Department of Psychiatry, Hospital de la Santa Creu i Sant Pau, Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM, Avenue Sant Antoni Maria Claret, 167, 08025 Barcelona, Spain.
J Clin Psychiatry. 2011 Jul;72(7):962-9. doi: 10.4088/JCP.09m05827blu. Epub 2010 Oct 19.
Since depression entails not only dramatic personal disruption but also a huge amount of medical and socioeconomic burden, slowness of antidepressant action and difficulties to attain remission are entangled issues to be solved. Given the controversial previous findings with enhancing strategies such as pindolol, we examined whether the speed of selective serotonin reuptake inhibitor (SSRI) action can be truly accelerated with optimized pindolol dosage. Additionally, we aimed at elucidating whether pindolol benefits emerge, particularly in a population with nonresistant depression.
Thirty outpatients with major depressive disorder (DSM-IV criteria) recruited between December 2002 and November 2005 were randomly assigned to receive citalopram + pindolol (5 mg tid) or citalopram + placebo for 6 weeks in a double-blind randomized clinical trial. A meta-analysis of randomized controlled trials of pindolol augmentation in patients with nonresistant depression was also performed. Outcome criteria were based on the 17-item Hamilton Depression Rating Scale. For the meta-analysis, efficacy was assessed by the number of treatment responders at 2 weeks and 4-6 weeks.
Clinical trial outcomes: Repeated-measures analysis of variance showed a significant group-by-time interaction (P = .01). Cumulative percentage showed a trend for sustained response (odds ratio [OR] = 2.09; 95% CI, 0.914-4.780; P = .08) and a well-defined increased likelihood of sustaining remission (OR = 5.00; 95% CI, 1.191-20.989; P = .03) in pindolol receivers. Median survival time until first response was 65% less in the pindolol group (22 days vs 30 days; P = .03). The negative binomial regression model yielded different rates of response per person-day for pindolol and placebo groups (7.6% vs 4.7%, respectively; P = .03). Meta-analysis: Outcome favored pindolol at 2 weeks' time (relative risk [RR] = 1.68; 95% CI, 1.18-2.39; P = .004) and also at 4-6 weeks' time (RR = 1.11; 95% CI, 1.02-1.20; P = .02).
Present findings represent further evidence of the acceleration and enhancement of efficacy with pindolol administered together with SSRIs, displaying a quicker and more pronounced decrease of symptoms in patients with nonresistant major depressive disorder.
clinicaltrials.gov Identifier: NCT00931775.
由于抑郁症不仅会造成个人严重的困扰，还会带来巨大的医疗和社会经济负担，因此，抗抑郁药起效缓慢和难以达到缓解是需要解决的问题。鉴于之前关于增强策略（如吡咯烷酮）的研究结果存在争议，我们研究了优化吡咯烷酮剂量是否真的可以加快选择性 5-羟色胺再摄取抑制剂（SSRIs）的作用。此外，我们旨在阐明吡咯烷酮的益处是否会出现，特别是在非耐药性抑郁症患者中。
2002 年 12 月至 2005 年 11 月期间招募的 30 名符合 DSM-IV 标准的重性抑郁障碍门诊患者被随机分配接受西酞普兰+吡咯烷酮（5mg tid）或西酞普兰+安慰剂治疗 6 周，采用双盲随机临床试验。我们还对非耐药性抑郁症患者的吡咯烷酮增效随机对照试验进行了荟萃分析。疗效评估标准基于 17 项汉密尔顿抑郁量表。对于荟萃分析，治疗 2 周和 4-6 周时的应答人数评估疗效。
临床试验结果：重复测量方差分析显示，组间存在显著的时间交互作用（P=0.01）。累积百分比显示出持续应答的趋势（比值比[OR]=2.09；95%置信区间，0.914-4.780；P=0.08），并且更有可能持续缓解（OR=5.00；95%置信区间，1.191-20.989；P=0.03）。吡咯烷酮组的首次应答中位生存时间减少了 65%（22 天 vs 30 天；P=0.03）。泊松回归模型显示吡咯烷酮组和安慰剂组的个体每日应答率不同（分别为 7.6%和 4.7%；P=0.03）。荟萃分析：在 2 周时，吡咯烷酮的疗效更好（相对风险[RR]=1.68；95%置信区间，1.18-2.39；P=0.004），在 4-6 周时也更好（RR=1.11；95%置信区间，1.02-1.20；P=0.02）。
目前的研究结果进一步证明了在 SSRIs 治疗的基础上联合使用吡咯烷酮可以加速和增强疗效，在非耐药性重性抑郁障碍患者中更快、更显著地减轻症状。
clinicaltrials.gov 标识符：NCT00931775。
