Introduction to Stimulants Cesar A. Soutullo, M.D. UC-3 Psychopharm Lectures

1. Stimulants Use throughout the day & on wk-endsUse throughout the day & on wk-ends –Not only during school –Improve social interact, leisure particip. –Improve oppositional, aggressive behaviors Methylphenidate short actingMethylphenidate short acting Dextroamphetamine long actingDextroamphetamine long acting Ritalin-SR, Dex-Spans longerRitalin-SR, Dex-Spans longer

1. Stimulants Use throughout the day & on wk-endsUse throughout the day & on wk-ends –Not only during school –Improve social interact, leisure particip. –Improve oppositional, aggressive behaviors Methylphenidate short actingMethylphenidate short acting Dextroamphetamine long actingDextroamphetamine long acting Ritalin-SR, Dex-Spans longerRitalin-SR, Dex-Spans longer

Stimulants: Pharmacokinetics Ritalin: Liver met, kidney excretRitalin: Liver met, kidney excret –Peak Serum Level 1.9 hr [ hr] –SR: 4.7 hr [ range] –Half-life: hrs. Dexedrine: Liver met, kidney excretDexedrine: Liver met, kidney excret –Peak: 2 hrs (Spansule 8-10 hr) –Half-life: 6-8 hr kids / adults

Stimulants: Side Effects Appetite suppression: HS snackAppetite suppression: HS snack –Effect on height rarely clinically signif Sleep difficulty: dose before 4 pmSleep difficulty: dose before 4 pm  Systolic BP (mild)  Systolic BP (mild) Exacerbate Tics & Tourette’sExacerbate Tics & Tourette’s Psychosis: discontinuePsychosis: discontinue Rebound effects:Rebound effects: –excitability, irritability 4-5 hrs after dose –give pm dose or use spansules

1.a. Methylphenidate [Ritalin] Peak 1-2 hrs, half-life 2.5Peak 1-2 hrs, half-life 2.5 Total daily dose 1 mg/kg/day (0.6-2)Total daily dose 1 mg/kg/day (0.6-2) In >6 y.o. start 5 mg qd or bid (AM & 12)In >6 y.o. start 5 mg qd or bid (AM & 12) –raise 5-10 mg/wk, (can add 4 pm dose) Tablets: 5, 10, 20 mgTablets: 5, 10, 20 mg SR 20 mgSR 20 mg Max> dose: 60 mg/dayMax> dose: 60 mg/day

1.b. Dextroamphetamine [Dexedrine] Half-life 6-8 hrsHalf-life 6-8 hrs Optimal dose mg/kg/dayOptimal dose mg/kg/day age mg/d,  2.5 once-twice wkage mg/d,  2.5 once-twice wk > 6 yo 5 mg/d,  5 mg once-twice wk> 6 yo 5 mg/d,  5 mg once-twice wk Tablets: 5 mg, scoredTablets: 5 mg, scored Spansules: 5, 10, 15 mgSpansules: 5, 10, 15 mg Max dose 40 mg/dayMax dose 40 mg/day Better for pt. with SeizuresBetter for pt. with Seizures

1.c. Adderall [dextr saccharate, sulph & amphet sulph, aspart] Half-life 7-8 hrsHalf-life 7-8 hrs Dose like DexedrineDose like Dexedrine Tablets 5, 10, 20, 30 mgTablets 5, 10, 20, 30 mg

1.d Mg Pemoline [Cylert] Least abuse potentialLeast abuse potential Rx once a day 37.5 mg/dRx once a day 37.5 mg/d Max dose mg/dayMax dose mg/day Reduced use, Side effects:Reduced use, Side effects: –choreoathetoid movements –insomnia –chronic hepatitis –fulminant liver failure (rare)

2. Antidepressants in ADHD TCAs: Helpful but cautionTCAs: Helpful but caution –IMI. Cardiac SE,  hyperactivity 1 mg/kg/day & over –PR, 210 msec, QT < 450 msec HR<130 bpm –Desipramine: sudden death reports? Bupropion: SzBupropion: Sz SSRI: Not helpfulSSRI: Not helpful Venlafaxine: Improves behavioral Sx?Venlafaxine: Improves behavioral Sx?

2.b. Bupropion [Wellbutrin]  Hyperactivity-Impulsivity  Hyperactivity-Impulsivity Improve cognitive performance?Improve cognitive performance? Effects: DA reuptake blockEffects: DA reuptake block Start 37.5 to 50 mg bid, gradual increaseStart 37.5 to 50 mg bid, gradual increase Seizure riskSeizure risk –Do not use > 150 mg/dose or 450 mg/day –Separate doses > 4 hours

3.a. Clonidine [Catapress] –Presinaptic Alpha-agonist,  NE release –  frustration tolerance,  hyperarousal –  hyperactivity Clonidine+Ritalin: 3 cases sudden deathClonidine+Ritalin: 3 cases sudden death –EKG, Hx of Syncope, FHx sudden death Helpful in ADHD + TicsHelpful in ADHD + Tics Start Dose 0.05 mg hs (tablets 0.1 mg)Start Dose 0.05 mg hs (tablets 0.1 mg) –slow up to mg/day –Slow D/C, rebound hyypertension Skin patch: toxic if eaten or damagedSkin patch: toxic if eaten or damaged