Plasma prolactin and central D2 receptor occupancy in antipsychotic drug-treated patients.
Previous studies of the relationship between plasma prolactin and clinical effects in patients treated with antipsychotic drugs have yielded inconsistent results. A possible explanation may be that most studies have not included subtherapeutic or low doses of antipsychotics. In this exploratory, double-blind study, the relationship between plasma prolactin concentration and central D2 receptor occupancy was examined in 13 schizophrenic patients treated with the experimental antipsychotic drug raclopride (2, 6, or 12 mg daily). D2 receptor occupancy was determined by positron emission tomography and was related to antipsychotic effect as measured by the Brief Psychiatric Rating Scale. Plasma prolactin concentration was increased in eight of nine patients with a D2 receptor occupancy greater than 50%, whereas it was normal among patients with a D2 receptor occupancy less than 50% (p < 0.01). Plasma prolactin concentration measured 4 hours after the morning dose of raclopride correlated significantly with plasma raclopride concentration (r = 0.92, p < 0.01), the degree of D2 receptor occupancy (r = 0.81,p < 0.01), and the antipsychotic effect (r = 0.79, p < 0.01). Further controlled studies that include low doses of antipsychotic drugs may warrant a reconciliation of plasma prolactin as a useful tool in clinical monitoring of antipsychotic drug treatment.
Department of Clinical Neuroscience, Karolinska Hospital, Stockholm, Sweden.
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D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001682:Biological Availability; D001921:Brain / Q000187:drug effects* / Q000503:physiopathology; D018492:Dopamine Antagonists / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D016903:Drug Monitoring; D005260:Female; D006801:Humans; D008297:Male; D011388:Prolactin / Q000097:blood*; D011569:Psychiatric Status Rating Scales; D011618:Psychotic Disorders / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D020891:Raclopride; D017448:Receptors, Dopamine D2 / Q000187:drug effects* / Q000502:physiology; D012457:Salicylamides / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D012559:Schizophrenia / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D014055:Tomography, Emission-Computed; D016896:Treatment Outcome
D014150:Antipsychotic Agents; D018492:Dopamine Antagonists; D017448:Receptors, Dopamine D2; D012457:Salicylamides; D020891:Raclopride; D011388:Prolactin