Tauscher J, Kufferle B, Asenbaum S, Fischer P, Pezawas L, Barnas C et al. In vivo 123I IBZM SPECT imaging of striatal dopamine-2 receptor occupancy in schizophrenic patients treated with olanzapine in comparison to clozapine and haloperidol. Psychopharmacology (Berl) 141: 175-181

Department of General Psychiatry, University of Vienna, Austria.
Psychopharmacology (Impact Factor: 3.99). 01/1999; 141(2):175-81. DOI: 10.1007/s002130050822
Source: PubMed

ABSTRACT We investigated the degree of striatal dopamine-2 (D2) receptor occupancy in six schizophrenic patients receiving clinically effective antipsychotic treatment with olanzapine 10-25 mg/day in comparison to patients treated with clozapine 300-600 mg/day (n = 6) or haloperidol 5-20 mg/day (n = 10). 123I Iodobenzamide (IBZM) and single photon emission computerized tomography (SPECT) were used for the visualization of striatal D2 receptors. For the quantification of striatal D2 receptor occupancy, striatal IBZM binding in patients treated with antipsychotics was compared to that in untreated healthy controls (n = 8) reported earlier. Olanzapine led to a mean striatal D2 receptor occupancy rate of 75% (range 63-85). Haloperidol-treated patients showed dose-dependently (Pearson r = 0.64; P < 0.05) a significantly higher (P < 0.05) mean occupancy rate of 84% (range 67-94). During clozapine treatment, the mean D2 receptor occupancy of 33% (range < 20-49) was significantly lower than with olanzapine (P < 0.005). The higher striatal D2 receptor occupancy of haloperidol was correlated with the incidence and severity of extrapyramidal motor side-effects (EPS). No clinical relevant EPS occurred during treatment with olanzapine or clozapine. There was no correlation between the degree of striatal D2 receptor occupancy and clinical improvement.

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Available from: Lukas Pezawas, Apr 26, 2014
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    • "Finally, they found no relationship between dose and occupancy, questioning the internal consistency of the data. Similar to schizophrenic patients, we found a dosedependent increase in D 2 receptor occupancy (Kapur et al., 1999; Raedler et al., 1999; Tauscher et al., 1999). "
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    ABSTRACT: We explored the relationship between striatal dopamine-2 (D(2)) receptor occupancy and extra-pyramidal symptoms (EPS) in bipolar patients receiving olanzapine. Seventeen patients with a DSM-IV diagnosis of bipolar disorder were treated with 5-45 mg/day olanzapine for at least 14 days. After that period, D(2) receptor occupancy was determined using Iodobenzamide (IBZM) and SPECT. EPS were assessed by the Simpson-Angus Scale (SAS) and Barnes-Akathisia Scale (BAS). We found a dose-dependent increase in occupancy: 5 mg led to 28-50%, 10 mg to 40-68%, 15 mg to 69%, 20 mg to 57-66%, 30 mg to 66% and 45 mg to 80% D(2) receptor occupancy; and a significant correlation between plasma levels and occupancy (R(2)=.55, P=.001). Similar to schizophrenic patients, bipolar patients did not exhibit EPS at D(2) occupancy levels of 28 to 80%. Although we did not find an increased vulnerability for acute EPS in bipolar patients receiving olanzapine at clinical relevant doses, this needs to be replicated with larger sample sizes.
    European Neuropsychopharmacology 02/2007; 17(2):102-7. DOI:10.1016/j.euroneuro.2006.07.001 · 5.40 Impact Factor
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    • "However, scanning a patient in the naïveor drug-free condition is difficult and too often unfeasible. For this reason, calculation of receptor occupancies using the mean receptor availability value from a control group is extensively used in the literature either using SPECT (Knable et al. 1997; Dresel et al. 1999; Tauscher et al. 1999a) or PET (Gefvert et al. 1998; Kapur et al. 1999; Talvik et al. 2004). The control group can either be an independent group of patients with the same characteristics as the target population or a group of healthy subjects under the assumption that there are no differences in receptor or transporter availability between healthy subjects and the patient population. "
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    ABSTRACT: To assess the paroxetine-induced serotonin transporter (SERT) occupancy (SERTocc) using in vivo (123)I-ADAM SPECT. (123)I-ADAM SPECT was used to investigate the SERTocc induced by paroxetine in major depression disorder (MDD) patients, to compare the SERT availability in drug-free MDD patients and healthy volunteers, and to study the relationship between paroxetine plasma concentrations (Cp) and SERTocc. Measures of SERT availability by means of (123)I-ADAM SPECT were obtained in ten MDD patients before and after 4- to 6-week treatment with paroxetine 20 mg/day. (123)I-ADAM SPECT measures of SERT availability from a group of ten previously studied age-matched healthy volunteers were used for comparison. The relationship between percentages of SERTocc and paroxetine Cp was studied using an E (max) model. Mean SERTocc values were 66.4 +/- 9.5% in midbrain, 63.0 +/- 9.6% in thalamus, and 61.3 +/- 10.9% in striatum. No significant differences in SERTocc were found among these three regions. No significant differences in mean SERT availability were found in any region between drug-free MDD patients (midbrain = 1.14 +/- 0.15; thalamus = 0.85 +/- 0.13; striatum = 0.70 +/- 0.07) and healthy volunteers (midbrain = 1.19 +/- 0.22; thalamus = 0.96 +/- 0.14; striatum = 0.67 +/- 0.15). The E (max) model returned a SERTocc(max) = 70.5% and a Cp(50) = 2.7 ng/ml. Using (123)I-ADAM SPECT, treatment with paroxetine 20 mg/day leads to more than 60% SERTocc on average in cerebral regions with known high SERT density. Data from this study do not support the existence of SERT availability differences between drug-free MDD patients and healthy volunteers. Finally, the E (max) model is suitable for the study of paroxetine Cp relationship to (123)I-ADAM SPECT-measured SERTocc. This approach may be useful for pharmacokinetic-pharmacodynamic relationships in drug development.
    Psychopharmacology 01/2007; 189(2):145-53. DOI:10.1007/s00213-006-0540-y · 3.99 Impact Factor
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    • "Classically, antipsychotic plasma levels have been used as an indirect measure of cerebral D2R occupancy. Positron emission tomography (PET) and SPECT have been shown to be useful tools for measuring D2R occupancy in vivo (Farde et al., 1989, Tauscher et al., 1999; Bernardo et al., 2001), although the relationship between in vitro (i.e. plasma levels) and in vivo (functional neuro-imaging) measurements remains unclear. "
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    ABSTRACT: The objective of the study is to investigate whether dopamine D2 receptor occupancy by risperidone and plasma levels over time can account for therapeutic efficacy and the latency period to response. Thirty-eight examinations with (123)I-IBZM single photon emission computed tomography were performed on 22 patients with schizophrenia, at diagnosis, 48 h after starting risperidone treatment and at a stable dose. Risperidone plasma levels were determined and psychopathologic evaluations (Brief Psychiatric Rating Scale, Positive and Negative Syndrome Scale) were carried out. No differences in the striatal/occipital (S/O) ratio or plasma levels were found between examinations at the 48-h time point and when a stable dose level had been established, so these parameters could not account for the latency period required for clinical response. D2 receptor occupancy at 48 h correlated positively with clinical improvement after 2 weeks of treatment. Therefore, if these results are confirmed, D2 receptor occupancy at the beginning of treatment with risperidone may be a predictor of subsequent clinical response.
    Psychiatry Research 01/2007; 148(2-3):175-83. DOI:10.1016/j.pscychresns.2006.02.001 · 2.68 Impact Factor
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