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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Delayed normalization of central D2 dopamine receptor availability after discontinuation of haloperidol decanoate. Preliminary findings.

BACKGROUND: Antipsychotic drugs in depot formulations may prevent psychotic relapses, even after complete withdrawal. To examine the duration of drug remaining in the brain, central D2 dopamine receptor occupancy was measured with positron emission tomography for a year after discontinuation of depot neuroleptic treatment. METHODS: Four schizophrenic patients were withdrawn from low-dose treatment with haloperidol decanoate (30-50 mg every 4 weeks). They were examined repeatedly with positron emission tomography and the radioligand carbon 11-labeled raclopride during the following year. At end point, a Scatchard analysis was performed to determine the density and affinity of D2 dopamine receptors. RESULTS: Occupancy of D2 dopamine receptors was highest 1 week after depot injection (66%, 77%, 82%, and 78% in 4 patients) and then decreased slowly. Six months after discontinuation of treatment, D2 dopamine receptor occupancy was 24%, 32%, and 34% in 3 patients. After 1 year, D2 dopamine receptor density and affinity in 2 patients were within the ranges of control subjects, suggesting no remaining haloperidol. CONCLUSIONS: Our preliminary finding of persistence of D2 dopamine receptor occupancy indicates that commonly used doses of haloperidol decanoate (200 mg every 4 weeks) maintain antipsychotic levels of receptor occupancy even 16 weeks after discontinuation of treatment. This may explain the lower relapse rates in patients withdrawn from depot neuroleptic treatment compared with those withdrawn from oral treatment. In addition, the remaining occupancy may confound the clinical evaluation of subsequent treatments. For controlled clinical trials of new antipsychotic drugs, we suggest a minimum washout of 6 months after the last depot injection.[1]


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