Choosing the right dose of antipsychotics in schizophrenia - Lessons from neuroimaging studies
Choosing the right dose of antipsychotics in schizophrenia - Lessons from neuroimaging studies
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DOI：
10.2165/00023210-200115090-00001
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发表时间：
2001-01-01
期刊：
影响因子：
6
通讯作者：
Kapur, S
中科院分区：
文献类型：
--
作者：
Tauscher, J;Kapur, S
尽管抗精神病药物的临床经验丰富，但对于这些物质的给药剂量没有广泛的共识。目前，大多数抗精神病药物都是根据临床剂量探索研究经验性地给药，在这些研究中，对任意选择的剂量进行测试，以在患者群体中找到“最有效”的剂量范围，而不考虑测试药物的分子效应。使用核医学技术的脑成像研究，如正电子发射断层扫描（PET）或单光子发射计算机断层扫描（SPECT），现在可以提供一个基本的剂量，直接从中枢作用的药物对神经递质受体在体内测量。PET结果表明，多巴胺D-2受体的占用率至少为65%，需要抗精神病药物的临床反应，而占用率超过72%和78%分别与催乳素水平升高和运动不良反应的高风险相关。例如，氟哌啶醇的临床研究并未指出剂量超过5 mg/天的优势。D-2受体结合率与药物给药的相关性也得到了相关动物模型中抗精神病药物与其D-2受体结合率相关性研究的证实，总之，神经影像学和临床研究以及动物模型为使用相对低剂量的典型抗精神病药物和等效剂量的新型抗精神病药物提供了依据。适当剂量的抗精神病药物不良反应的风险较低，可能会进一步提高依从性和结果。这似乎是特别重要的个人经历的第一次发作的精神分裂症，因为他们似乎是特别响应药物治疗和相当敏感的不良反应。
Despite vast clinical experience with antipsychotics, there is no broad consensus on the doses of these substances that should be administered. Currently, most antipsychotics are administered empirically according to clinical dose-finding studies, in which arbitrarily selected doses were tested to find the 'most efficient' dose range in a patient population, with no regard for the molecular effects of the tested drug.Brain imaging studies using nuclear medical techniques, such as positron emission tomography (PET) or single photon emission computed tomography (SPECT), can now provide a rationale for doses, directly derived from the central effects of the drugs on neurotransmitter receptors measured in vivo. PET results indicate that occupancy of at least 65% of dopamine D-2 receptors is needed for clinical response to antipsychotics, and that occupancy rates exceeding 72 and 78% are associated with a high risk for elevation of prolactin levels and motor adverse effects, respectively. For example, clinical studies with haloperidol do not point to an advantage of dosages exceeding 5 mg/day. The relevance of D-2 receptor occupancy for drug administration is also borne out by studies relating the effects of antipsychotics to their D-2 receptor occupancy in relevant animal models.Taken together, neuroimaging and clinical studies, as well as animal models, provide a rationale for the use of relatively low doses of typical antipsychotics and equivalent doses of novel antipsychotics. The lower risk of adverse effects with appropriate doses of antipsychotics may further enhance compliance and outcome. This seems to be particularly important in individuals experiencing a first episode of schizophrenia, as they appear to be especially responsive to pharmacotherapy and quite sensitive to adverse effects.