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: 3.88). 01/1999; 141(2):175-81. DOI: 10.1007/s002130050822
Source: PubMed


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.

Download full-text


Available from: Lukas Pezawas, Apr 26, 2014
    • "Furthermore, olanzapine presents higher cholinergic antagonism activity than risperidone or ziprasidone (Kapur, 2003), which could balance the cholinergic overactivity that occurs when D2R are blocked in the nigrostriatal pathway and therefore reduce EPS. As already reported in previous studies with haloperidol (Farde et al., 1992; Kasper et al., 1998; Tauscher et al., 1999) and risperidone (Dresel et al., 1998; Kasper et al., 1998; Catafau et al., 2006), in the present study a relationship between D2RO and EPS appearance was observed with those drugs. By contrast, such a relationship was observed neither in olanzapine nor in ziprasidone groups. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Levels above 75% of striatal dopamine 2 receptor occupancy (D2RO) have been associated with extrapyramidal symptoms (EPS). The aim of the present study is to investigate the relationship between D2RO and EPS in a sample of psychotic patients in current treatment with both typical and atypical antipsychotics. Brain iodine-123-iodobenzamide single photon emission computed tomography ((123)I-IBZM SPECT) was performed in 81 patients taking stable doses of haloperidol, risperidone, olanzapine, quetiapine, clozapine or ziprasidone. First, the degree of D2RO and Positive and Negative Syndrome Scale (PANSS) scores was compared between the group of patients who presented EPS and the group free of EPS. Afterwards, these variables were compared among the different antipsychotic medications. The group with EPS presented means of D2RO significantly higher than the group free of EPS. Significant differences in D2RO were found in clozapine, quetiapine and ziprasidone groups compared with the haloperidol group. No differences were observed between either olanzapine or risperidone and haloperidol. No quetiapine- or clozapine-treated patients developed EPS. Haloperidol and risperidone demonstrated a relationship between striatal D2RO and EPS. The findings suggest that higher D2RO is related to appearance of EPS. Occupancy in the group with EPS was in agreement with previous studies that suggested a high degree of D2RO is necessary for the occurrence of EPS.
    Psychiatry Research 01/2012; 201(1):73-7. DOI:10.1016/j.pscychresns.2011.02.004 · 2.47 Impact Factor
  • Source
    • "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). "
    [Show abstract] [Hide abstract]
    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 · 4.37 Impact Factor
  • Source
    • "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. "
    [Show abstract] [Hide abstract]
    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 · 3.88 Impact Factor
Show more