Suicide risk reduction in youths with attention-deficit/hyperactivity disorder prescribed methylphenidate: A Taiwan nationwide population-based cohort study

Liang, Sophie Hsin-Yi; Yang, Yao‐Hsu; Kuo, Ting-Yu; Liao, Yin-To; Lin, Tseng‐Hsi; Lee, Yena; McIntyre, Roger S.; Kelsen, Brent Allan; Wang, Tsu‐Nai; Chen, Vincent Chin‐Hung

doi:10.1016/j.ridd.2017.10.023

Cited by 46 publications

(54 citation statements)

References 40 publications

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“…Future investigations could test whether drugs for such core conditions can be repurposed for treating self-harming patients with either PLOS MEDICINE full-blown or subthreshold conditions. For example, prescription of methylphenidate for ADHD treatment was found to be associated with reduction of suicide risk [72]. As a note of caution, medicated schizophrenia cases were not at less risk of self-harm than non-medicated patients, whereas medicated MDD patients were at substantially higher risk for self-harm in the present sample.…”

Section: Discussionmentioning

confidence: 48%

Studying individual risk factors for self-harm in the UK Biobank: A polygenic scoring and Mendelian randomisation study

et al. 2020

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Background Identifying causal risk factors for self-harm is essential to inform preventive interventions. Epidemiological studies have identified risk factors associated with self-harm, but these associations can be subject to confounding. By implementing genetically informed methods to better account for confounding, this study aimed to better identify plausible causal risk factors for self-harm. Methods and findings Using summary statistics from 24 genome-wide association studies (GWASs) comprising 16,067 to 322,154 individuals, polygenic scores (PSs) were generated to index 24 possible individual risk factors for self-harm (i.e., mental health vulnerabilities, substance use, cognitive traits, personality traits, and physical traits) among a subset of UK Biobank participants (N = 125,925, 56.2% female) who completed an online mental health questionnaire in the period from 13 July 2016 to 27 July 2017. In total, 5,520 (4.4%) of these participants reported having self-harmed in their lifetime. In binomial regression models, PSs indexing 6 risk factors (major depressive disorder [MDD], attention deficit/hyperactivity disorder [ADHD], bipolar disorder, schizophrenia, alcohol dependence disorder, and lifetime cannabis use) predicted self-harm, with effect sizes ranging from odds ratio (OR) = 1.05 (95% CI 1.02 to 1.07, q = 0.008) for lifetime cannabis use to OR = 1.20 (95% CI 1.16 to 1.23, q = 1.33 × 10 −35) for MDD. No systematic differences emerged between suicidal and non-suicidal self-harm. To further probe causal relationships, two-sample Mendelian randomisation (MR) analyses were conducted, with MDD, ADHD, and schizophrenia emerging as the most plausible causal risk factors for self-harm. The genetic liabilities for MDD and schizophrenia were associated with self-harm independently of diagnosis and medication. Main limitations include the lack of representativeness of the UK Biobank sample, that self-harm was self-PLOS MEDICINE

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Section: Discussionmentioning

confidence: 48%

Studying individual risk factors for self-harm in the UK Biobank: A polygenic scoring and Mendelian randomisation study

et al. 2020

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“…For example, prescription of methylphenidate for ADHD treatment was found to be associated with reduction of suicide attempt risk. 46 As a note of caution, treated schizophrenia cases were not at less risk of self-harm than non-treated patients whereas treated MDD patients were at substantial higher risk for self-harm. This could be due to treated patients having more severe symptoms than untreated patients, or it could be due to adverse effects of medication, in particular in the case of MDD where suicidality might be an adverse effect of antidepressant treatment.…”

Section: Discussionmentioning

confidence: 99%

Identifying Potential Causal Risk Factors for Self-Harm: A Polygenic Risk Scoring and Mendelian Randomisation Approach

Lim¹,

Rijsdijk²,

Hagenaars³

et al. 2019

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1Background. Multiple individual vulnerabilities and traits are phenotypically associated with 2 suicidal and non-suicidal self-harm. However, associations between these risk factors and 3 self-harm are subject to confounding. We implemented genetically informed methods to 4 better identify individual risk factors for self-harm. 5 6 Methods. Using genotype data and online Mental Health Questionnaire responses in the UK 7Biobank sample (N = 125,925), polygenic risk scores (PRS) were generated to index 24 8 plausible individual risk factors for self-harm in the following domains: mental health 9 vulnerabilities, substance use phenotypes, cognitive traits, personality traits and physical 10 traits. PRS were entered as predictors in binomial regression models to predict self-harm. 11Multinomial regressions were used to model suicidal and non-suicidal self-harm. To further 12 probe the causal nature of these relationships, two-sample Mendelian Randomisation (MR) 13 analyses were conducted for significant risk factors identified in PRS analyses. 14 15 Outcomes. Self-harm was predicted by PRS indexing six individual risk factors, which are 16 major depressive disorder (MDD), attention deficit/hyperactivity disorder (ADHD), bipolar 17 disorder, schizophrenia, alcohol dependence disorder (ALC) and lifetime cannabis use. Effect 18 sizes ranged from β = 0.044 (95% CI: 0·016 to 0·152) for PRS for lifetime cannabis use, to β 19 = 0.179 (95% CI: 0·152 to 0·207) for PRS for MDD. No systematic distinctions emerged 20 between suicidal and non-suicidal self-harm. In follow-up MR analyses, MDD, ADHD and 21 schizophrenia emerged as plausible causal risk factors for self-harm. 22Interpretation. Among a range of potential risk factors leading to self-harm, core predictors 1 were found among psychiatric disorders. In addition to MDD, liabilities for schizophrenia 2 and ADHD increased the risk for self-harm. Detection and treatment of core symptoms of 3 these conditions, such as psychotic or impulsivity symptoms, may benefit self-harming 4 patients. 5 6

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“…There is now some evidence that appropriate medication for ADHD is associated with reduced suicide risk 2. This study highlights just how important suicide risk is in patients with ADHD, and reminds clinicians that this is another factor to consider when deciding whether to initiate pharmacological therapy, although the study itself did not directly assess the impact of medication on suicidality.…”

Section: Commentarymentioning

confidence: 95%

Attention deficit hyperactivity disorder was associated with increased risk of suicidal behaviour

Friend

2019

Arch Dis Child Educ Pract Ed

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Suicide risk reduction in youths with attention-deficit/hyperactivity disorder prescribed methylphenidate: A Taiwan nationwide population-based cohort study

Abstract: This nationwide population-based cohort study showed that among ADHD youths, reduction of suicide risk was observed in patients prescribed MPH for duration 90days and longer, underscoring the importance of appropriate ADHD pharmacotherapy and enhancing drug compliance.

Cited by 46 publications

References 40 publications

Studying individual risk factors for self-harm in the UK Biobank: A polygenic scoring and Mendelian randomisation study

Studying individual risk factors for self-harm in the UK Biobank: A polygenic scoring and Mendelian randomisation study

Identifying Potential Causal Risk Factors for Self-Harm: A Polygenic Risk Scoring and Mendelian Randomisation Approach

Attention deficit hyperactivity disorder was associated with increased risk of suicidal behaviour

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