{
  "abstract": "Abstract Objective To examine the effects of drug treatment for attention deficit/hyperactivity disorder (ADHD) on suicidal behaviours, substance misuse, accidental injuries, transport accidents, and criminality.Design Emulation of target trials.Setting Linkage of national registers in Sweden, 2007-20.Participants People aged 6-64 years with a new diagnosis of ADHD, who either started or did not start drug treatment for ADHD within three months of diagnosis.Main outcome measures First and recurrent events of five outcomes over two years after ADHD diagnosis: suicidal behaviours, substance misuse, accidental injuries, transport accidents, and criminality.Results Of 148 581 individuals with ADHD (median age 17.4 years; 41.3% female), 84 282 (56.7%) started drug treatment for ADHD, with methylphenidate being the most commonly prescribed at initiation (74 515; 88.4%). Drug treatment for ADHD was associated with reduced rates of the first occurrence of suicidal behaviours (weighted incidence rates 14.5 per 1000 person years in the initiation group versus 16.9 in the non-initiation group; adjusted incidence rate ratio 0.83, 95% confidence interval 0.78 to 0.88), substance misuse (58.7 v 69.1 per 1000 person years; 0.85, 0.83 to 0.87), transport accidents (24.0 v 27.5 per 1000 person years; 0.88, 0.82 to 0.94), and criminality (65.1 v 76.1 per 1000 person years; 0.87, 0.83 to 0.90), whereas the reduction was not statistically significant for accidental injuries (88.5 v 90.1 per 1000 person years; incidence rate ratio 0.98, 0.96 to 1.01). The reduced rates were more pronounced among individuals with previous events, with incidence rate ratios ranging from 0.79 (0.72 to 0.86) for suicidal behaviours to 0.97 (0.93 to 1.00) for accidental injuries. For recurrent events, drug treatment for ADHD was significantly associated with reduced rates of all five outcomes, with incidence rate ratios of 0.85 (0.77 to 0.93) for suicidal behaviours, 0.75 (0.72 to 0.78) for substance misuse, 0.96 (0.92 to 0.99) for accidental injuries, 0.84 (0.76 to 0.91) for transport accidents, and 0.75 (0.71 to 0.79) for criminality.Conclusions Drug treatment for ADHD was associated with beneficial effects in reducing the risks of suicidal behaviours, substance misuse, transport accidents, and criminality but not accidental injuries when considering first event rate. The risk reductions were more pronounced for recurrent events, with reduced rates for all five outcomes. This target trial emulation study using national register data provides evidence that is representative of patients in routine clinical settings.",
  "authors": [
    {
      "affiliations": [
        "Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden"
      ],
      "name": "Le Zhang"
    },
    {
      "affiliations": [
        "Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden"
      ],
      "name": "Nanbo Zhu"
    },
    {
      "affiliations": [
        "Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden"
      ],
      "name": "Arvid Sjölander"
    },
    {
      "affiliations": [
        "Centre for Innovation in Mental Health, School of Psychology, Faculty of Environmental and Life Sciences, and Clinical and Experimental Sciences (CNS and Psychiatry), Faculty of Medicine, University of Southampton, Southampton, UK",
        "Department of Biostatistics-Bioinformatics, Hospices Civils de Lyon, Lyon, France",
        "Université Claude Bernard Lyon 1, LBBE, UMR 5558, CNRS, VAS, Villeurbanne, France"
      ],
      "name": "Mikail Nourredine"
    },
    {
      "affiliations": [
        "Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden"
      ],
      "name": "Lin Li"
    },
    {
      "affiliations": [
        "Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden",
        "Centre for Innovation in Mental Health, School of Psychology, Faculty of Environmental and Life Sciences, and Clinical and Experimental Sciences (CNS and Psychiatry), Faculty of Medicine, University of Southampton, Southampton, UK",
        "School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden",
        "Centre for Population Health, Research Department, Division for Mental Health, Haukeland University Hospital, Bergen, Norway"
      ],
      "name": "Miguel Garcia-Argibay"
    },
    {
      "affiliations": [
        "Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden"
      ],
      "name": "Ralf Kuja-Halkola"
    },
    {
      "affiliations": [
        "Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden",
        "Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway",
        "Department of Biomedicine, Aarhus University, Aarhus C, Denmark"
      ],
      "name": "Isabell Brikell"
    },
    {
      "affiliations": [
        "Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden"
      ],
      "name": "Paul Lichtenstein"
    },
    {
      "affiliations": [
        "Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden",
        "Department of Psychological and Brain Sciences, Indiana University, Bloomington, IN, USA"
      ],
      "name": "Brian M D’Onofrio"
    },
    {
      "affiliations": [
        "Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden",
        "Centre for Innovation in Mental Health, School of Psychology, Faculty of Environmental and Life Sciences, and Clinical and Experimental Sciences (CNS and Psychiatry), Faculty of Medicine, University of Southampton, Southampton, UK",
        "School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden"
      ],
      "name": "Henrik Larsson"
    },
    {
      "affiliations": [
        "Centre for Innovation in Mental Health, School of Psychology, Faculty of Environmental and Life Sciences, and Clinical and Experimental Sciences (CNS and Psychiatry), Faculty of Medicine, University of Southampton, Southampton, UK",
        "Clinical and Experimental Sciences (CNS and Psychiatry), Faculty of Medicine, University of Southampton, Southampton, UK",
        "Hampshire and Isle of Wight Healthcare NHS Foundation Trust, Southampton, UK",
        "Hassenfeld Children’s Hospital at NYU Langone, New York University Child Study Center, New York City, NY, USA",
        "DiMePRe-J-Department of Precision and Regenerative Medicine-Jonic Area, University of Bari “Aldo Moro,” Bari, Italy"
      ],
      "name": "Samuele Cortese"
    },
    {
      "affiliations": [
        "Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden"
      ],
      "name": "Zheng Chang"
    }
  ],
  "title": "ADHD drug treatment and risk of suicidal behaviours, substance misuse, accidental injuries, transport accidents, and criminality: emulation of target trials",
  "uid": "e8e1133b-ad35-5719-91c2-70f1ca4ca625"
}