Nussbaumer Barbara, Morgan Laura C, Reichenpfader Ursula, Greenblatt Amy, Hansen Richard A, Van Noord Megan, Lux Linda, Gaynes Bradley N, Gartlehner Gerald
Department for Evidence-Based Medicine and Clinical Epidemiology, Danube University Krems, Dr.-Karl-Dorrek Strasse 30, 3500, Krems, Austria,
CNS Drugs. 2014 Aug;28(8):699-712. doi: 10.1007/s40263-014-0169-z.
Major depressive disorder (MDD) has detrimental effects on an individual's personal life, leads to increased risk of comorbidities, and places an enormous economic burden on society. Several 'second-generation' antidepressants are available as both immediate-release (IR) and extended-release formulations. The advantage of extended-release formulations may be the potentially improved adherence and a lower risk of adverse events.
We conducted a systematic review to assess the comparative efficacy, risk of harms, and patients' adherence of IR and extended-release antidepressants for the treatment of MDD.
English-language abstracts were retrieved from PubMed, EMBASE, the Cochrane Library, PsycINFO, and International Pharmaceutical Abstracts from 1980 to October 2012, as well as from reference lists of pertinent review articles and grey literature searches.
We included head-to-head randomized controlled trials (RCTs) of at least 6 weeks' duration that compared an IR formulation with an extended-release formulation of the same antidepressant in adult patients with MDD. We also included placebo-controlled trials to conduct a network meta-analysis. To assess harms and adherence, in addition to RCTs, we searched for observational studies with ≥1,000 participants and a follow-up of ≥12 weeks.
We dually reviewed abstracts and full texts and assessed quality ratings. Lacking head-to-head evidence for many comparisons of interest, we conducted network meta-analyses using Bayesian methods. Our outcome measure of choice was response on the Hamilton Depression Rating Scale.
We located seven head-to-head trials and 94 placebo- and active-controlled trials for network meta-analysis. Overall, our analyses indicate that IR and extended-release formulations do not differ substantially with respect to efficacy and risk of harms. The evidence is mixed with respect to differences in adherence, indicating lower adherence for IR formulations.
The lack of head-to-head comparisons for many drugs compromises our conclusions. Network meta-analyses have methodological limitations that need to be taken into consideration when interpreting findings.
Available evidence currently shows no clear differences between the two formulations and therefore we cannot recommend a first choice. However, if adherence or compliance with one medication is an issue, then clinicians and patients should consider the alternative medication. If adherence or costs are a problem with one formulation, consideration of the other formulation to provide an adequate treatment trial is reasonable.
重度抑郁症（MDD）对个人生活有不利影响，会增加共病风险，并给社会带来巨大经济负担。几种“第二代”抗抑郁药有速释（IR）和缓释两种剂型。缓释剂型的优势可能在于潜在的依从性提高和不良事件风险降低。
我们进行了一项系统评价，以评估速释和缓释抗抑郁药治疗MDD的疗效对比、危害风险及患者依从性。
从1980年至2012年10月的PubMed、EMBASE、Cochrane图书馆、PsycINFO和国际药学文摘数据库中检索英文摘要，以及相关综述文章的参考文献列表和灰色文献搜索结果。
我们纳入了至少为期6周的直接比较随机对照试验（RCT），这些试验在成年MDD患者中比较了同一抗抑郁药的速释剂型和缓释剂型。我们还纳入了安慰剂对照试验以进行网状Meta分析。为评估危害和依从性，除RCT外，我们还检索了参与者≥1000名且随访≥12周的观察性研究。
我们对摘要和全文进行了双重审查并评估质量评级。由于缺乏许多感兴趣比较的直接证据，我们使用贝叶斯方法进行网状Meta分析。我们选择的结局指标是汉密尔顿抑郁量表的反应。
我们找到了7项直接比较试验以及94项用于网状Meta分析的安慰剂对照和活性对照试验。总体而言，我们的分析表明，速释和缓释剂型在疗效和危害风险方面没有实质性差异。关于依从性差异的证据不一，表明速释剂型的依从性较低。
许多药物缺乏直接比较影响了我们的结论。网状Meta分析存在方法学局限性，在解释结果时需要考虑。
现有证据目前表明两种剂型之间没有明显差异，因此我们无法推荐首选。然而，如果一种药物的依从性或顺应性存在问题，那么临床医生和患者应考虑另一种药物。如果一种剂型的依从性或成本存在问题，考虑使用另一种剂型进行充分治疗试验是合理的。
