ADHD Medication

See Also

Attention Deficit Disorder in Children
School Problem Evaluation
Attention Deficit Disorder in Adults
ADHD Diagnosis
ADHD Differential Diagnosis
ADHD Comorbid Conditions
ADHD Non-Pharmacologic Management
ADHD Medications
Dextroamphetamine (Dexedrine, Dextrostat, Adderall) or Lisdexamfetamine (Vyvanse)
Methylphenidate (Ritalin, Methylin, Concerta)
Atomoxetine (Strattera)

Mechanism

Amphetamine-like agents have complex CNS effects
1. Slow rate behaviors (e.g. attention) are accelerated by Amphetamines, resulting in improved learning and memory
2. Fast rate behaviors (e.g. hyperactivity) are slowed by Amphetamines

General

Medication is not a ADHD cure, only a control
Medication holiday is not needed
1. Medication may be taken on weekends and holidays
2. Summer use of medication is optional
  1. Restart medication well before school
  2. Do not trial off medication at onset of school year
3. If taking a medication holiday, tapering and titration are not needed
  1. May simply stop and start the medication at the chronic dose
Myths (Stimulant non-causes)
1. Stimulants do not cause Sedation
2. Stimulants do not cause Growth Delay
  1. Weight does however need to be watched closely
3. Stimulants do not cause drug addiction (but stimulants are abused)
  1. Drug Abuse occurs six times more commonly in Attention Deficit Disorder
  2. Stimulants do not increase that risk (and might decrease Substance Abuse risk)
  3. Drug Diversion IS a higher risk
Stimulant Abuse
1. See Stimulant Use Disorder
2. See myths above
3. Up to 80% of Stimulant Abuse patients obtain medications from family or friends
  1. Up to 20% abuse their own medications
4. Polysubstance abuse with stimulants is common
  1. Be alert to patients on stimulants AND Opioids or Benzodiazepines
5. References
  1. (2023) Presc Lett 30(8): 45-6

Contraindications

See Specific medications
Age under 6 years old
1. May be used in ages 4-5 years old for severe refractory symptoms
2. If used in ages 4-5 years old, start with short-acting low dose Methylphenidate
  1. Methylphenidate has slower metabolism in young children
Cardiovascular Risks (relative)
1. Electrocardiogram (EKG) is NOT required before the initiation of Stimulant Medications
  1. Does not predict adverse cardiovascular events on Stimulant Medications
2. Stimulants are low risk of increased cardiovascular events
  1. (2012) Presc Lett 19(2): 12
  2. (2014) Presc Lett 21(9): 54
3. Monitor Blood Pressure and Heart Rate
4. See Attention Deficit Disorder for Electrocardiogram indications
5. Reasons to avoid stimulants
  1. Uncontrolled Hypertension
  2. Serious Arrhythmias
  3. Symptomatic heart disease
  4. Recent cardiovascular event (e.g. Syncope)
  5. Congenital Heart Defect (ask related PMH, Family History and screen on ADHD exam)
    1. Consider an EKG before prescribing
    2. Vetter (2008) Circulation 117(18):2407-23. [PubMed]

Adverse Effects
Stimulant Neuropsychiatric Effects (Methylphenidate and Amphetamines)

General
1. Many adverse effects resolve within 3 to 5 days after initiating agent or increasing dose
Rebound ADHD behavior when medication level wanes
Emotional lability, irritability or tearfulness
Social withdrawal
Flat affect
Insomnia (30%)
1. See Sleep Hygiene
2. Many ADHD patients have preexisting Insomnia before stimulants
3. Shift medication dosing to earlier in day
4. Consider shorter acting stimulant
5. Consider Melatonin
6. Evaluate for Iron Deficiency
Anxiety or Tic Disorder
1. Consider alternative medication (see below)
2. Consider lower stimulant dose
Headache
Psychosis (esp. at higher doses, occurs in 0.1% of patients)
1. More common with Amphetamines in teens and young adults
2. Stimulants may also unmask Bipolar Disorder or Schizophrenia
3. (2019) Presc lett 26(5)

Adverse Effects
Stimulant Gastrointestinal and Growth Effects (Methylphenidate and Amphetamines)

Poor appetite (40%) and Unintentional Weight Loss
1. Monitor weight every 3 months in young children
2. Monitor weight every 6 months in teens and adults
3. Take medication with food and avoid skipping meals
  1. Consider larger breakfast (before medication onset of action)
4. Consider holding medication on weekends
  1. Overall drug holidays are typically avoided
5. Consider decreased stimulant dose or shorter acting agent
6. Add high calorie snacks
  1. Consider high calorie supplements (e.g. Boost or Ensure)
Epigastric Pain
Unintentional Weight Loss
Reduced Growth Velocity

Management
Medication Protocol

Start with short acting first-line stimulant (below)
1. See Dextroamphetamine (Dexedrine, Dextrostat, Adderall) or Lisdexamfetamine (Vyvanse)
2. See Methylphenidate (Ritalin, Methylin, Concerta)
Advance dose to desired affect and per adverse affects
Advance to combine long-acting with short-acting agents
Consider rapid onset long-acting agents as single medication
1. Options: Concerta, Adderall XR or Vyvanse
2. Once daily dosing in sufficient in most cases (these agents typically last 12 hours)
3. Breakthrough symptoms at end of day
  1. Consider twice daily dosing of intermediate-acting agent (e.g. Ritalin SR)
  2. Consider using 12 hour preparation in morning, and a short-acting stimulant (e.g. Ritalin) in the afternoon
  3. (2013) Presc Lett 20(9): 50-1
Converting between stimulants
1. Methylphenidate 1 mg is roughly equivalent to 0.5 mg Amphetamine salt, Dextroamphetamine or dexmethylphenidate
2. Concerta 18 mg/day is roughly equivalent to Methylphenidate 15 mg/day
3. Switching from Adderall to Dextroamphetamine or Methylphenidate
  1. Start with same total daily dose and titrate up for effect
4. Switching from Methylphenidate to Adderall
  1. Start with one half of total daily dose and adjust based on effect and adverse effects
  2. Exception: Focalin (dexmethylphenidate) is equivalent to Amphetamine dosing
Refractory cases with inadequate Attention Deficit Control on a single agent (30% of cases)
1. Consider confounding diagnoses (comorbidity is present in 70% of attention deficit)
2. Consider increasing dose above labeled maximums in older teens and adults
  1. Consider Consultation with local expert opinion
  2. Methylphenidate has been used up to 100 mg/day
  3. Concerta has been used up to 108 mg/day
  4. Adderall has been used up to 60 mg/day
3. Consider adjunctive measures
  1. See ADHD Non-Pharmacologic Management
  2. Consider adding or switching to non-stimulants (e.g. Strattera) as below
  3. Consider Third-Line Medications (Antidepressants) as below
  4. Consider Adjunctive medications for modulating emotions as listed below
Long-acting chewable, sprinkle or dissolving preparations for children with difficulty Swallowing medication
1. Methylphenidate preparations (long acting)
  1. Generic
    1. Ritalin LA
    2. Metadate CD Sprinkle caps
  2. Expensive ($300/month)
    1. Aptensio XR spinkle caps (lasts 12 hours)
    2. QuilliChew ER chewable 20 and 40 mg tabs (lasts 8-13 hours)
    3. Quillavant XR Suspension 5 mg/ml (lasts 12 hours)
    4. Adhansia XR (lasts 13 hours)
    5. Jornay PM (taken at night and peaks 14 hours later, the next morning)
    6. Contempla XR 17.3 mg dissolving tablets (lasts 12 hours)
    7. Daytrana Transdermal Patch 10 mg (lasts 10-12 hours)
2. Amphetamine preparations (long acting)
  1. Generic
    1. Adderall XR (may be sprinkled on apple sauce)
  2. Expensive
    1. Adzenys XR Orally Disolving Tablet 6.3 mg (lasts 12 hours)
    2. Dynavel XR Suspension 2.5 mg/ml (lasts 12 hours)
3. References
  1. (2016) Presc Lett 23(3):16

Management
First Line Medications (Stimulants)

Rapid Onset agents with short duration (3 to 6 hours)
1. Methylphenidate (Ritalin)
2. Dextroamphetamine (Dexedrine)
3. Dexmethylphenidate (Focalin)
4. Dextroamphetamine/Amphetamine (Adderall)
Rapid Onset agents with long duration
1. Duration 8 hours
  1. Methylphenidate LA (Ritalin LA)
    1. May last up to 12 hours
  2. Amphetamine-Dextroamphetamine (Adderall XR, Focalin XR)
2. Duration 10 hours
  1. Lisdexamfetamine (Vyvanse)
    1. Onset delayed up to 2 hours
3. Duration 12 hours
  1. Methylphenidate (Concerta, Daytrana)
  2. Dexmethylphenidate (Focalin XR)
4. Duration 16 hours
  1. Dexmethylphenidate/SerDexmethylphenidate (Azstarys)
    1. Released in 2021 in U.S. for age >6 years old at $390/month ( 8x the cost of similar generics)
    2. (2021) Presc Lett 28(9): 54
Agents to use if Substance Abuse is a concern (see myths above)
1. Lisdexamfetamine (Vyvanse)
2. Bupropion (Wellbutrin)
3. Atomoxetine (Strattera)
4. Long acting stimulants (e.g. Methylphenidate ER or Concerta) are more difficult to abuse
Slow Onset agents with long duration (not recommended)
1. Methylphenidate (Ritalin-SR or Metadate ER)
2. Dextroamphetamine (Dexedrine Spansules)
Equivalent dosages
1. Methylphenidate (Ritalin) 20 mg SR
2. Dextroamphetamine (Dexedrine) 10 mg spansules
Investigational Agents (Stimulant)
1. Modafinil (Provigil)
Agents avoided due to toxicity risk
1. Pemoline (Cylert): Liver toxicity risks

Management
Second-Line Medications (Non-Stimulants)

Background
1. Non-stimulants are less effective than stimulants
2. See Antidepressants and cardiovascular agents below
Non-Stimulants
1. Atomoxetine (Strattera)
2. Viloxazine (Qelbree)
  1. Released in 2021 in U.S. as once daily agent at $300/month (3x the cost of generic Atomoxetine)
  2. (2021) Presc Lett 28(9): 54

Management
Third Line Medications (Antidepressants)

Newer Antidepressants (SNRI or Bupropion)
1. Indications
  1. Comorbid Major Depression or Anxiety Disorder
  2. Hyper-focused on activity (e.g. computer games)
  3. Obsessive-Compulsive type unproductive behavior
2. Atypical Agents
  1. Bupropion (Wellbutrin)
3. SNRIs
  1. Venlafaxine (Effexor)
  2. Viloxazine (Qelbree, see above)
4. Other Antidepressants
  1. SSRIs are unlikely to be beneficial
Tricyclic Antidepressants
1. Indications
  1. Rarely indicated in modern ADHD Management
  2. Insomnia
  3. Poor appetite
  4. Enuresis
2. Agents
  1. Imipramine (Preferred of tricyclics)
    1. Start 10 mg PO qhs (Up to 150 mg/day divided bid)
  2. Desipramine (Risk of sudden CV death)
    1. Start 10 mg PO qhs (Up to 150 mg/day divided bid)

Management
Adjunctive Medications for Modulating Emotions

Indications
1. Impulsivity
2. Hyperactivity
3. Conduct problems
4. Tics (Tourette's)
Cardiovascular Agents
1. Clonidine (Catapres)
  1. Indicated also in difficult sleep and Trauma-related Nightmares
  2. Regular release
    1. Start 0.05 mg qhs for 3-7 days, then increase to 3-4 doses per day
    2. Maximum 0.2 mg/day if <41 kg, 0.3 mg/kg if <45 kg and 0.4 mg/kg if >45 kg
  3. Extended release
    1. Start 0.1 mg qhs for 7 days
    2. Then increase by 0.1 mg twice daily each week as needed to a maximum of 0.4 mg/day
2. Guanfacine (Tenex)
  1. Indicated also in psychomotor tics
  2. Regular release
    1. Start 0.5 mg qhs for 7 days, then increase by 0.5 mg twice daily every 3-7 days
    2. Maximum 2 mg/day if <40.5 kg, 3 mg/day if <45 kg, and 4 mg/day if >45 kg
  3. Extended release
    1. 1 mg daily for 7 days, then increase by 1 mg/week up to maximum of 4 mg/day
3. Beta Blocker
Antiepileptic agents used as mood stabilizers
1. Carbamazepine (Tegretol)
2. Divalproex (Depakote)
Psychiatric agents
1. Risperidone (Risperdal)
  1. Indicated for severe Oppositional Defiant Disorder
  2. Avoid Antipsychotic agents in most cases
2. Wellbutrin (Bupropion)
  1. Indicated for aggression

References

Pease (2024) Mayo Clinic Pediatric Days, lecture 1/14/2024
(2011) Presc Lett 18(12):68
(2015) Presc Lett 22(4)
(2019) Presc Lett 26(9):50-1
(2011) Pediatrics 128(5):1007-22 [PubMed]
(1996) Pediatrics 98:301-4 [PubMed]
Andesman (1999) Pediatr Clin North Am 46:945-63 [PubMed]
Bennett (1999) Pediatr Clin North Am 46:929-44 [PubMed]
Challman (2000) Mayo Clin Proc 75:711-21 [PubMed]
Chang (2020) Am Fam Physician 102(10):592-602 [PubMed]
Felt (2014) Am Fam Physician 90(7): 456-64 [PubMed]
Silver (1999) Pediatr Clin North Am 46:965-75 [PubMed]
Syzmanski (2001) Am Fam Physician 64(8):1355 [PubMed]