Are lorazepam withdrawal symptoms followed by suicide described in the literature?/nA 45-year-old w

Fråga: Are lorazepam withdrawal symptoms followed by suicide described in the literature?

A 45-year-old woman with anxiety developed dependence after being treated with lorazepam (Temesta), 3.5-4 mg daily, for many years (probably 8 years). During an attempt to discontinue the treatment the patient committed suicide.

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Sammanfattning: Besides anxiety, depression is described in the literature during withdrawal of lorazepam. We also found one case of suicide during withdrawal of the drug.

Svar: Lorazepam is a short-acting benzodiazepine (1). It is known that long-term benzodiazepine usage, for example lorazepam, in therapeutic doses may lead to pharmacological dependence (1,2,3). Chronic use of benzodiazepines can induce depression or provoke suicide (4).

In general, long-term treatment, high plasma concentrations, short half-life and abrupt withdrawal are factors that provoke a withdrawal syndrome (5). Symptoms of benzodiazepine withdrawal include anxiety (6). Masked depressive states can also emerge after the acute withdrawal state which will demand specific pharmacological treatment (7). In one case report a 28-year-old man developed depression during withdrawal of lorazepam 3-4 mg daily. Treatment with amitriptyline was successful (8). It has been stated that when compared to other benzodiazepine, lorazepam withdrawal symptoms may be particularly severe (1). Symptoms are also occurring sooner (9) after discontinuing lorazepam treatment. Furthermore, in spite of a shorter half-life, lorazepam has a longer effect duration compared to diazepam probably due to higher affinity to the receptor (13). In a double-blind study (10), 68 patients with BZ dependence were given lorazepam, diazepam or bromazepam gradually reducing the dose. Seven and six patients respectively on diazepam or bromazepam dropped out during study. The corresponding number in the lorazepam group was ten, one of whom committed suicide after 12 weeks treatment.

It is strongly recommended that all benzodiazepine therapy, and particularly with short-acting compounds, should be withdrawn gradually (11) and generally without the use of another drug (12).

No case of death has been reported to the Swedish Adverse Drug Reactions Advisory Committee (SADRAC) in relation to lorazepam treatment. There are 2 cases of anxiety during lorazepam withdrawal and 3 cases of dependence connected to lorazepam treatment.

The case should be reported to SADRAC. 1 Martindale, The extra pharmacopoeia, 1996; 31th ed: 716-717 2 Bergman U, Dahlström M: Anxiety and antianxiety drug use in Sweden. In: Workshop - Pharmacological treatment of anxiety, National Board of Health and Welfare Drug Information Committee, Sweden. 1988:1; page 69 3 MacKinnon GL, Parker WA: Benzodiazepine withdrawal syndrome: a literature review and evaluation. Am J Drug Alcohol Abuse 1982; 9: 19-33 4 Davies, Textbook of adverse drug reactions. 1991; 4th ed: 612 5 Siwers B: Benzodiazepines in the treatment of anxiety. In: Workshop - Pharmacological treatment of anxiety, National Board of Health and Welfare Drug Information Committee, Sweden. 1988:1; page 98 6 Martindale, The extra pharmacopoeia, 1996; 31th ed: 675 7 Borg S: Dependence on hypnotic/sedative drugs. In: Workshop - Pharmacological treatment of anxiety, National Board of Health and Welfare Drug Information Committee, Sweden. 1988:1; page 140 8 Olajide D, Lader M: Depression following withdrawal from long-term benzodiazepine use: a report of four cases. Psychol Med 1984; 14: 937-940 9 Stewart RB, Salem RB, Springer PK: A case report of Lorazepam withdrawal. Am J Psychiatry 1980; 137: 1113-1114 10 Murphy SM, Tyrer P: A double-blind comparison of the effects of gradual withdrawal of lorazepam, diazepam and bromazepam in benzodiazepine dependence. Br J Psychiatry 1991; 158: 511-516 11 Drugline nr 12300 (year ) 12 Borg S: Dependence on hypnotic/sedative drugs. In: Workshop - Pharmacological treatment of anxiety, National Board of Health and Welfare Drug Information Committee, Sweden. 1988:1; page 139 13 Bergman U, Dahl ML, Rydberg U: Rationell användning förutsätter kontinuerlig uppföljning. Läkartidningen 1990; 87: 4401-4403