Sedative-hypnotics withdrawal from

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... 

A careful haseline physical examination, ECG, and laboratory work-up are essential. Underlying ECG changes (U waves, prolonged QT interval, or flattened T waves) secondary to hypokalemia or bradycardia and atrioventricular block from starvation may be present. AU antidepressants can cause seizures thus a careful risk-benefit assessment is warranted if the patient has predisposing factors such as a personal or family history of seizures, cerebrovascular disease, or alcohol or sedative-hypnotic withdrawal. 

Other sedative-hypnotic medications, such as barbiturates, may play a useful role in severe withdrawal from this group of drugs. For example, in a case series of GBL withdrawal, use of intravenous pentobarbital in the range of 1-2 mg/kg/hour lowered the total requirement for intravenous lorazepam (Sivilotti et al. 2001). Antipsychotic medications are often used to reduce psychotic agitation. However, because antipsychotic medications lower the seizure threshold and may contribute to loss of central control of temperature leading to hyperthermia or neuroleptic malignant syndrome (NMS), they are not indicated as first-line medications for GHB withdrawal delirium (Dyer and Roth 2001 McDaniel and Miotto 2001 Sharma et al. 2001). If anti-... 

Abrupt discontinuation Following the rapid dose decrease or abrupt discontinuation of sedative/hypnotics, signs and symptoms similar to those associated with withdrawal from other CNS-depressant drugs have occurred. 

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. 

Withdrawal from long-term high-dose use of alcohol or sedative-hypnotic drugs can be life threatening if physical dependence is present. Benzodiazepines, such as chlordiazepoxide Librium) and diazepam Valium), are sometimes used to lessen the intensity of the withdrawal symptoms when alcohol or sedative-hypnotic drug use is discontinued. Benzodiazepines are also employed to help relieve the anxiety and other behavioral symptoms that may occur during rehabilitation. 

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... 

Knowing the differential pharmacokinetics for a class of drugs allows the clinician to choose specific members to either achieve a faster onset or a delayed offset of action (13, 14, 17, 18). For example, lorazepam is rapidly absorbed from the gastrointestinal tract into the systemic circulation and from there distributed into the brain. In contrast, oxazepam, the most polar BZD, is slowly absorbed from the gastrointestinal tract. Even after oxazepam is in the systemic circulation, it slowly enters tissue compartments, including the brain, during the distribution phase. Unlike lorazepam, oxazepam is not available in either the intramuscular or intravenous formulations. Thus, lorazepam would be preferable to achieve acute control of alcohol withdrawal (e.g., delirium tremens), whereas oxazepam would better stabilize a dependency-prone patient on sedative-hypnotics, because it does not cause the euphoria seen with the more rapidly absorbed members of this class. 

Long-acting drugs such as chlordiazepoxide and diazepam and, to a lesser extent, phenobarbital are administered in progressively decreasing doses to patients during withdrawal from physiologic dependence on ethanol or other sedative-hypnotics. Parenteral lorazepam is used to suppress the symptoms of delirium tremens. 

Actions at benzodiazepine receptors are thought to underlie virtually all the pharmacological actions of the benzodiazepines, those that are desirable as well as those that are undesirable. This includes the desirable therapeutic actions of benzodiazepines as anxiolytics and sedative-hypnotics, as well as anticonvulsants and muscle relaxants. It also includes their undesirable side effects as amnestic agents and as agents that cause adaptations at the benzodiazepine receptor with chronic administration, which are thought to underlie the production of dependence and withdrawal from these agents (see Chapter 13). 

Longer-term difficulties associated with benzodiazepine use for insomnia come from observations that many patients develop tolerance for these agents, so that they stop working after a week or two. To avoid this, patients must take a sleeping pill only a few times within several days, or for only about 10 days in a row followed by several days or weeks with no drug treatment. Furthermore, if patients persist in taking benzodiazepines as sedative-hypnotics for several weeks to months, there can be a withdrawal syndrome once the medications are stopped, particularly if they are stopped suddenly. This is discussed in further detail in Chapter 13. 

Withdrawal from sedative-hypnotics may be accompanied by a delirium that can be life threatening. In severe withdrawal, seizures, visual, tactile, or auditory hallucinations may occur. 

RBD is characterized by a relative absence of the atonia characteristic of REM sleep. This lack of atonia permits the physical acting out of dream mentation, particularly dreams involving confrontation, aggression and violence. RBD is seen most frequently in older men. RBD occurs in both acute and chronic forms. Acute RBD can occur during withdrawal from alcohol or sedative-hypnotics. RBD has also been induced by the tricyclics, SSRIs and venlafaxine. The chronic form of RBD may occur as part of an identifiable underlying neurological disorder, but typically is idiopathic. RBD may also be an initial manifestation of parkinsonism. RBD is very responsive to clonazepam, although this use has not been FDA approved. 

Benzodiazepine (BZ) intoxication is manifested as slurred speech, poor coordination, swaying, drowsiness, hypotension, nystagmus, and confusion. Signs and symptoms of BZ withdrawal are similar to those of alcohol withdrawal, including muscle pain, anxiety, restlessness, confusion, irritability, haJlucinations, delirium, seizures, and cardiovascular collapse. Withdrawal from short-acting BZs (e.g., oxazepam, lorazepam, alprazolam) has an onset within 12 to 24 hours of the last dose. Diazepam, chlordiazep-oxide, and clorazepate have elimination half-lives (or active metabolites with elimination half-lives) of 24 to greater than 100 hours. So, withdrawal may be delayed for several days after their discontinuation. Sedative-hypnotic dependence is summarized in Table 73-2. 

Withdrawal from narcotics is also less hazardous than withdrawal from sedative-hypnotics. Alcohol, downers, and the minor tranquilizers can produce violent withdrawal, marked by convulsions and, sometimes, death. Narcotic withdrawal can be intensely unpleasant, but it is not life-threatening. 

Typically, antianxiety medications with short half-lives (see figure 16-A) are more likely to produce withdrawal symptoms (since the medications are more rapidly eliminated from the system). However, clearly, withdrawal can occur with all minor tranquilizers and sedative-hypnotics (with the exception of buspirone and possibly Zolpidem, which are chemical compounds unrelated to the benzodiazepines). 

ANTICONVULSANT, HYPNOTIC and SEDATIVE properties. It is used in some countries as a hypnotic in the elderly, for preoperative medication and in the managment of withdrawal from alcohol. 

Hypnosis Sedative-hypnotics promote sleep onset and increase the duration of the sleep state. Rapid eye movement (REM) sleep duration is usually decreased at high doses a rebound increase in REM sleep may occur upon withdrawal from chronic dmg use. 

---