Baclofen (Lioresal®) in the treatment of neuroleptic‐induced tardive dyskinesia

Abstract

A double-blind cross-over trial of the effects of baclofen and placebo was carried out in 20 female patients suffering from neuroleptic-induced tardive dyskinesia. After 14 days of treatment 15 patients showed improvement of baclofen, whereas none showed improvement on placebo; baclofen was thus significantly more effective than placebo. Baclofen is a GABA-like drug which passes through the blood-brain barrier and which reduces the neuroleptic-induced increase of dopamine turn-over. In tardive dyskinesia is found dopaminergic hypersensitivity, and baclofen is supposed to exert its action by inhibiting the dopamine activity. Side effects, although temporary, were observed in the form of sedation, muscular hypotonia, dizziness, vomiting, and muscular rigidity. One patient developed a depression. Baclofen or other gabergic drugs used in the treatment of dyskinesias do not increase the dopaminergic hypersensitivity, which is part of the pathogenesis of these conditions; gabergic therapy must therefore be preferred to treatment with dopamine receptor blocking drugs.

Baclofen in Parkinson's disease.

“…It is uncertain, however, whether this effect is exerted through GABA synapses (Davies and Watkins, 1974;Anden and Wachtel, 1977), or occurs as a direct effect on dopamine receptors. On the assumption that baclofen is a GABA agonist, it has been used to treat the chorea of Huntington's disease (Barbeau, 1973), tardive dyskinesias (Korsgaard, 1976), and schizophrenia (Frederiksen, 1975;Bigelow et al, 1977), and has been shown to aggravate neuroleptic-induced Parkinsonism (Gerlach, 1977). As a result of a previous report in which a patient with idiopathic Parkinson's disease on levodopa developed visual hallucinations, abnormal involuntary movements, and reduced levodopa tolerance after the abrupt withdrawal of baclofen (Lees et al, 1977a), the effect of baclofen on levodopatreated Parkinsonism has been investigated.…”

Current Psychopathological Theories of Tardive Dyskinesia and Their Implications for Future Research

“…Another interesting development in the same sphere is the use of baclofen, a GABA-like drug which passes through the blood brain barrier in the treatment of drug-induced TD. In a double-blind, placebo-controlled, cross over clinical trial with 20 female drug-in duced TD patients, baclofen was found to be beneficial in 15 patients while the placebo was not useful in any [104], However, the effectiveness of the drug may not be attribut able to enhancing GABA but may be related to its ability to decrease dopamine turnover [105]. Perhaps the potential therapeutic ef fects of these drugs can only act as catalysts for further research.…”

Phenylethylamine-Like Properties of Baclofen

“…1975;Korsgaard, 1976;Bigelow et al, 1977;Nair et al, 1980]. This drug has been postulated to exert its effects by acting as a GABA agonist inhibiting dopamine transmission [Anden, 1977], as an antagonist of substance P [Saito et al, 1975] and more recently as a phenyl ethylamine agonist , This report describes our clinical experience with ba clofen in subjects with prominent features of tardive dys kinesia and in chronic schizophrenic patients.…”