Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Download ADHD: CT Studies
Document related concepts
Transcript
Psychopharmacology of ADHD Psychopharmacology of ADHD Scott Carroll, MD Founder – Ayni Neuroscience Institute Author of Don’t Settle: How to Marry the Man You Were Meant For Psychopharmacology of ADHD DIAGNOSIS AND TREATMENT OPTIONS • Written evaluations (Connor/Vanderbuilt) from teachers, parents and pt (10yo+) to make diagnosis • No diagnosis by medication trial!!! (IT except) • Educate parents/pt about the dxn and txt options • Risk/benefit analysis, not everyone needs txt • Get baseline ht, wt, vitals and labs (EKG ?) • Repeat evals yearly and with dose increases Psychopharmacology of ADHD ADHD – Neurochemistry • Dopamine depletion hypothesis (Shaywitz et al 1977) • lower levels of homovanillic acid (HVA), dopamine metabolite in CSF of ADHD compared to controls • Executive function impairments caused by hypofrontality secondary to structural, biochemical changes in prefrontal cortex • Genetic studies showing associations with DAT1, DRD4 - 7 repeat alleles • Norepinephrine clearly involved but poorly studied • Serotonin - weak, inconsistent evidence of involvement • GABA - no evidence of involvement Psychopharmacology of ADHD ADHD - Medication Treatment • The psychostimulants are the most effective • Non-stimulants are mildly to moderately effective • Large individual differences in doses and to specific medications (25/50/25 rule of thumb) • Start with methylphenidate (no SCD, except w/Sz) • Hyperactive may require higher doses than inattention Psychopharmacology of ADHD ADHD Medications Classes of Medication • psychostimulants – regular, sustained-release • -adrenergic agents (clonidine and guanfacine) • atypical antidepressants (bupropion, mirtazapine) • NE-specific reuptake inhibitors (atomoxetine) • tricyclic antidepressants (no longer used) • dopaminergic agents (modafinil but risk of SJS) Psychopharmacology of ADHD ADHD - The Psychostimulants • methylphenidate (Ritalin) • d-amphetamine (Dexedrine) • amphetamine salt mixture (Adderall) • amphetamines increase risk of sudden cardiac death with structural cardiac abnormalities and other serious heart problems, esp. Adderall • Starting with long acting formulation is better Psychopharmacology of ADHD ADHD - Psychostimulants Methylphenidate (Ritalin) – 5, 10, 20mg Dosage/Schedule • 0.3 - 0.7 mg/kg/dose (5 - 20 mg/dose) • 0.3 - 2.0 mg/kg/day (10 - 80 mg/day) • 5 - 10 mg usual starting dose Psychopharmacology of ADHD ADHD - Psychostimulants Methylphenidate Advantages • clear positive effects on inattention, distractibility, hyperactivity • short duration of action (3 - 4 hours) allows individual fine-tuning • doesn’t show up in standard urine drug test • can increase HR/BP, no clear risk of SCD Psychopharmacology of ADHD ADHD - Psychostimulants Methylphenidate Disadvantages • short duration requires bid or tid dosing • abuse potential • FDA approval for 6yo and up • slightly lowers seizure threshold Psychopharmacology of ADHD ADHD - Psychostimulants Methylphenidate (Ritalin) More common side effects • loss of appetite • weight loss • insomnia • irritability • behavioral rebound • GI upset Psychopharmacology of ADHD ADHD - Psychostimulants Methylphenidate (Ritalin) Less common side effects • tics (likely increased rather than caused) • growth retardation (due to low appetite) • elevated heart rate and blood pressure • psychosis • depression and dysphoria • hyperfocus • decreased seizure threshold Psychopharmacology of ADHD ADHD - Psychostimulants Methylphenidate – Other Preparations • Ritalin LA – 10, 20, 30, 40 mg; 4-8 hour duration • Methylin – 5, 10, 20 mg; 5, 10 mg chewable; 5 mg/5ml, 10mg/5ml solutions • Methylin ER – 10, 20 mg; 4-8 hour duration • Focalin – 2.5, 5, 10 mg dex-methylphenidate (half dose) • Focalin XR – 5, 10, 15, 20, 30 mg; 10-12 hour duration Psychopharmacology of ADHD ADHD - Psychostimulants Methylphenidate – Other Preparations • Concerta – 18, 27, 36, 48, 54 and 72 mg tablets; 14 hour duration, allows once a day dosing for most patients • Metadate-ER – 10, 20 mg; 4-8 hour duration • Metadate-CD – 10, 20, 30 mg; 8-12 hour duration • Daytrana - methylphenidate patch (pediatric absorption?) • Quillivant XR – liquid, 12 hour duration (in theory) Psychopharmacology of ADHD ADHD - Psychostimulants Concerta • 18, 27, 36, 54, 72 mg • no noon (at school) dose • usual starting dose 18 mg • do not crush or chew Psychopharmacology of ADHD ADHD - Psychostimulants Methylphenidate - Metadate CD • 10, 20, 30 mg SR; ~ 8-12 hour duration • may open capsule and sprinkle on/in non-chewed food immediately prior to administration; do not crush or chew • Difucaps Psychopharmacology of ADHD ADHD - Psychostimulants D-amphetamine (Dexedrine) 5, 10 mg; 5, 10, 15 mg spansule Dosage/Schedule 0.15 - 0.5 mg/kg/dose (2.5 - 15 mg/dose) 0.15 - 1.5 mg/kg/day (5 - 40 mg/day) 2.5 - 10 mg usual starting dose Psychopharmacology of ADHD ADHD - Psychostimulants D-amphetamine (Dexedrine) Advantages • clear positive effects on inattention, distractibility, and hyperactivity • longer duration of action (6 - 8 hours) • long-acting spansules available (6-10 hours) • FDA approved for 3 years old and up • preferable in patients with seizure disorders Psychopharmacology of ADHD ADHD - Psychostimulants D-amphetamine (Dexedrine) Disadvantages • street reputation/diversion potential • abuse potential • longer action may complicate schedule Psychopharmacology of ADHD ADHD - Psychostimulants D-amphetamine (Dexedrine) Side effects •as with methylphenidate (Ritalin), except for d-amphetamine’s mild antiepileptic effect Psychopharmacology of ADHD ADHD - Psychostimulants Other Amphetamine Preparations •Adderall – 5, 7.5, 10, 12.5, 15, 20, 30 mg • dextroamphetamine saccharate + amphetamine aspartate + dextroamphetamine sulphate + amphetamine sulphate • 2.5 – 40 mg usual daily dose •1-2x/day dosing • start 5 mg qAM/bid • 4-8 hours duration Psychopharmacology of ADHD ADHD - Psychostimulants Other Amphetamine Preparations •Adderall-XR – 5, 10, 15, 20, 25, 30 mg SR • 10-12 hours duration • start 5-10 mg qAM; max 30 mg/d • may switch Adderall patients to same total daily dose qAM • do not cut, crush or chew capsules • may sprinkle on non-chewed food Psychopharmacology of ADHD ADHD - Psychostimulants Other Amphetamine Preparations • Vyvanse – 10, 20, 30, 40, 50, 60 and 70 mg caps • pro-drug, must be metabolized via 1st pass • non-oral admin leads to slow activation • 3.5 hour half life, but 1-2 hours to onset • start 20 - 30 mg qAM; max 70 mg/d • roughly equivalent to ½ the mg of Adderall • indicated for ADHD (6yo+) and binge eating • only appropriate if risk of abuse/diversion Psychopharmacology of ADHD Adderall, Adderall XR and Vyvanse Psychopharmacology of ADHD ADHD - Psychostimulants Side Effect Management • Anorexia • adjust timing of dosage – with or after meal • adjust amount of dosage • ask parents to provide an always-available snack • consider medication holidays (hours, days, weeks) • monitor weight, consider Remeron for wt gain. Psychopharmacology of ADHD ADHD - Psychostimulants Side Effect Management • Insomnia • adjust timing of dosage • adjust amount of dosage • reinforce good sleep hygiene • reassess diagnosis (ADHD, comorbidity) • consider a small evening stimulant dose (no research substantiation; use with caution) • sleep med (melatonin, Benedryl, clonidine, trazodone) Psychopharmacology of ADHD ADHD - Psychostimulants Side Effect Management • Irritability • reassess diagnosis (ADHD, comorbidity) • assess timing of doses- peak?, rebound?, nutrition? • adjust dosage or try long acting/short acting form • switch stimulants, try/stop drug holidays • ?add α-adrenergic agent or antidepressant Psychopharmacology of ADHD ADHD - Psychostimulants Side Effect Management • Rebound • adjust amount of dosage (up or down, usually down) • adjust timing of dosage • switch to long-acting stimulant • small dose of short-acting stimulant after long-acting • reassess diagnosis (ADHD, comorbidity) Psychopharmacology of ADHD ADHD - Psychostimulants Side Effect Management • Overfocus (‘hyperfocus’) • reduce dosage • switch to longer-acting preparation • reassess diagnoses (comorbidity, especially OCD, ASD) Psychopharmacology of ADHD ADHD - Psychostimulants Side Effect Management • Headache, GI Sx • reduce dosage • switch to longer-acting preparation • assess for migraine, other pathology • switch to alternate stimulant • hydration, give with food Psychopharmacology of ADHD Psychopharmacology of ADHD Psychopharmacology of ADHD Psychopharmacology of ADHD ADHD -Adrenergic Agents • originally mediocre antihypertensives • clonidine (Catapres), guanfacine (Tenex) • effective for impulsivity, impulsive aggression • clonidine available as a transdermal patch • not effective for hyperactivity/inattention Psychopharmacology of ADHD ADHD - -Adrenergic Agents Clonidine (Catapres) 0.1, 0.2, 0.3 mg tab;0.1/24h, 0.2/24h, 0.3/24h patch Dosage/Schedule •0.05 - 0.2 mg/dose (0.3mg max/dose in teens) •0.1 - 0.6 mg/day (1.0mg max/day in teens) (usually 0.05 mg bid to 0.1 mg tid) •0.05 - 0.1 mg usual starting dose at qhs • patch max 0.6mg/24h; ~5d duration in children Psychopharmacology of ADHD ADHD - -Adrenergic Agents Clonidine (Catapres) Advantages •effective for impulsivity (and possibly for emotional hyper-reactivity) •available as transdermal patch • if switching from PO to patch, continue PO for 1-2d, monitoring VS Psychopharmacology of ADHD ADHD - -Adrenergic Agents Clonidine (Catapres) Disadvantages • must be slowly titrated up to effective dose while monitoring blood pressure • danger of rebound HTN if stopped suddenly • shorter half-life for children – esp. the patch • baseline and repeat EKG’s Psychopharmacology of ADHD ADHD - -Adrenergic Agents Clonidine (Catapres) Side effects •sedation •low blood pressure •lightheadedness, dizziness •dysphoria (feeling bad) •headache •stomach upset •rebound HTN if stopped at high dose •local irritation from patch (rotate site) Psychopharmacology of ADHD ADHD - -Adrenergic Agents Guanfacine (Tenex) 1, 2 mg Dosage/Schedule •0.5 - 2.0 mg/dose •1.0 - 6.0 mg/day (usually 1 mg qAM to 1 mg tid) •0.5 - 1.0 mg usual starting dose Psychopharmacology of ADHD ADHD - -Adrenergic Agents Guanfacine (Tenex) Advantages •effective for impulsivity (and possibly for emotional hyper-reactivity •less sedating than clonidine •lowers blood pressure less than clonidine •somewhat longer duration than clonidine Psychopharmacology of ADHD ADHD - -Adrenergic Agents Guanfacine (Tenex) Advantages • extended release oral prep (Intuniv) Side effects •as with clonidine, except for less sedation and less lowering of blood pressure Psychopharmacology of ADHD ADHD - Bupropion (Wellbutrin) Bupropion (Wellbutrin) 75, 100 mg ($) Dosage/Schedule • 37.5 - 100 mg initial dose • 75 - 450 mg day IN DIVIDED DOSES • 150 mg max single dose for adolescents • 100 mg max single dose for children Psychopharmacology of ADHD ADHD - Bupropion (Wellbutrin) Wellbutrin-SR 100, 150, 200 mg ($$) Dosage/Schedule • 100 mg initial dose… • single am dose may be sufficient • 200 mg max single dose for adolescents • 150 mg max single dose for children • XL form expensive, not tested in children Psychopharmacology of ADHD ADHD - Bupropion (Wellbutrin) Bupropion (Wellbutrin) Advantages • also treat other conditions such as depression, drug abuse and smoking • also available as Wellbutrin-SR • effective alternative to stimulants • not a controlled substance • safe to combine with a stimulant Psychopharmacology of ADHD ADHD - Bupropion (Wellbutrin) Bupropion (Wellbutrin) Disadvantages • risk of seizures (4/1,000) • not FDA approved for < 18 years old • black box warning for suicide Psychopharmacology of ADHD ADHD - Bupropion (Wellbutrin) Side effects agitation stomach upset headache dizziness constipation dry mouth tremor seizures (rare liver toxicity) tinnitus CAUTION: Wellbutrin = Zyban = bupropion Psychopharmacology of ADHD ADHD – Atomoxetine Atomoxetine (Strattera) – 10, 18, 25, 40, 60 mg • name changed from tomoxetine to avoid confusion with anticancer drug tamoxifen • hypothesized to act via highly-selective blockade of the presynaptic NE transporter (increases synaptic NE) • specific FDA approval for Rx adult and child ADHD Psychopharmacology of ADHD ADHD – Atomoxetine Dosage • Adult - begin at 40 mg PO qAM x 3d; maximum of 100 mg/day • Child – start at 0.5 mg/kg PO qAM x 3d; maximun of 1.4 mg/kg/d • adjust dose for hepatic impairment, CYP2D6 competition • Initially given bid, but qd dosing equally effective. Psychopharmacology of ADHD ADHD – Atomoxetine Side Effects – serious: • • • • black box warning for SI can induce mania and psychosis HTN, ↑HR, orthostasis, palpitations angioedema and increased narrow-angle glaucoma – more common: • • • • • dry mouth, blurred vision urinary hesitancy/retention abdominal pain, nausea, constipation, dyspepsia insomnia, fatigue impotence, dysmorrhea, ↓libido Psychopharmacology of ADHD ADHD – Atomoxetine • Advantages – no known addictive potential; not a controlled substance – selective inhibitor of NE uptake – half-life (T1/2) of 5 hours → QD dosing • Disadvantages – Expensive (~$1,000/mo), but Wellbutrin is cheap – slower onset of positive effects – noradrenergic side effect profile
