Zuclopenthixol, a combined dopamine D1/D2 antagonist, versus haloperidol, a dopamine D2 antagonist, in tardive dyskinesia.

Animal data suggest that a D₁ antagonistic component in neuroleptic drugs counteracts development of dopamine supersensitivity and of tolerance to cataleptic effect. This has led to the hypothesis that neuroleptics with D₁ antagonistic activity should cause a better suppression of tardive dyskinesia (TD) and less rebound aggravation after withdrawal than pure D₂ antagonists. In this study the effect of zuclopenthixol (mixed D₁/D₂ antagonist) and haloperidol (D₂ antagonist) was evaluated in chronic psychotic patients with TD. Fifteen patients completed a randomized crossover study with blind evaluation of TD and parkinsonism. The test medications, haloperidol and zuclopenthixol, caused a significant suppression of TD and a significant increase of parkinsonism. No significant differences between haloperidol and zuclopenthixol were observed. No TD aggravation was seen. The lack of differences between the mixed D₁/D₂ antagonist and a D₂ antagonist suggest that tolerance and DA supersensitivity play no or a minor role for development of TD.