González-Pinto Ana, Aldama Ana, Mosquera Fernando, González Gómez Cristina
Stanley International Mood Disorders Research Center, Hospital Santiago Apóstol, University of the Basque Country, Vitoria, Spain.
CNS Drugs. 2007;21(8):611-26. doi: 10.2165/00023210-200721080-00001.
The presence of depressive symptomatology during acute mania has been termed mixed mania, dysphoric mania, depressive mania or mixed bipolar disorder. Highly prevalent, mixed mania occurs in at least 30% of bipolar patients. Correct diagnosis is a major challenge. The DSM diagnostic criteria, the most widely adopted clinical convention, require a complete manic and complete depressive syndrome co-occurring for at least 1 week. However, recent alternative categorical and dimensional studies of manic phenomenology have shown that there are certain depressive symptoms or constellations that have special clinical importance when describing mixed states, such as depressed mood and anxiety symptomatology that do not overlap with manic symptoms. Patients with mixed mania are over-represented in the subgroup with severe and treatment-resistant symptoms. The course and prognosis of mixed mania are worse than that of pure manic forms in the medium and long term, with higher recurrence rates, higher frequency of co-morbid substance abuse and greater risk of suicidal ideation and attempts. Moreover, mixed manic episodes are usually associated with increased depression during follow-up, greater risk of rapid cycling course and higher prevalence of physical co-morbidities, principally related to thyroid function. All these factors are very relevant to selection of treatment. There are three crucial steps in the treatment of mixed mania--making the correct diagnosis, starting treatment early, and considering not only the acute state but also maintenance treatment and the patient's long-term outcome. Although challenging, acute mixed episodes are treatable. To date there have been no controlled studies devoted exclusively to treatment of mixed mania, and the only controlled data available therefore derive from sub-analyses of randomised clinical trials. Both short-term and maintenance treatments of patients with mixed mania require experience and usually involve the combination of different treatments. As a general rule, there is some consensus about discontinuing antidepressants during mixed mania. Olanzapine, aripiprazole or valproate semisodium (divalproex sodium) are first-line drugs for mild episodes; severe episodes of mixed mania usually require treatment with a combination of valproate semisodium or lithium plus an antipsychotic, preferably an atypical agent. Carbamazepine is also useful for the treatment of mixed mania. High-dose medications are sometimes needed to control the episode, and time to remission is usually longer than in pure mania. Importantly, patients with mixed manic episodes have more adverse events of psychopharmacological treatment. In some cases, electroconvulsive therapy is required.
急性躁狂发作期间出现抑郁症状，被称为混合性躁狂、烦躁性躁狂、抑郁性躁狂或双相情感障碍混合型。混合性躁狂极为常见，至少30%的双相情感障碍患者会出现。正确诊断是一项重大挑战。《精神疾病诊断与统计手册》（DSM）的诊断标准是最广泛采用的临床规范，要求完整的躁狂综合征和完整的抑郁综合征同时出现至少1周。然而，最近对躁狂症候学进行的分类和维度研究表明，在描述混合状态时，某些抑郁症状或症状群具有特殊的临床重要性，如与躁狂症状不重叠的抑郁情绪和焦虑症状。在症状严重且难治的亚组中，混合性躁狂患者的比例过高。从中长期来看，混合性躁狂的病程和预后比单纯躁狂形式更差，复发率更高，共病物质滥用的频率更高，自杀观念和自杀企图的风险更大。此外，混合性躁狂发作在随访期间通常与抑郁加重、快速循环病程的风险增加以及身体共病的患病率更高有关，主要与甲状腺功能有关。所有这些因素都与治疗选择密切相关。混合性躁狂的治疗有三个关键步骤——做出正确诊断、尽早开始治疗，不仅要考虑急性期，还要考虑维持治疗和患者的长期预后。尽管具有挑战性，但急性混合发作是可以治疗的。迄今为止，尚无专门针对混合性躁狂治疗的对照研究，因此唯一可用的对照数据来自随机临床试验的亚组分析。混合性躁狂患者的短期和维持治疗都需要经验，通常涉及不同治疗方法的联合使用。一般来说，对于混合性躁狂期间停用抗抑郁药存在一些共识。奥氮平、阿立哌唑或丙戊酸钠（丙戊酸二钠）是轻度发作的一线药物；混合性躁狂的重度发作通常需要丙戊酸钠或锂盐与抗精神病药物联合治疗，最好是使用非典型药物。卡马西平对混合性躁狂的治疗也有效。有时需要高剂量药物来控制发作，缓解时间通常比单纯躁狂更长。重要的是，混合性躁狂发作的患者在精神药物治疗中出现的不良事件更多。在某些情况下，需要进行电休克治疗。
