maximizing treatment success new strategies for treating adhd and associated comorbidities provided...
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Maximizing Treatment SuccessNew Strategies for Treating ADHD and Associated Comorbidities
Provided by the Network for Continuing Medical Education
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Treatment of ADHD in Children
Learning Objectives Characterize the comorbid disorders commonly associated with
attention-deficit/hyperactivity disorder (ADHD) in children, adolescents, and adults
Apply effective approaches to screening for associated comorbidities, such as mood disorders, substance use disorder, and disruptive behavior disorders, in patients with ADHD
Discuss how to differentiate between ADHD and a disorder with similar features, and ADHD comorbid with that disorder
Assess current pharmacologic and behavioral treatment strategies for patients with ADHD and various comorbid disorders
Outline a comprehensive treatment plan that includes other healthcare professionals in the management of patients with ADHD and associated comorbidities
Contributing Faculty
Steven R. Pliszka, MD, ChairProfessor and ChiefDivision of Child and Adolescent Psychiatry University of Texas Health Science Center at San AntonioSan Antonio, Texas
Russell A. Barkley, PhDResearch ProfessorDepartment of PsychiatrySUNY Upstate Medical UniversitySyracuse, New YorkAdjunct Professor of PsychiatryMedical University of South CarolinaCharleston, South Carolina
James Robert Batterson, MDChild PsychiatristChildren’s Mercy Hospitals and Clinics Kansas City, Missouri
William W. Dodson, MDPrivate PracticeSpecializing in Adult ADHDDenver, Colorado
Robert D. Hunt, MDCEO and Medical DirectorCenter for Attention and Hyperactivity DisordersNashville, Tennessee
ADHD in Children: Objective
Present strategies for diagnosis and treatment of disorders commonly comorbid with ADHD in children and adolescents– Disruptive behavior disorders– Anxiety– Depression– Bipolar disorder
Empirically Proven Treatments for ADHD in Children: Psychopharmacology
Stimulants– Methylphenidate (Ritalin®, Concerta®)– Mixed amphetamine salts (Adderall®/Adderall XR®)
Nonstimulant – Atomoxetine (Strattera®)
Other noradrenergic medications – Bupropion (Wellbutrin®)
Tricyclic antidepressants – Desipramine (Norpramin®)
Antihypertensives– Clonidine (Catapres®)– Guanfacine (Tenex®)
Physicians’ Desk Reference. 59th ed. Montvale, NJ: Thomson PDR; 2005.
Empirically Proven Treatments for ADHD in Children: Psychosocial Interventions
Parent education about ADHD1,2
Parent training in child management3 – Children (<11 yrs, 65%-75% respond)– Adolescents (25%-30% show reliable change)
Family therapy for teens: problem-solving, communication training4 – 30% show change– Best to combine with BMT to reduce dropouts
1. Weiss M. Child Adolesc Psychiatr Clin North Am. 1992;1:467-479.2. Dulcan M. J Am Acad Child Adolesc Psychiatry. 1997;36:85S-121S.3. Barkley RA. Defiant Children: A Clinician’s Manual for Assessment and Parent Training.
2nd ed. New York: Guilford Press; 1997.4. Murphy K. J Clin Psychol. 2005;61:607-619.
Empirically Proven Treatments for ADHD in Children: Psychosocial Interventions (cont.)
Teacher education about ADHD Teacher training in classroom behavior management Special education services (IDEA, section 504) Regular physical exercise Residential treatment (5%-8%) Parent/family services (25+) Parent/client support groups (CHADD, ADDA,
independents)
Barkley RA. Attention-Deficit Hyperactivity Disorder: A Handbook for Diagnosis and Treatment. 2nd ed. New York: Guilford Press; 1998.
Major Behavioral Tactics for ADHD
Balance the following two strategies: Altering antecedents – getting proactive:
– Giving effective instructions
– Altering performance settings
– Point-of-performance prompts and cues Altering consequences – being reactive:
– Positive reinforcement (tokens, rewards, etc.)
– Punishment (time outs, grounding, fines, etc.)
– Changing schedules (increasing frequency and immediacy of consequences)
DuPaul GJ, Stoner G. ADHD in the Schools. 2nd ed. New York: Guilford Press; 2003.
ADHD in Childhood: Common Comorbid Diagnoses
Approximate Prevalence Rate in Children With ADHD (%)
Pliszka SR. J Clin Psychiatry. 1998;59(suppl 7):50-58.Biederman et al. J Am Acad Child Adolesc Psychiatry. 1999;38:966-975. Biederman et al. J Am Acad Child Adolesc Psychiatry. 1996;35:343-351.Spencer et al. Pediatr Clin North Am. 1999;46:915-927.
0 10 20 30 40 50 60
MaleFemale
Oppositional defiant disorder
Conduct disorder
Mood disorders
Anxiety disorders
Learning disorders
Disruptive Behavior Disorders
Conduct Disorder (CD) A repetitive and persistent pattern of behavior in
which the basic rights or well-being of others is disregarded1
Common symptoms1:– Aggression to people or animals– Destruction of property– Deceitfulness or theft– Serious violation of rules
CD may be more severe and persistent when comorbid with ADHD2
1. American Psychiatric Association. DSM-IV; 1994:85-91. 2. Kuhne et al. J Am Acad Child Adolesc Psychiatry. 1997;36:1715-1725.
Oppositional Defiant Disorder (ODD)
A negativistic, hostile, and defiant pattern of behavior that varies greatly in severity
Common symptoms– Often loses temper– Often actively defies adults– Often deliberately annoys people
American Psychiatric Association. DSM-IV; 1994:91-94.
Nature of CD and ODD
A descriptive diagnosis; does not imply etiology ODD may be secondary to ADHD CD/ODD may occur even without ADHD CD/ODD are sometimes due to environmental factors
(late onset) CD with ADHD may represent a distinct familial
subtype and genetic variant of ADHD CD with ADHD is a worse condition than either alone
or than their combination would suggest Most likely has multiple causes
ADHD Without and With CD/ODD
Without CD/ODD
With
CD/ODD
Prevalence of learning disorder
↑ ↑↑
Risk for delinquent behavior = ↑↑
Risk for substance abuse ↑ (adult) ↑↑ (adol & adult)
Family history of behavior problems
= ↑↑
Note: Symbol shows rate relative to controls.
Psychopharmacology of CD/ODD
ADHD children with (and without) CD/ODD respond to stimulants1
Indeed, effect-size changes in ODD symptoms may be as large as those in ADHD symptoms in comorbid cases
No evidence that stimulants increase aggression at appropriate doses; evidence shows decreased aggression2
Relative to placebo, ADHD children on stimulants engage in less antisocial behavior
1. MTA Cooperative Group. Arch Gen Psychiatry. 1999;56:1073-1086.2. Spencer et al. J Am Acad Child Adolesc Psychiatry. 1996;35:409-432.
ADHD and CD/ODD: Psychopharmacologic Recommendations
Divalproex: may be effective for explosive temper and mood lability1
Risperidone: has reduced disruptive behavior and hyperactivity2
Atomoxetine: has produced meaningful improvement in ADHD and ODD symptoms3
1. Donovan et al. Am J Psychiatry. 2000;157:818-820.2. Aman et al. J Child Adolesc Psychopharmacol. 2004;14:243-254.3. Newcorn et al. J Am Acad Child Adolesc Psychiatry. 2005;44:240-248.
Psychosocial Treatment of ADHD and CD/ODD in Children
When CD/ODD is present, interventions focused on parenting are essential given the recognized contribution of parenting to both disorders
Parent training (PT) in behavior management methods has strong empirical support, particularly for addressing the ODD problems in ADHD children
PT is most effective (65%-75%) with elementary school-age children but declines markedly by adolescence (30%)
Problem-solving communication training combined with behavior management training has the greatest evidence for effectiveness (30%) for those 14 and older– Traditional family therapies are less helpful (10% response rate)
Barkley RA. Attention-Deficit Hyperactivity Disorder: A Handbook for Diagnosis and Treatment. 2nd ed. New York: Guilford Press; 1998.
Psychosocial Treatment of ADHD and CD/ODD in Children (cont.)
Where CD is present, parental psychological disorders are highly likely and may require additional intervention beyond those for the ADHD child1
Family relocation to better neighborhoods and schools may also be important and assist with disrupting deviant peer groups, criminogenic neighborhood environments, and ineffective schools2
Avoid group treatment programs that bring antisocial youth together, as they have been shown to increase antisocial behavior outside the group (deviancy training)2
Multisystemic therapy that involves therapists in the home setting daily is an empirically supported alternative to traditional clinic-based therapies or incarceration for juveniles3
1. Biederman et al. J Am Acad Child Adolesc Psychiatry. 1996;35:343-351.2. Dishion et al. Am Psychol. 1999;54(9):755-764.3. Henggelar et al. J Am Acad Child Adolesc Psychiatry. 2003;42:543-551.
Anxiety and Depressive Disorders
ADHD and Anxiety Disorders Children with ADHD and comorbid anxiety disorders tend
to display:– High levels of arousal– Fearfulness, separation anxiety – Phobias, fear of sleeping alone– Fear of social situations– Anxiety beyond that associated with consequences
of misbehavior Anxiety symptoms must be overt; should not be assumed
to be present based on ADHD symptoms alone
ONLY SIGNIFICANT, IMPAIRING ANXIETY SHOULD BE A FOCUS OF PHARMACOLOGIC TREATMENT
Spencer et al. Pediatr Clin North Am. 1999;46:915-927.
ADHD and Comorbid Depression
Major depressive disorder– Pervasive sadness or
irritability nearly every day
– Loss of energy– Guilt– Serious suicidal
ideation– Suicidal gestures– Cannot be reassured– Chronic low self-
esteem
Dysphoria or “demoralization”– Brief periods of sadness
when frustrated– Energy normal– Lack of guilt except when
in trouble– Brief threats of self-harm
when frustrated– Responds to redirection– Positive attitude about
good areas of function
ONLY MAJOR DEPRESSIVE DISORDER SHOULD BE A FOCUS OF ANTIDEPRESSANT TREATMENT
American Psychiatric Association. DSM-IV; 1994:317-327, 339-350.
Pharmacologic Treatment of Depression in Children
Pooled all studies, published and unpublished Blinded reviewers at Columbia assessed each
adverse event as to its self-harm potential N >4,000 No completed suicides 4% suicidal ideation on drug vs 2% on placebo,
statistically significant difference
FDA Meta-analysisFDA Meta-analysis
FDA Public Health Advisory. October 15, 2004. Available at: http://www.fda.gov/cder/drug/antidepressants/SSRIPHA200410.htm. Accessed June 6, 2005.
Treatment for Adolescents With Depression Study (TADS)
Response rates– Fluoxetine + CBT: 71%– Fluoxetine alone: 61%– CBT alone: 43%– Placebo: 35%
Presence of SI– 29% at baseline– All 4 groups improved significantly,
but SI still higher in SSRI group
CBT = cognitive-behavioral therapy; SI = suicidal ideation; SSRI = selective serotonin reuptake inhibitor.
March et al. JAMA. 2004;292:807-820.
Treatment of ADHD With MDD:Stimulant First vs Antidepressant First
Stimulant first1,2
– ADHD chief complaint– ADHD symptoms more disabling– MDD found on interview, no current
functional impairment from depression– Mild neurovegetative signs– ADHD symptoms clearly preceded MDD
symptoms
1. Pliszka et al. ADHD with Comorbid Disorders: Clinical Assessment and Management. New York: Guilford Press; 1999.
2. Pliszka et al. J Am Acad Child Adolesc Psychiatry. 2000;39:908-919.
Treatment of ADHD With MDD: Stimulant First vs Antidepressant First
(cont.)
Antidepressant first1,2
– Clear history of stimulant nonresponse– Prominent neurovegetative signs/
health compromised– MDD present complaint– ADHD symptoms late onset or coincident
with MDD symptoms– Suicidal/psychotic
1. Pliszka et al. ADHD with Comorbid Disorders: Clinical Assessment and Management. New York: Guilford Press; 1999.
2. Pliszka et al. J Am Acad Child Adolesc Psychiatry. 2000;39:908-919.
Treatment of ADHD With Anxiety
Start with stimulant first unless1,2:– Full-blown panic symptoms– Full-blown separation anxiety with complete
refusal to separate, but: Studies conflict on whether children with
anxiety have poorer response to stimulants– Consider using atomoxetine for both ADHD and
anxiety or as a supplement to stimulant treatment– May add SSRI to stimulant to treat anxiety1,2
1. Pliszka et al. ADHD with Comorbid Disorders: Clinical Assessment and Management. New York: Guilford Press; 1999.
2. Pliszka et al. J Am Acad Child Adolesc Psychiatry. 2000;39:908-919.
Psychosocial Treatment of ADHD With Anxiety/Depression
Comorbid ADHD/anxiety shows best response to behavioral and social skills intervention1
Cognitive therapy relative to ADHD alone or with other disruptive disorders may be helpful2
– In behavioral token systems, keep thresholds for success low initially; high likelihood of success eliminates worry about earning quotas for privileges
Low self-esteem is specifically associated with comorbid depression, not due to ADHD
Use “go slow” approach to punishment contingencies (eg, time outs) in comorbid ADHD/depression so as not to contribute to depressive cognitive schemas – Start with all-reward programs until depression symptoms lift, then
introduce selective mild punishments
1. MTA Cooperative Group. Arch Gen Psychiatry. 1999;56:1088-1096.
2. Brent et al. Arch Gen Psychiatry. 1997;54:877-885.
Bipolar Disorder
DSM-IV Bipolar Disorders
Bipolar I disorder (manic-depressive illness)– Manic– Depressed– Mixed
Bipolar II disorder – Hypomania + depression
Cyclothymia– Hypomania– Depression
Bipolar disorder NOS
American Psychiatric Association. DSM-IV; 1994:350-366.
Bipolar Disorders in a Community Sample of Older Adolescents
1,709 high school students Mean age, 16.6 ± 1.2 yr Randomly selected from 9 senior high schools Time 1 assessment (1987-1989)
– Adolescent Interview– K-SADS/E/P
Time 2 assessment (14 mos later)– K-Life
Lewinsohn et al. J Am Acad Child Adolesc Psychiatry. 1995;34:454-463.
Bipolar Disorders in a Community Sample of Older Adolescents:
Summary 18 Cases – prevalence of ~1%
– 2 Bipolar I disorder – 11 Bipolar II disorder – 5 Cyclothymia
97 Bipolar disorder NOS Significant functional impairments High rates of:
– Psychiatric comorbidity– Mental health service utilization
Lewinsohn et al. J Am Acad Child Adolesc Psychiatry. 1995;34:454-463.
Bipolar Disorder:Adult vs Child Criteria
Elation vs irritability1
Definition of an “episode”2
– “Distinct period”– Simple cycling– Complex cycling
Strict adult criteria vs developmentally appropriate criteria
1. Geller et al. J Affect Disord. 1998;51:81-91.2. Wozniak et al. J Clin Psychiatry. 2001;62:10-15.
Bipolar Disorder in Children and Adults:Different Developmental Trajectories?
Mo
od
Sta
te
Euthymic
Manic
Depressed
Adult Subtype
Adolescent SubtypeBP II or I
BP NOS?
ADHD Rx
?Pediatric Euphoric BPs
Age/Years
0 2 4 6 8 10 12 14 16 18 20 22
Treatment of Pediatric Bipolar Disorder:Mood Stabilizers
Study of 42 outpatients (mean age, 11.4 yr) with bipolar I or II disorder randomized to open treatment with lithium, divalproex, or carbamazepine over a 6- to 8-week period– Low-dose chlorpromazine allowed as
“rescue medication” All 3 mood stabilizers showed a large effect
size, as measured by a ≥50% change from baseline to exit in the Y-MRS scores
Y-MRS = Young Mania Rating Scale.
Kowatch et al. J Am Acad Child Adolesc Psychiatry. 2000;39:713-720.
Mood Stabilizer Treatment of Pediatric Bipolar Disorder: Responders’ Pattern of Response
Random. 1 2 3 4 5 6 7 80
5
10
15
20
25
30
35
Me
an
Yo
un
g M
RS
Sc
ore
Week
Carbamazepine
Valproate
Lithium
Reproduced with permission from Kowatch et al. J Am Acad Child Adolesc Psychiatry. 2000;39:713-720.
Potential Mood Stabilizers
Gabapentin (Neurontin®): negative Lamotrigine (Lamictil®): BP depressed, maintenance
of BP, risk of rash/Stevens-Johnson syndrome Tiagabine (Gabitril®): negative Topiramate (Topamax®): trials in adults negative;
trials in children discontinued Oxcarbazepine (Trileptal®): new risk of rash/Stevens-
Johnson syndrome FDA performing review of anticonvulsants and the
risk of suicide
Atypical Antipsychotics Current agents
– Risperidone– Olanzapine– Quetiapine – Ziprasidone– Aripiprazole
Powerful Sometimes necessary Limit use because of
– Sedation– Weight gain
Kowatch et al. J Am Acad Child Adolesc Psychiatry. 2005;44:213-235.
Antipsychotic Weight Gain: Meta-analysis
-1
0
1
2
3
4
5
Kg
Allison et al. Am J Psychiatry. 1999;156:1686-1696.
Weight gain
PlaceboZiprasidoneHaloperidolRisperidoneChlorpromazineOlanzapineClozapine
ADHD and Mania: Treatment If floridly manic, stabilize mood before treating ADHD
(or discontinue ADHD treatment until mood stabilized)
– Stimulant may be added to mood stabilizer or atypical antipsychotic later
If mania/BP diagnosis is equivocal, treat ADHD first
– If all symptoms resolve, mania unlikely If stimulant or ADHD medication induces partial remission
of ADHD and manic symptoms without worsening of manic symptoms, may add atypical antipsychotic or classic mood stabilizer (lithium or valproate)
Spencer et al. Attention-deficit/hyperactivity disorder with mood disorders. In: Brown TE, ed. Attention-Deficit Disorders and Comorbidities in Children, Adolescents, and Adults. Washington, DC: American Psychiatric Press; 2000:79-124.
ADHD and Mania: Treatment (cont.)
Use diagnosis of intermittent explosive disorder for children with severe aggression but no other symptoms of mania– Atypical antipsychotic, lithium, or
valproate may be added to stimulant for treatment of aggression
Do not use atypical antipsychotic for ODD symptoms alone
Spencer et al. Attention-deficit/hyperactivity disorder with mood disorders. In: Brown TE, ed. Attention-Deficit Disorders and Comorbidities in Children, Adolescents, and Adults. Washington, DC: American Psychiatric Press; 2000:79-124.
Psychosocial Treatment of ADHD and Bipolar Disorder
Limit behavioral contingencies to all positive approaches to reduce explosive outbursts in response to parental limit-setting
Consider Ross Greene’s program for the explosive child Interventions are more likely to be focused on parental coping
with explosive episodes rather than remediation of disruptive behavior
Counsel parents on stress management– ADHD/BPD cases have the highest rates of physical abuse
and PTSD of all ADHD cases Special educational services in BPD/ED classes under IDEA
are likely given severely disruptive behavior
ADHD in Children: Summary Strategies for managing ADHD in children comprise a
combination of pharmacologic and psychosocial interventions, including parent training in behavior management
These strategies can also be effective in managing disorders commonly comorbid with ADHD– Disruptive behavior disorders– Depression and anxiety disorders– Bipolar disorder
Developing a treatment plan for children with ADHD and comorbid disorders requires careful evaluation of the symptoms and severity of each disorder
Guidelines for effective management of pediatric ADHD and associated comorbidities are evolving, based on research findings and clinical experience