current or very recent use of in extreme cases, smoking during the night. Caffeine or nico- the substance. tine taken immediately on arising reverses the sleepy state. Whereas most of the drugs of abuse are disruptive of sleep “When do you have your first morning cigarette?” is a question or daytime alertness, such disturbances are not major criteria clinicians can use to gauge the severity of nicotine addiction. for substance abuse in DSM-5. They are mentioned as pos- In amphetamine or cocaine abuse, excessive sleepiness during sible symptoms in a withdrawal syndrome, which is one of the the initial drug abstinence has been consistently reported. 11 criteria for a substance use disorder. DSM-5 emphasizes Again, use of these stimulants will reverse the sleepiness. that symptoms of tolerance development and withdrawal, only During a period of chronic drug use, daytime sleepiness occurring in the context of medical treatment with prescribed may also result from a drug-induced disturbance of nocturnal medications, should not receive a diagnosis of substance- sleep. All the stimulants as reviewed later disrupt nocturnal related disorder (distinguishing drug seeking from therapy sleep to some degree, depending on dose and
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