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Relation to Extrapyramidal Side Effects

Lars Farde, MD; Anna-Lena Nordström, MD; Frits-Axel Wiesel, MD; Stefan Pauli, MD; Christer Halldin, PhD; Göran Sedvall, MD

Arch Gen Psychiatry. 1992;49(7):538-544.

Abstract
• Positron emission tomography and selective radioligands were used to determine D_, and D₂ dopamine receptor occupancy induced by neuroleptics in the basal ganglia of drug-treated schizophrenic patients. In 22 patients treated with conventional dosages of classical neuroleptics, the D₂ occupancy was 70% to 89%. Patients with acute extrapyramidal syndromes had a higher D₂ occupancy than those without side effects. This finding indicates that neurolepticinduced extrapyramidal syndromes are related to the degree of central D₂ occupancy induced in the basal ganglia. In five patients treated with clozapine, the prototype atypical antipsychotic drug, a lower D₂ occupancy of 38% to 63% was found. This finding demonstrates that clozapine is also "atypical" with respect to the central D₂ occupancy in patients. During treatment with clozapine, there is a low frequency of extrapyramidal syndromes, which accordingly may reflect the comparatively low D₂ occupancy induced by clinical doses of clozapine. Classical neuroleptics, like haloperidol or sulpiride, did not cause any evident D_, occupancy, but the thioxanthene flupentixol induced a 36% to 44% occupancy. In four patients treated with clozapine, the D₁ occupancy was 38% to 52%. The D_, occupancy induced by clozapine and flupentixol may contribute to the antipsychotic effect of these drugs.

Author Affiliations
From the Department of Psychiatry and Psychology, the Karolinska Institute, Stockholm (Drs Farde, Nordström, Pauli, Halldin, and Sedvall), and the Department of Psychiatry, Ulleraker Hospital, Uppsala (Dr Wiesel), Sweden.

Footnotes
Accepted for publication November 19, 1991.

Read in part before the American College of Neuropsychopharmacology meeting, San Juan, PR, December 12, 1990.

Reprint requests to Department of Psychiatry and Psychology, Karolinska Institutet and Hospital, S-104 01 Stockholm, Sweden (Dr Farde).

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