Nyberg S, Farde L, Halldin C
Department of Clinical Neuroscience, Karolinska Institutet, Karolinska Hospital, Stockholm, Sweden.
Arch Gen Psychiatry. 1997 Oct;54(10):953-8. doi: 10.1001/archpsyc.1997.01830220079011.
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.
Four schizophrenic patients were withdrawn from low-dose treatment with haloperidol decanoate (30-50 mg every 4 weeks).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.
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.
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 This may explain the lower relapse rates in patients withdrawn from depot neuroleptic treatment compared with those withdrawn from oral treatment.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.
长效制剂的抗精神病药物即使在完全停药后也可能预防精神病复发。为了研究药物在大脑中残留的持续时间，在停用长效抗精神病药物治疗后，用正电子发射断层扫描测量了一年的中枢D2多巴胺受体占有率。
4例精神分裂症患者停止使用低剂量癸酸氟哌啶醇治疗（每4周30 - 50mg）。在接下来的一年中，他们接受了多次正电子发射断层扫描以及放射性配体碳11标记的雷氯必利检查。在研究终点，进行了Scatchard分析以确定D2多巴胺受体的密度和亲和力。
长效注射后1周，D2多巴胺受体占有率最高（4例患者分别为66%、77%、82%和78%），然后缓慢下降。停药6个月后，3例患者的D2多巴胺受体占有率分别为24%、32%和34%。1年后，2例患者的D2多巴胺受体密度和亲和力在对照组范围内，提示无氟哌啶醇残留。
我们关于D2多巴胺受体占有率持续存在的初步发现表明，常用剂量的癸酸氟哌啶醇（每4周200mg）即使在停药16周后仍能维持抗精神病水平的受体占有率。这可能解释了与口服治疗停药的患者相比，长效抗精神病药物治疗停药患者复发率较低的原因。此外，残留的占有率可能会混淆后续治疗的临床评估。对于新抗精神病药物的对照临床试验，我们建议在最后一次长效注射后至少洗脱6个月。
