Severe headache and disturbed liver function during treatment with zimelidine.

Abstract

Zimelidine is effective in the treatment of depression.' Both zimelidine and its pharmacologically active metabolite norzimelidine act by inhibiting the re-uptake of 5-hydroxytriptamine by neurones.2 In comparison with tricyclic antidepressant drugs zimelidine is fairly free of side effects.' We report two cases in which adverse effects developed during a clinical trial of the drug. Case reportsCase 1-A 34-year-old woman was prescribed zimelidine 200 mg per day for depression of three months' duration. Two weeks later she was admitted to hospital complaining of severe frontal headache and photophobia. The headache had gradually increased over three days, was exacerbated by movement and coughing, and was associated with muscular aches, vomiting, and shivering. The patient was afebrile and full systematic examination showed no abnormality. Lumbar puncture yielded normal cerebrospinal fluid. Results of liver function tests (previously normal) were disturbed, with enzyme activities of: aspartate aminotransferase 56 IU/1; alanine aminotransferase 193 IU/I; and y-glutamyltransferase 173 IU/1. Bilirubin concentration and alkaline phosphatase activity were normal. Zimelidine was withdrawn. The headaches and photophobia subsided over the next week and liver enzyme activities fell progressively to normal over 10 days. All other investigations gave normal results.Case 2-A 44-year-old man presented with one month's history of anxiety and depression. Previous history included gastric surgery seven years earlier and outpatient investigation of headache after head injury (no organic cause found) five years earlier. Two weeks after being prescribed zimelidine 200 mg per day he was admitted to hospital complaining of headache, which had gradually increased in severity over the preceding week. It was worsened by coughing and head movement and was associated with photophobia and muscular aches. He was afebrile and full systematic examination gave normal results, except for a candida throat infection. Lumbar puncture produced normal cerebrospinal fluid at a pressure of 320 mm of cerebrospinal fluid. Liver function tests (previously normal) showed: aspartate aminotransferase 131 IU/1; alanine aminotransferase 333 IU/1; y-glutamyltransferase 140 IU/l; and alkaline phosphatase 210 IU/1. Bilirubin concentration was

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“…due to a localizing predilection, (iv) reserpine also causes depletion of platelet 5-HT which outlasts the headache and probably reflects a general loss of 5-HT, (v) the initial depletion of 5-HT-and not the putative subsequent rise in plasma 5-HT-appears causally important, because replenishment of 5-HT resolved the headache. Other reports with respect to the effect of 5-HT depleting agents and headache are more difficult to interpret, but it seems that these agents all have headache as a prominent side effect (67,(80)(81)(82)(83)(84).…”

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“…Zimelidine, a serotonin uptake inhibitor, has been associated with a flu-like syndrome in 1.5 to 10070 of patients (Sommerville et al, 1982;Nilsson, 1983); this illness is characterised by chills, fever, muscle aches, headache, rash, hepatic dysfunction, and malaise. The Committee on the Safety of Medicines (1983) has also reported on the occurrence of peripheral neuropathy and the Guillain-Barre syndrome in several patients, associated with this flu-like syndrome.…”

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