Lipschitz Jessica M, Perez-Rodriguez Mercedes, Majd Marzieh, Larsen Emmett, Locascio Joseph, Pike Chelsea K, Shanahan Megan, Burdick Katherine E
Department of Psychiatry, Brigham and Women's Hospital, Boston, MA, United States.
Department of Psychiatry, Harvard Medical School, Boston, MA, United States.
Front Psychiatry. 2023 Sep 4;14:1246149. doi: 10.3389/fpsyt.2023.1246149. eCollection 2023.
Despite advances in the treatment of bipolar disorder (BD), most patients do not achieve complete inter-episode recovery and functional disability is common. During periods of relative remission, many patients continue to experience neurocognitive dysfunction, reduced daytime activity levels, and sleep disturbances. This 8-week, randomized, placebo-controlled pilot study evaluated the feasibility, safety and preliminary efficacy of the wake-promoting drug, modafinil (Provigil), on neurocognitive functioning, daytime sleepiness, and sleep quality in affectively-stable BD patients.
Twelve individuals with affectively-stable BD were recruited and randomized to a flexible dose of modafinil (100 to 200 mg/day) or placebo, adjunctive to a therapeutic dose of a mood stabilizer. Weekly in-person visits tracked sleep quality and daytime sleepiness as well as side effects and mood symptoms. Neurocognitive functioning was assessed at baseline, week 4, and week 8.
No serious adverse events were reported. Newly emergent side effects in the modafinil group included heart palpitations, itching, fatigue, and decreased energy. Two patients discontinued modafinil owing to side effects and one of these patients withdrew from the study. One patient discontinued placebo and was withdrawn from the study. Preliminary evaluations of clinical efficacy showed a marginally significant interaction between treatment group and time in two cognitive domains (speed of processing and verbal learning), indicating greater improvement in the modafinil group versus placebo. Additionally, there was a marginally significant effect of treatment group on daytime sleepiness, suggesting lower daytime sleepiness in the modafinil group versus placebo. Counterintuitively, we found a significant treatment group by time interaction effect on sleep quality, suggesting greater improvement in sleep quality in the placebo group versus the modafinil group.
Results suggest that modafinil is a relatively safe medication for affectively-stable BD patients when given with adjunctive mood stabilizers. Results are suggestive of cognitive benefit and improved daytime sleepiness, but worse sleep quality in those patients prescribed modafinil. A fully powered clinical trial is warranted with specific attention to the characteristics of patients who are most likely to benefit from treatment with modafinil and other methodological lessons learned from this pilot.
ClinicalTrials.gov, identifier NCT01965925.
尽管双相情感障碍（BD）的治疗取得了进展，但大多数患者并未实现发作间期的完全康复，功能残疾很常见。在相对缓解期，许多患者仍持续存在神经认知功能障碍、日间活动水平降低和睡眠障碍。这项为期8周的随机、安慰剂对照试验性研究评估了促醒药物莫达非尼（Provigil）对情感稳定的双相情感障碍患者的神经认知功能、日间嗜睡和睡眠质量的可行性、安全性及初步疗效。
招募了12名情感稳定的双相情感障碍患者，并将其随机分为灵活剂量的莫达非尼组（100至200毫克/天）或安慰剂组，辅助使用治疗剂量的心境稳定剂。每周进行面对面访视，跟踪睡眠质量、日间嗜睡情况以及副作用和情绪症状。在基线、第4周和第8周评估神经认知功能。
未报告严重不良事件。莫达非尼组新出现的副作用包括心悸、瘙痒、疲劳和精力下降。两名患者因副作用停用莫达非尼，其中一名患者退出研究。一名患者停用安慰剂并退出研究。临床疗效的初步评估显示，在两个认知领域（加工速度和言语学习）中，治疗组与时间之间存在边缘显著的交互作用，表明莫达非尼组比安慰剂组有更大改善。此外，治疗组对日间嗜睡有边缘显著影响，表明莫达非尼组的日间嗜睡程度低于安慰剂组。与直觉相反，我们发现治疗组与时间的交互作用对睡眠质量有显著影响，表明安慰剂组的睡眠质量改善程度高于莫达非尼组。
结果表明，莫达非尼与辅助性心境稳定剂联合使用时，对情感稳定的双相情感障碍患者是一种相对安全的药物。结果提示对认知有益且改善了日间嗜睡，但服用莫达非尼的患者睡眠质量较差。有必要进行一项充分有力的临床试验，特别关注最有可能从莫达非尼治疗中获益的患者特征以及从该试验性研究中学到的其他方法学经验。
ClinicalTrials.gov，标识符NCT01965925。
