Sedative-hypnotics abuse

Specific factors to consider are both psychiatric and physical contraindications. For example, bupropion is contraindicated in a depressed patient with a history of seizures due to the increased risk of recurrence while on this agent. Conversely, it may be an appropriate choice for a bipolar disorder with intermittent depressive episodes that is otherwise under good control with standard mood stabilizers. This consideration is based on the limited data suggesting that bupropion is less likely to induce a manic switch in comparison with standard heterocyclic antidepressants. Another example is the avoidance of benzodiazepines for the treatment of panic disorder in a patient with a history of alcohol or sedative-hypnotic abuse due to the increased risk of misuse or dependency. In this situation, a selective serotonin reuptake inhibitor (SSRI) may be more appropriate. 

In 1997, a large epidemiological study found that 11.3% of individuals with lifetime major depression had only episodes meeting atypical criteria ( 11). These patients (especially male patients) may also be at greater risk for sedative-hypnotic abuse. If the clinician is cognizant of these probabilities, preventive steps can be taken (e g., education about sedative-hypnotics). The identification of the nonclassic forms, as well as their differences in clinical presentation, has substantial implications for their differential treatment (see Chapter 7). 

Glassification of Substance-Related Disorders. The DSM-IV classification system (1) divides substance-related disorders into two categories (/) substance use disorders, ie, abuse and dependence and (2) substance-induced disorders, intoxication, withdrawal, delirium, persisting dementia, persisting amnestic disorder, psychotic disorder, mood disorder, anxiety disorder, sexual dysfunction, and sleep disorder. The different classes of substances addressed herein are alcohol, amphetamines, caffeine, caimabis, cocaine, hallucinogens, inhalants, nicotine, opioids, phencyclidine, sedatives, hypnotics or anxiolytics, polysubstance, and others. On the basis of their significant socioeconomic impact, alcohol, nicotine, cocaine, and opioids have been selected for discussion herein. 

Comparable findings for lifetime prevalence of psychiatric disorders were obtained in another study of 133 persons, which also found that 47% received a concurrent DSM-III diagnosis of substance abuse or dependence (Khantzian and Treece 1985). The most frequently abused substances were sedative-hypnotics (23%), alcohol (14%), and cannabis (13%). Similar rates of psychiatric disorders were found in other studies of drug abusers (Mirin et al. 1986 Woody et al. 1983). Although such diagnoses do not imply causality, and, in many cases, opioid dependence causes or exacerbates psychiatric problems, some causal link seems likely (Regier et al. 1990). 

Benzodiazepines and similar agents occupy a position of intermediate abuse potential, compared with most other sedative-hypnotics (Griffiths and Weerts 1997). Animal models of abuse habihty indicate that the reinforcing effects of benzodiazepines are less pronounced than are those of the barbiturates, opioids, and stimulants. Differences in abuse potential within the class have not been consistently demonstrated however, most chnicians agree that benzodiazepines with a rapid onset and short duration of action pose the greatest risk in susceptible individuals. 

Sporadic use (e.g., for the induction of sleep after a psychostimulant binge) does not require specific detoxification. Sustained use can be treated as described in the previous sections on detoxification from therapeutic or high dosages but with added caution. In mixed opioid and benzodiazepine abuse, the patient should be stabilized with methadone (some clinicians use other oral preparations of opioids) and a benzodiazepine. Buprenorphine should not be administered with benzodiazepines, because a pharmacodynamic interaction is possible (Ibrahim et al. 2000 Kilicarslan and Sellers 2000) and fatalities have been reported with the combination (Reynaud et al. 1998). Sedative-hypnotic withdrawal is the more medically serious procedure, and we usually... 

Glutethimide (3-ethyl-3-phenyl-2,6-piperidinedione) is a sedative-hypnotic drug that is now rarely used therapeutically because of wide variation in gastrointestinal absorption, fast development of pharmacodynamic tolerance, a fairly severe discontinuation syndrome, and potential for abuse. Reports of... 

Uni 1ke other drugs of abuse, the diagnosis of PCP intoxication is often difficult because of the wide spectrum of clinical findings that occurs with this drug. PCP toxicity sometimes can be mistaken for delirium tremens, acute psychiatric illness, sedative/ hypnotic overdosage, amphetamine intoxication, or sedative/ hypnotic withdrawal syndromes. 

Taper oft antipsychotics, benzodiazepines, or sedative-hypnotic agents if possible Treat substance abuse... 

Anxiety disorders (e.g., generalized anxiety disorder, obsessive-compulsive disorder) Substance abuse (alcohol or sedative-hypnotic withdrawal)... 

Sedative/Hypnotic/Anxiolytic Abuse, Sedative/Hypnotic/Anxiolytic Dependence Polysubstance Dependence... 

Nevertheless, sedative-hypnotic agents often play a useful role in treatment. In particular, by providing a successful night s sleep, these medications can break the cycle of anxious anticipation and dread that afflicts the insomnia sufferer during the night. We generally prefer using zolpidem or zaleplon as a first-line treatment for early-to-middle insomnia. Late insomnia often responds well to trazodone or eszopiclone, and trazodone often is a first choice in the presence of substance abuse for all insomnias. 

Drug abuse and dependence Sedative/hypnotics have produced withdrawal signs and symptoms following abrupt discontinuation. These reported symptoms range from mild dysphoria and insomnia to a withdrawal syndrome that may include abdominal and muscle cramps, vomiting, sweating, tremors, and convulsions. Zolpidem does not reveal any clear evidence for withdrawal syndrome. 

Exposure to toxicants can vary, producing what is known as acute or chronic poisoning. Poisoning can also be classified according to the intent of use. Poisoning can either be suicidal (non-accidental) or accidental in nature. Recreational poisoning, such as substance abuse, can be a source of harmful intoxication and, in some cases, can lead to addiction and withdrawal symptoms. Intentional harm is observed when there is criminal doping with sedative-hypnotic medicines, often associated with robberies. 

Compared to the benzodiazepine sedative-hypnotics, secobarbital is more lethal in overdosage, has a higher tendency for abuse and addiction, and is more likely to cause drug interactions via induction of hepatic microsomal enzymes few advan-fages if any in safety or efficacy over benzodiazepines... 

Psychotic symptoms may also occur with the withdrawal of alcohol, sedatives, hypnotics, and anxiolytics The following symptoms may occur persecutory delusions, perceptual distortions, and vivid hallucinations in any modality, most classically visual and tactile hallucination of insects crawling under the skin (formication) Substance abuse history may be elicited from the history and confirmed by finding urinary metabolites Confirmation of schizophrenia can only be made if the psychotic symptoms persist for at least a month following drug withdrawal... 

Unlike benzodiazepines, buspirone is not associated with sedative or abuse problems, but some clinicians have observed that bus-pirone s anxiolytic properties do not appear to be as potent as those of benzodiazepines, particularly in patients who have previously received a benzodiazepine. Because buspirone is not sedating and has no psychomotor effects, it has a distinct advantage over benzodiazepines when optimal alertness and motor performance are necessary. Response to buspirone occurs in approximately 2-4 weeks. Buspirone does not show cross-tolerance with benzodiazepines and other sedative or hypnotic drugs such as alcohol, barbiturates, and chloral hydrate. Therefore, buspirone does not suppress benzodiazepine withdrawal symptoms. In anxious patients who are taking a benzodiazepine and who require a switch to buspirone, the benzodiazepine must be tapered gradually to avoid withdrawal symptoms, despite the fact that the patient is receiving buspirone. 

Allgulander, C. History and current status of sedative-hypnotic drug use and abuse. Acta Psychiatr. Scand. 73, 465-478, 1986. 

One of the first quinazolone-based drugs, the sedative hypnotic methaqualone (83-4), gained considerable notoriety as a drug of abuse under the alias ludes after the original tradename Quaalude. The compound is prepared in a straightforward fashion by fusion of anthranilamide (83-1) with orf/zo-toluidine (83-2) [93] the reaction can be envisaged as proceeding via the di-amide (83-3). 

Anxiolytics and Sedative-Hypnotics. Because of their large therapeutic index, measurement of anxiolytic or sedative-hypnotic serum concentrations is not usually necessary in clinical practice, unless abuse, overdose, or inadvertent toxicity are suspected. Some data indicate that plasma alprazolam levels of 40 ng/mL may be required to manage panic disorder ( 51) (see the sections Adverse Effects of Anxiolytics and Adverse Effects of Sedative-Hypnotics in Chapter 12). 

Barbiturates, which preceded benzodiazepines as the most commonly abused sedative hypnotics (after ethanol), are now rarely prescribed to outpatients and therefore constitute a less common prescription drug problem than they did in the past. Street sales of barbiturates, however, continue. Management of barbiturate withdrawal and addiction is similar to that of benzodiazepines. 

Wesson, Donald R., D. E. Smith, and R. B. Seymour. 1992. "Sedative Hypnotics and Tricyclics." In Substance Abuse A Comprehensive Textbook, edited by Joyce H. Lowinson, Pedro Ruiz, Robert B. Millman, and J. G- Langrod. Baltimore Williams and Wilkins. 

Jasinski, D.R., Assessment of the abuse potentiality of morphinelike drugs (methods used in man), in Drug Addiction 1 Morphine, Sedative/Hypnotic and Alcohol Dependence, W.R. Martin, Ed., Springer-Verlag, Berlin, 1977. 

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