Bourin Michel, Lambert Olivier, Guitton Bernard
EA 3256 Neurobiologie de l'anxiété et de la dépression, Faculté de Médecine, 1 rue Gaston Veil, BP 53508 44035 Nantes Cedex 01 France.
Hum Psychopharmacol. 2005 Jan;20(1):15-26. doi: 10.1002/hup.657.
No consensus has been reached with regard to the treatment of bouts of acute mania in various parts of the world. Controlled clinical trials have, at last, provided irrefutable evidence of the activity of lithium, which has long been used alone, as well as that of divalproate or its derivatives and, to a lesser extent, carbamazepine. The new antipsychotic agents have more recently established their efficacy, especially olanzapine, risperidone and aripiprazole. It is paradoxical to note that, in Europe, haloperidol is still the reference substance used in clinical trials despite the fact that it is not officially indicated in the treatment of mania. In the USA, lithium, divalproate or antipsychotics can be prescribed as first-line treatment. In Europe, lithium remains the first-line medication, whereas divalproate and atypical antipsychotic agents are used only as second-line therapy. The conventional antipsychotic agents (such as haloperidol, loxapine or zuclopenthixol) which should no longer be prescribed during manic episodes given the potential risks and side effects associated with these substances (extrapyramidal side effects, depressogenic effect, malignant syndrome) are still prescribed extensively in Europe. Although both types of medication (antipsychotics, normothymic agents and/or anticonvulsants) have proved to be clinically effective in the management of mania by reducing the mania scores overall, the same does not apply, however, to all symptoms of mania. Factorial approaches to mania have all shown that since there are several clinical forms of mania, several lines of manic symptoms can be identified. Antipsychotic and normothymic agents and/or anticonvulsants do not appear to have the same effects on each of these identifiable clusters of symptoms, mainly psychotic features. We believe that it is vitally important for future clinical trials of mania treatment to focus on the treatment effect by adopting a factorial approach to the episode with an appropriate methodological structure provided to this end. These questions highlight the uncertainty shrouding the very structure of manic episodes, namely that these are predominantly of a thymic or psychotic nature. The Europeans undoubtedly consider mania to be more of a thymic episode and prefer lithium as the first-line treatment, whereas the Americans believe that psychotic symptoms dominate and widely prescribe antipsychotic agents. However, from the standpoint of clinical trials currently available, even though antipsychotic agents are certainly effective in reducing the scores on the mania scales, can they be considered purely as antimania treatments?
世界各地对于急性躁狂发作的治疗尚未达成共识。对照临床试验终于提供了确凿证据，证明长期单独使用的锂盐、丙戊酸盐及其衍生物以及在较小程度上的卡马西平具有活性。新型抗精神病药物最近也证实了其疗效，尤其是奥氮平、利培酮和阿立哌唑。矛盾的是，在欧洲，尽管氟哌啶醇并未被官方指明用于治疗躁狂症，但它仍是临床试验中使用的参考药物。在美国，锂盐、丙戊酸盐或抗精神病药物可作为一线治疗药物开具。在欧洲，锂盐仍然是一线用药，而丙戊酸盐和非典型抗精神病药物仅用作二线治疗。鉴于传统抗精神病药物（如氟哌啶醇、洛沙平或氯噻吨）存在潜在风险和副作用（锥体外系副作用、致抑郁作用、恶性综合征），在躁狂发作期间不应再开具此类药物，但在欧洲它们仍被广泛使用。尽管这两类药物（抗精神病药物、心境稳定剂和/或抗惊厥药物）在通过总体降低躁狂评分来治疗躁狂症方面已被证明具有临床疗效，但对于躁狂症的所有症状并非都适用。针对躁狂症的析因方法均表明，由于存在多种临床形式的躁狂症，因此可以识别出多条躁狂症状线。抗精神病药物、心境稳定剂和/或抗惊厥药物对这些可识别的症状群（主要是精神病性特征）中的每一个似乎并没有相同的效果。我们认为，对于未来躁狂症治疗的临床试验而言，至关重要的是通过对发作采用析因方法，并为此提供适当的方法结构来关注治疗效果。这些问题凸显了笼罩着躁狂发作结构的不确定性，即这些发作主要是心境性的还是精神病性的。欧洲人无疑认为躁狂症更多是一种心境发作，更倾向于将锂盐作为一线治疗药物，而美国人则认为精神病性症状占主导，并广泛开具抗精神病药物。然而，从目前可用的临床试验角度来看，尽管抗精神病药物在降低躁狂量表评分方面肯定有效，但它们能被纯粹视为抗躁狂治疗药物吗？
