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2/18/2015 1 PSYCHOPHARMACOLOGICAL TREATMENT OF ADHD AND COMMON CO-MORBID DISORDERS Molly Butler, PMHNP-BC Assistant Professor in Psychiatry Outline Diagnosing ADHD Treatment Recommendations Psychopharmacological Interventions Stimulants and Non-Stimulants Treatment Strategies Case Studies Diagnosing ADHD DSM Definition 18 official symptoms 6/9 symptoms of inattentiveness or hyperactivity/impulsivity for under 17 yo, only 5 in 17yo and older Lasting at least 6 months Maladaptive and exceeding norm for age Begins prior to age 12 Causes clinically significant impairment in two or more settings Not better accounted for by another disorder Inattentive Symptoms Fails to give close attention to details or makes careless mistakes Difficulty sustaining attention in tasks or play activities Doesn’t seem to listen when spoken to directly Doesn’t follow through on instructions and fails to complete tasks Difficulty organizing Avoids, dislikes or reluctant to engage in tasks that require sustained mental effort Loses things Easily distracted Forgetful Hyperactive/Impulsive Symptoms Fidgets Leaves seat when expected to remain seated Runs or climbs excessively Difficulty playing or engaging in leisure activities quietly Often “on the go” or acts as if “driven by a motor” Talks excessively Blurts our answers before questions have been completed Has difficulty waiting turn Interrupts or intrudes on others Hyperactivity Impulsivity
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  • 2/18/2015

    1

    PSYCHOPHARMACOLOGICAL TREATMENT OF ADHD AND COMMON CO-MORBID DISORDERSMolly Butler, PMHNP-BCAssistant Professor in Psychiatry

    Outline

    Diagnosing ADHD Treatment Recommendations Psychopharmacological Interventions Stimulants and Non-Stimulants

    Treatment Strategies Case Studies

    Diagnosing ADHD

    DSM Definition

    18 official symptoms

    6/9 symptoms of inattentiveness or hyperactivity/impulsivity for under 17 yo, only 5 in 17yo and older

    Lasting at least 6 months Maladaptive and exceeding norm for age

    Begins prior to age 12 Causes clinically significant impairment in two or more settings

    Not better accounted for by another disorder

    Inattentive Symptoms

    Fails to give close attention to details or makes careless mistakes Difficulty sustaining attention in tasks or play activities Doesnt seem to listen when spoken to directly Doesnt follow through on instructions and fails to complete tasks Difficulty organizing Avoids, dislikes or reluctant to engage in tasks that require

    sustained mental effort Loses things Easily distracted Forgetful

    Hyperactive/Impulsive Symptoms

    Fidgets Leaves seat when expected

    to remain seated Runs or climbs excessively Difficulty playing or

    engaging in leisure activities quietly

    Often on the go or acts as if driven by a motor

    Talks excessively

    Blurts our answers before questions have been completed

    Has difficulty waiting turn Interrupts or intrudes on

    others

    Hyperactivity Impulsivity

  • 2/18/2015

    2

    Whats New in DSM-V

    Autism Spectrum Disorder is not in exclusion criteria Specifiers:

    Severity: mild, moderate, severe Presentations: predominately inattentive,

    hyperactive/ impulsive or combined type Broader areas of defined impairment Developmentally appropriate descriptions

    7

    Rule Out Organic Causes

    Hyperthyroidism Seizures Lead toxicity Food or food additive sensitivity Sleep apnea Substance abuse

    Differential Diagnosis

    Depression

    Anxiety Disorders (PTSD)

    Bipolar Disorder

    Autism Spectrum Disorder

    ODD/ CD

    Substance Use

    Intellectual Disability

    Speech and/or language disorder

    Sudden life changes (divorce, death, move)

    Typical development

    Differential: Symptoms Specific to Depression

    Depressed mood Anorexia/ Weight loss SI Excessive Guilt Psychomotor retardation Mutism Fatigue

    Differential: Symptoms Specific to Anxiety

    Phobias Worries Stress induced onset Obsessions Compulsions Perfectionism Somatic complaints Posttraumatic play

    Differential: Symptoms Specific to Bipolar Disorder

    Positive family history

    Prolonged rages/ explosive irritability

    Episodic

    Euphoria- giddy or silly

    Grandiosity

    Risky acts without concern for safety

    Decreased need for sleep

    Nearly continuous need for 1 or more less hours per night than avg child without feeling tired

    Pressured speech

    So much or so fast they cant be understood or interrupted

    Racing thoughts

    Unintelligible, rapid changes in thought pattern, flight of ideas, sentence fragments

  • 2/18/2015

    3

    Differential: Symptoms Specific to Autism Spectrum Disorder

    Impaired nonverbal and verbal communication Restricted Interests Stereotyped/ repetitive movements Inflexible adherence to routine/ rituals Lack of: Fantasy play Social relatedness Imaginative play

    Treatment

    Treatment Guidelines

    NIMH multimodal treatment study of ADHD (MTA Cooperative Group 1999, 2004) 579 children ages 7-9 with ADHD treated for 14 months

    1) Monthly medication management with stimulant by specialist only2) Behavioral management only (35 group sessions, therapist visited school

    multiple times to work with staff, summer camp)3) Combined group: meds plus behavioral management4) Routine community care/ treatment as usual (TAU)

    -PCP visits 1-2 times / year

    RESULTS: Medication only and combined groups were superior to behavioral therapy alone and routine community care

    Follow-Up to MTA

    Superiority persisted for med and combination treatment over behavioral management and TAU Effect size was 50% smaller after 24 months

    Med only groups dosages were significantly higher than combination at 24 months

    PsychopharmacologicalInterventions

    Neurochemical Factors

    Sustaining focus and attention

    Mediating energy levels

    Motivation

    Interest

    Dopamine Norepinephrine

    Verbal fluency

    Serial learning Vigilance for executive

    functioning Sustaining and focusing

    attention Prioritizing behavior

    Modulating behavior based on social cues

  • 2/18/2015

    4

    How Medications Treat Symptoms

    Increase in norepinephrine increases strength of signals to the prefrontal

    cortex Increase in dopamine

    increase in saliency, decreases noise from extraneous stimuli

    19

    Whats out there?

    Methylphenidates Amphetamines

    Atomoxetine (Strattera) Alpha-2 Agonists Bupropion (Wellbutrin) TCAsModafinil (Provigil)

    Stimulants Non-Stimulants

    Stimulants

    Stimulants Compared to other pharm options:

    most studied, commonly used and effective first line agents

    In RCTs, effect sizes for stimulant treatment of ADHD are usually large for teacher ratings (0.8) and for parent ratings (0.5)

    70% of children will respond to 1st trial 90% will respond to 1st or 2nd trial Compared to placebo, stimulants:

    Reduce hyperactivity and disruptive behavior Improve parent-child interaction Improve problem solving with peers Reduce aggressive and antisocial behavior

    Stimulant Medications

    Methylphenidate

    Ritalin

    Methylin

    Focalin

    Ritalin SR

    Metadate ER

    Methylin SR

    Ritalin LA

    Metdate CD

    Focalin XR

    Daytrana

    Quillivant XR

    Concerta

    Amphetamine/ dextroamphetamine

    Adderall

    Dexedrine

    Dexedrine Spansules

    Dextro Stat

    Adderall XR

    Vyvanse

    Methylphenidates Amphetamines

    How stimulants work

    d,l- methylphenidate and d-amphetamine Release DA from presynaptic DA terminalsBlock DA transporter (so blocks reuptake)May reverse dopamine out of nerve terminal

    l-amphetamineSimilar effect on both DA and NE

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    5

    Immediate Release Methylphenidate

    Immediate release tablets Ritalin, D,L-Methylphenidate, Methylin and Focalin

    In quick, out quick: Behavioral effects in 30 minutes Peak plasma levels in 90 minutes Half-life 3 hours 3-5 hour duration TID dosing

    IR Methylphenidate Dosing

    Ritalin, D,L-Methylphenidate, Methylin Typically start 5 mg q am for children and 10 for adults May increase dose q 3 days- 1 week Add noon and afternoon doses first Max dose: 20mg TID (60 mg total)

    Focalin Start 2.5 mg Increase q 7 days Max: 20 mg total daily dose

    Most common uses in my practice: Initiating treatment in young or small children Appetite disruption with longer acting formulas Adjunctive to longer acting formulas in am or afternoon

    Longer Acting Methylphenidate

    Sustained release, long acting capsules, tablet or liquid and transdermal patch

    All methylphenidate BUT differ in number, rate and shape of methylphenidate pulses into blood stream

    Methylphenidate, Single Pulse, Sustained Release

    older sustained release tablets Ritalin SR, Metadate ER, Methylin SR FDA approved ages 6-15 Immediate release tablet coated with wax matrix Slower onset, lower serum concentrations Peak in 5 hours 6-8 hours duration Rarely used: BID Often need immediate release in morning to compensate

    Long Acting Methylphenidate Capsules

    Sustained Release Capsules Ritalin LA, Metadate CD, Focalin XR

    Ritalin LA and Focalin XR Beads inside capsule contain half dose as immediate

    release and half as delayed releaseMimics total dose given in immediate form about 4

    hours apart

    Long Acting Dosing

    Ritalin LA > 5 hours duration Start 10 mg q am May increase in weekly increments of 10 mg Max 60 mg daily

    Focalin XR Duration 12-16 hours Peaks at 1-2 and 6-7 hours Start 5 mg po q am Increase by 5 mg q week Max 40 mg daily After first peak 45% higher in women

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    6

    Metadate CD

    Ages 6-15 30% as immediate release and 70% delayed release Peaks 1-2 and 4-5 6-8 hours duration Start: 10 mg po q amMax: 60 mg po q am

    Methylphenidate ER (Concerta)

    Complex-release formulation Tablet coated with immediate release methylphenidate Osmotic pump releases rest of drug over 10-12 hours

    Produces ascending serum concentration Similar to TID immediate release dosing with less variation Start 18 mg po q am May increase by 18 mg q week Ages 6-12: max is 54 mg daily 13 and up: max is 72 mg daily Disadvantage: may not be as effective in am as dual pumps in early

    morning Also approved for comorbid ODD and LD

    Wont take a pill?

    Methylin Chewable Tabs or Oral SolutionComparable to immediate release

    Daytrana Transdermal Patch Apply in morning and take off 9 hours laterNo symptom reduction in first 2 hours Plasma levels peak at 7-9 hours Duration is 11.5 hours Start with 10 mg/9 hr patch, may increase to next size patch q7 days;

    Max: 30 mg/9 hr patch q day Produces higher plasma levels than dose equivalents of other preparations Tics more common and mild skin reactions are common

    Wont take a pill?

    Quillivant XR methylphenidate ER oral solution ages 6 and older initial dose: 20 mg once a day max dose: 60 mg once a day may increase daily dose by 10-20 mg at weekly

    intervals

    IR Amphetamines

    Adderall, Dextrostat generic, Dexedrine only medication with FDA approval down to age 3

    4-6 hour duration Plasma levels peak at 3 hours Start 5 q am Max 40 mg daily in split doses q 4-6 hours Titration and clinical indication same as immediate

    release forms of Methylphenidate

    Long-Acting Amphetamine

    Adderall XR capsules (d, l-amphetamine) Dual pulse with 1/2 immediate- and extended- release beads (just

    like Ritalin LA and Focalin XR) 6-8 hours duration Peak in 7 hours Start 5 or 10 mg q am Increase by 5-10 mg/day at weekly intervals as needed Max typically 30 mg daily

    Dexedrine Spansules (d- amphetamine) Peaks in 4 hours 6-8 hours duration Max 60 mg po q am

  • 2/18/2015

    7

    lisdexamfetamine dimesylate (Vyvanse)

    Prodrug of Dextroamphetamine After oral administration it is rapidly absorbed in GI tract and

    converted to active form, dextroamphetamine Reduces risk for abuse

    Ages 6-12, adults Can be swallowed whole or opened up and mixed with water,

    ice cream, applesauce or yogurt Full 12 hour duration More steady levels Start 30 mg

    but available in 20 mg capsule Increase by 10-20 mg q week Max: 70 mg daily

    Standard Warning on Stimulants

    Sudden death associated with cardiac abnormalities or other serious heart problems

    Baseline ECG/ echo and collaboration with cardiologist or PCP Hx of heart defects or heart disease Reports of murmur, syncope, chest pain, HTN or arrhythmias Family hx of heart disease < 40 years old Rates of unexpected sudden death on stimulants 0.19-0.5 in 100,000 patient-

    years and 1.3- 1.6 in 100,000 patient-years in general population

    Caution in adults with preexisting heart conditions and HTN Use with caution in:

    patients or patients with family members with history of SUDs patients with psychotic or bipolar disorders patients with tics or Tourettes

    Stimulant Side Effects

    Decreased appetite and weight loss Slowed growth rate (poorly documented) Headache Abdominal pain Delayed sleep onset New onset tics Rebound crankiness and tearfulness

    (immediate release) Overstimulation Nervousness Picking at skin/ nail biting Behavioral changes

    Irritability Aggression Depressed mood

    Sudden death

    Adverse cardiac events Angina

    Tachycardia

    Palpitations

    HTN

    Tactile and visual hallucinations

    Seizures

    Activation of hypomania or mania

    Common Rare but Serious

    Monitoring patients on stimulants

    Height/ Weight BP HR Rating Scales

    Stimulant Clinical Pearls

    May have greater effect on behavior than attention sxs If no improvement in target symptoms when dose is increased, drop back down Wont cause addiction in those with ADHD

    Actually a protective factor for SUDs If causes or increases nail biting, chewing or picking at skin consider baseline

    obsessive/ anxiety features If causes aggression and irritability consider comorbid process Little evidence of tolerance to stimulant effect

    But may need to increase with growth Take with food

    Appetite suppression Absorption and bioavailability may increase after meal

    Immediate release Can crush or break in half

    Capsules Can open up and sprinkle

    Stimulant Nonresponders

    Pt factors: Is it really ADHD? Is there a comorbid diagnosis? Are side effects interfering w response? Is the patient compliant?

    Medication factors: Is patient over- or underdosed? Is there a time of day when med is not effective? Are drug interactions effecting the response?

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    Stimulant Nonresponders

    Family Factors: Are there increased family stressors that contribute to

    diminished stimulant tx response? Is there a parent with undiagnosed ADHD or other

    psychiatric illness adding to family stress? Do care givers disagree on giving patient the med?

    Nonstimulants

    Nonstimulants

    Atomoxetine, Clonidine, Guanfacine, Buproprion, TCAs and Modafinil

    Typically used when: Inadequate response to stimulants

    Monotherapy Adjunct treatment

    Unable to tolerate stimulants Tic disorder Patient or family history of SUDs Caregiver preference Comorbid disorders

    Atomoxetine (Strattera)

    First drug approved for treatment of ADHD Approved for ages 6+

    Selective NE reuptake blocker causes increase in NE and DA levels in prefrontal cortex

    Peak plasma concentrations 1 hour without food and 3 hours with food

    Half-life 5 hours but duration of action is much longer than half-life so may dose once daily

    Hepatic metabolism in cytochrome P4502D6

    Atomoxetine (Strattera)

    Dosing: Children < 70 kg: start 0.5 mg/kg/day; after 3 days

    increase to 1.2mg/kg/day. Max: 1.4 mg/kg/day or 100 mg daily, whichever is less

    Adults and children >70 kg: start 40 mg; after 3 days increase to 80. May increase to max of 100 if needed after 2-4 weeks

    Drug interactions: Not within 14 days of MAOIs Decrease dose of atomoxetine with CYP450 2D6 inhibitors

    (fluoxetine and paroxetine) Co-administration with albuterol may increase HR and BP

    Atomoxetine: Adverse Events

    2 FDA warnings: Black Box Warning for suicidality

    September 2005- Eli Lilly study- 5 / 1,800 spontaneously reported suicidal ideation compared to 0 reports in placebo group

    Warning for liver injury December 2004, reports of severe liver injury and jaundice in two patients d/c in patients with jaundice, dark urine or lab findings of liver injury

    Side effects: GI upset and decreased appetite, drowsiness, increased HR (6-9

    bpm), increased BP (2-4 mm Hg), insomnia, dizziness, anxiety, irritability, dry mouth, dysmenorrhea, sweating, sexual dysfunction, urinary hesitancy or retention

  • 2/18/2015

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    Atomoxetine

    What to do about SEs:Wait Lower dose Split dose Change medication

    Monitor: Ht and wt BP and pulse

    Alpha-2 Agonists: Guanfacine and Clonidine

    Large number of alpha 2 adrenergic receptors in prefrontal cortex that mediate ADHD sxs These meds stimulate postsynaptic receptors to increase the

    strength of NE signals FDA-approved for use of HTN in adults since early 1970s

    IR guanfacine and clonidine NOT FDA approved for ADHD Grew in popularity for C/A psychiatry in 1990s

    Extended release versions approved by FDA for monotherapy or stimulant augmentation Clonidine Hydrochloride extended Release (Kapvay) Guanfacine XR (Intuniv)

    Alpha-2 Agonists: Clonidine and Guanfacine

    Studies suggest benefits for behavioral target sxs of: Aggression Hyperactivity Hyperarousal (anxiety/ PTSD) Impulsivity Sleep disturbance

    Fewer benefits for attentional and cognitive sxs of ADHD Additional uses:

    Adjunct therapy in ADHD Treatment of rebound symptoms with stimulants Comorbid tic disorder ADHD and/or Aggression with CD ADHD sxs in Autism Spectrum Disorder or Fragile X

    Clonidine (Catapres) Data

    Small controlled study by Hunt and Colleagues in 1985: Only 10 children Results: reduction in hyperactivity and aggression

    Improvements averaged 22.9% on parent ratings in 5 published studies on ADHD

    Conner and colleagues 2000: Pilot study comparing methylphenidate, clonidine and the

    combination in 24 children with ADHD and either ODD or CD All groups improved Clonidine alone effect size of 0.56 (moderate effect size) in ADHD

    sxs in children with comorbid conduct disorders, developmental delay and tic disorders

    Guanfacine (Tenex) Data

    Selective alpha-2A receptor agonist so has a reduced SE profile compared to clonidine

    Two open label trials with 23 children (Chappell et al., 1995; Hunt et al. 1995): No efficacy or safety data available

    Short Acting Alpha-2 Agonists

    Dosing: Clonidine (Catapres)

    0.1 mg strength tablet Start tab at bedtime May increase by 0.05 mg q 4-6 days Max typically 0.2- 0.3 mg total daily dosing QID dosing for optimal benefit

    Guanfacine (Tenex) 1 mg strength Start tab at bedtime May increase by 0.5 mg q 4-6 days Max typically 3 mg total daily dosing Dose TID less sedating than clonidine

  • 2/18/2015

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    Guanfacine XR (Intuniv)

    FDA approved in 2009 for tx of ADHD ages 6-17 2 clinical trials N= 345/324 8/9 weeks Double-blind, placebo-controlled, parallel-group, fixed

    dose design Increased by 1 mg/week No patients under 55 lbs

    Guanfacine XR (Intuniv) Clinical Trials

    ADHD sxs evaluated weekly with ADHD Rating Scale-IV Mean reductions in ADHD-RS at endpoint were statistically sig

    greater for intuniv Placebo adjusted changes from baseline were statistically sig

    for all dosages Improvements seen at 0.05-0.8mg/kg/day Additional benefit at 0.12mg/kg/day if tolerated No differences in gender response Most effective in 6-12 yo

    Only 25% were 13-17 Fixed doses may have been too low (avg was 0.01-0.04 mg/kg)

    Guanfacine XR (Intuniv)

    Dont substitute for IR guanfacine on mg-mg basis d/c IR then start intuniv

    Start 1mg once daily and increase by no more than 1 mg/day/week

    Max dosage: 4 mg/day Should be slowly tapered (by 1 mg q 3-7 days) due

    to risk of rebound hypertension and tachycardia Should re-titrate if miss two consecutive doses

    Clonidine HCL Extended Release (Kapvay)

    Approved 2010 for tx of ADHD monotherapy and was first to be approved for adjunctive therapy with a stimulant

    Two phase III trials which demonstrated improvements in core sxs at 5 weeks for ages 6-17

    SEs (incident >5% and 2x placebo) included: somnolence, fatigue, upper respiratory tract infection, irritability, sore

    throat, insomnia, nightmares, emotional disorder, constipation, nasal congestion, increased body temperature, drug mouth and ear pain

    Clonidine HCL Extended Release (Kapvay)

    Maintenance past 5 weeks not yet evaluated Start 0.1mg and increase weekly as needed to 0.4

    mg daily BID dosing

    Alpha-2 Agonists in General

    Side Effects: sedation, dizziness, orthostatic hypotension, dry mouth,

    bradycardia, irritability, sleep disturbance, syncope

    Caution: Documented sudden unexpected deaths in children

    taking clonidine Rebound HYPERtension associated with missed doses Rare disinhibition

    Monitoring BP, pulse

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    Buproprion (Wellbutrin)

    NDRI (Norepinephrine Dopamine Reuptake Inhibitor) antidepressant

    Preparations: Wellbutrin SR/XL, Budeprion, Zyban and Alplenzin

    Has been reported to be effective for ADHD symptoms in some placebo-controlled trials (Casat et al., 1989, Clay et al., 1988, Simeon et al., 1986)

    Conners et al., 1986: multisite, DB, placebo-controlled trial. Teachers reported improvement in ADHD symptoms but parents did not

    Not first line

    Buproprion (Wellbutrin)

    FDA Black Box Warning for suicidality Dosing:

    300-450 mg/ day immediate release OR

    300 mg /day SR SR form in C/A is metabolized more rapidly than adults- dose BID. No info on XL and Alplenzin form in C/A Contraindicated: seizure DO (risk is dose dependent) and eating DO Side Effects:

    Decreased seizure threshold Rare induction of mania Dry mouth, constipation, weight loss, anorexia Insomnia, dizziness, HA, agitation, tremor

    Tricyclic Antidepressants (TCAs)

    Not Approved for tx of ADHD d/t potentially serious CV events Most are NE reuptake inhibitors Imipramine (Tofranil)

    Some studies have found comparable effects but more dropouts with IMI vs Methylphenidate (Rapoport et al., 1974; Werry et al., 1980) SEs including sedation Tolerance to therapeutic effects in 6-10 weeks

    Nortriptyline (Pamelor) Superior to placebo but no head to head studies with methylphenidate

    Dosing: 2 mg/kg/day max 5 mg/kg/day (antidepressant dose) TCA SEs: cardiac tachyarrhythmias, drowsiness, anticholenergic SEs and

    seizures/ EEG changes Monitoring:

    ECG at baseline and at stable dose Draw levels Possible drug interactions

    Modafinil (Provigil)

    Non-stimulant w/o cardiovascular effects indicated for narcolepsy MOA not fully understood Alters balance of GABA and glutamate

    Biederman and Colleagues, 2005: Large RCT, DB, PC study 425 mg daily Improvement in ADHD core sxs at home and school

    Equivalent to 6 cups of coffee (600 mg caffeine) on alertness and performance tests in sleep deprived healthy adults (Wesensten et al., 2002)

    SEs: insomnia, HA, decreased appetite Manufacturer withdrew application for ADHD indication in children

    d/t report of Stevens-Johnson Syndrome and visual hallucinations

    FDA Approved Drugs for Adult ADHD Stimulants

    Adderall XR Vyvanse Quillivant XR Focalin XR Concerta

    Non-Stimulant Strattera

    65

    Treatment Strategies

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    How do we decide what to use?

    Practice Parameters recommend oral stimulants as first line: AACAP practice parameters for ADHD (Plizka and AACAP Work Group

    on Quality Issues 2007) An international consensus statement (Kuthcher et al., 2004) American Academy of Pediatrics (2001) The Texas Childrens Medication Algorithm Project: Revision of the

    Algorithm for Phamacotherapy of ADHD (Plizka et al., 2006) AACAP practice parameters say to start with long acting formulation

    of stimulant except with small or young child when long acting is not available in low- enough dose, then use immediate release formulation Start with atomoxetine when indicated Practice guidelines DO NOT require a treatment failure or adverse event

    before allowing trial of another agent

    The Texas Childrens Medication Algorithm Project: Revision of the Algorithm for Phamacotherapy of ADHD (Plizka et al., 2006)

    Algorithms for ADHD with no significant comorbid disorder and with comorbid: Anxiety MDD Tic Disorder Aggression

    Algorithm for ADHD with No Comorbid Condition

    Stage 0: Diagnostic assessment Non medication treatment alternatives

    Stage 1: Methylphenidate or Amphetamine

    Stage 2: Stimulant not used in stage 1

    Change in formulations (immediate to long acting) not considered stage change Proceed to stage 3 when one Methylphenidate and one Amphetamine have been used

    Stage 3: Atomoxetine

    Stage 4: Bupropion or TCA

    Stage 5: Agent not used in stage 4

    Stage 6: Alpha 2 agonist (clonidine or guanfacine)

    When to Use Adjunctive Pharmacotherapy

    Initial insomnia due to stimulant effect or ADHD sxs: Exogenous Melatonin

    OTC Natural hormone that regulates circadian rhythms As a drug can synchronize circadian clock to environmental cycle 1.5-9 mg at bedtime

    Antihistamine Benadryl 25-50 mg Hydroxyzine (Vistaril) Anticholinergic SEs

    Alpha-2 agonists Clondine up to 0.2 mg q hs

    Typically an interrupted and not restful sleep Tenex up to 2 mg q hs

    Adjunctive Therapy for Initial Insomnia Cont

    Antidepressants with sedation as major SE Trazodone (Desyrel)

    Serotonin 2 reuptake inhibitor 25-100 mg q hs 10% risk of priapism

    Mirtazapine (Remeron) Alpha 2 agonist and SNRI 7.5- 30 mg q hs Low doses= most sedating Increased appetite and wt gain

    Additional Indications for Adjunctive Pharmacotherapies

    Partial response Add alpha 2 agonist or atomoxetine to stimulant

    Breakthrough symptoms Add am or afternoon immediate release formulation to long

    acting formulation

    Rebound Symptoms Irritability, whining, crankiness, tearfulness Typically when stimulant wears off in afternoon or evening alpha 2 agonists another dose of stimulant

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    Stimulants + Alpha 2 Agonists

    Frequently used as adjunct therapies Kapvay and Intuniv both have FDA approval for adjunctive therapy 4 reported deaths of children on methylphenidate and clonidine IR

    All had additional risk factors Daviss and Colleagues, 2008:

    16 week MC, DB trial 122 children with ADHD 4 groups: Clonidine, methylphenidate, both or placebo Clonidine: 0.6 mg/ day Methylphenidate: 60 mg/day Monitored ECGs and vital signs More incidents of bradycardia in children on clonidine (17.5% versus 3.4%) No other group differences in ECG or CV outcomes No suggestion of interaction between clonidine and methylphenidate on CV

    outcomes

    Managing a Client in the Ideal World

    Monitor by direct contact, phone or e-mail Target sxs SEs Taking as prescribed Missed doses

    Teacher input at least twice per school year Weekly contact with initial dose adjustments then

    monthly for first few months then less frequent if stable

    Annual discontinuation trial (usually summer)

    Real World: ADHD Rarely Seen Without Comorbid Disorders

    2/3 of children with ADHD also meet criteria for other psychiatric disorders

    50% have ODD or CD 50% have learning disorders 25-30% have an anxiety disorders 2% have Tourettes

    Much higher with ADHD than random population sample or with other disorders

    Increased risk for mood disorders 10-30% of children develop depression Up to 20% may have bipolar do

    Other disorders increase the impairment associated with ADHD

    Treatment of ADHD with Comorbid Disorders

    What is causing the most impairment? Use Texas Childrens Medication Algorithms for

    ADHD with comorbid disorders AnxietyMDD Tic disoder aggression

    http://www.dshs.state.tx.us/mhprograms/adhdpage.shtm

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    Case Studies

    Case Study #1 Pt is a 9 y/o boy seen with GM for review of ADHD and

    conduct disorder Current Meds:

    Ritalin 10 mg q am and with lunch.

    He is now in 4th grade where they go to school for an extra 45 mins daily (8-3:45). He does well most of the day but, during last two classes he is having trouble with talking excessively, not being prepared for class and not getting classwork done. He is also not bringing home necessary supplies for homework and is still working on it as late as 9pm q night.

    Tolerating Ritalin without SEs. No change in sleep or appetite. No additional meds

    Case Study #2 Pt is a 15 yo fm seen for f/u of anxiety and depression. She is seen

    with and without mom today. Current Meds:

    Zoloft 200 mg Anxiety sxs are now well managed on current med regimen. Now, pt

    and mom report difficulty focusing, inability to sit down and complete work and distractability. Pt reports that she wants to do her work but she can't. Her grades have been dropping significantly due to incomplete work and lack of organization. She also reports sad mood and passive SI without plan or intent. She denies current SI/HI and recent SIB. She reports low energy and hypersomnia (>10 hours nightly). She denies use of drugs or ETOH and most recent UDS was negative. Mom gave provider several NICHQ Vanderbilt Assessment Scales completed by parents and teachers. One teacher and both parents were elevated for inattentive ADHD sxs.

    Case Study #3

    Pt is an 8 yo boy who presents with mom and PGM. Current Meds:

    Adderall XR 10 mg po q am Family reports a favorable response to Adderall XR 10 mg which was

    started 3 weeks ago. Mom reports that he is much more calm and that he has been "wonderful". Teacher reported that his school work has improved, behavior is good, no longer squirming or getting out of seat and has had good manners. Family is concerned that pt is agitated, hyper-emotional and angry in the late afternoon and early evenings when medication is wearing off. Overall mood is "happy.

    Some decrease in appetite but still eating well. No sleep disturbance. No tics or additional SEs noted.

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    Case Study #4 Pt is an 11 yo ca f seen for f/u for ADHD and adjustment d/o r/t family discord,

    neglect and variable involvement of bio-mom. Current Meds:

    Tenex 0.5 mg TIDConcerta 18 mg

    Pt has been taking Concerta 18 mg X 2 weeks. GM reports that pt c/o chest pain, agitation, nervousness, "not feeling like herself" and anger on Concerta. GM reports that pt was given EKG by PCP due to c/o chest pain on Vyvanse and it was wnl. No reports of syncope. Vital signs wnl.

    She continues to be hyperactive, impulsive and defiant. This is problematic at home, school and church. Current wt. 132 lbs, 60 kg

    Past medication trials: Vyvanse Adderall XR Concerta Focalin XR

    Pt c/o several SEs on all stimulants.

    References

    Barkley, Russell A (2000). Taking Charge of ADHD: The complete, authoritative guide for parents (Revised ed.). New York: Guildord Press.

    Barkley R, Murphey K (2005). Attention-Deficit Hyperactivity Disorder: A Clinical Workbook. New York: Guliford Press. .

    Findling, Robert L. (2008). Clinical Manuel of Child and Adolescent Psychopharmacology (4th ed.). Arlington: American Psychiatric Publishing, Inc.

    Green, Wayne H. (2007). Child and Adolescent Clinical Psychopharmacology. Philadelphia: Lippincott, Williams and Wilkins.

    Kolevzon A, Stewart D (2004). Psychiatry Pearls: The Pearls Series. United States: Hanley & Belfus, Inc.

    Lewis (2007). Lewiss Child and Adolescent Psychiatry: A Comprehensive Textbook (4th ed.). Philadelphia: Lippincott, Williams and Wilkins.

    Sadock B, Sadock V. (2003). Synopsis of Psychiatry: Behavioral Sciences/Clinical Psychiatry (9th ed.). Philadelphia: Lippincott, Williams and Wilkins.

    Stahl, Stephen M. (2000). Essential Psychopharmacology: Neuroscientific Basis and Practical Applications (2nd ed.). Cambridge: Cambridge University Press. S

    Stahl, Stephen M. (2008). Everything You Wanted to Know About ADHD But Forgot You Wanted to Ask. Carlsbad, California: NEI Press.

    The End


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