ADHDの長期治療と心血管疾患との関連に関する新たな知見(New findings on long-term treatment of ADHD and link to cardiovascular disease)

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2023-11-28 カロリンスカ研究所(KI)

◆ADHD薬の服用を始める患者、特に若い成人の多くが、特に初年度に服用を中止する傾向があります。しかし、長期かつ平均以上の用量で使用すると、一部の心血管疾患のリスクが高まる可能性があります。
◆これはカロリンスカ研究所の研究者が主導した2つの新しい研究によるもので、欧州の多国での1.2百万人以上の患者の処方データを分析し、全般的な傾向が同様であることを示しました。18〜19歳の中止率が最も高く、成人精神医学への移行時にリスクが増加します。デンマークは他の国々と比較して中止率が低く、ADHD薬の処方も少ないことが指摘されています。
◆さらに、別の研究では、長期および高用量のADHD薬の使用が高血圧や動脈疾患などの心血管疾患のリスクと関連していることが示されました。これらの結果は観察研究であり、直接的な因果関係は言えませんが、適切なリスクと利益の検討と患者のフォローアップが重要であるとされています。

<関連情報>

ADHDの服薬中止と持続:集団ベースのデータベースを用いた後方視的観察研究 ADHD medication discontinuation and persistence across the lifespan: a retrospective observational study using population-based databases

Isabell Brikell, Honghui Yao, Lin Li, Aske Astrup, Le Gao, Malcolm B Gillies, Tian Xie, Yanli Zhang-James, Søren Dalsgaard, Anders Engeland, Stephen V Faraone, Jan Haavik, Catharina Hartman, Prof Patrick Ip, Unnur Jakobsdóttir Smári, Henrik Larsson, Kenneth KC Man, Juliana de Oliveira Costa, Sallie-Anne Pearson, Nina Pil Hostrup Nielsen, Harold Snieder, Theresa Wimberley, Ian CK Wong, Le Zhang, Helga Zoega, Kari Klungsøyr, Zheng Chang
Lancet Psychiatry  Published:November 27, 2023
DOI:https://doi.org/10.1016/S2215-0366(23)00332-2

Summary

Background
Although often intended for long-term treatment, discontinuation of medication for ADHD is common. However, cross-national estimates of discontinuation are missing due to the absence of standardised measures. The aim of this study was to determine the rate of ADHD treatment discontinuation across the lifespan and to describe similarities and differences across countries to guide clinical practice.

Methods
We did a retrospective, observational study using population-based databases from eight countries and one Special Administrative Region (Australia, Denmark, Hong Kong, Iceland, the Netherlands, Norway, Sweden, the UK, and the USA). We used a common analytical protocol approach and extracted prescription data to identify new users of ADHD medication. Eligible individuals were aged 3 years or older who had initiated ADHD medication between 2010 and 2020. We estimated treatment discontinuation and persistence in the 5 years after treatment initiation, stratified by age at initiation (children 日付未入力, adolescents 日付未入力, young adults 日付未入力, and adults 日付未入力) and sex. Ethnicity data were not available.

Findings
1 229 972 individuals (735 503 [60%] males, 494 469 females [40%]; median age 8–21 years) were included in the study. Across countries, treatment discontinuation 1–5 years after initiation was lowest in children, and highest in young adults and adolescents. Within 1 year of initiation, 65% (95% CI 60–70) of children, 47% (43–51) of adolescents, 39% (36–42) of young adults, and 48% (44–52) of adults remained on treatment. The proportion of patients discontinuing was highest between age 18 and 19 years. Treatment persistence for up to 5 years was higher across countries when accounting for reinitiation of medication; at 5 years of follow-up, 50–60% of children and 30–40% of adolescents and adults were covered by treatment in most countries. Patterns were similar across sex.

Interpretation
Early medication discontinuation is prevalent in ADHD treatment, particularly among young adults. Although reinitiation of medication is common, treatment persistence in adolescents and young adults is lower than expected based on previous estimates of ADHD symptom persistence in these age groups. This study highlights the scope of medication treatment discontinuation and persistence in ADHD across the lifespan and provides new knowledge about long-term ADHD medication use.

Funding
European Union Horizon 2020 Research and Innovation Programme.

注意欠陥・多動性障害治療薬と心血管疾患の長期リスク Attention-Deficit/Hyperactivity Disorder Medications and Long-Term Risk of Cardiovascular Diseases

Le Zhang, Lin Li, Pontus Andell, Miguel Garcia-Argibay, Patrick D. Quinn, Brian M. D’Onofrio, Isabell Brikell, Ralf KujaHalkola, Paul Lichtenstein, Kristina Johnell, Henrik Larsson, Zheng Chang
JAMA Psychiatry  Published online November 22, 2023
DOI:10.1001/jamapsychiatry.2023.4294

Selection of Cases and Matched Controls

Key Points

Question Is long-term use of attention-deficit/hyperactivity disorder (ADHD) medication associated with an increased risk of cardiovascular disease (CVD)?

Findings In this case-control study of 278 027 individuals in Sweden aged 6 to 64 years who had an incident ADHD diagnosis or ADHD medication dispensation, longer cumulative duration of ADHD medication use was associated with an increased risk of CVD, particularly hypertension and arterial disease, compared with nonuse.

Meaning Findings of this study suggest that long-term exposure to ADHD medications was associated with an increased risk of CVD; therefore, the potential risks and benefits of long-term ADHD medication use should be carefully weighed.

Abstract

Importance Use of attention-deficit/hyperactivity disorder (ADHD) medications has increased substantially over the past decades. However, the potential risk of cardiovascular disease (CVD) associated with long-term ADHD medication use remains unclear.

Objective To assess the association between long-term use of ADHD medication and the risk of CVD.

Design, Setting, and Participants This case-control study included individuals in Sweden aged 6 to 64 years who received an incident diagnosis of ADHD or ADHD medication dispensation between January 1, 2007, and December 31, 2020. Data on ADHD and CVD diagnoses and ADHD medication dispensation were obtained from the Swedish National Inpatient Register and the Swedish Prescribed Drug Register, respectively. Cases included individuals with ADHD and an incident CVD diagnosis (ischemic heart diseases, cerebrovascular diseases, hypertension, heart failure, arrhythmias, thromboembolic disease, arterial disease, and other forms of heart disease). Incidence density sampling was used to match cases with up to 5 controls without CVD based on age, sex, and calendar time. Cases and controls had the same duration of follow-up.

Exposure Cumulative duration of ADHD medication use up to 14 years.

Main Outcomes and Measures The primary outcome was incident CVD. The association between CVD and cumulative duration of ADHD medication use was measured using adjusted odds ratios (AORs) with 95% CIs.

Results Of 278 027 individuals with ADHD aged 6 to 64 years, 10 388 with CVD were identified (median [IQR] age, 34.6 [20.0-45.7] years; 6154 males [59.2%]) and matched with 51 672 control participants without CVD (median [IQR] age, 34.6 [19.8-45.6] years; 30 601 males [59.2%]). Median (IQR) follow-up time in both groups was 4.1 (1.9-6.8) years. Longer cumulative duration of ADHD medication use was associated with an increased risk of CVD compared with nonuse (0 to ≤1 year: AOR, 0.99 [95% CI, 0.93-1.06]; 1 to ≤2 years: AOR, 1.09 [95% CI, 1.01-1.18]; 2 to ≤3 years: AOR, 1.15 [95% CI, 1.05-1.25]; 3 to ≤5 years: AOR, 1.27 [95% CI, 1.17-1.39]; and >5 years: AOR, 1.23 [95% CI, 1.12-1.36]). Longer cumulative ADHD medication use was associated with an increased risk of hypertension (eg, 3 to ≤5 years: AOR, 1.72 [95% CI, 1.51-1.97] and >5 years: AOR, 1.80 [95% CI, 1.55-2.08]) and arterial disease (eg, 3 to ≤5 years: AOR, 1.65 [95% CI, 1.11-2.45] and >5 years: AOR, 1.49 [95% CI, 0.96-2.32]). Across the 14-year follow-up, each 1-year increase of ADHD medication use was associated with a 4% increased risk of CVD (AOR, 1.04 [95% CI, 1.03-1.05]), with a larger increase in risk in the first 3 years of cumulative use (AOR, 1.08 [95% CI, 1.04-1.11]) and stable risk over the remaining follow-up. Similar patterns were observed in children and youth (aged <25 years) and adults (aged ≥25 years).

Conclusions and Relevance This case-control study found that long-term exposure to ADHD medications was associated with an increased risk of CVDs, especially hypertension and arterial disease. These findings highlight the importance of carefully weighing potential benefits and risks when making treatment decisions about long-term ADHD medication use. Clinicians should regularly and consistently monitor cardiovascular signs and symptoms throughout the course of treatment.

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