KeyPoint, Consultoria Científica, Lda, Algés, Portugal.
Clin Drug Investig. 2011;31(1):61-71. doi: 10.2165/11586690-000000000-00000.
Depressive disorders are common health problems. Both preclinical and clinical studies have shown that pirlindole, a tetracyclic compound, is suitable for the management of depression; however, a systematic review is needed to accurately select randomized controlled trials (RCTs) for a meta-analysis that will provide more consistent and accurate results regarding the efficacy and tolerability of the drug.
To evaluate the efficacy and frequency of adverse events with pirlindole in comparison with active comparators (monoamine oxidase inhibitors [MAOIs], tricyclic antidepressants, tetracyclic antidepressants, and selective serotonin reuptake inhibitors [SSRIs]) for the treatment of major depression.
Data were searched through MEDLINE (via PubMed), EMBASE, the Cochrane Central Register of Controlled Trials and a manual search through the sponsor's available archives (1966 to 30 August 2010). The meta-analysis was performed using the Mantel-Haenszel technique and analysing data through Comprehensive Meta-Analysis software version 1.0.23. Studies were included if they were RCTs evaluating the efficacy and number of reported adverse events with pirlindole in comparison with active comparators for the treatment of major depression in adults. Placebo-controlled trials were excluded to minimize study heterogeneity.
This systematic review included ten published articles and one non-published report corresponding to a total of 13 clinical trials in the adult population. Two RCTs were excluded from the meta-analysis because the comparator was placebo. Two more studies were excluded, one because randomization could not be confirmed and the other because it described follow-up data on patients from a study that had already been included in the meta-analysis. Therefore, only nine RCTs were included in the meta-analysis. No differences were found between pirlindole and its active comparators with regard to the percentage of patients whose clinical condition improved by 50% according to the Hamilton Depression Rating Scale (HDRS) [odds ratio (OR) 1.52; 95% confidence interval [CI] 0.92, 2.51; p = 0.11] and Hamilton Anxiety Rating Scale (HARS) [OR 1.15; 95% CI 0.69, 1.90; p = 0.59]. With regard to the improvements in HDRS and HARS, the results were favourable for patients treated with pirlindole (depression: absolute value 0.18; 95% CI -0.01, 0.37; p = 0.06; anxiety: absolute value 0.26; 95% CI 0.03, 0.48; p = 0.03).
This systematic review and meta-analysis showed that all RCTs included reported efficacy outcomes for pirlindole comparable to those of its comparators, and that pirlindole was significantly better in terms of reducing anxiety symptoms. However, the analysis of these results should take into account the quality of the original included articles, which had a mean Jadad trial quality score of 3.7 (out of 5). Therefore, further clinical trials should be conducted to evaluate the benefits of pirlindole.
抑郁障碍是常见的健康问题。临床前和临床研究都表明，吡咯吲哚是一种四环化合物，适用于抑郁症的治疗；然而，需要进行系统评价，以便准确选择随机对照试验（RCT）进行荟萃分析，从而提供更一致和准确的关于药物疗效和耐受性的结果。
评估吡咯吲哚与活性对照物（单胺氧化酶抑制剂[MAOIs]、三环抗抑郁药、四环抗抑郁药和选择性 5-羟色胺再摄取抑制剂[SSRIs]）相比治疗重度抑郁症的疗效和不良事件发生率。
通过 MEDLINE（通过 PubMed）、EMBASE、Cochrane 对照试验中心注册库和赞助商可用档案的手动搜索（1966 年至 2010 年 8 月 30 日）检索数据。使用 Mantel-Haenszel 技术进行荟萃分析，并通过 Comprehensive Meta-Analysis 软件版本 1.0.23 分析数据。如果研究是 RCT，评估吡咯吲哚与活性对照物治疗成人重度抑郁症的疗效和报告的不良事件发生率，并与安慰剂进行比较，则纳入研究。排除安慰剂对照试验，以尽量减少研究异质性。
本系统评价纳入了 10 篇已发表的文章和 1 篇非发表的报告，共计 13 项成人临床试验。由于对照物是安慰剂，因此有 2 项 RCT 被排除在荟萃分析之外。另外 2 项研究被排除在外，一项是因为无法确认随机分组，另一项是因为它描述了已经包含在荟萃分析中的研究中患者的随访数据。因此，只有 9 项 RCT 被纳入荟萃分析。根据汉密尔顿抑郁评定量表（HDRS）[优势比（OR）1.52；95%置信区间（CI）0.92，2.51；p=0.11]和汉密尔顿焦虑评定量表（HARS）[OR 1.15；95%CI 0.69，1.90；p=0.59]，吡咯吲哚与活性对照物相比，改善 50%的患者比例没有差异。就 HDRS 和 HARS 的改善而言，接受吡咯吲哚治疗的患者结果更为有利（抑郁：绝对值 0.18；95%CI-0.01，0.37；p=0.06；焦虑：绝对值 0.26；95%CI 0.03，0.48；p=0.03）。
本系统评价和荟萃分析表明，纳入的所有 RCT 都报告了吡咯吲哚的疗效结果与对照物相当，且吡咯吲哚在降低焦虑症状方面明显更好。然而，应该考虑到原始纳入文章的质量，这些文章的平均 Jadad 试验质量评分为 3.7（满分 5 分）。因此，应该进行进一步的临床试验来评估吡咯吲哚的益处。
