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# Attention Deficit/Hyperactivity Disorder (ADHD) Agents
## Overview
ADHD medications are primarily classified into **stimulants** (methylphenidate and amphetamine derivatives) and **non-stimulants** (atomoxetine, guanfacine ER, clonidine ER). Stimulants act via presynaptic release and reuptake inhibition of norepinephrine and dopamine. Non-stimulants provide alternative mechanisms targeting norepinephrine reuptake or postsynaptic alpha-2 receptor agonism.
## Primary Indications
* ADHD (all ages)
* Narcolepsy (stimulants only)
* Binge Eating Disorder (lisdexamfetamine only)
## Adult Dosing
* **Methylphenidate (Immediate Release):** 5 mg PO BID/TID; titrate weekly. Max: 60 mg/day.
* **Methylphenidate (Extended Release):** 18–36 mg PO daily. Max: 72 mg/day.
* **Mixed Amphetamine Salts (Adderall XR):** 20 mg PO daily. Max: 60 mg/day.
* **Lisdexamfetamine:** 30 mg PO daily. Max: 70 mg/day.
* **Atomoxetine:** Start 40 mg PO daily; increase to 80 mg after 3 days. Max: 100 mg/day.
## Pediatric Dosing
* **Methylphenidate (IR):** 0.3–0.7 mg/kg/dose PO BID/TID. Max: 60 mg/day.
* **Lisdexamfetamine:** 30 mg PO daily. Max: 70 mg/day.
* **Atomoxetine (Children/Adolescents <70kg):** 0.5 mg/kg/day PO; increase to 1.2 mg/kg/day after 3 days.
* **Guanfacine ER:** 1 mg PO daily; adjust by 1 mg/week. Max: 4 mg/day (for ADHD).
## Dose Adjustments
* **Renal/Hepatic:** Atomoxetine requires 50% dose reduction in patients with moderate hepatic impairment (Child-Pugh B) and 75% in severe impairment (Child-Pugh C). Stimulants generally do not require dose adjustments based on organ function, but use with caution.
* **Slow Metabolizers:** Genetic testing for CYP2D6 may be relevant for atomoxetine; consider lower starting doses in known PMs.
## Contraindications
* Known hypersensitivity to sympathomimetic amines.
* Advanced arteriosclerosis, symptomatic cardiovascular disease, or moderate-to-severe hypertension.
* Hyperthyroidism or glaucoma.
* Concomitant use of MAOIs (must have 14-day washout period).
* History of drug abuse (high potential for misuse).
## Adverse Effects
* **Stimulants:** Insomnia, decreased appetite/weight loss, xerostomia, tachycardia, elevated blood pressure, agitation, and potential tics.
* **Non-stimulants:** Somnolence (clonidine/guanfacine), nausea, fatigue, hepatotoxicity (rare with atomoxetine), and orthostatic hypotension.
## Key Drug Interactions
* **MAOIs:** Risk of hypertensive crisis.
* **Antihypertensives:** Synergistic effect with α-agonists (risk of bradycardia/hypotension).
* **CYP2D6 Inhibitors (e.g., fluoxetine, paroxetine):** Increase plasma concentrations of atomoxetine and some amphetamines.
* **Serotonergic agents:** Increased risk of serotonin syndrome.
## Monitoring
* Baseline and periodic blood pressure and heart rate.
* Growth (height/weight) in pediatric patients.
* Cardiac screening in patients with family history of sudden cardiac death.
* Assessment of psychiatric symptoms: emergence of tics, anxiety, or suicidal ideation (specifically with atomoxetine).
## Clinical Pearls
* **"Start low, go slow":** Titration is patient-specific and depends on clinical response vs. side effects. Always refer to institutional protocols.
* **Dosing Time:** Administer stimulants early in the morning to minimize insomnia.
* **Non-stimulant onset:** Atomoxetine and α-agonists take 2–4 weeks to achieve full clinical effect, unlike stimulants which are immediate.
* **Drug Holidays:** Some clinicians use weekend/holiday breaks to mitigate growth suppression or tolerance development; evidence is mixed.
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**EDUCATIONAL DISCLAIMER:** This information is for educational purposes only. Drug dosing, contraindications, and clinical practices change frequently. Always verify current prescribing information via the manufacturer's package insert, standardized references (e.g., Lexicomp, UpToDate), or your local institutional pharmacy protocol before prescribing or administering medication.
