HYPNOTIC AND SEDATIVE DRUG WITHDRAWAL DEFINITION A syndrome of autonomic hyperactivity that occurs as a result of withdrawal of a sedative-hypnotic drug from a physically and/or psychologically dependent individual, following a period of chronic use or abuse. TOXIC CAUSES None. NON-TOXIC CAUSES Administration of a benzodiazepine antagonist (flumazenil) Cessation of hypnotic or sedative drug use Inhibition of absorption of a hypnotic or sedative drug Reduction of dose of a hypnotic or sedative drug CLINICAL FEATURES Symptoms typically begin 1 to 3 days after cessation of drug use and peak at 5 to 6 days, but may occur later with sedative-hypnotics that have long half lives. Administration of flumazenil may result in abrupt appearance of symptoms including convulsions. In this case, the withdrawal syndrome resolves rapidly as the effect of flumazenil diminishes. Manifestations include seizures, drug craving, dysphoria, headache, insomnia, anxiety, anorexia, nausea, vomiting, muscle weakness, tachycardia and tremor. Agitation and confusion may progress to delirium, disorientation, hallucinations. Seizures are a frequent presenting symptom and may commence up to 7 or 8 days following cessation of the sedative-hypnotic. DIFFERENTIAL DIAGNOSIS Metabolic disturbances: hypoxia, hypoglycaemia, hyponatremia, thyrotoxicosis. CNS infection Ethanol withdrawal Heat stroke Neuroleptic malignant syndrome Neurological and psychiatric disorders Opioid withdrawal Serotonin syndrome Sepsis Toxic delirium Anticholinergics Disulfiram Drugs of abuse Levodopa Lithium Salicylates Theophylline RELEVANT INVESTIGATIONS Arterial blood gases Blood and other cultures as indicated CPK CT scan head and lumbar puncture, if indicated ECG Serum electrolytes, urea, creatinine, glucose Toxicological screening TREATMENT In severe cases, treatment of convulsions takes priority. General symptomatic and supportive care is very important and includes reassurance and provision of a calm environment. Clinical features may abate with replacement of the sedative or hypnotic drug or by substitution with a similar sedative-hypnotic such as: Phenobarbitone 60 to 120 mg orally and repeat every hour until symptoms of withdrawal resolve. Diazepam 20 mg orally and then 10 mg every hour until symptoms of withdrawal resolve. Once the patient has been stabilised, gradual drug withdrawal can be undertaken. CLINICAL COURSE AND MONITORING In severe cases, death may occur in the absence of adequate treatment. Duration of the withdrawal syndrome depends on the half-life of the agent and/or that of any active metabolites. Careful observation is required during that period. Adequate nutritional and fluid intake should be ensured. Appropriate social and psychological support is an essential component of medical management. LONG-TERM COMPLICATIONS Social and psychological problems. AUTHOR(S)/REVIEWERS Author: Dr J.N. Bernstein Florida Poison Information Center/Miami Department of Pediatrics P.O. Box 016960 (R-131) Miami, Florida 33101 USA Reviewers: Treatment Guide Working Group members in Ankara London 3/98: T. Della Puppa, L. Murray, A. Nantel, M. Nicholls, J.Tempowski.