Li Lin, Zhu Nanbo, Zhang Le, Kuja-Halkola Ralf, D'Onofrio Brian M, Brikell Isabell, Lichtenstein Paul, Cortese Samuele, Larsson Henrik, Chang Zheng
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Department of Psychological and Brain Sciences, Indiana University, Bloomington.
JAMA. 2024 Mar 12;331(10):850-860. doi: 10.1001/jama.2024.0851.
Attention-deficit/hyperactivity disorder (ADHD) is associated with increased risks of adverse health outcomes including premature death, but it is unclear whether ADHD pharmacotherapy influences the mortality risk.
To investigate whether initiation of ADHD pharmacotherapy was associated with reduced mortality risk in individuals with ADHD.
DESIGN, SETTING, AND PARTICIPANTS: In an observational nationwide cohort study in Sweden applying the target trial emulation framework, we identified individuals aged 6 through 64 years with an incident diagnosis of ADHD from 2007 through 2018 and no ADHD medication dispensation prior to diagnosis. Follow-up started from ADHD diagnosis until death, emigration, 2 years after ADHD diagnosis, or December 31, 2020, whichever came first.
ADHD medication initiation was defined as dispensing of medication within 3 months of diagnosis.
We assessed all-cause mortality within 2 years of ADHD diagnosis, as well as natural-cause (eg, physical conditions) and unnatural-cause mortality (eg, unintentional injuries, suicide, and accidental poisonings).
Of 148 578 individuals with ADHD (61 356 females [41.3%]), 84 204 (56.7%) initiated ADHD medication. The median age at diagnosis was 17.4 years (IQR, 11.6-29.1 years). The 2-year mortality risk was lower in the initiation treatment strategy group (39.1 per 10 000 individuals) than in the noninitiation treatment strategy group (48.1 per 10 000 individuals), with a risk difference of -8.9 per 10 000 individuals (95% CI, -17.3 to -0.6). ADHD medication initiation was associated with significantly lower rate of all-cause mortality (hazard ratio [HR], 0.79; 95% CI, 0.70 to 0.88) and unnatural-cause mortality (2-year mortality risk, 25.9 per 10 000 individuals vs 33.3 per 10 000 individuals; risk difference, -7.4 per 10 000 individuals; 95% CI, -14.2 to -0.5; HR, 0.75; 95% CI, 0.66 to 0.86), but not natural-cause mortality (2-year mortality risk, 13.1 per 10 000 individuals vs 14.7 per 10 000 individuals; risk difference, -1.6 per 10 000 individuals; 95% CI, -6.4 to 3.2; HR, 0.86; 95% CI, 0.71 to 1.05).
Among individuals diagnosed with ADHD, medication initiation was associated with significantly lower all-cause mortality, particularly for death due to unnatural causes.
注意力缺陷多动障碍（ADHD）与包括过早死亡在内的不良健康结局风险增加相关，但尚不清楚ADHD药物治疗是否会影响死亡风险。
探讨ADHD药物治疗的启动是否与ADHD患者的死亡风险降低相关。
设计、设置和参与者：在瑞典进行的一项全国性观察性队列研究中，我们采用目标试验模拟框架，确定了2007年至2018年期间年龄在6岁至64岁之间、首次诊断为ADHD且诊断前未使用过ADHD药物的个体。随访从ADHD诊断开始，直至死亡、移民、ADHD诊断后2年或2020年12月31日（以先到者为准）。
ADHD药物治疗的启动定义为在诊断后3个月内开始用药。
我们评估了ADHD诊断后2年内的全因死亡率，以及自然原因（如身体状况）和非自然原因死亡率（如意外伤害、自杀和意外中毒）。
在148578例ADHD患者中（61356例女性[41.3%]），84204例（56.7%）开始使用ADHD药物治疗。诊断时的中位年龄为17.4岁（四分位间距，11.6 - 29.1岁）。启动治疗策略组的2年死亡风险（每10000人中有39.1人）低于未启动治疗策略组（每10000人中有48.1人），风险差值为每10000人 - 8.9（95%置信区间， - 17.3至 - 0.6）。ADHD药物治疗的启动与全因死亡率显著降低相关（风险比[HR]，0.79；95%置信区间，0.70至0.88）以及非自然原因死亡率（2年死亡风险，每10000人中有25.9人 vs 每10000人中有33.3人；风险差值，每10000人 - 7.4；95%置信区间， - 14.2至 - 0.5；HR，0.75；95%置信区间，0.66至0.86），但与自然原因死亡率无关（2年死亡风险，每10000人中有13.1人 vs 每10000人中有14.7人；风险差值，每10000人 - 1.6；95%置信区间， - 6.4至3.2；HR，0.86；95%置信区间，0.71至1.05）。
在被诊断为ADHD的个体中，药物治疗的启动与显著降低的全因死亡率相关，特别是对于非自然原因导致的死亡。
