Treatment of Attention Deficit Hyperactivity Disorder

1. James H. Johnson, Ph.D., ABPP University of Florida Treatment of Attention Deficit Hyperactivity Disorder

2. Treatment of ADHD: Basic Assumptions • ADHD is a chronic disorder and should be managed as such! • Elements of Chronic-condition care: • Educating parents and child regarding the condition • Developing individual treatment plans • Helping coordinate multiple services • Encouraging parents to have contact with parents of other children with chronic conditions. American Academy of Pediatrics (2005)

3. Treatment of ADHD: Basic Assumptions • Treatment of ADHD will be based on a comprehensive assessment of the child’s • core symptoms • comorbid conditions. • areas of impairment • Assessment to rule out “mimics”. • Physical exam • Evidence-based assessment measures (See Pelham, et al, 2005)

4. Treatment of ADHD: Basic Assumptions • Treatments should take into account core symptoms: • hyperactive/impulsive behavior • attention difficulties • The choice of treatment for core symptoms should be evidence-based (Pelham, et al 2008). • In choosing treatments - consideration should be given to treatment effectivenessand potential for side effects, considered within a risk/benefit framework.

5. Treatment of ADHD: Basic Assumptions • Treatment should address areas of impairment. • These areas can include: • academic impairment • social impairment • Impairments in adaptive behavior • impairments in family functioning. • DSM IV places a relatively greater emphasis on core symptoms compared to impairment • This may be a misplaced emphasis (Pelham, et al. 2005)

6. Treatment of ADHD: Basic Assumptions • DSM IV symptoms are not especially good predictors of long-term outcome • Symptoms are not usually the major reason for referral for treatment • In contrast, areas of impairment that are commonly seen in children with ADHD (academic, social, and family functioning are: • predictive of negative long-term outcomes • are common reasons for referral • and can be thought of as target behaviors to be modified to improve current and long term functioning Pelham, et al (2005)

7. Treatment of ADHD: Basic Assumptions • Treatment plans should address relevant diagnosed comorbid conditions and co-occurring difficulties • In some instances comorbid conditions may be more closely related to long term negative outcomes than ADHD itself (e.g. Conduct Disorder) • Comorbid conditions may contribute to various types of impairment over and beyond ADHD core symptoms. • Multimodal treatments addressing core symptoms and comorbidities may be required to address the full range of factors that contributing to impairment.

8. Evidence-base for Treatments of ADHD • The assumption that treatments of children with ADHD should be evidence-based raises the question of • what treatments, • for what difficulties • are supported by empirical research? • These questions have been addressed by a summary of evidence-based treatments for ADHD undertaken by the American Academy of Pediatrics (2006). • This review was based on information provided by three major sources.

9. Evidence-base for Treatments of ADHD – McMaster Review • The first source was a review by the McMaster University Evidence-based practice Center. • Focused on studies of grade school children treated for > 12 weeks. • Emphasis was on the efficacy (and safety) of pharmacological interventions with ADHD • The efficacy of single versus combined treatments of children with ADHD. • Stimulant drugs examined included methylphenidate (MPH), dexadrine (DEX) and pemoline (PEM - Cylert) as well as trycyclic antidepressants.

10. Evidence-base for Treatments of ADHD – McMaster Review • Review included 92 empirical articles reflecting 78 investigations from a pool of 2,405 citations compiled from traditional databases. • Two reviewers independently rated articles to determine the quality of the methodology. • Studies were included in the evidence-based review if they were • randomized controlled trial studies • involved human subjects • published as a full report which included participants with ADHD.

11. Evidence-base for Treatments of ADHD – McMaster Findings • Drug-to-Drug Comparisons • Stimulant drug comparisons documented few, if any, overall differences between MPH, DEX, and PEM (Cylert) • Studies comparing different formulations of the same drugs found no significant effects. • Combined Interventions: • MPH + dexadrine, caffeine, desipramine (a TCA) or haloperidol and a single medication; • behavior or cognitive therapy + stimulant medication compared to single treatment • No evidence that non-pharmacological interventions alone (behavioral intervention) performed as well as the non-pharmacological intervention plus stimulant medication.

12. Evidence-base for Treatments of ADHD – McMaster Findings • Adverse Effects • Across studies the most frequent examples of adverse effects were appetite suppression, sleep disturbances, headaches, motor tics, abdominal pain, irritability , nausea, and fatigue. • Many of thee effects were mild, of short duration, and responsive to dosing or timing adjustments. • There were few if any differences in adverse effects across stimulants (MPH, DEX, PEM).

13. Evidence-base for Treatments of ADHD – McMaster Findings • Conclusions from this review: • Stimulant medication significantly out performs non-pharmacologic interventions in controlling the core symptoms of ADHD. • There was insufficient information to conclude • whether drug combinations outperform stimulant medications alone, or • that non-pharmacologic interventions adds to drug treatment effects.

14. Evidence-base for Treatments of ADHD Canadian Coordinating Office for Health Technology Assessment (1998) • A second source of evidence-based research was reviewed by the Canadian Coordinating Office for Health Technology Assessment (1998) • Reviewed empirical evidence from 195 treatment studies of ADHD published after 1980; • Studies were RCT’s involving parallel group designs or within-subject crossover designs with participants randomly assigned, and involving children 18 or younger. • The review provided findings regarding: • the efficacy of MPH in treating symptoms of ADHD and • the efficacy of combined interventions.

15. Evidence-base for Treatments of ADHD Canadian Coordinating Office for Health Technology Assessment (1998) • Review concluded that: • Evidence consistently supports the efficacy of drug therapy in managing core symptoms of ADHD • No clear differences between MPH, DEX, and PEM. • Psychological/behavioral treatments without medication treatment were not efficacious in managing core symptoms of ADHD. • Combined therapy did not out perform medication alone, at least with core symptoms. • Finding were inconsistent with regard to the value of combining psychological/behavioral therapies with medications - as compared to drug therapies alone.

16. The Multimodal Treatment Study: Background • Until fairly recently there were no well controlled long-term treatment studies in the area of ADHD. • There were many double-blind/placebo controlled studies, designed to assess the effects of various stimulant medications. • Results of these studies most often supported the use of these medications. • However, these studies were typically short duration studies.

17. The Multimodal Treatment Study: Background • While such studies often provided support for the effectiveness of stimulant medications in treating ADHD, they provided little information regarding their long term effectiveness. • Likewise, there were few well-controlled studies on the relative effectiveness of different approaches to treatment of children with ADHD. • Little information was available regarding the long-term effectiveness of combined treatment approaches (e.g., stimulants and psychosocial interventions) in ADHD treatment.

18. The Multimodal Treatment Study: Background • Late 1990’s, NIMH sponsored a large multi-site, 14 - month, investigation of the treatment of ADHD. • Multimodal Treatment Study of Children with ADHD – ("MTA“) • 18 nationally recognized authorities in ADHD. • At different university medical centers and hospitals • Goal: To evaluate the effectiveness of leading treatments for ADHD – notably stimulant drug and behavioral treatment.

19. Multimodal Treatment Study: Background • Research sites included: • New York State Psychiatric Institute at Columbia University, New York, N.Y. • Mount Sinai Medical Center, New York, N.Y. • Duke University Medical Center, Durham, N.C. • University of Pittsburgh, Pittsburgh, PA. • Long Island Jewish Medical Center, New Hyde Park, N.Y. • Montreal Children's Hospital, Montreal, Canada • University of California at Berkeley, CA. • University of California at Irvine, CA.

20. Multimodal Treatment Study: Subject Recruitment • Only children determined to have Combined Type ADHD were included in the MTA study. • Children diagnosed with the hyperactive/impulsive subtype and inattentive subtype were excluded • This decision was made because the combined type is the most frequently diagnosed type of ADHD. • All in all, the study included 579 children ages 7 to 9.9 years •  Approximately 20% were female and approximately the same percentage was African American.

21. The Multimodal Treatment Study: Overview • After participants were identified, were determined to have meet study criteria, & pre-treatment assessment measures were obtained, they were assigned at random to 1 of 4 treatment conditions. • medication alone; • psychosocial/behavioral treatment alone; • Combined treatment; or • routine community care. • Fourteen months later, the participants were again assessed so that the impact of the different treatments could be evaluated.

22. The Multimodal Treatment Study: Assessment Measures • Primary ADHD symptoms- ratings provided by parents and teachers; • Aggressive and oppositional behavior- ratings provided by parents, teachers, and classroom observers; • Internalizing symptoms(e.g. anxiety and sadness) - ratings provided by parents, teachers, and children; • Social skills- ratings provided by parents, teachers, and children; • Parent-child relations- rated by parent; • Academic achievement- assessed by standardized tests

23. The Multimodal Treatment Study: Overview • The MTA Study was designed to answer three basic questions regarding the treatment of ADHD;  • How do long-term treatments with medication and psychosocial (behavioral) interventions compare with one another? • Are there additional benefits of combining these two treatments in treating individual children? • What is the effectiveness of systematic, carefully delivered treatments vs. the way these treatments are usually applied in routine community care?

24. MTA: Medication Alone Group • Children assigned to the Medication Managementcondition received drug treatment only. • Treatment: 28-day, double-blind placebo-controlled trial in which the effects of 4 different doses of short-acting methylphenidate were evaluated. • The doses tested were 5, 10, 15, and 20 mg. • Children received a full dose at breakfast and lunch, and a half-dose in the afternoon. • Parent and teacher ratings of children's behavior oneach dose were compared by a team of experienced clinicians, and the best dose for each child was selected by consensus.

25. MTA: Medication Alone Group • In this double-blind placebo-controlled trial, the child was administered actual medication on some days and a placebo during other days. • Neither the child, the teacher, nor the parent knew when the real medication was being received and when placebo was being given. • This was designed to insure that parent and teacher ratings of the child's behavior were not biased by the knowledge that the child was on medication.

26. MTA: Medication Alone Group • If children did not show a response to methylphenidate in the initial trial, alternate medications were tested (non-double-blind procedures) in the following order until a satisfactory medication/dose was found: • dextroamphetamine (the generic version of dexedrine), • pemoline (the generic version of Cylert), and • imipramine (a tricyclic antidepressant).

27. MTA: Medication Alone Group • A total of 289 participants were initially assigned to receive medication in either the medication only condition or the combined condition. • A total of 256 (88.6%) successfully completed this initial titration period used to select an effective medication. • In the case of the remaining children, parents either • refused to try their child on medication, • there were intolerable side effects, or • parents could not cooperate with the careful titration procedures.

28. MTA: Medication Alone Group • An adequate response with at least one of the doses of methylphenidate was obtained for about 69% of the children completing the initial medication trial - they began treatment on this dose. • Twenty-six children  who did not respond to methylphenidate were found to do well on dextroamphetamine and began on this medication. • A final 32 did not begin on any medication because they had such a strong placebo response that no clear benefits of medication could be demonstrated.

29. MTA: Medication Alone Group • Monthly visits were scheduled during which time the provider for the child reviewed information about the child's behavior over the past month that had been provided by parent and teacher. • After reviewing this information, any needed dosage adjustments were made using predetermined guidelines. • Adjustments that involved increases or decreases of more than 10 mg/dose needed to be approved by a cross-site panel of experts.

30. MTA: Medication Alone Group • At the end of the study, some 14 months later, approximately 74% of participants in the medication or combined treatment groups were being successfully maintained on methylphenidate. • 10% were being successfully maintained on dextroamphetamine. • 1% were being successfully maintained on Cylert. • Only two children were on any other type of medication.

31. MTA: Medication Alone Group • Side effects were monitored monthly for all children who were on medication. • Over 85% of the sample reported either no or mild side effects.

32. MTA: Medication Alone Group • It is important to note how different this approach to pharmacological treatment was from what often occurs in community treatment. • The primary differences are • the use of a double-blind trial to establish the best initial dose and type of medication for each child; and, • regular follow-up visits to evaluate ongoing medication effectiveness based on parent and teacher reports • systematic adjustments made as needed.

33. MTA: Medication Alone Group • Almost all children were effectively managed on one of the standard stimulants. • None required a combination of medications to effectively manage their ADHD symptoms. • This suggests that combination of mediations is rarely needed to treat ADHD, if a careful procedure is used to test out the different types of stimulants that are available. 

34. MTA: Behavioral Treatment • Behavioral treatment included 1) parent training, 2) child-focused treatment, and a 3)school-based intervention program. • Parent training involved a total of 27 group sessions and 8 individual sessions per family. • The focus was on teaching parents specific behavioral strategies to deal with the challenges that children with ADHD often present.

35. MTA: Behavioral Treatment • The Child-focused Treatmentwas a summer treatment program that children attended for 8 weeks, 5 days a week, during the summer. • This program employed intensive behavioral interventions that were administered by counselors/aides who were supervised by the therapists conducting the parent training. • The basic model was one in which children were able to earn various rewards based on their ability to follow well-defined rules and meet certain behavioral expectations. • Social skills training and specialized academic instruction was also provided.

36. MTA: Behavioral Treatment • The School-based Treatment had 2 components: • 10 to 16 sessions of biweekly teacher consultation focused on classroom behavior management strategies, and 12 weeks of a part-time aide who worked directly in the classroom with the child. • During the school year, a Daily Report Card was used to link the child's behavior at school to consequences at home. • The Daily Report Card was a 1-page teacher-completed rating of the child's success on specific behaviors. • This was brought home daily by the child to be reviewed by parents with rewards for a successful day provided as indicated.

37. MTA: Behavioral Treatment • Consistent with what occurs in actual clinical practice, the family and child's involvement in behavioral treatment was gradually tapered over the 14 month period (Note: BT stopped but meds not – implications for findings??) • In most cases, contact had been reduced to once monthly or stopped altogether by the end of this period. • It can be noted that the behavioral treatment received here, reflects state-of-the-art practice that would be difficult for most children to get. • Thus, one would assume that the benefits of behavioral treatment seen here would likely be much greater than which would typically be obtained.

38. MTA: Combined Treatment • Children in the combined treatment group received all of the treatments received by children in the Medication and Behavioral Treatment conditions. • Consistent with prior studies, by the end of the study, children in the combined group were being maintained on lower daily doses of methylphenidate than children who received medication alone. • Here, average doses were 31.2 mg/day for the Combined group and 37.7 mg/day for the Medication Only group.

39. MTA: Community Treatment • As it would clearly be unethical to assign children with ADHD to a no-treatment control group for 14 months, some children were randomly assigned to a group that received "community care". • In this condition, following the child's diagnosis of ADHD, parents were provided with a list of community mental health resources and made whatever treatment arrangements they preferred for their child.

40. MTA: Community Treatment • Most of the 97 children in this group (over 2/3) received medication from their own provider sometime during the 14 months. • Several things are interesting about the medication these children received compared to children who received medication as part of the study. • Community care children received less medication. • For those treated with methylphenidate, the average daily dose was 22.6 mg/day compared to the average daily doses of 31.2 mg and 37.7 mg for children in the other groups receiving medication. • Community care children received an average of 2.3 doses per day compared to 3 times/day dosing for children in the study groups.

41. MTA: Community Treatment • None of the children receiving medication in the study groups were maintained on clonidine or a combination of medications • 4 children seen by community physicians were treated with clonidine and 10 children received more than one medication. • Thus, physicians in the community were in some ways more conservative in their use of medication, using lower doses of methylphenidate. • But less conservative, being more likely to use medications other than the stimulants for treating ADHD.

42. MTA: Research Questions • As noted earlier, the MTA study was designed to address 3 fundamental questions about ADHD treatment: • How do long-term medication and behavioral treatments compare with one another in treatment effectiveness in children with ADHD? • Are there additional benefits when these two treatments are used together? • What is the effectiveness of systematic, carefully delivered treatments vs. routine community care in the management of ADHD?

43. MTA: Overall Findings • Children in all groups(i.e. medication only, behavioral treatment only, combined treatment, and treatment in the community) showed significant reductions in their level of symptoms over time in most areas. • Even though some treatments were superior to others in certain domains, even children receiving the "least effective" treatment showed improvements. • Thus, these data should not be interpreted in a framework of "what worked" and "what did not work". • Rather, it is a matter of what was the most effective among treatments that showed positive effects.

44. Long-term Medication vs Behavioral Treatment • For both parent and teacher ratings of ADHDcore symptoms,medication management alone was clearly superior to behavioral treatment alone. • Medication management and behavioral treatment did not typically differ significantly on other outcome measures. • While medication was found to be superior to behavioral treatment in managing core symptoms, these findings did not hold for other problems such as oppositional behavior, peer relations, internalizing behavior and academic achievement.

45. Combined vs Single Treatments • Combined Treatment & Medication Management treatment did not differ significantly on any of the 6 domains assessed in this study. • This suggests that for most children with ADHD, adding behavioral intervention on top of well-conducted medication management is not likely to yield substantial incremental gains. 

46. Combined vs Single Treatments • However, when one looks at the rank ordering on different outcomes for children in the different groups, children in the combined treatment group did best on 12 of 19 outcome measures. • Those in the Medication Management group were best on only 4. • In addition, when the individual outcome measures were combined into composite measures, or when children's outcomes were grouped into “Excellent Response” vs. “Less Dramatic Response” categories,  children receiving combined treatment did modestly, but significantly, better.

47. Combined vs Single Treatments • Compared to Behavioral Treatment alone, Combined Treatment was found to be superior; • on parent and teacher ratings of ADHD core symptoms, • on parent ratings of aggressive/oppositional behavior, • on parent ratings of children's internalizing symptoms, • and on results of the standardized reading assessment. • Thus, adding medication to the treatment of a child already receiving behavioral intervention is likely to yield additional benefits for most children.

48. MTA Treatments vs Community Care • Both Combined Treatment and Medication Treatment were superior to community care for parent and teacher reports of ADHD core symptoms, • Behavioral treatment was not. • In general, parents and teachers tended to report a decline of approximately 50% in inattentive and hyperactive/impulsive symptoms for children in the medication and combined treatment groups. • For children receiving community care, the declines reported were in the 25% range. • These were comparable to those reported for children receiving behavioral treatment.

49. MTA Treatments vs Community Care • In the non-ADHD domains, with children displaying oppositional behavior, internalizing symptoms, social skills deficits and reading problems, Combined Treatment was always superior to Community Based Treatment. • Here there were particularly dramatic differences in parent reports of oppositional and aggressive behavior.

50. MTA Treatments vs Community Care • These data indicate that, although children treated in the community made modest gains, those receiving medication treatment in the MTA study (either alone or in combination with behavioral treatment) did significantly better. • This was especially true for children receiving the combined treatments.