Scientific Institute IRCCS Eugenio Medea, 23842 Bosisio Parini, Lecco, Italy.
Unit of Clinical Pharmacology, Department of Biomedical and Clinical Sciences L. Sacco, "Luigi Sacco" University Hospital, Università di Milano, 20157 Milan, Italy.
J Affect Disord. 2018 Oct 1;238:161-178. doi: 10.1016/j.jad.2018.05.021. Epub 2018 May 22.
ADHD is frequently comorbid with anxiety and mood disorders, which may increase the severity of inattention and hyperactivity symptoms. Emotional symptoms (anxiety, irritability, mood lability) also affect patients without comorbidity or emerge as adverse drug events. The influence of ADHD drugs on emotional symptoms demands investigation to improve therapies.
Systematic review of trials reporting adverse events in patients pharmacologically treated for ADHD. Meta-analysis of the occurrence of irritability, anxiety, apathy, reduced talk, sadness, crying, emotional lability, biting nails, staring, perseveration, euphoria. Meta-regression analysis.
Forty-five trials were meta-analysed. The most frequently reported outcomes were irritability, anxiety, sadness, and apathy. Methylphenidates, especially immediate-release formulations, were most studied; amphetamines were half as studied and were predominantly mixed amphetamine salts. Reports on atomoxetine were scant. Meta-analysis showed that methylphenidates reduced the risk of irritability, anxiety, euphoria, whereas they worsened the risk of apathy and reduced talk; amphetamines worsened the risk of emotional lability. Factors influencing risks were study year and design, patients' sex and age, drug dose and release formulation.
Possible discrepancy between adverse events as indicated in clinical trials and as summarised herein. Confounding due to the aggregation of drugs into groups; uninvestigated sources of bias; incomplete lists of adverse events; lack of observations on self-injury.
Methylphenidates appeared safer than amphetamines, although younger patients and females may incur higher risks, especially with high-dose, immediate-release methylphenidates. Only atomoxetine holds a black-box warning, but amphetamines and methylphenidates also did not show a safe profile regarding mood and emotional symptoms.
ADHD 常与焦虑和情绪障碍共病，这可能会增加注意力不集中和多动症状的严重程度。情绪症状（焦虑、易怒、情绪不稳定）也会影响无共病的患者，或者作为药物不良反应出现。ADHD 药物对情绪症状的影响需要进行调查，以改善治疗方法。
对报告药物治疗 ADHD 患者不良事件的试验进行系统评价。对易怒、焦虑、淡漠、言语减少、悲伤、哭泣、情绪不稳定、咬指甲、凝视、固执、欣快等不良事件的发生率进行荟萃分析。进行元回归分析。
对 45 项试验进行了荟萃分析。最常报告的结局是易怒、焦虑、悲伤和淡漠。哌醋甲酯，特别是速释制剂，研究最多；安非他命研究了一半，主要是混合安非他命盐。关于托莫西汀的报道很少。荟萃分析显示，哌醋甲酯降低了易怒、焦虑、欣快的风险，而增加了淡漠和言语减少的风险；安非他命增加了情绪不稳定的风险。影响风险的因素包括研究年份和设计、患者的性别和年龄、药物剂量和释放制剂。
临床试验中报告的不良事件与本文总结的不良事件可能存在差异。由于药物分组而产生的混杂因素；未调查的偏倚来源；不良事件列表不完整；缺乏对自伤的观察。
虽然年轻患者和女性可能会有更高的风险，尤其是使用高剂量、速释哌醋甲酯时，但哌醋甲酯似乎比安非他命更安全。只有托莫西汀有黑框警告，但安非他命和哌醋甲酯在情绪和情感症状方面也没有显示出安全的特征。
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