Introduction to StimulantsIntroduction to Stimulants

Cesar A. Soutullo, M.D.Cesar A. Soutullo, M.D.

UC-3 Psychopharm LecturesUC-3 Psychopharm Lectures

1. Stimulants1. Stimulants

• Use throughout the day & on wk-endsUse throughout the day & on wk-ends– Not only during schoolNot only during school– Improve social interact, leisure particip.Improve social interact, leisure particip.– Improve oppositional, aggressive behaviorsImprove oppositional, aggressive behaviors

• Methylphenidate short actingMethylphenidate short acting

• Dextroamphetamine long actingDextroamphetamine long acting

• Ritalin-SR, Dex-Spans longerRitalin-SR, Dex-Spans longer

1. Stimulants1. Stimulants

• Use throughout the day & on wk-endsUse throughout the day & on wk-ends– Not only during schoolNot only during school– Improve social interact, leisure particip.Improve social interact, leisure particip.– Improve oppositional, aggressive behaviorsImprove oppositional, aggressive behaviors

• Methylphenidate short actingMethylphenidate short acting

• Dextroamphetamine long actingDextroamphetamine long acting

• Ritalin-SR, Dex-Spans longerRitalin-SR, Dex-Spans longer

Stimulants: PharmacokineticsStimulants: Pharmacokinetics

• Ritalin: Liver met, kidney excretRitalin: Liver met, kidney excret– Peak Serum Level 1.9 hr [0.3 - 4.4 hr]Peak Serum Level 1.9 hr [0.3 - 4.4 hr]– SR: 4.7 hr [1.3-8.2 range]SR: 4.7 hr [1.3-8.2 range]– Half-life: Half-life: 2-2.5 hrs2-2.5 hrs..

• Dexedrine: Liver met, kidney excretDexedrine: Liver met, kidney excret– Peak: 2 hrs (Spansule 8-10 hr)Peak: 2 hrs (Spansule 8-10 hr)– Half-life: Half-life: 6-8 hr6-8 hr kids / 10-12 adults kids / 10-12 adults

Stimulants: Side EffectsStimulants: Side Effects• Appetite suppression: HS snackAppetite suppression: HS snack

– Effect on height rarely clinically signif 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 doseexcitability, irritability 4-5 hrs after dose– give pm dose or use spansulesgive pm dose or use spansules

1.a. Methylphenidate [Ritalin]1.a. Methylphenidate [Ritalin]

• Peak 1-2 hrs, half-life 2.5Peak 1-2 hrs, half-life 2.5

• Total daily dose Total daily dose 1 mg/kg/day1 mg/kg/day (0.6-2) (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)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 1.b. Dextroamphetamine [Dexedrine][Dexedrine]

• Half-life 6-8 hrsHalf-life 6-8 hrs• Optimal dose 0.3-1.5 mg/kg/dayOptimal dose 0.3-1.5 mg/kg/day• age 3-5 2.5 mg/d, age 3-5 2.5 mg/d, 2.5 once-twice wk 2.5 once-twice wk• > 6 yo 5 mg/d, > 6 yo 5 mg/d, 5 mg once-twice wk 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, 1.c. Adderall [dextr saccharate, sulph & amphet sulph, aspart]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]1.d Mg Pemoline [Cylert]

• Least abuse potentialLeast abuse potential• Rx once a day 37.5 mg/d Rx once a day 37.5 mg/d • Max dose 112.5 mg/dayMax dose 112.5 mg/day• Reduced use, Side effects:Reduced use, Side effects:

– choreoathetoid movementschoreoathetoid movements– insomniainsomnia– chronic hepatitischronic hepatitis– fulminant liver failure (rare)fulminant liver failure (rare)

2. Antidepressants in ADHD2. Antidepressants in ADHD

• TCAsTCAs: Helpful but caution : Helpful but caution – IMI. Cardiac SE, IMI. Cardiac SE, hyperactivity 1 hyperactivity 1

mg/kg/day & overmg/kg/day & over– PR , 210 msec, QT < 450 msec HR<130 bpmPR , 210 msec, QT < 450 msec HR<130 bpm– Desipramine: sudden death reports?Desipramine: sudden death reports?

• BupropionBupropion: Sz : Sz

• SSRI: Not helpfulSSRI: Not helpful

• Venlafaxine: Improves behavioral Sx?Venlafaxine: Improves behavioral Sx?

2.b. Bupropion [Wellbutrin]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/dayDo not use > 150 mg/dose or 450 mg/day– Separate doses > 4 hoursSeparate doses > 4 hours

3.a. Clonidine [Catapress]3.a. Clonidine [Catapress] – Presinaptic Alpha-agonist, Presinaptic Alpha-agonist, NE releaseNE release– frustration tolerance, frustration tolerance, hyperarousal hyperarousal hyperactivityhyperactivity

• Clonidine+Ritalin: 3 cases sudden deathClonidine+Ritalin: 3 cases sudden death– EKG, Hx of Syncope, FHx sudden deathEKG, 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 0.15-0.3 mg/dayslow up to 0.15-0.3 mg/day– Slow D/C, rebound hyypertensionSlow D/C, rebound hyypertension

• Skin patch: toxic if eaten or damagedSkin patch: toxic if eaten or damaged