A monkey model of tardive dyskinesia (TD): evidence that reversible TD may turn into irreversible TD

Three Cebus apella monkeys were treated with biweekly injections of fluphenazine enanthate for 1 year. Two distinct motor syndromes were produced. The first consisted of acute dystonic, dyskinetic, parkinsonian, and akathisia-like reactions, which worsened after each injection, were not exacerbated by drug withdrawal, and could be abolished or prevented with benztropine. The second appeared after cessation of neuroleptic treatment and consisted of abnormal movements very similar to those of patients with tardive dyskinesia (TD). This syndrome was abolished completely by reinstitution of fluphenazine treatment. One monkey was given a second and third course of fluphenazine, each course lasting 4 weeks. The second syndrome was seen after but not during each course and remained robust for a longer period after the third than after the first or second courses of treatment. We conclude that the first syndrome is analogous to the early appearing extrapyramidal symptoms of neuroleptic-treated patients and that, according to preliminary evidence, reversible TD may turn into irreversible TD with continued periods of on and off neuroleptic treatment.