Richards Cynthia, Iosifescu Dan V, Mago Rajnish, Sarkis Elias, Geibel Brooke, Dauphin Matthew, McIntyre Roger S, Weisler Richard, Brawman-Mintzer Olga, Gu Joan, Madhoo Manisha
Adult Psychopharmacology Program, Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY.
Mood Disorders Program, Department of Psychiatry and Human Behavior, Thomas Jefferson University, Philadelphia, PA.
J Clin Psychopharmacol. 2018 Aug;38(4):336-343. doi: 10.1097/JCP.0000000000000897.
PURPOSE/BACKGROUND: Psychostimulant augmentation is considered a potential treatment strategy for individuals with major depressive disorder who do not adequately respond to antidepressant monotherapy. The primary objective of this 12-month open-label extension study was to evaluate the safety and tolerability of lisdexamfetamine dimesylate (LDX) as augmentation therapy to an antidepressant in adults with major depressive disorder.
METHODS/PROCEDURES: Eligible adults who completed 1 of 3 short-term antecedent LDX augmentation of antidepressant monotherapy studies were treated with dose-optimized LDX (20-70 mg) for up to 52 weeks while continuing on the index antidepressant (escitalopram, sertraline, venlafaxine extended-release, or duloxetine) assigned during the antecedent short-term studies. Safety and tolerability assessments included the occurrence of treatment-emergent adverse events and vital sign changes.
FINDINGS/RESULTS: All 3 antecedent studies failed to meet the prespecified primary efficacy endpoint, so this open-label study was terminated early. Headache (15.5% [241/1559]), dry mouth (13.6% [212/1559]), insomnia (13.1% [204/1559]), and decreased appetite (12.1% [189/1559]) were the most frequently reported treatment-emergent adverse events. The greatest mean ± SD increases observed for systolic and diastolic blood pressure and for pulse were 2.6 ± 10.85 and 1.7 ± 7.94 mm Hg and 6.9 ± 10.27 bpm, respectively. Monitoring determined that less than 1% of participants experienced potentially clinically important changes in systolic blood pressure (10 [0.6%]), diastolic blood pressure (8 [0.5%]), or pulse (6 [0.4%]).
IMPLICATIONS/CONCLUSIONS: The overall safety and tolerability of long-term LDX augmentation of antidepressant monotherapy was consistent with the profiles of the short-term antecedent studies, with no evidence of new safety signals.
目的/背景：对于对抗抑郁药单一疗法反应欠佳的重度抑郁症患者，精神振奋剂增效疗法被视为一种潜在的治疗策略。这项为期12个月的开放标签扩展研究的主要目的是评估二甲磺酸赖右苯丙胺（LDX）作为重度抑郁症成年患者抗抑郁药增效疗法的安全性和耐受性。
方法/程序：完成了3项短期前期LDX抗抑郁药单一疗法增效研究中1项的符合条件的成年人，接受剂量优化的LDX（20 - 70毫克）治疗长达52周，同时继续服用前期短期研究中分配的索引抗抑郁药（艾司西酞普兰、舍曲林、缓释文拉法辛或度洛西汀）。安全性和耐受性评估包括治疗中出现的不良事件的发生情况和生命体征变化。
所有3项前期研究均未达到预先设定的主要疗效终点，因此这项开放标签研究提前终止。头痛（15.5% [241/1559]）、口干（13.6% [212/1559]）、失眠（13.1% [204/1559]）和食欲减退（12.1% [189/1559]）是最常报告的治疗中出现的不良事件。观察到的收缩压、舒张压和脉搏的最大平均±标准差升高分别为2.6±10.85和1.7±7.94毫米汞柱以及6.9±10.27次/分钟。监测确定，不到1%的参与者在收缩压（10例[0.6%]）、舒张压（8例[0.5%]）或脉搏（6例[0.4%]）方面出现了可能具有临床重要意义的变化。
意义/结论：长期LDX抗抑郁药单一疗法增效的总体安全性和耐受性与前期短期研究的情况一致，没有新的安全信号的证据。
