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Slide 1 - Pharmacological Management of Attention Deficit Hyperactivity Disorder & Disruptive Behavior Disorders Annual Pharmacological Conference for Advanced Practice Nurses Terri Mathews, Ph.D., APRN-NP, BCBA-D July 21, 2011
Slide 2 - Attention Deficit Hyperactivity Disorder (ADHD) Incidence – Approx. 3-8% of children 60% of children will continue to have diagnosis in teenage years and adulthood Male: female ratio 4:1 Symptoms often occur in children as young as three year of age Comorbidities with ADHD 54-80% ODD/Conduct disorder 25 – 35% Language Disorder 33% Anxiety Disorders 0-33% Mood disorders 16% - Met criteria for Mania
Slide 3 - Definition Deficits in Hyperactivity, Impulsivity and Regulating Attention Deficits in executive functioning Processes that maintain appropriate problem solving to set a future goal Impaired response inhibition Impaired vigilance Impaired working memory Poor planning capacity
Slide 4 - Etiology Genetic - Heritability - 76% Seven genes have shown significant association with ADHD Non - Genetic Exposure to infection Prenatal toxic exposure Perinatal stress Low birth weight Prematurity Traumatic brain injury Very severe early neglect
Slide 5 - ADHD – Diagnosis Inattention Fails to pay close attention to details/makes careless mistakes Does not listen when spoken directly to Does not follow through on instructions Difficulty organizing tasks Avoids, dislikes and does not engage in tasks that require sustained mental efforts Loses things necessary for tasks or activities Easily distracted by external stimuli Forgetful in Daily activities
Slide 6 - Hyperactivity – Fidgets – squirms in seat Leaves seat in classroom excessively Runs or climbs excessively Difficulty engaging or playing in leisure activity quietly Often “on the go” or “driven by a motor” Talks excessively Impulsivity - Blurts outs answers before questions complete Difficulty waiting turn Interrupts or Intrudes on others
Slide 7 - DSM – IV –TR Diagnosis At least some impairment before seven years of age Symptoms present in at least two settings Clinically significant impairment in social, academic or occupational functioning Not other accounted for by a mental condition
Slide 8 - Assessment Semi-structured interview Rating Scales from 2 environments CBCL Connor’s Vanderbilt ADHD DSM-IV-TR ADHD scales Sampling of school work Accuracy Completeness Time involved Check desk for preparation Observation of amount of time on-task
Slide 9 - Treatment Recommendations Comprehensive Treatment Plan Parental and Child Psychoeducation Psychotherapy Parent Management Training Medication Management Careful evaluation for cardiac risk factors Monitor for Side Effects Evaluation
Slide 10 - Pharmacological Management Before Starting Complete History and Physical Consider Cardiovascular Health History If history of arrhythmias, structural heart defect, or family history of arrhythmias or sudden death, pediatric cardiology consult and EKG prior to initiation. Height and Weight on All Patients Consideration of Substance Abuse Stigma Family Lifestyle (Adherence)
Slide 11 - Stimulant Medications Stimulant medications are the most studied, most commonly used first-line agents for ADHD treatment Stimulant medications improve: Core symptoms: inattention, impulsivity, hyperactivity Associated symptoms: cognition, on-task behavior, academic performance, social function, defiance, and aggression Effective in preschoolers, school-age children, adolescents and adults
Slide 12 - Stimulant Medications Two primary classes of stimulants Amphetamines and methylphenidate (MPH) Response rate for any one particular stimulant is approx. 70% No predictors of response have been identified All stimulants are generally of comparable efficacy There is significant individual variability in response to a particular stimulant
Slide 13 - Stimulant Medications MPH-based and amphetamine-based stimulants have different effects at the neurotransmitter level MPH Inhibits the activity of the presynaptic dopamine transporter protein involved in the reuptake of dopamine from the synaptic cleft Amphetamines Blocks the reuptake of dopamine and norepinephrine through inhibition of the dopamine transporter protein Increases retrograde release of catecholamines (dopamine and norepinephrine) through the transporter
Slide 14 - Methylphenidate Effect
Slide 15 - Amphetamine based effect
Slide 16 - Preparations methylphenidate (Ritalin, Methylin, Metadate) Long acting preparations: Ritalin-SR, Ritalin LA, Methylin-ER, Metadate-ER, Metadate-CD, Concerta, Daytrana Methylin comes in an liquid and chewable tablet form Daytrana delivers MPH via a transdermal patch dexmethylphenidate (Focalin) Long acting preparation: Focalin XR
Slide 17 - Amphetamine based mixed amphetamine salts products (Adderall) Long acting preparation: Adderall XR lisdexamfetamine dimesylate (Vyvanse) Prodrug of dextroamphetamine dextroamphetamine (Dexedrine, Dextrostat) Long acting preparation: Dexedrine spansules
Slide 18 - Long-Acting Stimulant Preparations
Slide 19 - Side Effects Most side effects are transient and dose dependent Common side effects include: insomnia, decreased appetite, mild increase in heart rate and BP, weight loss, headache, nausea Rare side effects include: behavioral rebound, psychosis, anxiety or depression Dexmethylphenidate (Focalin) may have fewer side effects than MPH
Slide 20 - Management of Side Effects Anorexia – Small frequent snacks Highly dense calories Instant Carnation breakfast Assure good breakfast before am dose Cyproheptadine 2- 4 mg tid Insomnia Good bedtime hygiene Decrease late afternoon stimulant Melatonin 1-6 mg at HS
Slide 21 - Dosing Start low and titrate up slowly Each patient has a unique-response curve FDA Maximum doses – Methylphenidate – 60 mg Daytrana – 30 mg Concerta – 72 mg Focalin XR – 30mg Adderall XR – 40 mg Vyvanse – 70 mg
Slide 22 - Contraindications to Stimulant Use Glaucoma Hyperthyroidism Overt cardiovascular disease Psychosis Substance abuse disorders (abuse potential is very low with medical supervision) Uncontrolled hypertension Concomitant prescription with MOAIs
Slide 23 - Selective Norepinephrine Reuptake Inhibitor Atomoxetine (Strattera) – First non-stimulant, FDA approved medication for treatment of ADHD in children, adolescents and adults (November, 2002) Highly selective inhibition of presynaptic norepinephrine reuptake in the prefrontal cortex Preferentially binds to areas of known high distribution of noradrenergic neurons in the fronto-cortical subsystem Increases noradrenergic transmission Important for attention, learning, memory and adaptive responses
Slide 24 - Indications Effective in reducing scores on ADHD – RS from baseline to endpoint As effective as immediate release stimulants but not as effective as osmotically-release MPH or amphetamine salts May be first line of treatment for those with history or concern of substance abuse, tics & anxiety Comorbid conditions May show effectiveness with comorbid anxiety (Sumner, 2005) & possibly Oppositional Defiant Disorder (Dittman et al., 2011)
Slide 25 - Selective Norepinephrine Reuptake Inhibitor Atomoxetine (Strattera) Safety data Diastolic BP and heart rate increase but not clinically significant No significant lab or EKG changes No exacerbation of tics or anxiety No abuse potential Monitor for liver dysfunction Drug interactions with paroxetine and to a less extent fluoxetine *** Black box warning – may increase suicidal thoughts
Slide 26 - Atomoxetine Side Effects Headache Abdominal pain Anorexia Nausea up to several weeks Vomiting Sedation and fatigue Irritability Dizziness
Slide 27 - Atomoxetine Dosing Once or twice daily (evenly divided doses) 0.5 mg/kg and titrate to target dose of 1.2 mg/kg after minimum 3 days maximum dose of 1.4 mg/kg May discontinue without tapering Several weeks before effective – can take up to 6-8 weeks
Slide 28 - Alpha-2 adrenergic agonists guanfacine (Tenex and Intuniv) clonidine (Catapres) Reduces brainstem vasomotor center-mediated CNS activation Reduces hyperactivity and impulsivity Helps with regulation of attention
Slide 29 - Indications Often used in conjunction with stimulants Stimulants at max dose or side effects and lack effectiveness May help modulate mood level Tics related to stimulant use Sleep disturbances Comorbid aggression
Slide 30 - Side Effects Sedation Mild decreases in HR and BP Abdominal pain Dizziness Dry mouth Constipation Need to discontinue medications slowly because of rebound hypertension and tachycardia
Slide 31 - Dosing Intuniv – FDA approved Extended release – once daily 1-4 mg daily Costly Tenex BID to TID dosing Start at 0.5 mg and gradually increase to a max of 4 mg/ day Clonidine QID dosing 0.05mg, 0.1mg and 0.2mg
Slide 32 - Evaluation Monitor after one to two weeks with med change Evaluate every three months Monitor height and weight at each visit Reevaluate ADHD rating scales Consider school updates, grade reports Reconsider diagnosis with non-responders or co-morbidity Monitor for CV risk factors, tics, other SE, etc.
Slide 33 - Oppositional Defiant Disorder (ODD) Prevalence – 2-16 % of school age children Can be diagnosed as early as 3 years of age, and typically diagnosed by 8 years of age. Not typically diagnosed in adolescence. More common in boys than girls prior to adolescence, there after sex ratio is equal Etiology Genetic Temperamental Predisposition Coercive interactions with parents
Slide 34 - Diagnosis DSM – IV –TR (Four behaviors for at least six months) Loses temper Argues with adults Defies or refuses to comply with requests Deliberately annoys people Blames others for mistakes or behaviors Touchy or easily annoyed by others Angry and resentful Spiteful or vindictive
Slide 35 - Treatment Behavioral Therapy Preschoolers Parent-Child Interaction Therapy Improves self-esteem Increases parent-child interaction Reduces coercive parent interactions School Age Children Parent Management Training Use of contingency Management Reduction of Aversive Punishment Increase positive reinforcement Set firm consistent rules Social skills training (practice appropriate responses)
Slide 36 - Pharmacological Currently, no FDA approval for medication treatment of ODD Few studies have shown effectiveness with the use of medications Most studies have examined comorbid ADHD and ODD Methylphenidate Atomoxetine Reduction of oppositional behaviors (Turgay, 2009)
Slide 37 - Atypical Antipsychotics Treatment of aggression Risperidone Effective in children 5 -12 years of age with subaverage intellectual functioning (Turgay et al., 2003)
Slide 38 - Conduct Disorder Incidence/Prevalence 1-10% of population More common in boys than girls (4:1 to 12:1 ration) Etiology More common with parental psychopathology Harsh, punitive punishment Substance use Child abuse and neglect Divorced families
Slide 39 - Etiology (cont.) Urban environments Lack of social support system Neurobiological Possible decreased noradrenergic functioning Possible elevated serotonin levels
Slide 40 - Diagnosis DSM – IV – TR (Three or more in past 12 months) Aggression to people and animals Bullies, threatens or intimidates Initiates physical fights Use of weapons to cause harm Physically cruel to animals and humans Stolen while confronting a victim Forces sexual activity
Slide 41 - Destruction of property Engaged in fire setting or serious damage Deliberately destroyed property Deceitfulness or Theft Breaking into home Lies to obtain goods or favors or avoid obligations Stolen items of nontrivial value Serious violations or rules Stays out late at night Runs away from home at least twice Truant from school
Slide 42 - Treatment Multisystemic Therapy Individual, Group and Family Therapy Behavioral Therapy Begin treatment as early as possible Social Skills Training Family support interventions Boot camps Be aware of Deviant Training Residential Treatment
Slide 43 - Pharmacological Treatment No FDA approval for medications for Conduct Disorders If behavioral interventions have failed – consider: Off label use Methylphenidate Atypical Antipsychotics - treatment of aggression risperidone (Risperdal) aripiprazole (Abilify)
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Slide 45 - References AACAP (2007). Practice parameters for the assessment and treatment of children and adolescents with oppositional defiant disorder. Journal of the American Academy of Child and Adolescent Psychiatry, 46, 1, 126-141. Dittman, R. W. et al. (2011). Atomoxetine versus placebo in children and adolescents with attention-deficit/hyperactivity disorder and comorbid oppositional defiant disorder: A double-blind, randomized, multicenter trial in Germany. Journal of Child and Adolescent Psychopharmacology, 21, 2, 97-110. Eyberg, S. M., Nelson, M. M., & Boggs, S.R. (2008). Evidenced-based psychosocial treatments for children and adolescents with disruptive behaviors. Journal of Clinical Child & Adolescent Psychology, 37, 215-237. Garland, A. F. et al. (2008). Identifying common elements of evidence-based psychosocial treatment for children’s disruptive behavior problems. Journal of American Academy of Child and Adolescent Psychiatry, 47, 505-514. Garnock-Jones, K. P., & Keating, G. M. (2009). Atomoxetine. A review of its use in attention-deficit hyperactivity disorder in children and adolescents. Pediatric Drugs, 11 ,203-226. Greydanus, D. E., Nazeer, A., & Patel, D. (2009). Psychopharmacology of ADHD in pediatrics; current advances and issues. Neuropsychiatric Disease and Treatment, 5, 171-181. Kaplan, G. & Newcorn, J. H. (2011). Pharmacotherapy for child and adolescent attention-deficit hyperactivity disorder. Pediatric Clinics of North America, 58, 99-120. Kratochvil, C. et al. (2005) Atomoxetine alone or combined with fluoxetine for treating ADHD with comorbid depressive or anxiety symptoms. Journal of the American Academy of Child and Adolescent Psychiatry, 44, 915-924. Plizka, S. et al. (2007). Practice parameters for the assessment and treatment of children and adolescents with attention-deficit/hyperactivity disorder. Journal of the American Academy of Child and Adolescent Psychiatry, 46, 7, 894-921. Turgau, A. et al. (2002). Long-term safety and efficacy of risperidone for the treatment of disruptive behavior disorders in children with subaverage IQs. Pediatrics, 110, e 34 DOI:10.1542/peds. 110.3 e34 Turgay, A. (2009). Psychopharmacological treatment of oppositional defiant disorder. CNS Drugs, 23, 1, 1-17.