Symptomatic Improvement in Children With ADHD Treated With Long-Term Methylphenidate and Multimodal...

S P E C I A L S E C T I O N

Symptomatic Improvement in Children With ADHDTreated With Long-Term Methylphenidate and

Multimodal Psychosocial TreatmentHOWARD ABIKOFF, PH.D., LILY HECHTMAN, M.D., RACHEL G. KLEIN, PH.D., GABRIELLE WEISS, M.D.,

KAREN FLEISS, PSY.D., JOY ETCOVITCH, M.A., LORNE COUSINS, PH.D., BRIAN GREENFIELD, M.D.,

DIANE MARTIN, M.A., AND SIMCHA POLLACK, PH.D.

ABSTRACT

Objective: To test the hypotheses that in children with attention-deficit/hyperactivity disorder (ADHD) (1) symptoms of

ADHD, oppositional defiant disorder, and overall functioning are significantly improved by methylphenidate combined

with intensive multimodal psychosocial treatment compared with methylphenidate alone and with methylphenidate plus

attention control and (2) more children receiving combined treatment can be taken off methylphenidate. Method: One

hundred three children with ADHD (ages 7–9), free of conduct and learning disorders, who responded to short-term

methylphenidate were randomized for 2 years to (1) methylphenidate alone; (2) methylphenidate plus psychosocial

treatment that included parent training and counseling, social skills training, psychotherapy, and academic assistance,

or (3) methylphenidate plus attention psychosocial control treatment. Assessments included parent, teacher, and psy-

chiatrist ratings, and observations in academic and gym classes. Results: Combination treatment did not lead to

superior functioning and did not facilitate methylphenidate discontinuation. Significant improvement occurred across all

treatments and continued over 2 years. Conclusions: In stimulant-responsive children with ADHD, there is no support

for adding ambitious long-term psychosocial intervention to improve ADHD and oppositional defiant disorder symptoms.

Significant benefits from methylphenidate were stable over 2 years. J. Am. Acad. Child Adolesc. Psychiatry,

2004;43(7):802–811. Key Words: attention-deficit/hyperactivity disorder, oppositional defiant disorder, school obser-

vations, long-term stimulant treatment, psychosocial treatment.

The merits of stimulant medication in the treatment ofattention-deficit/hyperactivity disorder (ADHD) havelong been established. In addition to improving cardi-nal symptoms, short-term stimulants also enhance aca-demic productivity and accuracy (Carlson et al., 1992;Douglas et al., 1986) and teacher, parent, and peerinteractions (Granger et al., 1996) as well as improvingantisocial behavior (Hinshaw, 1991; Hinshaw et al.,1992; Klein et al., 1997). However, improvement isnot maintained when medication is discontinued, andthe lack of long-term efficacy has been a concern (Abi-koff and Gittelman, 1985a; Gittelman-Klein et al.,1976). Although there may be long-term benefits ofearly stimulant treatment (Paternite et al., 1999), dif-ficulties often continue through adolescence and early

Accepted January 30, 2004.Drs. Abikoff, Klein, and Fleiss are with the NYU Child Study Center, New

York University School of Medicine, New York; Drs. Hechtman and Greenfieldare with the Department of Psychiatry, McGill University and MontrealChildren’s Hospital, Montreal, Quebec, Canada; Ms. Etcovitch is withMontreal Children’s Hospital, Dr. Weiss is with the University of BritishColumbia and British Columbia Children’s and Women’s Hospital, Vancouver,British Columbia,Canada; Dr. Cousins is with McGill University and theSummit School, Montreal, Quebec, Canada, Ms. Martin is with Nassau Com-munity College, Garden City, NY; and Dr. Pollack is with the Department ofComputer Information Systems and Decision Science, St. John’s University,Queens, NY.

The study was supported NIMH grants RO1 MH44848 (H.A.) and RO1MH44842 (L.H.).

Correspondence to Dr. Abikoff, NYU Child Study Center, 215 LexingtonAvenue, 13th Floor, New York, NY 10016; e-mail: [email protected]/04/4307–0802©2004 by the American Academy of Child

and Adolescent Psychiatry.DOI: 10.1097/01.chi.0000128791.10014.ac

J . AM. ACAD. CHILD ADOLESC. PSYCHIATRY, 43:7, JULY 2004802

adulthood (Barkley, 1990; Gittelman et al., 1985;Mannuzza et al., 1993; Weiss and Hechtman, 1993).Symptomatic persistence adversely affects multiplefunctions including academic and occupational attain-ment and interpersonal relationships. Notably, the per-sistence of ADHD is a significant risk factor for laterantisocial and substance use disorders (Gittelman et al.,1985; Mannuzza et al., 1993).In the hope of reversing these patterns, psychosocial

treatments have been developed to have an effect ondysfunctions not regularly normalized by stimulants(Hinshaw et al., 2002). The current study providessystematic information of the incremental benefit ofcombining stimulant and psychosocial treatments foran extended period of time. It evaluates the adjunctiveefficacy of intensive multimodal psychosocial treatment(MPT) in children with ADHD treated with methyl-phenidate. The study tests whether 1 year of combinedmethylphenidate and MPT confers significantly betterfunction in social, behavioral, emotional, and academicdomains and better parental functioning comparedwith treatment with methylphenidate alone in childrenwith ADHD and whether gains are maintained over asecond year.This paper reports treatment effects on ADHD and

oppositional defiant disorder (ODD) symptoms andchildren’s overall functioning. Other treatment out-comes, i.e., children’s social and academic perfor-mance, are communicated in Abikoff et al. (2004) andHechtman et al. (2004a,b).The following hypotheses are addressed: Over a

1-year period (year I), (1) there is significant advantageto adding a multimodal psychosocial intervention tomethylphenidate treatment and (2) after year I, stimu-lant treatment can be withdrawn more successfully inthe combination treatment than methylphenidatealone group. Additionally, we predicted that the supe-riority of the combination over methylphenidate alonewould result from the specific content of the psycho-social treatment and not from its nonspecific features.Therefore, it was hypothesized that the combination ofmethylphenidate and MPT would be superior to meth-ylphenidate plus attention control psychosocial treat-ment (ACT).Finally, it was hypothesized that relative advantages

associated with 1 year of combined treatment wouldpersist. Hence, we predicted superiority of combinedtreatment during a second year (year II) of mainte-

nance treatment. We hypothesized that treatmentgroups would demonstrate different patterns of func-tion over time. Specifically, significant incremental im-provement during year II was predicted with combinedtreatment, relative to methylphenidate alone, andmethylphenidate plus an attention control. In the lattertwo groups, a flattening of treatment effects was pre-dicted.

METHOD

Details of the design and its rationale are presented in Klein et al.(2004). Briefly, the study was conducted at two large medical cen-ters (New York and Montreal) between 1990 and 1995. Medica-tion-free boys and girls, 7.0 to 9.9 years of age (mean 8.2 ± 0.8),93% male, mostly white, without a diagnosis of conduct or learningdisorder, met diagnostic and severity criteria for ADHD (n = 103).Because treatment included 2 years of methylphenidate, childrenhad to exhibit meaningful improvement in a 5-week open trial ofmethylphenidate.

Treatments

Children were randomly assigned for 2 years to (1) methylphe-nidate alone (M) (n = 34), (2) methylphenidate plus MPT (M +MPT) (n = 34), or (3) methylphenidate plus ACT (M + ACT) (n =35).

Measures

Parent Ratings. Parents completed the Conners Parent RatingScale (Goyette et al., 1978), whose Hyperkinesis Index was anoutcome measure; and the Home Situations Questionnaire (Bark-ley, 1990). It yields the number of problematic situations and theirseverity.

Teacher Ratings. Teachers completed the Hyperactivity and Con-duct Problem Factors of the Conners Teacher Rating Scale (Goy-ette et al., 1978) and the School Situations Questionnaire (Barkley,1990). Like the Home Situations Questionnaire, the School Situ-ations Questionnaire yields the number of problematic situationsand a severity score. Both scales have adequate norms, reliability,and validity and demonstrate sensitivity to treatment effects (Bar-kley, 1990).

Psychiatric Ratings. Based on clinical interviews, child psychia-trists completed a DSM-III R checklist for ADHD, ODD, andconduct disorder (CD) symptoms, and a Children’s Global Assess-ment Scale (C-GAS), a measure of functional competence withgood interrater and test–retest reliability (Shaffer et al., 1985).

School Observations. Because the treatment blind could not beprotected, objective assessments of classroom behavior providedindependent assessment of treatment effects. Children were ob-served twice at each assessment in academic and gym classes. TheClassroom Observation Code (Abikoff et al., 1980), which differ-entiates children with ADHD from normal children and is sensitiveto treatment effects (Abikoff and Gittelman, 1985b), was usedduring academic classes. Categories of interference, off task (mea-sures of impulsivity and sustained inattention), and gross motor–allwere combined into an ADHD composite used previously as anoutcome measure (Klein and Abikoff, 1997).

TREATMENT EFFECTS ON ADHD SYMPTOMS

J. AM. ACAD. CHILD ADOLESC. PSYCHIATRY, 43:7, JULY 2004 803

After gym observations, observers completed the CTRS Hyper-kinesis Index and IOWA CTRS (Loney and Milich, 1982), bothwith demonstrated sensitivity to treatment effects (Abikoff and Git-telman, 1984) (behaviors coded in gym are presented elsewhere[Abikoff et al., 2004]).Trained observers rated two children: the study child and an

“average” classmate of unremarkable comportment identified byteachers. Whenever study children changed classes, another peerwas observed. (Because comparison children were anonymous andwere unaware of being observed, parental consent was not requiredby the institutional review board or schools.)Children were evaluated twice before experimental treatment:

once at pretreatment and at the end of the 5-week open methyl-phenidate trial (medication baseline, when only classroom observa-tions were repeated). Assessments were obtained after 6, 12, 18, and24 study months to identify the timing of hypothesized treatmentdifferences.

Data Analyses

There were no significant group × site or group × site × timeinteractions. Repeated measures over time for dependent variableswere modeled as a mixed-model analysis of covariance implementedin Proc Mixed (SAS v8.1, Cary, NC), controlling for socioeco-nomic status. Empirical data exploration indicated that an unstruc-tured covariance model best fit the data. Model parameter estimatesand their standard errors were generated through maximum likeli-hood functions.Differential treatment effects in year I compared status at pre-

treatment and at medication baseline with status at 6 and 12months. For hypothesized differential maintenance effects, ProcMixed analyses compared the 12-, 18-, and 24-month data fordifferential patterns of change. The above tests yield main effects forgroup and time and group × time interaction effects. The latter arethe main interest of the study.To control for multiple tests, α was set at p < .01, two tailed;

p values between .05 and .01 are noted as trends in the tables. Fulltables with F values are available from the authors.

RESULTS

Children were in the clinical range on all measuresobtained from parents, teachers, classroom observers,and clinicians (Tables 1–6). For example, on theteacher hyperactivity factor, children obtained a meanscore of 2.4 (range 0–3). In school, children were ratedas problematic in nine of 12 situations and on averagehad 11 of 13 ADHD symptoms. The C-GAS mean(<55) indicates impaired overall function. Observedrates of disruptive and inattentive behavior were mark-edly elevated.

Year I Treatment Effects From Pretreatment

These analyses test the hypothesis that, over year I,M + MPT led to superior function compared with Malone and M + ACT, relative to function before treat-ment.

Parent and Teacher Ratings. No significant groupdifferences or group × time interactions were obtainedfor any parent or teacher ratings (Tables 1 and 2).

Psychiatric Ratings. No differential treatment effectwas obtained for ADHD or ODD symptoms at homeor school (Table 3) or for rates of diagnosed ADHD,ODD, and CD (Table 4). Overall, only 12.1% con-tinued to meet DSM-III-R criteria for ADHD by theend of year I.Before treatment, 53% of the children received a

diagnosis of ODD. As shown in Table 4, the rate ofODD decreased significantly in all groups without dif-ferential treatment effects.

TABLE 1Conners Parent Rating Scale and Home Situations Questionnaire

Measure

Treatment Group

M M + MPT M + ACT

Mean SD Mean SD Mean SD

CPRSHyperkinesis Indexa,c

Pretreatment 1.9 0.5 1.9 0.5 1.9 0.56 mo 1.2 0.5 1.2 0.6 1.1 0.512 mo 1.1 0.6 1.2 0.6 1.0 0.618 mo 0.9 0.6 1.0 0.5 1.0 0.624 mo 1.0 0.6 0.9 0.5 0.8 0.4

HSQSituations (N )a,b,d


Severitya,e


Note: CPRS = Conners Parent Rating Scale (range 0–3); M =methylphenidate; MPT = multimodal psychosocial treatment;ACT = attention control psychosocial treatment; HSQ = HomeSituations Questionnaire (situations, range 1–16; severity, range0–9). Group × time interactions: none significant.

a Time effects in year I: pretreatment versus 6 and 12 months,p < .001.

b Time effects in year I: 6 versus 12 months, p < .01.c Time effects in year II: 12 versus 18 months, p < .03; 12 versus

24 months, p < .01.d Time effects in year II: 12 versus 18 months, p < .04.e Time effects in year II: 12 versus 24 months, p < .02.

ABIKOFF ET AL.


Clinical assessments of overall functioning on theC-GAS also failed to differ across treatments(Table 4).

Classroom Observations. Interobserver agreement wasconducted in approximately 15% of observations. Eachsite’s trainer functioned as the “standard.” Phi coeffi-cients of interval scores for categories ranged from 0.83to 0.92.Impulsive, inattentive, and hyperactive behaviors

(interference, off task, and gross motor) showed nosignificant advantage of M + MPT. The compositemeasure of ADHD also failed to reveal significanttreatment differences (Table 5).

Table 6 presents observer ratings on the IOWACTRS for subjects and normal peers. Inattention andoppositional behavior in structured classes and gymshowed significant improvement in all groups (p = .01)without advantage for combination treatment.

Year I Treatment Effects From Medication Baseline.Classroom observations, which were the only measuresof ADHD repeated after the 5-week clinical methyl-phenidate trial, showed no differential treatment effectcompared with functioning after brief methylphenidatetreatment. As shown in Tables 5 and 6, scales com-pleted by observers showed no relative advantage forchildren on the combination treatment.

TABLE 2Conners Teacher Rating Scale and School

Situations Questionnaire

Measure

Treatment Group

M M + MPT M + ACT


CTRS factorHyperactivitya


Conduct problemsb


SSQa

SituationsPretreatment 9.2 2.9 9.5 2.7 10.1 1.76 mo 5.1 4.0 5.7 4.1 6.4 4.012 mo 4.6 4.0 6.1 4.5 5.5 4.318 mo 5.0 4.2 5.8 3.4 5.2 4.624 mo 6.2 3.8 5.1 4.2 5.3 3.8

Severitya


Note: CTRS = Conners Teacher Rating Scale (range 0–3); SSQ =School Situations Questionnaire (situations, range 1–12; severity,range 0–9). Group × time interactions: none significant.

a Pretreatment versus 6 and 12 months, p < .001.b Pretreatment versus 6 and 12 months, p < .000.

TABLE 3Mean Number of ADHD and ODD Symptoms

Symptoms

Treatment Group

M M + MPT M + ACT


ADHDSchoola,b


Homea,b


ODDSchoola,b,c


Homea,b,c


Note: ADHD = attention-deficit/hyperactivity disorder; ODD,oppositional defiant disorder. Group × time interactions: none sig-nificant.

a Pretreatment versus 6 and 12 months, p < .001.b 6 versus 12 months, p < .01–.001.c Trend in group × time effect in year II: M + MPT versus M at

18 months, p < .01.



Placebo Substitution at the End of Year I

Relapse was defined as fulfilling diagnostic criteriafor ADHD, being rated “worse” by two of three raters,and a 25% increase on the CTRS hyperactivity factor.We tested for differential survival to single-blind pla-cebo substitution as well as time maintained on pla-cebo.All children (100%) relapsed when switched to pla-

cebo and were placed back on methylphenidate regard-less of the treatment received during the previous year.The mean number of days to reinstitution of methyl-phenidate for each group was as follows: M alone, 8.6 ±5.4 (range 1–22); M + MPT, 17.1 ± 16.2 (range5–62); and M + ACT, 11.7 ± 12.8 (range 1–69). A

trend in favor of M + MPT over M treatment wasfound (p < .04). No other difference occurred.

Year II Treatment Effects

Year I findings fail to support the superiority of thecombination of M + MPT over M alone. In light ofthese results, there is little relevance to testing the hy-pothesis that year I advantages persist during a secondyear of maintenance treatment. Nonetheless, year IIoutcomes inform on the hypothesis that M + MPT issignificantly superior to other treatments during main-tenance treatment.

Parent and Teacher Ratings. None of the parent orteacher questionnaires yielded significant group or in-teraction effects, failing to support a differential clinicaltrajectory across the three treatments during year II(Tables 1 and 2).

Psychiatric Ratings. Psychiatrists’ ratings of ADHDsymptoms in school and at home did not differentiatethe treatment groups (Table 3). With regard to ODDsymptoms, significantly fewer occurred at 18 monthsin the M + MPT group than the M alone group (p <.01) (Table 3) but not at other time points. Rates ofdiagnosed ADHD, ODD, and CD did not differacross treatments (overall, 11.1%, 15.8%, and 2.5%,respectively). Similarly, treatment groups did not differsignificantly in global functioning during year II.

Classroom Observations. Classroom behaviors duringyear II yielded no significant group or interaction ef-fects (Tables 5 and 6).

Time Effects

Main effects for time, which reflect change over timeregardless of treatment condition, were examined toprovide heuristic information regarding the possible at-tenuation of effects with long-term methylphenidatetreatment. Time effects during year I, relative to pre-treatment, and after brief methylphenidate treatmentare summarized as well as time effects during year II.

Year I Time Effects Relative to Pretreatment. Signifi-cant time effects were obtained on all measures, show-ing improvement at 6 and 12 months. Moreover,children continued to improve between 6 and 12months of treatment on parent ratings of problematicsituations (Table 1) and on symptoms of ADHD andODD at home and school (Table 2) but not on teacherratings (Table 3).

TABLE 4Psychiatric Ratings of ADHD, ODD, CD, and Overall Function

Treatment Group

M M + MPT M + ACT

Na % Na % Na %

ADHDb

Pretreatment 34/34 100 34/34 100 35/35 1006 mo 9/32 28.1 6/31 19.4 5/31 16.112 mo 5/30 16.7 4/30 13.3 2/31 6.518 mo 6/25 24.0 3/29 10.3 4/38 14.324 mo 5/25 20.0 1/29 3.4 3/27 11.1

ODDb

Pretreatment 16/34 47.1 18/30 58.1 19/35 54.36 mo 8/32 25.0 5/31 16.1 5/31 16.112 mo 7/30 23.3 4/30 13.3 2/31 6.518 mo 6/24 20.8 3/27 11.1 3/28 10.724 mo 5/26 17.2 4/29 13.8 4/27 14.8

CDb

Pretreatment 0/34 0 0 0/35 06 mo 0/32 0 2/31 6.5 1/31 3.212 mo 0/30 0 0/30 0 1/31 3.218 mo 1/24 4.2 0/27 0 0/22 024 mo 1/24 4.0 1/29 3.4 0/27 0

C-GASb Mean SD Mean SD Mean SD


Note: ADHD = attention-deficit/hyperactivity disorder; ODD =oppositional defiant disorder; CD = conduct disorder; C-GAS =Children’s Global Assessment Scale.

a Number diagnosed/total number in group. Missing data anddropouts account for varying numbers.

b No contrast significant.

ABIKOFF ET AL.


Year I Time Effects Relative to Medication Baseline.Relative to medication baseline, school observationsdid not reflect reduced rates of ADHD behaviors(Table 5). However, all groups improved on theinattention/overactivity ratings in academic (p < .01)and gym classes (p < .001) (Table 6).

Year II Time Effects. All groups maintained treat-ment gains during year II, with some further improve-ment over time. Parents reported lower scores on theHyperkinesis Index (p < .01) and trends on HomeSituations Questionnaire problematic situations (p <.04) and severity (p < .02) (Table 1).

Teacher ratings, psychiatrist ratings of ADHD andODD symptoms, and observer ratings did not showsignificant time effects between 12 and 24 months.

DISCUSSION

This dual-site study represents an effort to provide abroad psychosocial treatment program aimed at opti-mizing multiple aspects of function in children withADHD treated with methylphenidate. Measures ofADHD and related behavior problems did not indicateany meaningful advantage for the combination of

TABLE 5Mean Rates of Observed ADHD Behaviors in Academic Classes

Observed Behavior

Treatment Group

Normal M M + MPT M + ACT

Mean SD Mean SD Mean SD Mean SD

Interferencea

Pretreatment 8.0 5.9 16.3 11.1 15.8 8.1 17.4 7.8Medication baseline — — 8.1 5.7 9.2 5.9 9.0 6.06 mo 5.9 4.6 9.0 7.7 7.1 6.6 6.7 5.812 mo 6.1 5.1 7.4 5.6 8.2 8.2 6.3 6.118 mo 5.6 5.3 6.8 7.1 6.7 6.9 4.3 4.324 mo 4.5 4.3 6.6 7.5 7.6 7.4 5.1 5.4

Off taska


Gross motora,b


ADHD Compositea,c,d


Note: ADHD = attention-deficit/hyperactivity. Group × time interactions: none significant.a Time effects in year I: pretreatment versus 6 and 12 months, p < .001.b Trend in group × time interaction: M + MPT versus M + ACT at 6 months, p < .02; M + MPT versus M at 6 months, p < .003.c Trend for time effects in year II: 12 versus 18 months, p < .05.d Time effects in normals: Pretreatment to 12 months, p < .02; 12 to 24 months, p = .12.



methylphenidate and MPT over methylphenidatealone, and methylphenidate could not be discontinuedmore successfully in children who received the combi-nation treatment.Negative findings were obtained in spite of efforts to

disprove the null hypothesis, i.e., to find treatmentdifferences. Thus, multiple sources of information wereobtained. The statistical analytic strategy reflectsgreater concern for type II errors (β, power) compared

with the conventional, conservative strategy of concernfor type I errors (α, significance). We conducted mul-tiple analytic methods including repeated measures,heuristic random regression, and mixed models analysisof variance. In addition, the facts that parents, teachers,and psychiatrists were not blind to treatment and thatparents were involved in treatment delivery shouldhave biased the results in favor of psychosocial treat-ment. The MTA Cooperative Group study is the only

TABLE 6IOWA CTRS Ratings in Academic and Gym Classes

Setting and Factor

Treatment Group

Normal M M + MPT M + ACT

Mean SD Mean SD Mean SD Mean SD

ClassroomInattention/overactivitya,b,c

Pretreatment 0.3 0.3 1.1 0.6 0.9 0.6 1.2 0.6Medication baseline 0.4 0.4 0.6 0.5 0.6 0.5 0.5 0.56 mo 0.2 0.2 0.6 0.6 0.3 0.3 0.4 0.412 mo 0.3 0.3 0.4 0.4 0.4 0.4 0.3 0.118 mo 0.2 0.3 0.3 0.3 0.2 0.2 0.3 0.324 mo 0.2 0.3 0.4 0.5 0.5 0.6 0.3 0.5

Oppositional/defianta,d


GymInattention/overactivitya,b,e

Pretreament 0.2 0.3 0.7 0.5 0.6 0.4 0.7 0.5Medication baseline 0.2 0.2 0.4 0.4 0.3 0.3 0.3 0.36 mo 0.2 0.2 0.4 0.6 0.3 0.3 0.2 0.312 mo 0.2 0.3 0.1 0.2 0.2 0.3 0.2 0.318 mo 0.2 0.3 0.2 0.2 0.2 0.3 0.1 0.124 mo 0.1 0.2 0.2 0.5 0.2 0.2 0.2 0.3

Oppositional/defianta


Note: IOWA CTRS = Conners Teacher Rating Scale (range 0–3).a Time effects in year I: pretreatment versus 6 and 12 months, p < .02–.001.b Medication baseline versus 12 months, p < .01–.001.c Significant time effects in year II: 18 versus 24 months, p < .012.d Trends in group × time interaction: M + MPT versus M at 6 months and M + ACT versus M at 6 months, p < .02; M + ACT versus

M at 12 months, p = .01.e M + ACT < M at 6 months, p < .03.

ABIKOFF ET AL.


other systematic investigation that has implemented anintensive psychosocial intervention (MTA CooperativeGroup, 1999). Unlike theMTA (multimodal treatmentof ADHD) study, we did not assess the role of psycho-social treatment alone because more than three treat-ment groups would have limited power, and ourprevious findings indicated that psychosocial treatmentwas not competitive with stimulant treatment (Kleinand Abikoff, 1997). Indeed, in the MTA study, psy-chosocial treatment was significantly inferior to medi-cation, even though a sizable proportion of childrenrandomized to psychosocial treatment were placed onmedication during the course of the study and eventhough treatment evaluators (parents and teachers)were actively involved in the delivery of psychosocialtreatment. Unlike the MTA study, we did not imple-ment active intervention in the classroom or an inten-sive therapeutic summer program. Finally, our studylasted 24 months, in contrast to 14-month MTA study.In spite of these methodological differences, resultsfrom the two studies are strikingly similar. Both failedto document that MPT provides benefits above thoseobtained with methylphenidate alone for ADHD andODD dimensional ratings (MTA Cooperative Group,1999). Moreover, an additional year of maintenancetreatment failed to produce differential benefits in chil-dren who received combination treatment comparedwith those treated solely with methylphenidate. How-ever, treatment gains from year I were maintained dur-ing year II.We considered possible reasons for the lack of ad-

junctive efficacy of psychosocial treatment. Perhaps ifattendance at psychosocial treatment sessions werepoor, as has occurred in other studies (Firestone et al.,1981; Schachar et al., 1997), many might have receivedinadequate treatment. This explanation seems unlikelybecause families attended at least 75% of all treatmentsessions.Perhaps treatment fidelity was compromised and

psychosocial treatments were not delivered as intended.Ongoing supervision and audiotape reviews throughoutthe course of the study protected against this possibility.Perhaps medication compliance differed among

treatment groups, thereby affecting treatment out-come. However, results of methylphenidate checks donot support this explanation (Klein et al., 2004).We considered the possibility that multimodal treat-

ment would be especially effective in ODD children

with ADHD and reanalyzed year I results with ODDdiagnosis entered as another factor. Children with andwithout ODD responded similarly and positively in allthree treatment groups. Finally, a ceiling effect withshort-term methylphenidate might have been reached,precluding accrued benefits from the combinationtreatment over medication alone. This possibility ap-pears unlikely because time effects were found, indicat-ing continued improvement with methylphenidate.The hope was that the combination treatment would

reduce the incidence of CD. This was not the case.Relatively few children in the study (4.7%) developedCD by ages 9 to 12, when such onsets are not unusualin boys with ADHD and ODD (Lahey et al., 2000). Aswith other time effects, it is not clear whether methyl-phenidate treatment, the common denominator acrosstreatments, was instrumental in reducing the develop-ment of full-fledged CD. However, what is clear is thatoppositional symptoms, significant risk factors for CD,were markedly reduced.There was a slight advantage for children who re-

ceived combination treatment insofar as they remainedon placebo 8.5 days longer than those on methylphe-nidate alone after 1 year. However, this difference fallsshort of meaningful clinical advantage.The absence of an untreated control group precludes

unambiguous conclusions regarding improvementsover time because maturational effects cannot be ruledout. In spite of their ambiguous implications, time ef-fects in children with ADHD point to functions thatmight continue to improve with methylphenidatetreatment. During year I, children had significant re-ductions in ODD and ADHD symptoms, which weremaintained during year II. Furthermore, the severity ofADHD continued to improve over year II. Such im-provements over time are all relatively small, and theirclinical significance is limited. Importantly, findings donot indicate a loss of treatment efficacy over 2 years ofmethylphenidate treatment. This finding argues againstconcerns that stimulant effects attenuate with long-term use (Cantwell, 1975; Kupietz et al., 1988). To ourknowledge, this 2-year study is one of the longest todemonstrate the long-term efficacy of stimulant treat-ment in children with ADHD.

Limitations

As in all clinical trials, the generalizability of findingsis defined in part by inclusion and exclusion criteria.



Results are relevant to young, mostly white childrenwith ADHD who demonstrate some meaningful ben-efit with short-term treatment. However, it wouldseem pointless, if not unethical, to administer long-term medication to children who did not demonstrateshort-term benefit. Divergent results might occur inother clinical subgroups, such as groups with low so-cioeconomic status, greater disadvantage, and comor-bidity.Findings do not apply to children with ADHD who

also have CD, although 30% of the children had symp-toms of CD and 53% had ODD (Klein et al., 2004).Virtually identical results were obtained in the MTAstudy, which had broader inclusion criteria. Because ofthe ambitious goal of altering the long-term course ofADHD, both the MTA study and the current studywere restricted to 7- to 9-year-old children. Whethersimilarly negative findings would apply to youngerchildren is unknown. So far, studies of psychosocialinterventions in young children have not includedmedication comparisons (Barkley et al., 2000; Sonuga-Barke et al., 2001).Our study obtained daily report cards from teachers

but did not implement a school-based treatment. Tothe extent that such interventions are crucial, we mayhave missed efficacy for psychosocial treatment. Thisprobability seems unlikely because the MTA study ob-tained similarly negative results in spite of providingschool-based treatment.

Clinical Implications

Findings document that initial benefits of methyl-phenidate do not diminish over time; rather, incremen-tal gains appear likely with extended stimulanttreatment. The study does not support the expectationthat stimulant-treated children with ADHD shouldroutinely receive psychosocial treatment to reduceADHD, ODD, and CD symptoms.

Disclosure: Dr. Abikoff is a member of the ADHD Advisory Board anda principal investigator in clinical trials, Shire Pharmaceutical Co.,and a member of the Metadate CD Advisory Board of Celltech Phar-maceuticals. He is a recipient of an investigator-initiated grant fromMcNeil Consumer and Specialty Pharmaceuticals. Dr. Hechtman re-ceived research funding from Eli Lilly, Janssen Ortho, Purdue, ShirePharmaceutical Co., and GlaxoSmithKline Beecham and is on thespeakers roster of Shire Pharmaceutical Co., Janssen Ortho, and EliLilly. Dr Klein is a member of the ADHD Advisory Board of ShirePharmaceutical Co.

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