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Titolo:
Relationship between dopamine D-2 occupancy, clinical response, and side effects: A double-blind PET study of first-episode schizophrenia
Autore:
Kapur, S; Zipursky, R; Jones, C; Remington, G; Houle, S;
Indirizzi:
Univ Toronto, PET Ctr, Clarke Div, Ctr Addict & Mental Hlth,Dept Psychiat,Toronto, ON M5T 1R8, Canada Univ Toronto Toronto ON Canada M5T 1R8 ychiat,Toronto, ON M5T 1R8, Canada Univ Toronto, Schizophrenia & Continuing Care Program, Toronto, ON, CanadaUniv Toronto Toronto ON Canada tinuing Care Program, Toronto, ON, Canada
Titolo Testata:
AMERICAN JOURNAL OF PSYCHIATRY
fascicolo: 4, volume: 157, anno: 2000,
pagine: 514 - 520
SICI:
0002-953X(200004)157:4<514:RBDDOC>2.0.ZU;2-E
Fonte:
ISI
Lingua:
ENG
Soggetto:
D2-DOPAMINE RECEPTOR OCCUPANCY; POSITRON EMISSION TOMOGRAPHY; AUTOMATED IMAGE REGISTRATION; ATYPICAL NEUROLEPTICS; ANTIPSYCHOTIC-DRUGS; PARKINSONS-DISEASE; PLASMA-LEVELS; RATING-SCALE; HALOPERIDOL; CLOZAPINE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Social & Behavioral Sciences
Clinical Medicine
Life Sciences
Citazioni:
48
Recensione:
Indirizzi per estratti:
Indirizzo: Kapur, S Univ Toronto, PET Ctr, Clarke Div, Ctr Addict & Mental Hlth,Dept Psychiat,250 Coll St, Toronto, ON M5T 1R8, Canada Univ Toronto 250 Coll St Toronto ON Canada M5T 1R8 5T 1R8, Canada
Citazione:
S. Kapur et al., "Relationship between dopamine D-2 occupancy, clinical response, and side effects: A double-blind PET study of first-episode schizophrenia", AM J PSYCHI, 157(4), 2000, pp. 514-520

Abstract

Objective: Since all antipsychotics block dopamine D-2 receptors, the authors investigated how well D-2 receptor occupancy in vivo predicts clinical response, extrapyramidal side effects, and hyperprolactinemia. Method: In adouble-blind study, 22 patients with first-episode schizophrenia were randomly assigned to 1.0 or 2.5 mg/day of haloperidol. After 2 weeks of treatment, D-2 receptor occupancy was determined with [C-11]raclopride and positron emission tomography and clinical response, extrapyramidal side effects, and prolactin levels were measured. Patients who showed adequate responses continued taking their initial doses, those who did not respond had their doses increased to 5.0 mg/day, and evaluations were repeated at 4 weeks for all patients. Results: The patients showed a wide range of D-2 occupancy (38%-87%). The degree of receptor occupancy predicted clinical improvement, hyperprolactinemia, and extrapyramidal side effects. The likelihood of clinical response, hyperprolactinemia, and extrapyramidal side effects increased significantly as D-2 occupancy exceeded 65%, 72%, and 78%, respectively. Conclusions: The study confirms that D-2 occupancy is an important mediator of response and side effects in antipsychotic treatment. The data are consistent with a "target and trigger" hypothesis of antipsychotic action, i.e., that the D-2 receptor specificity of antipsychotics permits them to target discrete neurons and that their antagonist properties trigger within those neurons intracellular changes that ultimately beget antipsychotic response. While limited to haloperidol, the relationship between D-2 occupancy and side effects in this study helps explain many of the observed clinical differences between typical and atypical antipsychotics.

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Documento generato il 25/01/20 alle ore 07:13:04