Charpeaud T, Samalin L, Llorca P-M
EA U7280, université d'Auvergne, CHU de Clermont-Ferrand, Clermont-Ferrand, France.
EA U7280, université d'Auvergne, CHU de Clermont-Ferrand, Clermont-Ferrand, France.
Encephale. 2014 Feb;40(1):62-73. doi: 10.1016/j.encep.2013.12.002. Epub 2014 Jan 18.
Problem of the choice of antipsychotic dose is a key issue in clinical practice. It determines the efficacy and safety of treatment. Aripiprazole is recommended at a dose of between 10 and 15 mg/day in the treatment of schizophrenia, with a dose range considered to be effective, between 10 and 30 mg/day. This wide therapeutic range prompted us to investigate the existence of a possible dose-effect relationship for aripiprazole in the treatment of schizophrenia.
We conducted a literature review from PubMed and EMBASE database, with the keywords: aripiprazole, schizophrenia. We limited it to studies published in English and French, with the main objective to assess the efficacy of aripiprazole in patients with schizophrenia. We selected only randomized clinical trials, double-blind, controlled against placebo or against an active comparator. Studies in which aripiprazole was studied added to another antipsychotic were not retained.
Twenty-two randomized, double-blind, controlled studies were selected. Three studies assessed the efficacy of aripiprazole on agitation symptoms in patients with schizophrenia and for which a dose of aripiprazole between 1 and 15mg showed significant efficacy compared to placebo. Seven clinical trials focused on the effect of aripiprazole short term (less than 12weeks). For the primary endpoint (PANSS scores), aripiprazole was superior to placebo or equivalent to active comparators (risperidone, olanzapine or haloperidol). These short-term studies revealed a range of effective doses from 10 mg/day to 20 mg/day. Five studies, lasting between 16 and 52 weeks, with a primary endpoint being the time to discontinuation for any cause for two studies, the time before relapse in one study, and the improvement in PANSS scores for the two other studies. On these different endpoints, aripiprazole was effective at average doses between 15 and 28.1 mg/day. The safety of aripiprazole was particularly favourable in these trials. Finally, we listed seven post-hoc analyses. In support of these long-term analyses on different endpoints, aripiprazole showed significant efficacy at higher doses (20 and 30 mg/day) than those used in the agitation treatment.
No study was designed to compare aripiprazole doses in schizophrenia. Nevertheless, efficacy on agitation and hostility components had been observed for doses of 10mg/day, or lower; whereas the antipsychotic effect in acute or maintenance phase appeared optimal for doses ranging from 10 to 25 mg/day. Only one study retained a minimum effective dose of 10mg/day on the PANSS scores. This literature review reveals an effective dose range between 10 and 25 mg/day for aripiprazole in schizophrenia. Less than 10 mg/day did not show significant efficacy on symptoms of schizophrenia, apart from a specific short-term effect on agitation, at very low doses (starting at 1mg). Optimization of treatment, at doses above 25 mg/day, cannot be the subject of evidence-based recommendations.
抗精神病药物剂量的选择问题是临床实践中的关键问题。它决定了治疗的有效性和安全性。在精神分裂症治疗中，阿立哌唑的推荐剂量为每日10至15毫克，有效剂量范围被认为是每日10至30毫克。这种较宽的治疗范围促使我们研究阿立哌唑在精神分裂症治疗中是否存在可能的剂量效应关系。
我们从PubMed和EMBASE数据库进行了文献综述，关键词为：阿立哌唑、精神分裂症。我们将其限制在以英文和法文发表的研究，主要目的是评估阿立哌唑对精神分裂症患者的疗效。我们仅选择随机临床试验，双盲，与安慰剂或活性对照药对照。阿立哌唑与另一种抗精神病药物联合使用的研究未被纳入。
选择了22项随机、双盲、对照研究。三项研究评估了阿立哌唑对精神分裂症患者激越症状的疗效，与安慰剂相比，1至15毫克剂量的阿立哌唑显示出显著疗效。七项临床试验关注阿立哌唑的短期（少于12周）效应。对于主要终点（阳性和阴性症状量表评分），阿立哌唑优于安慰剂或等同于活性对照药（利培酮、奥氮平或氟哌啶醇）。这些短期研究显示有效剂量范围为每日10至20毫克。五项研究持续16至52周，两项研究的主要终点是因任何原因停药的时间，一项研究是复发前的时间，另外两项研究是阳性和阴性症状量表评分的改善。在这些不同终点上，阿立哌唑在每日15至28.1毫克的平均剂量下有效。在这些试验中，阿立哌唑的安全性特别良好。最后，我们列出了七项事后分析。为支持这些关于不同终点的长期分析，阿立哌唑在高于用于激越治疗的剂量（每日20和30毫克）时显示出显著疗效。
没有研究设计用于比较精神分裂症中阿立哌唑的剂量。然而，已观察到每日10毫克或更低剂量对激越和敌对成分有效；而在急性或维持期的抗精神病作用在每日10至25毫克的剂量范围内似乎最佳。只有一项研究在阳性和阴性症状量表评分上保留了10毫克/天的最低有效剂量。这篇文献综述揭示了阿立哌唑在精神分裂症中的有效剂量范围为每日10至25毫克。低于10毫克/天对精神分裂症症状未显示出显著疗效，除了在非常低的剂量（从1毫克开始）对激越有特定的短期效应。高于25毫克/天的治疗优化不能成为基于证据的推荐主题。
