OPIOID WITHDRAWAL DEFINITION Clinical syndrome produced by withdrawal of an opioid drug from an opioid-dependent individual. by: (1) the cessation or abrupt reduction in dosage of an opioid; or (2) the administration of an opioid antagonist. TOXIC CAUSES Administration of an opioid antagonist including: Naloxone Naltrexone Nalorphine For this reason, in opioid-dependent individuals, opioid antagonists should be used with caution. NON-TOXIC CAUSES Cessation or reduction in dose of an opioid drug including: Buprenorphine Butorphanol Codeine Fentanyl Heroin (Diamorphine) Hydrocodone Hydromorphine Levorphanol Meperidine (Pethidine) Methadone Morphine Nalbuphine Oxycodone Oxymorphone Pentazocine Phenoperidine Propoxyphene CLINICAL DIAGNOSIS A history of cessation or abrupt reduction in dosage of an opioid, or the administration of an opioid antagonist, in an opioid-dependent individual. Initial symptoms and signs may develop immediately after the administration of an opioid antagonist or up to 48 hours after cessation or reduction in dosage of the opioid, depending upon the half-life of the drug concerned. These include restlessness, mydriasis, lacrimation, rhinorrhea, sneezing, piloerection, yawning, perspiration, restless sleep and aggressive behavior. Severe manifestations include: muscle spasms, back aches, abdominal cramps, hot and cold flashes, insomnia, nausea, vomiting, diarrhoea, tachypnoea, hypertension, hypotension, tachycardia, bradycardia and cardiac dysrhythmias. Seizures may be observed in neonates (only). DIFFERENTIAL DIAGNOSIS Ethanol or benzodiazepine withdrawal Psychogenic origin Simulated withdrawal Other toxic states may mimic certain features of opioid withdrawal. RELEVANT INVESTIGATIONS Serum electrolytes (Na, K, Cl), creatinine, blood glucose and hematocrit may be of value in managing patients and should be ordered as necessary. Similarly, an ECG, arterial blood gas analysis and renal function tests may be judged to be necessary clinically. TREATMENT The management of the withdrawal syndrome should not be exclusively pharmacological in nature but should include a full evaluation of the patient to determine the most appropriate approach to therapy. One of two general approaches is commonly adopted. The first comprises substitution of the drug with a longer-acting opioid, such as methadone, followed by a gradual reduction in dosage of the substitute drug. The second comprises use of various pharmacological agents, such as clonidine and/or a benzodiazapine, which will mitigate symptoms and signs of withdrawal. Psychological support may be necessary. Indeed, some schools of thought contend that psycho-social support alone is the only effective treatment for opioid withdrawal states. When clonidine is employed, the dose is 0.006 mg/kg/day, in divided doses, adjusted as necessary according to withdrawal symptoms and clonidine side-effects (such as sedation and/or postural hypotension). The dosage of clonidine should then be gradually reduced, typically over a one- to two-week period. If symptoms and signs of opioid withdrawal do not respond to the use of clonidine and/or benzodiazepines, then the use of propantheline (for stomach cramps) or atropine (for diarrhoea) may be considered. Opioid-dependent individuals with co-existent medical or surgical conditions requiring pain relief should receive conventional treatment, including if necessary the administration of opioids. CLINICAL COURSE AND MONITORING The time course and severity of opioid withdrawal depends on the opioid involved and the use history of the individual. That following withdrawal of morphine, has an onset at about 12 hours after the last dose, peaks within 48 to 72 hours and resolves over a period of days. Withdrawal of shorter-acting opioids (e.g. meperidine) produces a shorter more intense clinical syndrome. Withdrawal of longer-acting opioids such as methadone produced a withdrawal syndrome with a more delayed onset, milder severity and prolonged duration. The withdrawal syndrome produced by administration of naloxone is intense, occurs within five minutes, peaks at approximately 30 minutes and subsides within 2 hours. The management of the opioid withdrawal syndrome should include admission to hospital with monitoring of haemodynamic status, pupil size, and bowel sounds. The patient should be placed in a quiet, dark and comfortable environment. Where relevant, it is important to ensure that the patient does not continue to receive an illicit supply of opioid. AUTHOR(S)/REVIEWERS Author: K. Hartigan-Go National Poisons Control and Information Service, Manila, Phillipines. Peer Review: Cardiff 3/95, Berlin 10/95: V. Danel, T. Meredith, A. Nantel, L. Murray, A. Wong, J. Pronczuk.