ADHD Pharmacotherapy in Adults

We Start with a Case!

  • GH is a 26yo patient with the following CC: “I can’t seem to keep up with my work assignments lately… my mentor has just about had it. I’m ready to drop out.”
  • HPI: ~1 year ago, GH noticed increased daydreaming and trouble concentrating on assignments, inability to complete tasks on time. GH recalls restlessness, fidgeting and tapping as a child that continued into adulthood. Not problematic in past. 
  • PMH: GAD, obesity
  • Medications: sertraline 50 mg once daily, daily multivitamin with folic acid
  • Social History: Denies alcohol or tobacco use; occasional marijuana (“helps with anxiety”)
    • Occupation: oceanography graduate student
    • Exercise: walking ~30 min 2x/week
    • Diet: 3-4 meals/day (1-2 cups coffee qAM, 1 soda qPM)
  • Family History: brother with ADHD and PGM with unspecified tic disorder

ADHD Diagnostic Criteria

The recognition that attention deficit-hyperactivity disorder (ADHD) persists after adolescence has led to an increase in its diagnosis and treatment in adults.

Volkow et al. N Engl J Med. 2013 Nov 14;369(20):1935-44.

The DSM-5 criteria are used to diagnose ADHD in both children and adults.

Source: Volkow ND, Swanson JM. Clinical practice: Adult attention deficit-hyperactivity disorder. N Engl J Med. 2013 Nov 14;369(20):1935-44.

Treatment: Initial Factors to Consider

Social: 

  • Social norms, standards, bias
  • Household member substance use or diversion
  • Cost of medication management and prescription

Patient-specific: 

  • Co-existing conditions
    • Mental health: anxiety, depression, disordered eating, bipolar disorder
    • Cardiovascular: cardiomyopathy, MI, Raynaud’s disease, HTN, tachycardia
    • Epilepsy: risk for decrease seizure threshold
    • Substance use disorders
  • Duration of desired medication effect
  • Family history
    • Cardiovascular disease
    • Experience with stimulant medications
    • Substance use disorders
  • Patient preferences or concerns

Pharmacotherapy vs Psychotherapy

Regarding pharmacotherapy, randomized trials show clinically significant improvements in ADHD symptoms and in daily functioning with the use of approved medications (stimulants and the non-stimulant atomoxetine) for ADHD in adults.

Nevertheless, while pharmacotherapy can reduce the core symptoms of ADHD, it often insufficiently addresses difficulties in executive self-management with respect to time and organization, as well as problems in social and emotional self-regulation, leading to continued distress and impairment for adults with ADHD. Cognitively based psychotherapies therapies have been developed to address these problems.

Also of note, clinical trials of medications for ADHD have been largely short-term and have predominantly involved young and middle-aged adults. Data are lacking on long-term benefits and risks and on risks among elderly patients.


Non-Stimulant Pharmacotherapy

Atomoxetine (Strattera)

  • The ONLY non-stimulant medication approved for adult ADHD
  • MOA: Selective norepinephrine reuptake inhibitor 
  • Dose: 40 mg/day (increase to 80 mg/day after day 3 treatment) 
    • Max Dose: 100 mg/day (daily or twice daily) 
  • Place in Practice: 
    • Unable to tolerate stimulant medications 
    • Substance abuse concerns 
    • Continues to struggle with sustained attention and response to external stimuli on stimulant regimen 
  • Benefits: 
    • Not controlled substance
    • Discontinuation without tapering

Other drugs used off-label for treatment of adult ADHD include bupropion, TCAs (e.g., desipramine, nortriptyline), and alpha-2 adrenergic agonists (e.g., guanfacine, clonidine). 


Stimulants: Amphetamines vs Methylphenidates

Amphetamines:

  • Examples: dextroamphetamine (e.g., Dexedrine, Dextrostat), dextroamphetamine-amphetamine (e.g., Adderall), lisdexamfetamine (e.g., Vyvanse)
  • Mechanism: Blocks reuptake of dopamine and norepinephrine, and promotes release of dopamine and norepinephrine (dual MOA) 
  • BBW: Cardiovascular Events; Tolerance 
  • Patients: children ≥6yo and adults 
  • Dosing Considerations: Duration of Action

Methylphenidates: 

  • Examples: methylphenidate (e.g., Concerta, Metadate, Ritalin), dexmethylphenidate (e.g., Focalin)
  • Mechanism: Blocks reuptake of dopamine and norepinephrine 
  • BBW: Tolerance 
  • Patients: Guideline recommended for 4-6yo children
  • Dosing Considerations: Timing of peaks

Drug-drug interactions with stimulants: 

  • Serotonergic agents (e.g., SSRI, SNRI, triptans)
    • Amphetamines may enhance the serotonergic effect of SSRIs that are strong CYP2D6 inhibitors, which could result in serotonin syndrome. Additionally, these SSRIs may increase the serum concentration of amphetamines.
  • Antihypertensive agents
    • Amphetamines may diminish the antihypertensive effect of these agents. 
  • Bupropion and antipsychotics (e.g., risperidone) may enhance the neuroexcitatory and/or seizure-potentiating effect of amphetamines. 

Amphetamines

Immediate Release (IR): 

Extended Release (ER):


Methylphenidates

Immediate Release (IR):

Extended Release (ER):


Back to the Case!

Plan:

  • Start Adderall IR 10 mg – Take 1 tablet by mouth every morning (#14)

Counseling Points:

  • Take medication in the morning with food 
  • Monitor for increases in HR, headache, dry mouth, etc. 
  • Try to avoid taking medication w/ caffeine or immediately before cardio workouts 

Follow-up:

  • Return to clinic in 2 weeks for evaluation of stimulant efficacy, tolerability and need for dose/formulation changes

Monitoring ADEs

Source: Volkow ND, Swanson JM. Clinical practice: Adult attention deficit-hyperactivity disorder. N Engl J Med. 2013 Nov 14;369(20):1935-44.

The absolute risk of serious cardiovascular adverse events associated with ADHD medications appears to be very low. However, the observed increases in pulse rate and blood pressure with stimulant use underscore the need for caution in prescribing these agents for patients with cardiovascular disease.

Volkow et al. N Engl J Med. 2013 Nov 14;369(20):1935-44.

Monitoring parameters: 

  • What time do you take the medication?
  • What time did you notice it kick-in?
  • Did you notice the medication wear off?
  • How long after taking the medication did it wear off?
  • How often do you take the medication?

Common ADEs: 

  • Increased BP, HR
  • Headache, sweating, insomnia
  • Nervousness, anxiety
  • Decreased or loss of appetite (ask about weight loss!)
  • Nausea, dry mouth

Blog post based on Med-Peds Forum talk by Elizabeth Salisbury, PharmD