BACKGROUND Psychiatric comorbidity is frequent among persons with attention-deficit/hyperactivity disorder (ADHD). Whether pharmacological treatment of ADHD influences the incidence of psychiatric comorbidity is uncertain. OBJECTIVE To investigate associations and causal relations between pharmacological treatment of ADHD and incidence of subsequent comorbid psychiatric diagnoses. METHODS We employed registry data covering all individuals aged 5-18 years in Norway who were diagnosed with ADHD during 2009-2011 (n=8051), followed until 2020. We used linear probability models (LPM) and instrumental variable (IV) analyses to examine associations and causal effects, respectively, between pharmacological treatment and subsequent comorbidity. FINDINGS From time of ADHD diagnosis to 9 years of follow-up, 63% of patients were registered with comorbid psychiatric disorders. For males, LPM showed associations between ADHD medication and several incident comorbidities, but strength and direction of associations and consistency over time varied. For females, no associations were statistically significant. IV analyses for selected categories isolating effects among patients 'on the margin of treatment' showed a protective effect for a category of stress-related disorders in females and for tic disorders in males for the first 2 and 3 years of pharmacological treatment, respectively. CONCLUSIONS Overall, LPM and IV analyses did not provide consistent or credible support for long-term effects of pharmacological treatment on later psychiatric comorbidity. However, IV results suggest that for patients on the margin of treatment, pharmacological treatment may initially reduce the incidence of certain categories of comorbid disorders. CLINICAL IMPLICATIONS Clinicians working with persons with ADHD should monitor the effects of ADHD medication on later psychiatric comorbidity. TRIAL REGISTRATION NUMBER ISRCTN11891971.

中文翻译：

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注意力缺陷/多动障碍的药物治疗对后期精神合并症的影响：一项基于人群的前瞻性长期研究。


背景精神合并症在注意力缺陷/多动障碍（ADHD）患者中很常见。 ADHD 的药物治疗是否影响精神合并症的发生率尚不确定。目的 调查 ADHD 的药物治疗与随后合并精神病诊断的发生率之间的关联和因果关系。方法 我们使用了涵盖 2009 年至 2011 年期间被诊断为 ADHD 的所有挪威 5-18 岁个体的登记数据 (n=8051)，并跟踪至 2020 年。我们使用线性概率模型 (LPM) 和工具变量 (IV) 分析来分别检查药物治疗与随后的合并症之间的关联和因果效应。结果 从 ADHD 诊断到 9 年随访，63% 的患者患有共存精神疾病。对于男性来说，LPM 显示 ADHD 药物与多种并发症之间存在关联，但关联的强度和方向以及随时间的一致性会有所不同。对于女性来说，没有统计学上的显着关联。对“处于治疗边缘”的患者中选定类别隔离效应的 IV 分析显示，在药物治疗的前 2 年和 3 年中，分别对女性应激相关疾病和男性抽动障碍有保护作用。结论 总体而言，LPM 和 IV 分析并未为药物治疗对后期精神合并症的长期影响提供一致或可信的支持。然而，静脉注射结果表明，对于处于治疗边缘的患者，药物治疗可能最初会降低某些类别的合并症的发生率。 临床意义 与 ADHD 患者一起工作的临床医生应监测 ADHD 药物对后期精神合并症的影响。试用注册号 ISRCTN11891971。