Summary
Forty-five patients suffering from a major depression were administered zimeldine, amitriptyline or placebo (15 patients in each group) in a double-blind controlled study. In the zimeldine group, seven of the 14 patients treated for more than one week presented a toxic syndrome consisting in a severe prostration, fever, myalgias and arthralgias. In all patients presenting this syndrome, laboratory analyses revealed an elevation of alkaline phosphatase and of aspartate and alanine aminotransferases and a decrease in white blood cell and platelet counts. Three patients presented a mild proteinuria and hematuria. Although an immunological mechanism cannot be ruled out, several characteristics of this reaction suggest the formation of a metabolite of zimeldine with direct cellular toxicity. The relatively high starting dose of 200 mg/day of zimeldine administered in the present study and the increment to 300 mg/day after only seven days might have contributed to the high incidence of toxic reactions observed.
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References
Ogren SO, Ross SB, Hall H, Hokm AC, Renyi AL (1981) The pharmacology of zimelidine: a 5-HT selective reuptake inhibitor. Acta Psychiatr Scand 63 [Suppl 290]: 127–151
Blier P, de Montigny C (1983) Electrophysiological investigations of the effect of repeated zimelidine administration on serotoninergic neurotransmission in the rat. J Neurosci 3: 1270–1278
Claghorn J, Gershon S, Goldstein BJ, Behrnetz S, Busil DF, Huitfeldt B (1983) A double-blind evaluation of zimelidine in comparison to placebo and amitriptyline in patients with major depressive disorder. Neuro-Pharmacol Biol Psychiatr 7: 367–382
Coppen A, Rama Roa VA, Swade C, Wood K (1979) Zimelidine: a therapeutic and pharmacokinetic study in depression. Psychopharmacology 63: 199–202
Mondeth CH, Feighner JP (1983) A double-blind, controlled evaluation of zimelidine, imipramine and placebo in patients with primary affective disorders. Acta Psychiatr Scand 68 [Suppl 308]: 70–79
Montgomery SA, McAuley R, Rani SJ, Roy D, Montgomery B (1981) A double-blind comparison for zimelidine and amitriptyline in endogenous depression. Acta Psychiatr Scand 63 [Suppl 290]: 314–327
Nilsson BS (1983) Adverse reactions in connection with zimelidine treatment – a review. Acta Psychiatr Scand [Suppl 308] 68: 115–119
Larsen FW, Hansen CE (1984) Zimeldine versus amitriptyline in endogenous depression. A double-blind study. Acta Psychiatr Scand 69: 343–349
American Psychiatric Association, Committee on Nomenclature and Statistics (1980) Diagnostic and statistical manual of mental disorders, 3rd edn. American Psychiatric Association. Washington, D.C.
Spitzer RL, Endicott J, Robins E (1978) Research diagnostic criteria. Arch Gen Psychiatr 35: 773–782
Hamilton MA (1960) A rating scale for depression. J Neurol Neurosurg Psychiat 23: 56
Caillé G, Kouassi E, de Montigny C (1983) Pharmacokinetic study of zimelidine using a new GLC method. Clin Pharmacokinet 8: 530–540
Clarkson AR, Seymour AE, Woodroffe AJ (1983) Primary renal hematuria: IgA nephropathy. In: Massry SG and Glassock RJ (eds). Textbook of nephrology, vol 1. Williams and Wilkins, Baltimore, pp 6.56
Griffin JP (1983) Drug-induced allergic and hypersensitivity reactions. Practitioner 227: 1283–1297
Kloss MW, Rosen GM, Rauckman EJ (1984) Cocaine-mediated hepatotoxicity. Biochem Pharmacol 33: 169–173
Pecknold J (1983) Discussion on adverse reactions to zimelidine treatment. Acta Psychiatr Scand 68 [Suppl 308]: 120–121
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Langlois, R., Cournoyer, G., de Montigny, C. et al. High incidence of multisystemic reactions to zimeldine. Eur J Clin Pharmacol 28, 67–71 (1985). https://doi.org/10.1007/BF00635710
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DOI: https://doi.org/10.1007/BF00635710