Striatal and extra-striatal D(2)/D(3) dopamine receptor occupancy by quetiapine in vivo. [(123)I]-epidepride single photon emission tomography(SPET) study.

BACKGROUND: Selective action at limbic cortical dopamine D(2)-like receptors could mediate atypical antipsychotic efficacy with few extrapyramidal side-effects. AIMS: To test the hypothesis that quetiapine has 'limbic selective' D(2)/D(3) receptor occupancy in vivo. METHOD: The high-affinity D(2)/D(3) ligand [(123)I]-epidepride and single photon emission tomography were used to estimate D(2)/D(3) specific binding and an index of relative percentage D(2)/D(3) occupancy in striatal and temporal cortical regions for quetiapine-treated patients (n=6). Quetiapine-, and previously studied typical-antipsychotic- and clozapine-treated patients were compared. RESULTS: Mean (s.d.) relative percentage D(2)/D(3) receptor occupancy by quetiapine was 32.0% (14.6) in striatum and 60.1% (17.2) in temporal cortex (mean daily dose 450 mg: range 300-700 mg/day). Quetiapine treatment resulted in limbic selective D(2)/D(3) blockade similar to clozapine and significantly higher than typical antipsychotics. CONCLUSIONS: Preliminary data suggest that limbic selective D(2)/D(3) receptor blockade is important for atypical drug action.

Striatal and temporal cortical D2/D3 receptor occupancy by olanzapine and sertindole in vivo: a [123I]epidepride single photon emission tomography (SPET) study.

RATIONALE: Previous work suggests clozapine preferentially targets limbic cortical dopamine systems, which could help account for its lack of extrapyramidal side effects (EPS) and superior therapeutic efficacy. OBJECTIVES: To test the hypothesis that olanzapine, a novel atypical antipsychotic drug, occupies temporal cortical D2/D3 receptors to a greater extent than striatal D2/D3 receptors in vivo. METHODS: Nine schizophrenic patients taking either olanzapine [(n=5; mean (SD) age: 32.5 (6.5) years; daily dose: 18.3 (2.6) mg] or sertindole [(n=4; mean (SD) age: 30.3 (7.4) years; daily dose: 16 (5.6) mg] were studied with [123I]epidepride ((S)-N-[(1-ethyl-2-pyrrolidinyl)methyl]-5-iodo-2,3-dimethoxybenz amide) and single photon emission tomography (SPET). An estimate of [123I]epidepride 'specific binding' to D2/D3 receptors was obtained in patients and age-matched healthy volunteers. A summary measure was generated representing striatal and temporal cortical relative %D2/D3 receptor occupancy by antipsychotic drugs. Occupancy data were compared with previously studied groups of patients receiving typical antipsychotic drugs (n=12) and clozapine (n=10). RESULTS: Mean striatal and temporal cortical %D2/D3 receptor occupancy in olanzapine-treated patients was 41.3% (SD 17.9) and 82.8% (SD 4.2), respectively. Unexpectedly low levels of striatal relative %D2/D3 receptor occupancy were seen in two patients with typical antipsychotic-drug-induced movement disorder prior to switching to olanzapine. In the temporal cortex, mean D2/D3 dopamine receptor occupancy levels above 80% were seen for all antipsychotic drugs studied. CONCLUSIONS: The atypical antipsychotic drugs olanzapine and sertindole, in common with clozapine, demonstrate higher occupancy of temporal cortical than striatal D2/D3 dopamine receptors in vivo at clinically useful doses. This could help mediate their atypical clinical profile of therapeutic efficacy with few extrapyramidal side effects. Limbic selective blockade of D2/D3 dopamine receptors could be a common action of atypical antipsychotic drugs.

In vivo occupancy of striatal and temporal cortical D2/D3 dopamine receptors by typical antipsychotic drugs. [123I]epidepride single photon emission tomography (SPET) study.

BACKGROUND: The dopamine hypothesis proposes that antipsychotic drugs act primarily through limbic cortical D2/D2-like dopamine receptor blockade. AIM: To evaluate this hypothesis with the D2/D3-selective SPET probe [123I]-epidepride. METHOD: [123I]-epidepride SPET scans were performed on 12 patients with schizophrenia treated with antipsychotics and II age-matched healthy controls. [123I]-epidepride 'specific binding' to D2/D3 dopamine receptors was estimated, and relative percentage D2/D3 receptor occupancy by typical antipsychotic drugs determined. RESULTS: Mean (s.d.) daily dose was 669.12 (516.8) mg chlorpromazine equivalents. Mean percentage D2/D3 receptor occupancy was 81.6 (8.1) and 73.2 (13.9) in the temporal cortex and striatum respectively. CONCLUSIONS: Typical antipsychotic drug treatment is associated with substantial temporal cortical D2/D3 receptor occupancy. The relationship between this and efficacy is poor in patients with treatment-resistant schizophrenia.

Psychiatric morbidity among the elderly in a primary care setting--report from a survey in São Paulo, Brazil.

Brazil has been experiencing a steady increase in the elderly population during the past few years, and as a result old age health-related problems are increasing continuously in number. Psychiatric symptoms are among the most prevalent health problems of the elderly and are an important source of distress for patients and carers, being also associated with significant growth in the costs and demand for the provision of health care services. This study aimed to investigate the prevalence of mental health problems among the elderly attending a regional primary care unit in the city of São Paulo, Brazil. A total of 351 patients older than 60 were assessed during a 6-month period with the SRQ-20 (a scale for the detection of minor psychiatric problems), four questions on psychotic symptoms. AMTS (a scale for the assessment of cognitive functioning) and CAGE (a scale for the assessment of alcoholism); demographic variables were also recorded. Subjects' mean age was 71.22 (CI = 70.51-71.92) and 83.5% were female. Thirty-two per cent of subjects were considered 'cases' as they scored more than 7 on the SRQ-20 (26.8% of total), or more than 1 on the CAGE (1.4% of total), or at least 1 on the questions assessing psychotic symptoms (12.2% of total). There was a significant excess of women among those found to suffer from psychiatric problems (90.1% vs 80.4%). Cases were also more likely to be illiterate (23.4% vs 12.1%) and to have a lower income (2.21 vs 4.01 minimum wages). Depressive symptoms and tension were highly prevalent (72.9% of subjects). Somatic complaints and signs of inefficient functioning were also common (50.4% and 45.9% respectively). Only five patients answered affirmatively two or more CAGE questions and 12.2% scored at least 1 on the questions assessing psychotic symptoms. Cognitive deficit, as determined by the AMTS, was observed in 13.4% of the sample and was associated with ageing, being illiterate and having higher total SRQ-20 scores. We suggest, that the organization of health care services should take into account the needs of this population, and should also emphasize professional training for the correct assessment and treatment of the most frequent mental health problems in old age.