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The discovery of the therapeutic properties of chlorpromazine (Delay and Deniker 1952; Laborit et al. 1952) was soon followed by the description of its tendency to produce extrapyramidal side effects (EPS) that were indistinguishable from classical Parkinson's syndrome. A debate soon arose regarding the relationship between EPS and therapeutic efficacy. Flügel (1953) suggested that a therapeutic response from chlorpromazine required the development of EPS. Haase (1954) postulated that the neuroleptic dose that produced minimal subclinical rigidity and hypokinesis (i.e., the "neuroleptic threshold") was the minimal neuroleptic dose necessary for therapeutic antipsychotic effect and that it was manifested by micrographic handwriting changes. Other investigators also reported that EPS were necessary for therapeutic efficacy (see Denham and Carrick 1960; Karn and Kasper 1959).

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