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Attention Deficit Hyperactivity Disorder
March  2017

A family is applying for life insurance for their 20-year-old college student daughter. The applied for amount, while high, appears consistent with siblings. The potential insured’s (PI) attending physician statement (APS) has regular routine health maintenance checkups, with a few emergency room follow ups for injuries, including a forearm fracture at age 13 without specifics mentioned, a foot fracture from falling after trying to climb out of a second story bedroom window at the age of 15, and a follow up from a motor vehicle accident where the PI was a passenger at the age of 17 years.

The young lady was diagnosed with ADHD at the age of 7 and has been treated with stimulants since that time. She and her family have participated in family counseling on and off throughout the years. Her BMI and vital signs fall within normal limits. She is on no other medications except for methylphenidate.

1. Does ADHD present a mortality risk?
2. Are there any indicators that increase or decrease that risk?

Epidemiology
Attention Deficit Hyperactivity Disorder (ADHD) is an oft discussed and frequently diagnosed disorder. As of 2011, the CDC reports that approximately 11% of children aged 4-17 years of age have been diagnosed with ADHD. Approximately 4.1% of adults in the US also carry the same diagnosis. The average age at diagnosis is 7 years, and the male:female ratio is 2.6:1.

It appears that genetics plays a strong role, but other factors are being examined, including prematurity, exposures to toxins in utero (such as drugs or alcohol), brain injury, etc. Research does not support some popularly held views that family chaos, lack of discipline, lack of a full night of sleep, etc. are causes, although all can certainly contribute to worsening of symptoms.

Diagnosis
The diagnosis of ADHD in the Diagnostic and Statistical Manual of Mental Disorders (DSM) 5 now encompasses both ADHD and the former Attention Deficit Disorder (ADD). This change was made as it is believed that ADHD may look different at different stages of life. One can present with predominantly inattentive, predominantly hyperactive/impulsive or with combined features, yet the prevalent symptoms can change over time.

To receive the diagnosis, several inattentive or hyperactive impulsive symptoms must be present before age 12 years; they must be present in two or more settings; and there must be clear evidence that the symptoms interfere with the quality of social, school or work functioning.

Inattention
Six or more of the following symptoms must be present for children up to age 16 years or five or more symptoms must be present for those 17 years or older. Symptoms must be present for more than six months and must be inappropriate for the developmental level of the individual.

  • Often fails to give close attention to details or makes careless mistakes
  • Often has trouble holding attention on tasks or play activities
  • Often does not seem to listen when spoken to directly
  • Often does not follow through on instructions and fails to finish tasks
  • Often has trouble organizing tasks and activities
  • Often avoids, dislikes or is reluctant to do tasks that require mental effort over a long period of time
  • Often loses things necessary for tasks and activities
  • Is often easily distracted
  • Is often forgetful in daily activities

Hyperactivity and Impulsivity
Six or more of the following symptoms must be present for children up to age 16 years or five or more symptoms must be present for those 17 years or older. Symptoms must be present for more than six months and must be disruptive and inappropriate for the developmental level of the individual.

  • Often fidgets with or taps hands or feet or squirms in seat
  • Often leaves seat in situations when remaining seated is expected
  • Often runs about or climbs in situations where it is not appropriate (adolescents or adults may be limited to feeling restless)
  • Often unable to play or take part in leisure activities quietly
  • Is often “on the go” acting as if “driven by a motor”
  • Often talks excessively
  • Often blurts out an answer before a question has been completed
  • Often has trouble waiting his/her turn
  • Often interrupts or intrudes on others (e.g., butts into conversations or games)

American Academy of Pediatrics Recommendations
It is recommended by the American Academy of Pediatrics in their 2011 ADHD: Clinical Practice Guideline for the Diagnosis, Evaluation, and Treatment of Attention-Deficit/ Hyperactivity Disorder in Children and Adolescents Clinical Practice that a primary care clinician should evaluate all children aged 4-18 years who present with academic or behavioral problems and symptoms of inattention, hyperactivity or impulsivity.

The evaluation should include assessing for any contributing or coexisting impairments such as emotional, behavioral, developmental or physical conditions.

If ADHD is diagnosed, the treatment should include age appropriate counseling and behavior therapy for both at home and school and stimulant medication if needed.

Pharmacotherapy
First line medications are stimulants (methylphenidate and amphetamine) and norepinephrine reuptake inhibitor (atomoxetine). Second line medications are reserved for first line drug failures or unacceptable side effects and include alpha 2-adrenergic agonists (clonidine, guanfacine), antidepressants (tricyclic antidepressants and bupropion) and atypical antipsychotics (risperdone, ziprasidone, aripiprazole). Some of these medications (atypical antipsychotics) are used off label or when there are comorbidities such as autism spectrum disorder, agitation or aggression (Table 1).

Table 1 - ADHD Medications

CommonSecondary
MethylphenidateAlpha2-adrenergic agonists

- ​Ritalin

​- Clonidine / Catapres
​- Focalin​- Guanfacine / Intuniv
​- MetadateAntidepressants
- ​Concerta​- Tricyclic antidepressants
- ​Daytrana Patch​- Desipramine
Amphetamine​- Nortiptyline
​- Dextroamphetamine​- Bupropion / Wellbutrin
​- VyvanseAtypical Antipsychotics
​- Lisdexamfetamine​- Risperidone / Risperdal
Atomoxetine / Strattera​- Ziprasidone / Geodon
​- Aripiprazole / Abilify


Natural History

Barbaresi et al. Pediatrics 2013 examined the records of 5,718 children born in Minnesota between 1976-1982 and diagnosed with ADHD. The prospective portion of their study revealed that of all of the children who received the diagnosis of childhood ADHD, during adulthood, 5.6% had only adult ADHD, 23.7% had adult ADHD and a psychiatric disorder, 33.2% carried a diagnosis of only a psychiatric disorder, while 37.5% of the population had no diagnosed condition at all. It appears from these findings that some children outgrow the symptoms, while others have symptoms which evolve into another diagnostic category.

Mortality Implications
Dalsgaard et al in Lancet 2015 followed 1.92 million Danish individuals born 1981-2011, from first birthday until 2013, including 32,061 with ADHD. The adjusted mortality rate ratio is shown in Table 2.

Table 2 - Adjusted Mortality Rate Ratio (MRR)

​Diagnosis​Adjusted MRR
​ADHD​1.50
​ADHD + ODD or CD​2.17
​ADHD + Substance Use Disorder​5.63
​ADHD + ODD or CD + Substance Abuse Disorder​8.29
​ODD or CD or Substance Abuse Disorder​3.55
Control​​1.00

ODD = Oppositional Defiant Disorder, CD = Conduct Disorder

There is a baseline elevation of mortality risk with ADHD alone. The addition of the comorbidities of Oppositional Defiant Disorder (ODD), Conduct Disorder (CD) and/or Substance Use Disorder increase the mortality risk in a dose-response fashion.

When looking at the results broken down by gender, a higher relative mortality rate is realized by females (Table 3). This effect may be due to a combination of factors. Females are diagnosed with ADHD less frequently than males, and one might hypothesize that those girls who receive the ADHD diagnosis may have more severe and impairing symptoms. Girls also tend to receive pharmacotherapy less frequently than boys, which may also contribute to the difference.

Table 3 - ADHD without ODD, CD or Substance Use Disorder (by Gender)

Gender​MRR
​Male​1.27
​Female​2.85


The results of the study also determined that the increased mortality was driven by deaths from unnatural causes, most commonly accidents. This fits with our understanding of the disorder where impulsivity often rules over caution.

Returning to the Case
Our young applicant has been diagnosed with ADHD and is being treated pharmacologically with a first line medication. She does not, as far as we know, carry any comorbid diagnoses that increase mortality. She has been successfully treated for a few accidents which may or may not have been a direct result of her ADHD. Given our current understanding of the ADHD and the recent mortality data, the case was assessed at mild to moderate excess mortality.

Postscript
Sections of SOLEM Americas Underwriting Guide on Hypertrophic and Dilated Cardiomyopathies have been updated. Addition of guidance, tables and calculators for Juvenile Build are currently in production. Look for these to be added by the end of the second quarter 2017.

References
Barbaresi, William J., Robert C. Colligan, Amy L. Weaver, Robert G. Voigt, Jill M. Killian, and Slavica K. Katusic. “Mortality, ADHD, and psychosocial adversity in adults with childhood ADHD: a prospective study.” Pediatrics 131, no. 4 (2013): 637-644.

Dalsgaard, Søren, Søren Dinesen Østergaard, James F. Leckman, Preben Bo Mortensen, and Marianne Giørtz Pedersen. “Mortality in children, adolescents, and adults with attention deficit hyperactivity disorder: a nationwide cohort study.” The Lancet 385, no. 9983 (2015): 2190-2196. https://www.cdc.gov/ncbddd/adhd/data.html accessed 2/17/2017

UpToDate last accessed 2/17/2017