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Home , Medazepam

Treatment 0of CaseI dependence with a tapering; Reports withdrawal regimen

A.N. Singh,* MB, BS, FRCPC, FRC Psych, FRCP, DPM Marion Chemij,t BA, RN Jacklynn Jewell,t BSc, RN

riazolam is a widely used minimal anxiety, was worrying, ruminative and derivative that has hypnotic, distrustful of others and related on a superficial and muscle-relaxant properties.' 3 Since it is level because of feelings of inferiority. absorbed rapidly and has a half-life of only 3 After admission the patient continued to re- hours, it is likely to become the preferred drug in ceive 1 mg/d of triazolam, although the 0.25-mg treating insomnia. We found only one report of morning dose was delayed to verify physical de- triazolam dependence in the literature, and the pendence by the appearance of withdrawal symp- patient had been abusing other drugs as well.4 toms. The symptoms were recorded by the nurses and by the patient in a diary; they included a feeling of pressure in the back of his head, Case report itchiness, nausea, a bad taste in his mouth, irrita- bility, tactile hallucinations, anergy, slowed menta- A 43-year-old man employed as a mechanical tion, blurred vision, muscle stiffness, sensitivity to engineer was admitted to our program because of light and buzzing in his ears, beginning about 2 triazolam dependence. He had started to take the hours after the missed dose. drug, 0.25 mg intermittently, 5 years earlier be- Since abrupt withdrawal from benzodiaze- cause of difficulty sleeping. He had doubled the pines is to be avoided,56 the patient accepted our dosage when hospitalized for depression 3 years proposal that the drug be gradually withdrawn by later, and at the time of admission was taking 0.75 his receiving eight tablets a day that contained mg at bedtime in order to sleep and 0.25 mg in the decreasing amounts of triazolam and increasing morning to avoid withdrawal symptoms. When amounts of placebo (Fig. 1). To minimize anxiety the patient tried to decrease the dosage he had and "pseudowithdrawal"7 he was not to be told experienced slowed mentation, depression, burn- when the drug would be replaced by placebo. No ing in his legs and a bitter taste in his mouth the other drugs were used during the withdrawal following morning; the symptoms were relieved by period, but the patient was taught progressive taking the omitted dose. relaxation exercises. He also met with the nurses Physical examination and base-line laboratory for 30 minutes daily to express his concerns and to studies gave normal results, but triglyceride and learn alternative ways of dealing with stress. fasting serum glucose levels were elevated (4.38 Fig. 1 shows the hours of sleep the patient had mmol/L and 10.9 mmol/L respectively). A Minne- under the various withdrawal conditions. During sota Multiphasic Personality Inventory test withdrawal he experienced the symptoms attribut- showed that the patient had some depression with ed to delaying the daytime dose (Table I); by the 40th day of treatment the symptoms had complete- From the Adverse Drug Reaction Programme, Hamilton ly disappeared. At the time of discharge, on day 86, Psychiatric Hospital, Hamilton, Ont. the patient was completely recovered and was in a normal mental state. *Director tPrimary nurse

Reprint requests to: Dr. A.N. Singh, Director, Adverse Drug Comments Reaction Programme, Hamilton Psychiatric Hospital, PO Box 585, Hamilton, Ont. L8N 3K7 Our report shows that this patient was psy-

CAN MED ASSOC J, VOL. 134, FEBRUARY 1,1986 243 chologically and physically dependent on triazo- Dependence may initially be psychologic, but lam. There was no evidence of abuse of or if high dosages (i.e., two to five times the normal of any other drug. therapeutic dosage) are given over a long period, Tolerance is defined as the necessity to in- physical dependence will result.11,13 Our patient crease the dosage of a drug to maintain symptom- had been taking triazolam in increasing dosages atic improvement.8 Our patient showed tolerance for 3 years before admission. to triazolam by needing to increase his originally Withdrawal reactions should be differentiated prescribed dosage in order to sleep. from return of the symptoms of the primary Psychologic dependence involves purely emo- illness. Withdrawal symptoms occur within the tional components, with no physical signs of first few days after the drug is stopped, usually withdrawal.9 It can be regarded as an anxiety- between the third and sixth day.9 They reach a avoidance or a positive operant-conditioning effect peak and then gradually decrease in intensity.7 of the drug itself.9 Our patient showed psychologic Return of the symptoms of the primary illness dependence in his self-report of feeling relieved and relaxed after taking his usual morning dose of triazolam to avoid withdrawal symptoms. He also reported feeling depressed and craving the drug when the dose was delayed.7 These observations confirm the finding by Morgan and Oswaldlo that a high dosage of triazolam each evening can be rapidly metabolized and can produce daytime re- bound anxiety. Physical dependence on a drug results when the drug or one or more of its metabolites becomes necessary for the continued functioning of certain body processes." Physical dependence is revealed by withdrawing the drug, which elicits a variety of physiologic disturbances known collectively as the withdrawal syndrome.5 When the drug is readmin- istered, the symptoms of the withdrawal syndrome disappear. The withdrawal symptoms in our pa- tient were comparable to those described by Peck- nold and colleagues.12 Administration of triazolam resulted in the disappearance of the symptoms.

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a . .,~~~~~5. , a I I I 0 IIII I III II I I 1 1 3 5 7 8 10 12 14 16 18 20 22 24 26 28 30 32 33 35 37 39 40 42 44 45 47 48 50 52 54 56 DAY

Triazolam Triazolam 0.75mg 19:00 Triazolam Triazolam Triazolam Placebo Placebo No 0.75mg 19:00 Placebo 0.25mg 12:00 0.50mg 19:00 0.25mg 19:00 0.125mg 19:00 0.25mg 12:00 0.375mg 19:00 Treatment Triazolam Placebo Placebo Placebo Placebo Placebo 0.25mg 12:00 0.25mg 12:00 0.25mg 12:00 0.25mg 12:00 0.75mg 19:00 0.125mg 12:00 Placebo Placebo Placebo Placebo 0.25mg 19:00 0.50mg 19:00 0.625mg 19:00 0.125mg 19:00

Fig. 1 -Sleep pattern before, during and after withdrawal from triazolam. * = sleep with many awakenings; * = uninterrupted sleep.

244 CAN MED ASSOC J, VOL. 134, FEBRUARY 1,1986 usually starts 3 or 4 days after the drug has been triazolam (Halcion) and (Dalmane). J Clin Phar- stopped. They are relatively mild at first and then macol 1978; 18: 302-309 3. Wang R, Stockdale S: The hypnotic efficacy of triazolam. J increase in intensity. In our patient withdrawal Int Med Res 1973; 1: 600-607 symptoms were observed earlier because of the 4. Fleming JAE: Triazolam abuse [C]. Can Med Assoc J 1983; short half-life of triazolam. There were no indica- 129: 324-325 tions of return of the primary illness when the 5. Lapierre YD: Benzodiazepine withdrawal. Can J Psychiatry withdrawal regimen was completed or at the 1981; 26: 93-95 1-month or 6-month follow-up appointment. 6. Committee on the Review of Medicines: Systematic review of the . Guidelines for data sheets on Marks7 has commented that "it is fallacious to , , medazepam, , loraze- believe that short-acting compounds have a lower pam, , , triazolam, , and risk of producing dependence". However, this is flurazepam. Br MedJ 1980; 280: 910-912 the first report of successfully treated triazolam- 7. Marks J: The benzodiazepines - for good or evil. Neuro- specific dependence, although one case of un- psychobiology 1983; 10: 115-126 treated dependence on triazolam and other drugs 8. Therapeutic monograph on - drugs. Can Med AssocJ1981; 124: 1439-1446 has been reported.4 9. Singh AN: A clinical picture of benzodiazepine dependence The advantage of tapering dosages in the and guidelines for reducing dependence. In Current Obser- treatment of triazolam dependence is illustrated by vations on Benzodiazepine Therapy, Excerpta Medica, Am- the minimal suffering and complete cooperation of sterdam, 1983: 14-18 our patient. 10. Morgan K, Oswald I: Anxiety caused by a short-life hypnotic. Br Med J 1982; 284: 942 11. Marks J: The Benzodiazepines: Use, Overuse, Misuse, Abuse, MTP Pr, Lancaster, Engl, 1978: 80 References 12. Pecknold JC, McClure DJ, Fleury D et al: Benzodiazepine withdrawal effects. Prog Neuropsychopharmacol Biol Psy- 1. Chatwin J, Johns W: An effective hypnotic in general chiatry 1982; 6: 517-522 practice. Curr Ther Res 1976; 21: 207-214 13. Petursson H, Lader M: Withdrawal from long-term ben- 2. Leibowitz M, Sunshine A: Long-term efficacy and safety of zodiazepine treatment. Br MedJ 1981; 283: 643-645

Scarves and engines

Ian Mitchell, MB, FRCPC Husam Z. Darwish, MD, FRCPC

espite the decline in the rate of death from Case reports all causes among children, injuries remain the commonest cause of death in those Patient 1 aged 1 to 14 years.1 Pediatricians, as child advo- cates, have a responsibility to identify types of A healthy 12-year-old girl was alone in a barn childhood accidents that can be prevented and then loading grain. She climbed onto an elevator to load bring them to the attention of the medical profes- the sacks, and her scarf became entangled in the sion and the public. driving rod that connected the engine to the We report two cases of severe central nervous conveyor belt. The scarf was pulled tight. She was system injury caused by the entanglement of a found, possibly 5 minutes later, held tightly scarf in an engine. against the equipment, with the scarf constricting her throat. A pulse could not be felt, and she was apneic and cyanotic. She was disentangled, and From the divisions of Intensive Care and Neurology, Alberta cardiopulmonary resuscitation was started and Children's Hospital, and the Department of Paediatrics, Uni- continued while she was transported to the nearest versity of Calgary hospital. Reprint requests to: Dr. Ian Mitchell, Alberta Children's On arrival at the hospital, 45 minutes later, Hospital, 1820 Richmond Rd. SW, Calgary, Alta. T2T 5C7 her pulse had reappeared, but she remained apneic

CAN MED ASSOC J, VOL. 134, FEBRUARY 1, 1986 245