Olié J P, Baylé F J
Université Paris V, Centre Hospitalier Sainte-Anne, Paris.
Encephale. 1997 Apr;23 Spec No 2:2-9.
Particular features are involved in the atypical antipsychotic concept: efficacity on refractory patients and negative symptoms, less or no extrapyramidal side effects, less tardive dyskinesia and less increase in prolactinemia. The imprecision of the atypical neuroleptic class must be underlined. In fact, the pharmacological agents who are included in this class potentially induce few neurological side effects. These effects appearing in doses very much higher than in the therapeutical range. In this case, atypical should refer to a particularity in the links between doses, efficacy and side effects more than to a definition in a specific category. Dopaminergic hypothesis is explained more and more by a dopaminergic system dysregulation than by a simple dopaminergic hyperactivity. This dysregulation might be autonomous or linked to other monoaminergic systems. These new antipsychotics show affinity for different monoaminergic receptors. After clozapine, several agents are now available (risperidone) or just about to be (olanzapine, seroquel, sertindole, ziprasidone, zotépine). Therapeutical effects are probably linked with a dual antagonist effects on 5HT2 and D2 receptors. The atypical antipsychotic efficacy on negative symptoms remains controversial. While very few patients are found to be "purely" negative, most of the schizophrenic patients will show sooner or later some negative symptoms mixed with positive ones. The obvious difficulties in methodological and clinical evaluation of negative symptoms are at least dual: depressive symptoms; extrapyramidal side effects. Secondary negative symptoms usually don't last, while primary negative symptoms are more permanent. Kraepelin describes them as the avolutionnal syndrome of dementia praecox. Usually negative symptoms improve during therapeutic trials, including those using classical neuroleptics. This should not lead us to the conclusion that we have today at our disposal pharmacological agents effective on avolutionnal syndrome or primary negative symptoms. More studies are still necessary. Similarities and differences between the new antipsychotic are not yet evaluated, except partly for clozapine and risperidone. Some new neuroleptics might simplify greatly the therapeutic range. Studies concerning risperidone clearly prove its efficacity on a daily dose of 6 +/- 2 mg. A daily dose of 10 mg doesn't bring any additional improvement. This aspect must be underlined while the efficacy-dose ratio of the classical neuroleptics are still questioned. Consequently too many patients might be given insufficient doses and others excessive doses resulting in side effects and no additional benefits. These new antipsychotics must add a positive modification in schizophrenic care. They might lead to a limited use of additional therapeutics and a better observance thus allowing less relapses and less rehospitalisations.
对难治性患者和阴性症状有效，锥体外系副作用较少或无，迟发性运动障碍较少，催乳素血症增加较少。必须强调非典型抗精神病药物分类的不精确性。事实上，归入此类的药物可能仅引起极少的神经副作用。这些副作用出现在远高于治疗剂量的水平。在这种情况下，非典型应更多地指剂量、疗效和副作用之间联系的特殊性，而非特定类别的定义。多巴胺能假说越来越多地被解释为多巴胺能系统失调，而非单纯的多巴胺能亢进。这种失调可能是自主性的，或与其他单胺能系统有关。这些新型抗精神病药物对不同的单胺能受体具有亲和力。继氯氮平之后，现在已有几种药物（利培酮）可供使用，或即将可供使用（奥氮平、喹硫平、舍吲哚、齐拉西酮、佐替平）。治疗效果可能与对5HT2和D2受体的双重拮抗作用有关。非典型抗精神病药物对阴性症状的疗效仍存在争议。虽然极少有患者是“纯粹”阴性的，但大多数精神分裂症患者迟早会出现一些与阳性症状混合的阴性症状。阴性症状在方法学和临床评估上的明显困难至少有两方面：抑郁症状；锥体外系副作用。继发性阴性症状通常不会持续，而原发性阴性症状更持久。克雷佩林将它们描述为早发性痴呆的衰退综合征。通常在治疗试验中，包括使用经典抗精神病药物的试验中，阴性症状会有所改善。但这不应使我们得出结论，即我们目前拥有对衰退综合征或原发性阴性症状有效的药物。仍需要更多研究。除了部分关于氯氮平和利培酮之外，新型抗精神病药物之间的异同尚未得到评估。一些新型抗精神病药物可能会极大地简化治疗范围。关于利培酮的研究清楚地证明，每日剂量6±2毫克时其有效。每日剂量10毫克并不会带来额外改善。在经典抗精神病药物的疗效 - 剂量比仍受到质疑的情况下，这一点必须强调。因此，可能有太多患者剂量不足，而其他患者剂量过大，导致出现副作用且无额外益处。这些新型抗精神病药物必须在精神分裂症治疗中带来积极改变。它们可能会导致对额外治疗的有限使用和更好的依从性，从而减少复发和再住院次数。
