ADHD + Stimulants

ADHD

•Attention deficit/hyperactivity disorder (ADHD) is a chronic disorder of attention and/or hyperactivity-impulsivity. Symptoms must be present before 7 yr of age, last at least 6 mo, and cause functional impairment in multiple settings.

•A diagnosis of ADHD should be considered whenever a child presents with developmentally inappropriate inattention, impulsivity, and/or hyperactivity. Symptom presence and severity vary with the situation. It is unusual for a child to display signs of the disorder in all settings or even in the same setting at all times.

ADHD in Children

7-8% prevalence

• Easy to diagnose

• Diagnosed by pediatrician, child psychiatrist, child psychologist

• High levels of identification and treatment > 50% treated

• Stimulants prescribed first and second line

• 2/3 of stimulants are under age 18, most of this under age 13

• 1/3 of atomoxetine is under age 18, most of this over age 12

ADHD in Adults > 18

4-5% prevalence

• Hard to Dx

  • Inaccurate retrospective recall of onset

  • Onset by age 7 too stringent

  • Late onset, some genetics, comorbidity, and impairment

  • Diagnosed by adult psychiatrist, adult mental/medical health professionals

  • Low levels of identification and treatment < 20% treated

  • Nonstimulants often prescribed first line

  • 1/3 of stimulant use is age 18 +

  • 2/3 of atomoxetine use is age 18 or over

ADHD Patho

Prefrontal cortex is a functional deficit (NE and Dopamine) and if not enough then we have hyperactivity and impulsivity

ADHD considerations (1)

•The duration of desired coverage (completion of homework or driving may require coverage into the evening)

•The ability of the child to swallow pills or capsules

•The time of day when the target symptoms occur

•The desire to avoid administration at school

•Potential adverse effects

•Coexisting tic disorder (avoidance of stimulants or use of alpha-2 adrenergic agonists may be warranted)

ADHD considerations (2)

•Coexisting emotional or behavioral condition (an alpha-2-adrenergic agonist may be useful for patients who are over-aroused, easily frustrated, highly active, or aggressive)

•History of substance abuse in patient or household member: avoid stimulants or use stimulants with less potential for abuse (lisdexamfetamine, osmotic-release preparation, methylphenidate patch)

Preference of the child/adolescent and his/her parent/guardian

ADHD considerations (3)

•Expense

–Generally, short acting stimulants are least expensive

–Among long-acting stimulants, pulse formulations are less expensive than bead preparations, osmotic-release preparations, and the methylphenidate patch

–Generic drugs are less expensive than brand-names, but not available for all formulations)

–Generic medications may be used as long as they are systematically titrated

First Line Pharmacotherapy

•The 2001 AAP guideline recommends the use of stimulant medications as 1st-line in treatment.

•A 2nd type of stimulant should be tried if the 1st treatment fails.

Second Line Pharmacotherapy

•Nonstimulant:

–Atomoxetine carries a “black box” warning regarding potential exacerbation of suicidality (similar to selective serotonin reuptake inhibitors).

• The manufacturer recommends weekly visits for 4 sessions, then every-other-week visits for 4 sessions, then every-12-weeks visits.

• Atomoxetine has also been associated with hepatic injury in a small number of cases, and the manufacturer recommends checking liver enzymes if symptoms (jaundice, fatigue, malaise) develop.

Amoxetine (Strattera)

Second-Line 

•Selective norepinephrine reuptake inhibitor; 0.5–2 mg/kg/d every morning (10 mg, 18 mg, 25 mg, 40 mg, 60 mg). Maximum dose, 1.4 mg/kg/d or 100 mg/d, whichever is less:

–Slower onset of efficacy; gastrointestinal side effects and sedation. Not addictive.

–Atomoxetine interacts with paroxetine (Paxil), fluoxetine (Prozac), and quinidine.

•Other nonstimulant drugs (e.g., clonidine, tricyclic antidepressants, SSRIs): Owing to the mixed efficacy and high side effects of these drugs, they are not recommended for use without a consultant.

CNS Stimulants

Biochemical Action:

•Increase the activity of CNS neurons

•Enhance neuronal excitation; a few suppress neuronal inhibition

Clinical Role:

Stimulants are considered first-line therapy in most cases of ADHD; however, comorbid conditions impact the drug selection process. Pharmacotherapy should be considered whenever a thorough diagnostic assessment results in a diagnosis of ADHD.

CNS Stimulant AE: Nutrition

•Decreased appetite – Administer the medication at or after a meal

•Encourage the child to eat nutrient dense foods before those with “empty calories”

•Offer food that the child likes for the noon meal, which is often affected.

•When making these changes, an important caveat is that meals with high fat content may delay the onset and increase peak concentrations of some formulations (Metadate CD®, Methylin® chewable tablets or oral solutions, Adderall XR®).

CNS Stimulant AE: Growth

•Poor growth – Drug holidays may be beneficial for children in whom stimulant therapy is associated with a growth trajectory that crosses two major percentiles (5^th, 10^th, 25^th, 50^th, 75^th, 90^th, and 95^th). Drug holidays should only be undertaken if they can be tolerated without marked impairment in functioning.

CNS Stimulant AE: Dizziness

• Dizziness – Monitor blood pressure and pulse; ensure adequate fluid intake; if associated only with peak effect, try a longer-acting preparation.

CNS Stimulant AE: Insomnia/Nightmares

 Establish a bedtime routine and good sleep hygiene habits; omit or reduce the last dose of the day or, if using a long-acting preparation, change to a short-acting preparation or administer earlier in the day.

CNS Stimulant AE: Mood Lability/Shifts

•If mood lability occurs at the time of peak concentration, try reducing the dose or switching to a longer acting preparation.

–Irritability, sadness, and increased activity as the medication wears off is particularly common when short-acting medication is used on a morning and noon twice-a-day schedule.

–Try adding an afternoon dose or switching to long-acting form; referral for coexisting mood disorder or anxiety disorder may be warranted.

CNS Stimulant AE: Rebound

•“Rebound” refers to symptoms or adverse effects that occur as the medication is wearing off.

–Rebound effects may improve by stepping down the dose at the end of the day (by increasing the dose of the long-acting agent administered in the morning or adding a smaller dose of short-acting medication at the end of the day).

CNS Stimulant AE: Tics

•Conduct a drug trial at different doses, including no medication, to be sure that tics are drug-related

–If tics abate on no medication, reconsider the risks and benefits of treatment with the patient and family.

–Exacerbated or triggered/stimulant associated

–Take of stimulant and use non-stimulant if so

CNS Stimulant AE: Psychosis

•If children taking stimulant medications develop psychotic symptoms (suicidality, hallucinations, or increased aggression), verify that the dose is appropriate and that the medication is being administered as prescribed.

•If so, discontinue the stimulant; stimulant medications can be discontinued abruptly, without tapering.

•Referral to a qualified mental health specialist or psychopharmacologist may be warranted to assess for bipolar disorder or a thought disorder.

CNS Stimulant AE: Diversion and Misuse

• It is important to monitor symptoms and prescription refills for evidence of misuse or diversion of ADHD medication.

•Stimulant diversion and misuse can be prevented, to some extent, by prescribing long-acting stimulants with less potential for abuse, and by keeping track of prescription dates.

•Have a discussion about stimulant diversion and misuse with patients and parents so that students can be prepared if they are approached by peers to sell or misuse medications and so that parents can remain vigilant in monitoring medications.

Atomoxetine (Strattera)

Biochemical Action:

•Selectively inhibits the reuptake of norepinephrine with little to no activity at the other neuronal reuptake pumps or receptor sites.

Clinical Role:

•Stimulants are considered first-line therapy in most cases of ADHD; however, comorbid conditions impact the drug selection process. Pharmacotherapy should be considered whenever a thorough diagnostic assessment results in a diagnosis of ADHD.

Atomoxetine (Strattera) AE

• HA, Insomnia, Somnolence

• Xerostoma, Nausea, abdominal pain, appetite decreased, vomiting

• Postmarketing and or case reports

  • Aggressiveness, agitation, akathisia, allergic reactions, allergy, anaphylaxis, angioedema, anxiety, delusional thinking, depression, flatulence, growth suppression (children), hallucinations, hepatotoxicity, hostility