Two cases of long term dopamine D2 receptor blockade after depot neuroleptics

Meer, C. Harasko-van der; Brücke, Thomas; Wenger, S.; Fischer, Peter; Deecke, Lüder; Podreka, I.

doi:10.1007/bf01277026

Cited by 16 publications

(4 citation statements)

References 8 publications

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“…This Þnding conÞrmed previously reported long term D 2 receptor blockade for up to 7 weeks after depot neuroleptics (Baron et al 1989;Harasko-van der Meer et al 1993). The second SPECT study in case 2 was probably not inßuenced by the pretreatment with depot neuroleptics, because it was performed more than 15 weeks after the last depot injection.…”

Section: Discussionsupporting

confidence: 87%

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Previous treatment as a confounding variable in studies with novel antipsychotics: two cases of high dopamine-2 receptor occupancy with quetiapine

Tauscher¹,

Küfferle²,

Asenbaum

et al. 1997

Psychopharmacology

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Previous treatment can be a confounding variable in studies with novel antipsychotics. Quetiapine is a new antipsychotic substance with a low affinity for dopamine-2 (D2) receptors. Preliminary SPECT and PET investigations revealed only a low striatal D2 receptor occupancy rate. However, we present two cases of high striatal D2 receptor occupancy (51% and 71%) measured with 123I IBZM SPECT during quetiapine monotherapy. Both patients had previously received continuous treatment with typical neuroleptics. We present evidence that the previous antipsychotic therapy influenced D2 receptor binding of 123I IBZM during quetiapine treatment weeks after cessation of typical neuroleptics. This might be of importance for the design of clinical trials and brain imaging studies in the future.

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Section: Discussionsupporting

confidence: 87%

“…Carry-over e¤ects of prior treatment with oral antipsychotics were thought to be negligible after 2 weeks (Baron et al 1989). Not surprisingly, PET (Baron et al 1989) and SPECT (Harasko-van der Meer et al 1993) investigations revealed that injectable depot neuroleptics blocked D 2 receptors for considerably longer.…”

Section: Introductionmentioning

confidence: 96%

Previous treatment as a confounding variable in studies with novel antipsychotics: two cases of high dopamine-2 receptor occupancy with quetiapine

Tauscher¹,

Küfferle²,

Asenbaum

et al. 1997

Psychopharmacology

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“…One of the most important confounding variable is premedication with typical neuroleptics and speciÞcally with depot formulations. As already previously shown, pretreatment with depot-neuroleptics with a pause for as long as 3 months is associated with higher striatal D 2 receptor occupancy rates (Harasko-van der Meer et al 1993;Tauscher et al 1997). We were also able to detect this phenomenon during sertindole treatment in two of our patients who were pretreated with depot medication.…”

Section: Discussionsupporting

confidence: 64%

Sertindole and dopamine D 2 receptor occupancy in comparison to risperidone, clozapine and haloperidol - a 123 I-IBZM SPECT study

et al. 1998

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The striatal D2 dopamine binding was studied in schizophrenic patients treated with the novel atypical antipsychotic drug sertindole (n=10). Comparisons were obtained with haloperidol (n=8), clozapine (n=6), risperidone (n=11) and untreated healthy controls (n=8) of a dataset which has partly been reported previously. 123I-Iodobenzamide (IBZM) single photon emission computerized tomography (SPECT) was used for estimation of striatal dopamine D2 receptor binding. Sertindole-treated patients exhibited significantly (P < 0.001) lower levels of striatal D2 binding (BG/FC ratio:1.28) compared with those treated with haloperidol (BG/FC ratio:1.09) and risperidone (8 mg:1.18) but significantly (P < 0.005) higher levels compared with clozapine (BG/FC ratio: 1.49). However, if patients were pretreated with a depot neuroleptic, significantly (P < 0.05) higher striatal D2 binding (BG/FC ratio:1.12) has been obtained. Since sertindole has been shown to exert distinct clinical efficacy for treatment of positive and negative symptoms, our data are indicative that antipsychotic efficacy is not associated with a high degree of striatal D2 receptor occupancy in schizophrenic patients.

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“…In the PET examination of a single patient, Farde and colleagues (23) found that after withdrawal of oral haloperidol for up to 54 hours, there was a rapid fall in serum drug levels without a significant reduction in D 2 receptor occupancy. Withdrawal of depot preparations of fluphenazine decanoate (24) and haloperidol decanoate (25) resulted in high D 2 dopamine receptor occupancy for several months.…”

Section: Discussionmentioning

confidence: 99%

Persistence of Haloperidol in Human Brain Tissue

Kornhuber¹,

Schultz²,

Wiltfang³

et al. 1999

AJP

132

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Objective: After discontinuation of neuroleptic drugs, their antipsychotic and antiparkinsonian effects are still present for a prolonged period. It is not known whether the extended effects of neuroleptic drugs in humans are due to the continued presence of drug in brain tissue or to long-lasting drug-induced physiologic changes. The aim of this study was to directly examine haloperidol concentrations in human brain tissue in relation to drug-free time. Method: Haloperidol concentrations were measured in five regions (temporal cortex, cingulate gyrus, caudate nucleus, dentate nucleus, corpus callosum) of the postmortem brains of 11 patients previously treated with haloperidol. Haloperidol was analyzed by means of high-performance liquid chromatography with ultraviolet detection. The half-life in brain tissue was estimated by a population kinetic analysis. Results: Haloperidol concentrations in the human brain tissue were 10-30 times higher than optimal serum concentrations used in the treatment of schizophrenia. Haloperidol concentrations appeared to be homogeneously distributed across different brain areas within a single patient. There was no apparent relation between duration of treatment and mean haloperidol concentration. Higher doses of haloperidol seemed to be related to higher concentrations in brain tissue. The elimination half-life from brain tissue was calculated to be 6.8 days. Conclusions: The results may have implications for clinical treatment decisions and the design of clinical research protocols. Patients exposed to haloperidol cannot be considered to be free of residual effects of the drug for a number of weeks after withdrawal.(Am J Psychiatry 1999; 156:885-890)

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Two cases of long term dopamine D2 receptor blockade after depot neuroleptics

Abstract: Two patients with extrapyramidal side effects after the use of fluphenazine decanoate were evaluated by means of IBZM-SPECT. Dopamine D2 receptor occupancy 1.5 months after withdrawal still amounted to 83% and 50%. More attention should be focused on long term effects of neuroleptics.

Cited by 16 publications

References 8 publications

Previous treatment as a confounding variable in studies with novel antipsychotics: two cases of high dopamine-2 receptor occupancy with quetiapine

Previous treatment as a confounding variable in studies with novel antipsychotics: two cases of high dopamine-2 receptor occupancy with quetiapine

Sertindole and dopamine D 2 receptor occupancy in comparison to risperidone, clozapine and haloperidol - a 123 I-IBZM SPECT study

Persistence of Haloperidol in Human Brain Tissue

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