Tricyclic antidepressant-induced extrapyramidal side effects.

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Abstract

Two cases of tricyclic antidepressant-related extrapyramidal side effects are reported and, the authors review the literature describing these effects. Despite clear case reports, these side effects are not well known. Given the wide prescription of tricyclic antidepressants (TCA) and the low number of case reports, the prevalence of these side effects is indeed low, but clinical implications exist. The extrapyramidal symptoms induced by TCA alone are acute or tardive dyskinesia, akathisia, myoclonus, rabbit syndrome and dystonia. These symptoms seem to be non age-related, but often dose-related, and were responders to antiparkinsonian agents or propranolol. The factors that predispose an individual to the development of these side effects are not completely understood. Some risk factors such as prior exposure to neuroleptics and/or lithium or estrogens could facilitate the development of these side effects. In some cases, they can disappear even though the same dose of TCA is continued, and they do not seem to be a drug class reaction. The susceptibility of each individual patient to the development of these disorders may be limited to only one or a few of these agents.

Introduction

Extrapyramidal symptoms may be drug-induced and due to an antidopaminergic effect.

Therefore, if neuroleptics are well known to cause such neurologic symptoms, extrapyramidal symptoms are not generally considered to be a complication of antidepressants, although in recent years several reports have appeared. Recently a number of investigators (Arya, 1994) have recognized that the selective serotonin reuptake inhibitors (SSRIs) produce them, but concerning tricyclic antidepressants (TCA) these side effects are not well-known (Sachdev, 1995) or are not reported in a literature review on drug-induced parkinsonism (Montastruc et al., 1994), despite case reports since 1970 (Darcourt et al., 1970).

After a report of our own TCA induced extrapyramidal effects (2 cases), this paper reviews the literature on reported cases of these side effects to underline this TCA potentiality and to present the main characteristics of these effects. These symptoms are perhaps infrequent, but may affect tolerance and compliance. In the review, the TCAs were: amitriptyline, imipramine, desipramine, clomipramine, doxepine. The amoxapine case reports were not taken into account, amoxapine has indeed intrinsic neuroleptic activity, one of its metabolites (7-hydroxy derivative) having dopamine blocking properties.

Section snippets

Case reports

In a previous article (Vandel et al., 1995) we reviewed the drug side effects observed in our ward over 5 years. The incidence was low, 3%, (116 cases on 3809 hospitalizations). Among them, we reported to the pharmacovigilance center only 4 cases of extrapyramidal syndrome occurring during administration of antidepressants, 2 with tricyclic antidepressants (clomipramine and amitriptyline), 1 with a serotonergic antidepressant (fluoxetine), 1 with amoxapine.

The two following cases illustrated

Review

The review of the literature describing the tricyclic antidepressant-related extrapyramidal side effects suggests that they are infrequent, but, with Garvey and Tollefson (1987), we suggest that they are more common than previously believed. They are perhaps ignored because they are not well known. In Table 1, Table 2, we present 14 reports describing 21 cases where the side effect was clearly induced by the TCA, and one report (Garvey and Tollefson, 1987) presenting a prospective study on the

Discussion

These observations of TCA-induced extrapyramidal side effects are apparently paradoxical given that these medications are highly atropinic drugs. But abnormal involuntary movements (dyskinesias) induced by anticholinergic therapy had been reported by Birket-Smith (1974)despite the fact that anticholinergics have been the most popular therapy for Parkinson's disease for 25 years. Moreover, administration of anticholinergics may aggravate tardive dyskinesias.

The theoretical interpretation of the

Conclusion

Due to the wide prescription of tricyclic antidepressants and the low number of extrapyramidal TCA-related effect case reports, the prevalence of these side effects is low. But, even if we think, as Yassa et al. (1987), that the occurrence of extrapyramidal effects with TCA is not a public health problem, these effects must be known.

The extrapyramidal symptoms induced by TCA alone are dyskinesia, akathisia, myoclonus, rabbit syndrome and dystonia. These symptoms seem to be non age related, but

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