ADHD Pharmacotherapy and Mortality in Individuals With ADHD

This cohort study suggests that pharmacological treatment of a patients with ADHD increases their life expectancy by reducing unnatural deaths (suicides, homicides, MVAs, etc.). James W. Mold, MD, MPH

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Importance: 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.

Objective: 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.

Exposures: ADHD medication initiation was defined as dispensing of medication within 3 months of diagnosis.

Main outcomes and measures: 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).

Results: 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).

Conclusions and relevance: Among individuals diagnosed with ADHD, medication initiation was associated with significantly lower all-cause mortality, particularly for death due to unnatural causes.

Author/s:

Lin Li, Nanbo Zhu, Le Zhang, Ralf Kuja-Halkola, Brian M D'Onofrio, Isabell Brikell, Paul Lichtenstein, Samuele Cortese, Henrik Larsson, Zheng Chang

Attention Deficit Hyperactivity Disorder: Diagnosis and Treatment in Children and Adolescents Comparative Effectiveness Review No. 203

John Bayhi — Fri, 01 Nov 2019 16:52:29 +0000

Date Added:

November 1, 2019

Journal/Publication:

AHRQ Website

Publisher:

Agency for Healthcare Research and Quality

Publication Date:

January 25, 2019

URL:

Attention Deficit Hyperactivity Disorder: Diagnosis and Treatment in Children and Adolescents

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.23970/AHRQEPCCER203

Keywords

ADHD

attention deficit disorder with hyperactivity

ADHD treatment

children

adolescent

MeSH

attention deficit disorder with hyperactivity/therapy

Cognitive Behavioral Therapy

Complementary Therapies

Fatty Acids/administration & dosage

Humans

Neurofeedback

Parents/education

The key points can be found on page 4 (from 2011 report) and page ii (from this report).

Objectives. Attention deficit hyperactivity disorder (ADHD) is a common pediatric neurobehavioral disorder often treated in the primary care setting. This systematic review updates and extends two previous Agency for Healthcare Research and Quality (AHRQ) systematic evidence reviews and focuses on the comparative effectiveness of methods to establish the diagnosis of ADHD, updates the comparative effectiveness of pharmacologic and nonpharmacologic treatments, and evaluates different monitoring strategies in the primary care setting for individuals from birth through 17 years of age.

Data sources. We searched PubMed®, Embase®, PsycINFO®, and the Cochrane Database of Systematic Reviews for relevant English-language studies published from January 1, 2011, through November 7, 2016.

Review methods. Two investigators screened each abstract and full-text article for inclusion, abstracted the data, and performed quality ratings and evidence grading. Random-effects models were used to compute summary estimates of effects when sufficient data were available for meta-analysis.

Results. Evidence was contributed from 103 articles describing 90 unique studies. Twenty-one studies related to diagnosis, 69 studies related to treatment, and no studies were identified on monitoring. The Attention and Executive Function Rating Inventory and Childhood Executive Functioning Inventory performed better than the Cambridge Neuropsychological Test Automated Battery for the diagnosis of ADHD for ages 7–17 years (strength of evidence [SOE]=low). Evidence was insufficient on the use of electroencephalography (EEG) or neuroimaging to establish the diagnosis of ADHD for ages 7–17 years. No studies directly assessed the harms to children labeled as having ADHD. Limited additional evidence published since the original 2011 report was available on ADHD medications approved by the Food and Drug Administration (FDA) compared with placebo or compared to different FDA-approved ADHD medications (SOE=insufficient). For atomoxetine and methylphenidate, the most commonly reported adverse events were somnolence and mild gastrointestinal problems. Atomoxetine had slightly higher gastrointestinal effects than methylphenidate (SOE=low). Cognitive behavioral therapy improved ADHD symptoms (SOE=low). Child or parent training improved ADHD symptoms (SOE=moderate) but made no difference in academic performance (SOE=low). Omega-3/6 fatty acid supplementation made no difference in ADHD symptoms (SOE=moderate). Across all treatments, little evidence was reported on the risk of serious adverse events, including cardiovascular risk.

Conclusions. The 2011 AHRQ systematic review highlighted the benefit of psychostimulants for children 6–12 years of age with ADHD for up to 24 months and found that adding psychosocial/behavioral interventions to psychostimulants is more effective than psychosocial/behavioral interventions alone for children with ADHD and oppositional defiant disorder. This targeted update found insufficient evidence regarding new approaches to the diagnosis (e.g., EEGs, neuroimaging). Little is known about the impact of being labeled as having ADHD. Although cognitive behavioral therapy or child or parent training may decrease symptoms of ADHD, more information is needed regarding the relative benefit of these approaches compared to, or combined with, medication treatment. Omega-3/6 supplementation does not appear to improve ADHD outcomes. No information was identified regarding the optimal strategy for monitoring after diagnosis.

Author/s:

Kemper, AR, Maslow, GR, Hill, S, Namdari, B, Allen LaPoint, NM, Goode, AP, Coeytaux, RR, Befus, D, Kosinski, AS, Bowen, SE, McBroom, AJ, Lallinger, KR, Sanders, GD