Maximizing Treatment SuccessNew Strategies for Treating ADHD and Associated Comorbidities

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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