zimeldine and Drug-Hypersensitivity

Lymphocyte transformation test (LTT) was applied to 28 patients who had developed a hypersensitivity syndrome (HSS) during treatment with the antidepressant drug zimeldine. Twenty-seven patients treated with zimeldine without any symptom of an HSS were matched controls. Zimeldine and its metabolites norzimeldine and CPP 200 all induced statistically significant increased [3H]thymidine incorporation in cultured lymphocytes from the HSS patients compared with the controls, norzimeldine being the most potent inducer. The results indicate an immunoreactive process in the development of the HSS induced by zimeldine.

Topics: Adult; Aged; Antidepressive Agents; Dose-Response Relationship, Drug; Drug Hypersensitivity; Female; Humans; Lymphocyte Activation; Lymphocyte Culture Test, Mixed; Male; Middle Aged; Thymidine; Zimeldine

The results of clinical trials have shown that the general level of side-effects is substantially lower with zimeldine than with tricyclic antidepressants. Data from ordinary clinical usage in Sweden and the U.K. (as opposed to clinical research experience) shows a similar picture. Hypersensitivity reactions, characterized by fever, myalgia and/or arthralgia, and transient increases in transaminases, occur in approximately 1.5% of patients. In rare cases potentially serious neuropathies have been reported.

Topics: Clinical Trials as Topic; Drug Hypersensitivity; Humans; Sweden; United Kingdom; Zimeldine

Adverse experiences during licensed treatment with the antidepressant serotonin (5-HT) reuptake inhibitor zimeldine in Sweden are presented. Data were obtained from a written inquiry of 694 patients and 67 reports to the Medical Products Agency. The spectrum of adverse symptoms was in agreement with those reported in previous studies on zimeldine. The most frequent adverse experiences were headache, nausea, myalgia, signs of liver function disturbance, arthralgia, neurological symptoms, fever and insomnia. No new case of the Guillain-Barré syndrome was found. The estimated frequency of the zimeldine-induced hypersensitivity syndrome (HSS), comprising fever, myalgia and/or arthralgia and signs of liver function disturbance, ranged from 1.4% to 13% in the inquiry and from 0.63% to 3.4% in the report part of the study. Adverse experiences usually had a considerably higher incidence during the first 6 weeks of zimeldine treatment than thereafter. This is in agreement with the clinical experience that most of the adverse reactions occur early during zimeldine treatment. However, a number of adverse experiences did occur with a later onset. This may justify a prolongation of the compulsory 4 weeks' testing of liver function that is required during licensed treatment. There were significantly fewer patients who developed fever among the patients who had experienced previous zimeldine treatment than among those who had not. Otherwise there was no statistically significant difference in frequency of adverse symptoms between these two groups. Consequently zimeldine treatment per se does not seem to predispose to development of an HSS or other types of adverse reactions during subsequent therapy.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Depressive Disorder; Drug Approval; Drug Hypersensitivity; Female; Follow-Up Studies; Humans; Male; Middle Aged; Neurologic Examination; Zimeldine

Five patients who reacted with the hypersensitive syndrome to zimeldine showed no reaction to one of two other selective 5-HT reuptake inhibitors, citalopram or paroxetine. This further strengthens the impression that the mechanism for the hypersensitivity syndrome induced by zimeldine does not seem to be related primarily to the 5-HT reuptake inhibition as such.

Topics: Aged; Aged, 80 and over; Antidepressive Agents; Citalopram; Combined Modality Therapy; Depressive Disorder; Drug Hypersensitivity; Female; Follow-Up Studies; Humans; Liver Function Tests; Male; Paroxetine; Piperidines; Serotonin Antagonists; Zimeldine

Topics: Adult; Depressive Disorder; Drug Hypersensitivity; Female; Fluoxetine; Humans; Middle Aged; Zimeldine

The first of a series of 5HT reuptake inhibitors, zimelidine was withdrawn because of associated hypersensitivity reactions. There was concern that such reactions might be seen with other compounds of this class. Two depressed patients who had a sensitivity reaction to treatment with zimelidine were crossed over to treatment with fluoxetine and no abnormalities were observed. Both patients remained well during uneventful long term treatment with fluoxetine.

Topics: Chemical and Drug Induced Liver Injury; Depressive Disorder; Drug Hypersensitivity; Fluoxetine; Humans; Middle Aged; Polyradiculoneuropathy; Syndrome; Zimeldine

Topics: Adult; Cross Reactions; Drug Hypersensitivity; Female; Fluoxetine; Humans; Propylamines; Zimeldine