Efficacy, safety, and tolerability of augmentation pharmacotherapy with aripiprazole for treatment-resistant depression in late life: a randomised, double-blind, placebo-controlled trial.
Efficacy, safety, and tolerability of augmentation pharmacotherapy with aripiprazole for treatment-resistant depression in late life: a randomised, double-blind, placebo-controlled trial.
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DOI：
10.1016/s0140-6736(15)00308-6
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发表时间：
2015-12-12
期刊：
影响因子：
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通讯作者：
Reynolds CF 3rd
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作者：
Lenze EJ;Mulsant BH;Blumberger DM;Karp JF;Newcomer JW;Anderson SJ;Dew MA;Butters MA;Stack JA;Begley AE;Reynolds CF 3rd
难治性重度抑郁障碍在老年人中很常见，可能危及生命，他们对加强药物治疗的好处和风险知之甚少。我们进行了一项多点、安慰剂对照、随机的临床试验，以测试阿立哌唑强化治疗老年难治性抑郁症的有效性和安全性。我们用文拉法辛缓释剂(ER)治疗了468名年龄在60岁及以上的患者，其中96人(20.5%)没有完成这一开放阶段，191人(40.8%)缓解，181人(38.7%)没有缓解，并被随机分成12周，用阿立哌唑或安慰剂进行双盲强化治疗。计算机生成的随机化是按区块进行的，并按地点分层。主要终点是缓解，定义为蒙哥马利-阿斯伯格抑郁评定量表在最后两次连续就诊时得分≤10(且在随机阶段开始时至少低于得分2分)。我们还通过心脏代谢和神经测量来评估自杀意念的解决，以及安全性和耐受性。按意向处理原则进行分析。这项试验在ClinicalTrials.gov注册，编号NCT00892047。服用阿立哌唑的老年人的缓解率高于服用安慰剂的老年人(44%对29%；优势比[OR]=2.0，95%可信区间1.1-3.7，p=0.03；需要治疗的人数[NNT]=6.6[95%可信区间3.5-81.8])。总体而言，在另外12周的持续治疗中，缓解是稳定的。与安慰剂相比，阿立哌唑对自杀意念的解决效果更显著。静坐不能是最常见的不良反应(27%的受试者服用阿立哌唑)。与安慰剂相比，阿立哌唑也与更多的帕金森综合征相关，但与治疗后出现的自杀念头、QTC延长或肥胖、血糖、胰岛素或血脂增加无关。在使用一线抗抑郁药物未能缓解抑郁症的老年人中，添加阿立哌唑在实现和维持缓解方面是有效的。耐受性问题包括潜在的静坐不能和帕金森氏症。国家心理健康研究所、UPMC老年精神病学捐赠基金、泰勒家族创新精神病学研究所、国家高级翻译科学中心和坎贝尔家庭心理健康研究所。
Treatment-resistant major depressive disorder is common and potentially life-threatening in older persons, in whom little is known about the benefits and risks of augmentation pharmacotherapy. We conducted a multi-site, placebo-controlled, randomized clinical trial to test the efficacy and safety of aripiprazole augmentation for older adults with treatment-resistant depression. We treated 468 participants aged 60 and older with current major depressive episode with venlafaxine extended-release (ER); 96 (20.5%) did not complete this open phase, 191 (40.8%) remitted, and 181 (38.7%) did not remit and were randomized to 12 weeks of double-blind augmentation with aripiprazole or placebo. The computer-generated randomization was done in blocks and stratified by site. The primary endpoint was remission, defined as Montgomery-Asberg Depression Rating Scale scores ≤10 (and at least two points below the score at the start of the randomized phase) at both of the final two consecutive visits. We also assessed resolution of suicidal ideation, and safety and tolerability with cardiometabolic and neurological measures. Analyses were conducted according to the intention-to-treat principle. This trial is registered with ClinicalTrials.gov, number NCT00892047. Older adults on aripiprazole had a higher remission rate than those on placebo (44% versus 29%; odds ratio [OR]=2.0, 95% CI 1.1–3.7, p=0.03; number needed to treat [NNT]=6.6 [95% CI 3.5–81.8]). Overall, remission was stable during 12 additional weeks of continuation treatment. The resolution of suicidal ideation was more marked with aripiprazole than with placebo. Akathisia was the most common adverse effect (27% of participants on aripiprazole). Compared to placebo, aripiprazole was also associated with more Parkinsonism but not with treatment-emergent suicidal ideation, QTc prolongation, or increases in adiposity, glucose, insulin, or lipids. In older adults who fail to achieve remission from depression with a first-line antidepressant, the addition of aripiprazole is effective in achieving and sustaining remission. Tolerability concerns include potential for akathisia and Parkinsonism. National Institute of Mental Health, UPMC Endowment in Geriatric Psychiatry, Taylor Family Institute for Innovative Psychiatric Research, National Center for Advancing Translational Sciences, and the Campbell Family Mental Health Research Institute.