Association between Attention Deficit Hyperactivity Disorder Medication and Depression: A 10-year Follow-up Self-controlled Case Study

Abstract

Objective There is clinical concern that the stimulant methylphenidate (MPH) might increase the risk of depression, particularly in children. This study aimed to investigate the association between MPH use and the risk of depression. Methods A population-based electronic medical records database was used. We obtained claims data for prescription of ADHD medication, diagnosis of depression, and prescription of antidepressant medication between January 2007 and December 2016 for 43,259 individuals aged 6 to 19 who were diagnosed with ADHD between July 1, 2007 and December 31, 2007. The final analysis was based on 2,330 eligible participants. A self-controlled case series design was used to identify risk factors for major depressive disorder (MDD). Results An elevated MDD risk was found during the 90 days before MPH exposure, with an incidence rate ratio (IRR) of 12.12 (95% confidence interval [95% CI] 10.06−14.61, p < 0.0001). During methylphenidate treatment, the IRR was 18.06 with a 95% CI of 16.67 to 19.56 ( p < 0.0001), but it returned to baseline levels after day 31 of MPH treatment discontinuation. The IRR for patients aged 6 to 9 years was 13.11 (95% CI 9.58−17.95) during the 90 days before MPH exposure, and 17.7 (95% CI 15.6−20.08) during MPH treatment, but returned to baseline levels after discontinuation of MPH treatment. Conclusion We confirmed the temporal relationship between depression and methylphenidate use in young people with ADHD. Though the absolute risk is low, the risk of depression should be carefully considered, particularly in the period directly following the start of methylphenidate treatment.

The Loudness Dependence of Auditory Evoked Potentials is associated with the Symptom Severity and Treatment in Boys with Attention Deficit Hyperactivity Disorder

“…Children with ADHD have high rates of depression and anxiety (25−41%) [74][75][76]. Recently, Oh et al [77] also showed a temporal connection between depression and MPH use in adolescents with ADHD. Therefore, the association between LDAEP and ADHD can also be interpreted in terms of emotional comorbidities [43,70,78].…”

Rearing in an enriched environment ameliorates the ADHD-like behaviors of Lister hooded rats while suppressing neuronal activities in the medial prefrontal cortex

“…Rearing LHRs with many conspeci cs did not signi cantly ameliorate ADHD-like behaviors, suggesting that stimulation from the environment is more effective in improving ADHD-like behavior than stimulation from interaction with many children of the same age. Although medications are the rst line treatment for ADHD [52], the most prevalent psychostimulant methylphenidate may give negative impact physically and mentally [53][54][55]. Taken such risks of pharmacological interventions, it may be necessary to become more proactive in nurturing ADHD children in an EE.…”

Rearing in an Enriched Environment Ameliorates the ADHD-like Behaviors of Lister Hooded Rats While Suppressing Neuronal Activities in the Medial Prefrontal Cortex

“…Rearing LHRs with many conspecifics did not significantly ameliorate ADHD-like behaviors, suggesting that stimulation from the environment is more effective in improving ADHD-like behavior than stimulation from interaction with many children of the same age. Although medications are the first-line treatment for ADHD [ 63 ], the most prevalent psychostimulant methylphenidate may have negative impacts physically and mentally [ 64 , 65 , 66 ]. With such risks of pharmacological interventions, it may be necessary to become more proactive in nurturing ADHD children in an EE.…”