Efficacy of methylphenidate, psychosocial treatments and their ...

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Clinical Psychology Review 28 (2008) 783 – 800

Efficacy of methylphenidate, psychosocial treatments and their combination in school-aged children with ADHD: A meta-analysis S. Van der Oord a,⁎, P.J.M. Prins a , J. Oosterlaan b , P.M.G. Emmelkamp a a

Department of Clinical Psychology, University of Amsterdam, Roeterstraat 15, 1018 WB Amsterdam, The Netherlands b Department of Clinical Neuropsychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands Received 15 November 2006; received in revised form 31 July 2007; accepted 26 October 2007

Abstract Introduction: This meta-analysis compares effect-sizes of methylphenidate and psychosocial treatments and their combination on ADHD, concurrent oppositional, conduct symptoms, social behaviors and academic functioning. Method: Several databases (PubMed, PsycInfo, ISI Web of Science) were searched for articles published between 1985 and September 2006. Inclusion criteria were: a diagnosis of ADHD; age from 6–12 years; a randomized controlled treatment design; efficacy established with parent and teacher rating scales; psychosocial treatments used were described as behavioral or cognitivebehavioral; the methylphenidate treatment was short-acting; and finally, treatment was conducted in a clinical setting. Results: ADHD outcomes showed large mean weighted effect-sizes for both methylphenidate and combined treatments, psychosocial treatments had a moderate mean weighted effect-size; a similar pattern emerged for oppositional and conducted behavior symptoms. Social behavior outcomes showed comparable moderate mean weighted effect-sizes for all treatments, while on academic functioning, all treatments had low mean weighted effect-sizes. There was no correlation between duration of psychosocial treatment and effect-size. Conclusions: Both methylphenidate and psychosocial treatments are effective in reducing ADHD symptoms. However, psychosocial treatment yields smaller effects than both other treatment conditions. Psychosocial treatment has no additional value to methylphenidate for the reduction of ADHD and teacher rated ODD symptoms. However, for social behavior and parent rated ODD the three treatments were equally effective. For improvement of academic functioning no treatment was effective. © 2007 Elsevier Ltd. All rights reserved. Keywords: Attention-Deficit Hyperactivity Disorder; Children; Psychosocial treatment; Stimulant treatment; Meta-analysis

Contents 1. 2. 3. 4.

Introduction . . . . . . . . . . . Methods . . . . . . . . . . . . . Statistical analyses . . . . . . . . Results . . . . . . . . . . . . . . 4.1. Description of the studies .

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⁎ Corresponding author. Tel.: +31 20 5256687; fax: +31 20 6391369. E-mail address: [email protected] (S. Van der Oord). 0272-7358/$ - see front matter © 2007 Elsevier Ltd. All rights reserved. doi:10.1016/j.cpr.2007.10.007

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4.2. ADHD symptoms . . . 4.3. ODD/CD symptoms . . 4.4. Social behavior . . . . 4.5. Academic functioning . 4.6. Moderators of treatment 5. Discussion . . . . . . . . . . 6. Strengths and limitations . . . 6.1. Clinical implications . . References . . . . . . . . . . . . .

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1. Introduction Attention-Deficit Hyperactivity Disorder [ADHD] is one of the most common disorders among school-aged children, with a prevalence of 3–7% in the general population (Diagnostic and Statistical Manual of Mental Disorders, fourth edition revised [DSM-IV-R], American Psychiatric Association [APA], 2000). The most frequent comorbid conditions are oppositional defiant and conduct disorder (August, Realmuto, MacDonald, Nugent & Crosby, 1996). Further, children with ADHD often show academic deficiencies (Jensen, Martin, & Cantwell, 1997) and deficient social skills (Van der Oord et al., 2005). It has generally been agreed in the empirical literature that only two treatments and their combination have been validated as effective short-term treatment modalities for school-aged children with ADHD: psychosocial treatments (behavioral or cognitive-behavioral treatments), stimulant treatments (mostly methylphenidate), and the combination of both (Richters et al., 1995; Kutcher et al., 2004). The benefits of short-term treatments with stimulants have been relatively well documented (e.g., Schachter, Pham, King, Langford, & Moher, 2001; Spencer et al., 1996; Swanson, 1993), but the empirical evidence for long-term efficacy of stimulants has been meager (Schachar et al., 2002; Schachter et al., 2001). The efficacy of psychosocial treatments alone and the combination of stimulant treatment and psychosocial treatments is less well documented (Pelham, Wheeler, & Chronis, 1998). In fact, the number of studies that have involved stimulant treatments far exceeds the number of studies that have evaluated the effects of psychosocial interventions (Pelham et al., 1998). Studies of the short-term beneficial effects of stimulants on the symptoms of ADHD constitute the largest body of treatment literature on any childhood-onset psychiatric disorder (Greenhill, Halperin, & Abikoff, 1999). About 70% of the children with ADHD respond when a single stimulant is tried. If another stimulant is tried after stopping a failed trial with an initial medication, a clinical response of up to 90% can be achieved (Spencer et al., 1996). Children treated with stimulants, however, often show side effects (Schachter et al., 2001). For example, about 1 in 4 children treated with stimulants report decreased appetite, and about 1 in 7 children report insomnia (Schachter et al., 2001). A further disadvantage of methylphenidate is that it does not cover very important home routines, such as the morning or bedtime routines. Sustained release methylphenidate, however, covers most of the day. Short-term studies have reported that improvement due to stimulants is most salient on ADHD symptoms; on long-term academic achievement and social skills, stimulants have failed to show consistent benefits (Greenhill et al., 1999; Whalen & Henker, 1991). Improvement, however, is not maintained when medication is discontinued (Abikoff et al., 2004a,b). Further, lack of improvement in peer relationships is a disadvantage of medication treatment (Hoza et al., 2005). A review of several meta-analyses on methylphenidate also shows that the most robust effect of methylphenidate is shown on core symptoms as hyperactivity, inattention and impulsivity, and that on academic achievement the results of methylphenidate have been less pronounced (Conners, 2002). Considering these limitations of stimulant treatment, the need for examining the utility of psychosocial treatments remains. Psychosocial treatments for ADHD can be divided into four categories (Pelham & Murphy, 1986; Pelham et al., 1998), (1) clinical behavior therapy (e.g., behavioral parent training) (2) direct contingency management (e.g., behavioral classroom interventions), (3) intensive packaged behavioral treatments (e.g., a combination of clinical behavior therapy and direct contingency management), and (4) cognitive-behavioral treatments (e.g., verbal selfinstructions, social skills training, problem-solving strategies, and cognitive modeling).


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Several authors, using the task force criteria (Task Force on Promotion and Dissemination of Psychological Procedures, 1995), conclude that (1) clinical behavior therapy, (2) direct contingency management (behavioral treatments, such as behavioral parent training, behavioral classroom interventions) and (3) intensive multimodal behavioral treatments, meet criteria for empirically supported treatments for ADHD, but that (4) cognitive-behavioral treatments do not (Chambles & Ollendick, 2001; Hinshaw et al., 2002; Pelham et al., 1998). There is only limited evidence for certain types of cognitive-behavioral interventions, such as social skills training and problem-solving interventions, which may only show efficacy in the treatment of ADHD, when combined with intensive multimodal behavioral treatment packages (Pelham et al., 1998). Results of a meta-analysis of school-based interventions for ADHD showed that behavioral interventions were more effective than cognitive-behavioral interventions in terms of improving classroom behavior (DuPaul & Eckert, 1997). On academic performance, however, cognitive-behavioral school-based interventions were more effective than behavioral school-based interventions (DuPaul & Eckert, 1997). Up to now, however, no systematic comparison of effect-sizes between the cognitive-behavioral and behavioral treatments is present, other than for school-based interventions for children with ADHD. A disadvantage of psychosocial treatments is that considerable room for improvement remains, especially in the domain of peer relationships (Pelham et al., 1998). It has been suggested that more intensive psychosocial treatments may be necessary (Wells et al., 2000; Pelham et al., 1998). The limitations of stimulant and psychosocial treatments have led to combining these two treatment modalities (Pelham et al., 2000), since combined treatment is suggested to enhance the treatment effects of just one treatment modality (Pelham et al., 1998; Pelham & Waschbusch, 1999). This enhancement of treatment effects by means of combining the methylphenidate and psychosocial treatments may work through different mechanisms (Pelham & Murphy, 1986). First, the two treatments may potentiate each other, yielding a combined effect that is greater than the total of the two treatment effects. Second, the two treatments may interact to inhibit each other, yielding an effect that is less than the effects of either treatment. Third, the effect may be additive, equaling the total of both treatment effects. Finally, reciprocation may occur in which the combined treatment has the same effect as one of both treatments (Pelham & Murphy, 1986). Comparing the effect-sizes of the two separate treatments and their combination can clarify the mechanism underlying these enhanced effects. Psychosocial treatments may improve outcome on some symptoms, and medication may improve outcomes on other symptoms, while both interventions may be necessary to maximize change in or normalize functioning on all areas of functioning (Pelham & Murphy, 1986). Combined treatments are often suggested to enhance the effects of methylphenidate especially on ADHD-related symptoms, such as social behavior, oppositional symptoms and academic functioning (e.g., Klein, Abikoff, Hechtman, & Weiss, 2004; Wells et al., 2000). Also, combined treatment is expected to produce long-term benefits in a variety of functional domains (Klein et al., 2004). Laboratory studies have shown that low doses of methylphenidate and behavioral treatments have additive effects (e.g., Carlson, Pelham, Milich, & Dixon, 1992; Pelham, Carlson, Sams, Vallano, Dixon, & Hoza, 1993), but behavioral treatments did not have additional effects to high doses of methylphenidate. It should be noted, however, that combined treatments have been understudied compared to pharmacological or psychosocial interventions alone (Pelham et al., 2000). Several reviews (e.g., Farmer, Compton, & Burns, 2002; Greenhill et al., 1999; Hinshaw, Klein & Abikoff, 1998; Pelham et al., 1998; Pelham & Fabiano, in press) and meta-analyses (Klassen, Miller, Raina, Lee, & Olsen, 1999; Schachter et al., 2001; Spencer et al., 1996; Swanson, 1993) have been published on treatments of childhood ADHD, but to date no meta-analysis has been conducted that systematically compares the effect-sizes of psychosocial, stimulant treatments and their combination, on ADHD symptoms and related symptom domains. In a critical appraisal of prior reviews and meta-analyses on treatment of ADHD of Jadad et al. (1999) it is shown that most reviews on ADHD had major methodological flaws, since the methods used by the authors to identify, select and assess information were not described properly. More importantly, only one of the selected thirteen reviews on treatment of ADHD has dealt with the efficacy of psychosocial treatments, focusing on school-based treatments (DuPaul & Eckert, 1997). The current meta-analysis was designed to assess the relative efficacy of methylphenidate, psychosocial treatments, and their combination on four outcome domains; ADHD, ODD symptoms, social skills and academic functioning. To date, all studies on combined treatments have included short-acting methylphenidate conditions only. Therefore, in the present review only methylphenidate studies using short-acting methylphenidate were included. Since the main interest of the present study was to examine the clinical utility of these treatments and because the great majority of children with ADHD is being treated in clinical settings, only studies conducted in clinical settings were included, rather than studies in analogue or controlled settings.

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Several authors have argued that, given the multifaceted nature of ADHD and its impairments and the fact that considerable room for improvement remains after psychosocial treatment, regular, short-term psychosocial treatments may not be adequate for many ADHD children. More intensive, lengthy psychosocial treatments programs may be necessary for these children (e.g. Pelham & Waschbusch, 1999). Consequently, duration of treatment may affect the efficacy of treatment (Barkley, 2002; Pelham et al., 1998; Schachter et al., 2001; Wells et al., 2000). In this study we investigated the relation between duration of treatment and efficacy of treatment. Although it has been often suggested that cognitive-behavioral treatments do not meet criteria for empirically supported treatments, and do not provide clinically significant changes in the behavior of children with ADHD (Pelham et al., 1998; Chambles & Ollendick, 2001), a systematic comparison of effect-sizes of behavioral and cognitivebehavioral interventions for children with ADHD is not yet available. Therefore, in the present study the effect-sizes of “cognitive-behavioral” and “behavioral” treatments were compared. In psychosocial treatment research single-case designs and within-subjects designs are used more often than between subjects designs (Pelham & Fabiano, in press). The review of Pelham and Fabiano (in press) on evidencebased psychosocial treatments of the last 10 years, reports very large effect-sizes for single-case studies on behavioral interventions. Actually, the single-case studies have considerably larger effect-sizes than the between-group studies on behavioral interventions (Pelham & Fabiano, in press). However, given the potential selection bias involved in such single-case designs (Kazdin, 2003), our meta-analysis is limited to between-group designs. 2. Methods Studies were retrieved that were published between January 1, 1985 and September 30th, 2006. We searched for studies in the English language in the following databases: PubMed, PsycInfo and ISI Web of Science. Also e-publishments ahead on the internet were included in this search. The reference lists of published articles were then used to locate other relevant studies. The following keywords were used for all searches: ADHD, child and treatment. A total of 397 articles were found. Studies included in the present meta-analysis met the following criteria: (1) a randomized controlled design, (2) use of parent or teacher scales as outcome measures, (3) children had received a primary diagnosis of ADHD, (4) if applicable, the medication treatment used short-acting methylphenidate (see exclusion below), (5) if applicable, the psychosocial treatment was clearly described as behavioral or cognitive-behavioral, (6) treatment was conducted in a clinical (outpatient) setting, studies with treatments conducted in analogue or controlled settings were excluded (7) children participating in the study were between 6 and 12 years old (mean sample age within this age range; some children may have been younger or older) (8) data were reported that allowed calculation of pre- to posttreatment effect-sizes, (9) studies had to report outcomes in terms of either ADHD symptoms, ODD/CD symptoms, social behavior or academic functioning, and finally, (10) the methylphenidate dose was administered individually at a fixed dose, or an optimally titrated dose, rather than at varying doses. Studies on mentally retarded children with ADHD were excluded. Finally, single-case studies were excluded. Also, since all treatment studies on combined treatments used short-acting formulations combined with psychosocial treatments, for purpose of comparison of treatments, only studies on short-acting methylphenidate were included for the medication condition.

3. Statistical analyses Analyses were conducted using a computer program developed by Borenstein and Rothstein (1999). The within group effect-sizes were calculated for each study using Cohen's d statistic (Cohen, 1988) and was defined as the difference between the pre- and post-intervention mean divided by the pooled SD. In this study a positive effect-size was taken to indicate improvement. The mean weighted effect-size, was weighted by sample size of the individual studies. To calculate the mean weighted effect-size, random effects analyses were used, since this permits generalization beyond the studies included in the meta-analysis. Then, confidence intervals of 95% were calculated. Further, to determine the variation of the effect-sizes of the individual studies, a homogeneity test (Q test) was applied. If the Q test is statistically significant, a heterogeneous distribution of effect-sizes is assumed (Borenstein & Rothstein, 1999), indicating a substantial variability in the effect-sizes between studies. Following Cohen's guidelines, effect-sizes of 0.20, 0.50 and 0.80 were used as thresholds to define small, medium and large effects respectively (Cohen, 1988). This study focused on the immediate effects of interventions. Therefore effect-sizes were calculated using the posttest assessment closest to active intervention. If outcome was determined with more than one measure on one of the four outcome domains, ADHD symptoms, ODD symptoms, social skills or academic functioning, the most widely used measure was utilized. In case the measure consisted of several subscales, effect-sizes of these subscales were


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averaged to obtain an aggregate effect-size. Different informants may validly contribute information about different aspects of behavior. Thus, in this meta-analysis a mean weighted effect-size was calculated separately for each informant on each outcome domain. In order to assess informant discrepancies, differences between effect-sizes of informants were calculated. One major criticism of meta-analysis is publication bias. Publication bias is the tendency for journals to publish studies reporting statistically significant findings, and a reduced tendency to publish studies with statistically nonsignificant results. Rosenthal (1991) referred to this issue as the “file-drawer” problem (representing the unpublished non-significant-result reports residing in the file drawers of researchers). The fail-safe N is used to determine the likelihood of the publication bias. If the fail-safe N is large, a large number of unpublished non-significant trials are required to reduce the found effect-size of the study to a trivial effect. It is unlikely that the obtained effect is seriously biased by the file-drawer problem. To determine the likelihood of publication bias or the “file-drawer problem” (Rosenthal, 1991), the fail-safe N was computed (Orwin, 1983). Fail-safe N's were computed for each informant and outcome domain separately. In three studies (Horn, Ialongo, Greenberg, Packard, & Smith-Winberry, 1990; Miranda & Presentación, 2000; Pfiffner & McBurnett, 1997) different kinds of cognitive-behavioral or behavioral interventions were compared. To preserve this information, each intervention was entered as a separate study effect-size. If separate groups of ADHD children were compared and no effect-size of the total sample was available, one mean effect-size was computed (Klorman, Brumaghin, Fitzpatrick, Borgstedt, & Strauss, 1994; Diamond, Tannock, & Schachar, 1999). Most studies only reported data for participants who completed pre- and post-test. Therefore, effect-sizes were based on children who had completed both pre- and post-test assessments. 4. Results 4.1. Description of the studies Twenty-six studies met the inclusion criteria. These studies are described in Table 1. For some studies data were missing. In that case, authors were contacted, However, some authors were not able to provide missing data. In that case studies were excluded from analyses. In several instances, especially for the combined condition, only a few studies were available. Meta-analytic procedures may be applied to as few as two studies, but with very few studies meta-analytic results can be very unstable (Rosenthal, 1995). In the case of few studies (less than 5 ratings) we will use a more narrative approach to describe the metaanalytic findings. Tables with the effect-sizes of individual studies are available from the first author. 4.2. ADHD symptoms The final sample of studies including outcomes on ADHD symptoms consisted of twenty-four studies. Table 2 displays the number of studies per treatment condition, total number of participants, mean weighted effect-size, the confidence intervals, heterogeneity statistics and fail-safe N values. In the psychosocial treatment condition the weighted mean effect-size of parents and teachers was large and moderate, respectively. The effect-sizes of the individual studies of parents were distributed homogeneously and of teachers heterogeneously. Further, effect-sizes of both informants were not significantly different (Q(1) = 0.00, p ≥ 0.05). The methylphenidate treatment condition yielded large improvements for both parents and teachers. The effect-sizes of the individual studies of both informants were distributed heterogeneously. Effect-sizes of teachers were significantly higher than parent's effect-sizes (Q(1) = 12.73, p ≤ 0.01). In the combined treatment conditions the mean weighted effect-size of parents and teachers were large and effect-sizes of the individual studies of parents and of teachers were distributed heterogeneously. Effect-sizes of both informants did not differ significantly (Q(1) = 0.02, p ≥ 0.01). All treatment conditions showed significant improvement after treatment. For both raters, the behavioral treatment condition was significantly less effective than the methylphenidate and combined treatment conditions, while the latter two were equally effective. In all conditions fail-safe N's were substantial. 4.3. ODD/CD symptoms The final sample of studies with outcomes on ODD/CD symptoms consisted of 17 studies (Table 2). In the behavioral treatment condition, the mean weighted effect-size of parents was medium, and of teachers small. For both informants the effect-sizes of the individual studies were distributed homogeneously. Effect-sizes of both informants did not differ significantly (Q(1) = 0.79,

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Table 1 Characteristics of studies included in the meta-analysis a Study

Stimulantia Interventions N of patients prior to randomized study b

Drop- Age outs

Diagnosis

Comorbidity

Duration (PSY: hours) (MPH: weeks)

Behavioral (B) Outcomes or cognitivemeasured behavioral (CB)

Abikoff et al. (2004a,b) c

20.4%

DSM-III-R by DISC–P

53% ODD by DISC–P No learning disorders/ conduct disorder d

MPH: 104

B

MPH

34 MPH

29.4% 8.2

MPH + PSY

34 MPH + PSY

17.7%

20.6%

PSY

19 PSY

5.6%

8.1

Antshel and Remer (2003)

100%

PSY

80 PSY

0%

9.6

Barrickman et al. (1995) 66.7%

MPH

15 MPH

16.7% 11.8

DSM-III-R e

Brown et al. (1985)

0%

MPH PSY MPH + PSY

NA

DSM-III e + academic difficulties h

Brown et al. (1986)

NA

MPH + PSY i

10 MPH 10 PSY 10 MPH + PSY 9 MPH + PSY 10 PSY + PLA

PSY + PLA k

Buitelaar et al. (1996)

Diamond et al. (1999)

Efron et al. (1997)

0%

0%

NA

MPH

MPH

MPH

21 MPH

19 MPH ADHD + ANX 27 MPH ADHDANX 125 MPH

11.4

12.5% 9.1

3.9%

9.4

21.1% 8.6

DSM-III-R by Barkley interview + T-score ≥ 67 attention CBCL DSM-IV by DICA-RP + T-score ≥ 67 attention CBCL

DSM-III e + academic difficulties j

DSM-III-R e + scores in clinical range CTRS hyperactivity subscale and attention CBCL + deficits in attention performance (reaction task or CPT) DSM-III-R by PICS + TTI

18.5% 8.2

NA

8.7

DSM-IV by DuPaul ADHD rating scale + T-score ≥ 1.5 SD above mean on attention CBCL or TRF

ODD/CD

ODD 41.18% e

PSY: 13.5 PT f

B

Social ADHD

ODD 43.75% e

PSY: 12 CT + 3 PT g = 15 MPH: 6

CB

Social

–

ADHD ODD/CD ADHD Academic

15% CD g

15% DSM-III-R depressive disorder e 42% DSM-III-R anxiety disorder e 41% anxiety by PICS or ≥ 60 on RCMAS 2% CD by PICS

PSY: 24 CT MPH: 12

CB

PSY: 22 CT

CB

ADHD

MPH: 12

Academic

MPH: 4

Social ODD/CD ADHD

–

ODD/CD

MPH: 4

–

ADHD

ODD/CD

MPH: 2

–

ADHD ODD/CD


Anastopolous et al. (1993)

PSY: 72 PT + 64 CT = 136

ADHD

Fehlings et al. (1991)

0%

DSM-III-R by DICA + score ≥ 15 Conners HI index parents + ≥150 SCRS DSM-III by DICA

13 PSY

0%

9.3

Fitzpatrick et al. (1992) 0%

MPH

19 MPH

NA

8.7

Horn et al. (1990)

PSY: PT + TC PSY: SC + TC PSY: PT + SC + TC

12 PT + TC

21.4% 8.7

11 SC + TC

15.4% 9.2

11 PT + SC + TC

21.4% 8.5

8 PT 8 SC 8 PT + SC

25% 9.8 25% 9.7 12.5% 9.5

ADD-H diagnosis m + 2 SD above mean CPRS-HI index

10 PSY

10%

8.0

DSM-IV n + HoNOSCA ≥ 11

PSY + PLA k 28 PSY + PLA MPH 29 MPH PSY + MPH 29 PSY + MPH

3.4%

7.8

DSM-III o + hyperactivity factor score CTRS ≥ 1.8

Kratochvil et al. (2002) 100%

MPH

44 MPH

43%

Klorman et al. (1994)

0%

MPH

44 MPH ADD 6.1% 34 MPH ADD +ODD

Miranda and Presentación (2000)

0%

PSY 16 PSY PSY + Anger 16 PSY + Anger

Miranda et al. (2002)

0%

PSY

0%

Horn et al. (1987)

0%

Hoath and Sanders (2002) Klein and Abikoff (1997)

72.43% 0%

PSY: PT PSY: SC PSY: PT + SC PSY

29 PSY

CD by DICA exclusion 68.42% ODD 5.26% CD by DICA-P

DSM-III-R parents l + CPRS-HI index 2 SD above mean + CTRS-HI index 2 SD above mean

PSY: 12 CT + 16 FT = 28 MPH: 2

CB

ADHD

–

ADHD ODD/CD

PSY: 18 PT + 3 TC g = 21 18 SC + 3 TC g = 21 18 PT + 18 SC + 3 TC g = 39 PSY: 12 PT 12 SC 12 PT + 12 SC = 24 PSY: 9.5 PT

PT + TC = B

ADHD

SC + TC = CB

ODD/CD

PT + SC + C = B

Academic

PT = B SC = CB PT + SC = B

ADHD ODD/CD Academic

B

ADHD

B

ADHD

MPH: 8 PSY: NA

10.4

DSM-IV by K-SADS + 1 SD above norm ADHD-RS

8.6

ADD m by ≥1.05 HAS + 1 SD above mean IOWA CTRS I/O

NA

9.7

DSM-III-R by ≥ 15 ACRS-T + ≥ 16 DSM-III-R parent interview

3.3%

8.6

DSM-IV by CSI parents + teachers

59.4% ODD 13.6% Major Depressive Disorder 11% enuresis by DICA-IV ODD by 1 SD above mean IOWA CTRS A/D ODD by ≥ 7 A/D scale of IOWA-T

ODD/CD Social Academic ADHD

MPH: 10

–

MPH: 3

–

ADHD ODD/CD

PSY: 22 CT PSY + Anger: 22 CT

PSY = CB PSY + Anger = CB

ADHD Social

PSY: 21 TT

B


PSY

ODD/CD ADHD Social ODD/CD Academic 789

(continued on next page)

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Table 1 (continued) Stimulantia Interventions N of patients prior to randomized study b

Drop- Age outs

Diagnosis

Comorbidity

Duration (PSY: hours) (MPH: weeks)

Behavioral (B) Outcomes or cognitivemeasured behavioral (CB)

The MTA Cooperative Group (1999a)

MPH 32% PSY 26%

MPH PSY

144 MPH 144 PSY

5.6% 2.1%

8.6 8.3

DSM-IV by DISC–P

39.9% ODD 33.5% anxiety disorder

MPH: 60 PSY: 48.5 PT + 16 TT + 100 CT = 164.5

B

MPH + PSY 30% Total 31%

MPH + PSY

145 MPH + PSY

2.1%

8.4

Pfiffner and McBurnett 44% (1997)

SST-PG SST

9 SST-PG 9 SST

0%

8–10 DSM-III-R by Barkley (no interview + above 1.5 CLAM mean) or SNAP-R or T-score N 60 attention CBCL

Pliszka et al. (2000)

20.6%

MPH

20 MPH

5%

8.1

Schachar et al. (1997)

0%

MPH

37 MPH

14.3% 8.4

DSM-III-R by PICS + TTI

Steele et al. (2006)

NA

MPH

73 MPH

17%

DSM-IV by K-SADS + CGI-S ≥ 4

9.1

DSM-IV by DISC–P + 1 SD above mean IOWA CTRS I/O + 1 SD above mean CGI-P

ADHD Social

83% CD

ODD/CD

10.9% Tic disorder 3.8% Affective disorder by DISC-IV 76% ODD 12% CD

Academic

36% anxiety disorder 8% dysthymic disorder by Barkley interview 70% ODD 5% CD 20% anxiety disorder by DISC 59.5% ODD 8.1% CD 24.3% anxiety disorder by PICS/TTI 38.4% ODD 0% CD 2.7% anxiety disorder

PSY: SST = 12 CT SST = CB SST + PG = 12 SST + PG = B CT + 12 PT = 24

Social

MPH: 3

–

ADHD ODD/CD

MPH: 16

–

ADHD

MPH: 8

–

ADHD ODD/CD


Study

Tutty, Gephart, and Wurzbacher (2003) Van der Oord et al. (2007)

100%

PSY

59 PSY

0%

MPH

23 MPH 10% 27 MPH + PSY

MPH + PSY

5%

9.0

DSM-IV p

10.0 9.8

DSM-IV by DISC–P

ODD/CD exclusion p MPH: 62% ODD/CD MPH + PSY: 42% ODD/CD by DISC–P

PSY: 7 PT q + 7 CT q = 14 MPH: 10 PSY: 15 PT + 2 TT + 12.5 CT = 29.5

B

ADHD

B

ADHD ODD/CD

Social


Note: MPH = methylphenidate treatment; PSY = psychosocial treatment; PT = parent training; TC = teacher consultation; FT = family training; SC = self-control therapy; Anger = anger management training; CT = child training; SST = social skills training; PG = parent generalization; TT = teacher training; PLA = placebo. NA = not available; ADHD = Attention-Deficit Hyperactivity Disorder; ADD = attention-deficit disorder; Anx = anxiety disorder; ODD = oppositional deviant disorder; CD = Conduct Disorder. DISC–P = Diagnostic Interview Schedule for Children–Parent interview; DICA-RP = Diagnostic Interview for Children and Adolescents-Revised-Parent version; attention CBCL = attention problems subscale of Child Behavior Check List; CTRS = Conners Teachers Rating Scale; CPT = Continuous Performance Task; PICS = Parent Interview for Child Symptoms; TTI = Teacher Telephone Interview; RCMAS = Revised Children's Manifest Anxiety Scale; TRF = Teacher Report Form; DICA = Diagnostic Interview for Children and Adolescents; CTRS-HI index = Conners Teacher Rating Scale Hyperkinesis index; CPRS-HI index = Conners Parent Rating Scale Hyperkinesis index; SCRS = Self-Control Rating Scale; K-SADS = Schedule for Affective Disorders and Schizophrenia for School-age children ADHD module; ADHD-RS = ADHD-IV Rating Scale Parent version Investigator Administered; DICA-IV = Diagnostic Interview for Children and Adolescents-IV Computerized Version; HAS = Home Activity Scale; CSI = Child Symptoms Inventory; ACRS-T Abbreviated Conners Rating Scale-Teachers; CLAM = Conners, Loney, Milich Rating Scale; SNAP-R = Swanson, Nolan And Pelham Questionnaire; IOWA CTRS I/O = Inattention Overactivity with Aggression Conners Teacher Rating Scale Inattention/Overactivity subscale; IOWA CTRS A/D = Inattention Overactivity With Aggression Conners Teacher Rating Scale Aggression/Defiant subscale; CGI-P = Conners Global Index Parents; CGI-S = Clinical Global Impression Severity; Barkley interview = semi-structured interview Barkley; HoNOSCA = Health of the National Outcome Scales for Children and Adolescents. a Appendix A displays references of included studies. b If available percentages for separate groups are displayed, otherwise for total sample. c Since Hechtman et al. (2004) and Abikoff et al., (2004a) used the same dataset as Abikoff et al., (2004b), data from these three studies are displayed here. d Only MPH responders included. e Not clearly stated how diagnosis made. f Not clearly stated in the article, but manual prescribes 90-minute sessions. g Not clearly stated so set at 1 h per session. The parent training was mostly limited to psycho-education therefore this treatment was labeled as CB. h At least reading deficit of two grade levels. i No medication at post-test. j One year behind in at least one area of Wide Range Achievement Test (WRAT). k Included as PSY only condition. l Based on clinical interview by first author. m Which DSM used is not stated. n Clinical diagnosis by pediatrician or mental health professional. o Not official since the study initiated prior to publication, but adequate support provided for DSM-III labels. p Based on questionnaires and clinical protocol, however diagnosis decision-making is not clearly stated. q 8 50-minute sessions.

791

792

PSY

MPH

N-study N ADHD—parent 12 ADHD—teacher 11 ODD—parent 3 ODD—teacher 7 Social—parent 5 Social—teacher 5 Academic—child 6

402 381 167 289 292 203 274

ES

CI

0.87 0.75 0.66 0.43 0.54 0.71 0.19

(0.73–1.01)⁎⁎ 13.54 40.2 (0.49–1.01)⁎⁎ 34.47⁎⁎ 30.3 (0.16–1.16)⁎⁎ 9.49 6.9 (0.26–0.60)⁎⁎ 5.97 8.05 (0.37–0.70)⁎⁎ 6.71 8.5 (0.51–0.92)⁎⁎ 5.16 12.7 (0.03–0.36)⁎ 5.65 0.35 a

Q-stat

Fs N

PSY + MPH

N-study N

ES

CI

Q-stat

15 13 10 12 3 4 4

1.53 1.83 0.61 1.08 0.62 1.06 0.33

(1.23–1.82)⁎⁎ (1.43–2.12)⁎⁎ (0.39–0.83)⁎⁎ (0.77–1.39)⁎⁎ (0.42–0.83)⁎⁎ (0.69–1.43)⁎⁎ (− 0.14–0.81)

40.40⁎⁎ 99.8 64.22⁎⁎ 106 23.17⁎⁎ 20.5 58.15⁎⁎ 52.8 0.06 6.3 6.47 17.2 11.52⁎⁎ 2.6

705 588 529 579 189 199 216

Note: PSY = psychosocial treatment condition; MPH = methylphenidate treatment condition. ⁎p ≤ 0.05/⁎⁎p ≤ 0.01. a Number of studies needed to raise to a effect-size of 0.20.

Fs N

N-study N

ES

CI

6 6 3 5 3 5 5

1.89 1.77 1.23 0.92 0.71 1.08 0.35

(1.39–2.40)⁎⁎ 12.30⁎ (1.08–2.46)⁎⁎ 31.47⁎⁎ (0.64–1.83)⁎⁎ 8.56⁎ (0.45–1.39)⁎⁎ 16.12⁎⁎ (0.50–0.92)⁎⁎ 0.38 (0.85–1.31)⁎⁎ 4.71 (− 0.02–0.71) 8.66

242 240 191 232 191 207 227

Q-stat

Fs N 50.7 47.1 15.4 18 7.65 22 3.75


Table 2 Number of studies (N-study), total number of participants (N), total weighted mean effect-sizes (ES), confidence intervals (CI), heterogeneity statistic (Q-stat) and fail-safe N (Fs N) per condition and outcome domain


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p ≥ 0.05). In the methylphenidate treatment condition, the mean weighted effect-size of parents was medium and of teachers large. Individual study effect-sizes of both informants were distributed heterogeneously. Effect-sizes of teachers were significantly higher than parent's effect-sizes (Q(1) = 20.44, p ≤ 0.01). In the combined conditions, only three studies included parent ratings (Klein & Abikoff, 1997; MTA Cooperative Group, 1999a; Van der Oord, Prins, Oosterlaan, & Emmelkamp, 2007) of ODD/CD symptoms. The latter two studies showed comparable large effect-sizes (0.93, 0.96 respectively), while the first study (Klein & Abikoff, 1997) showed a much larger effect-size of 1.95. The mean weighted effect-size was large, and effect-sizes of these individual studies were distributed heterogeneously. Five studies included teacher ratings, three of these studies (Abikoff et al., 2004b; MTA Cooperative Group, 1999a; Van der Oord et al., 2007) showed comparable moderate to high effect-sizes (0.71, 0.85, 0.61 respectively) and one study showed a low effect-size (0.29; Brown, Borden, Wynne, Schleser, & Clingerman, 1986). However, similar to the result with parent ratings, the study of Klein and Abikoff (1997) showed a much larger effect-size (2.08) for teacher ratings. The mean weighted effect-size was large, and effect-sizes of the individual studies were distributed heterogeneously. Effect-sizes of parents and teachers did not differ (Q(1) = 1.17, p ≥ 0.05). The three treatment conditions showed significant improvements after treatment. Parents rated the three treatment conditions as equally effective. Teachers rated the methylphenidate and combined conditions as equally effective. The psychosocial treatment condition, however, was significantly less effective than the methylphenidate treatment condition. For the ODD/CD symptom outcome domain, fail-safe N's ranged from 6.9 to 53. 4.4. Social behavior The selected sample for social behavior consisted of nine studies. In the behavioral condition, only one study used the child as informant (Antschel & Remer, 2003), showing a medium effect-size (0.78). Both mean weighted effect-size of parents and teachers were in the medium range, and effect-sizes of individual studies were distributed homogeneously. Effect-sizes of parents and teachers showed no significant difference (Q(1) = 1.69, p ≥ 0.01). In the methylphenidate condition only one study used the child as informant (Abikoff et al., 2004a), with a low effect-size (0.19). Three studies used parents and four studies teachers as informants. Effect-sizes of the three studies (Abikoff et al., 2004a,b; MTA Cooperative Group, 1999a; Van der Oord et al., 2007) with parent ratings were comparable and in the medium range (0.57, 0.64, 0.62). The mean weighted effect-size of the studies with parents as informant was in the medium range and distributed homogeneously. Four studies used the teacher as informant (Klein & Abikoff, 1997; Abikoff et al., 2004a,b; MTA Cooperative Group, 1999a; Van der Oord et al., 2007), effect-sizes were somewhat less consistent than the parent ratings. Two studies (Klein & Abikoff, 1997; Van der Oord et al., 2007) showed moderate effect-sizes (0.76, 0.70) and two studies (Abikoff et al., 2004a,b; MTA Cooperative Group, 1999a) showed high effect-sizes (1.63, 1.02). The mean weighted effect-size of studies with teachers as informants was high (1.03) and effect-sizes of the individual studies were distributed homogeneously. Teachers showed significantly higher effect-sizes than parents (Q(1) = 7.40, p ≤ 0.01). In the combined treatment condition, only one study used the child as informant (Abikoff et al., 2004a), showing a moderate effect-size (0.51). Three studies included the parent as informant (Abikoff et al., 2004a,b; MTA Cooperative Group, 1999a; Van der Oord et al., 2007), all showing comparable moderate to high effect-sizes (0.62, 0.72, 0.87). The mean weighted effect-size was in the medium range and effect-sizes of the individual studies were distributed evenly. Although only five studies with ratings of teachers were present (Abikoff et al., 2004a,b; Klein & Abikoff, 1997; Brown et al., 1986; MTA Cooperative Group, 1999a; Van der Oord et al., 2007), the effect-sizes were consistent across studies and all but one in the large range (1.20, 1.03, 1.19, 0.94 respectively). The Brown et al. (1986) study showed a small effect-size (0.17). Also, the mean weighted effect-size was large, and effect-sizes of the individual studies were distributed homogeneously. Teachers showed significantly higher effect-sizes than parents (Q(1) = 7.38, p ≤ 0.01). In all treatment conditions, both raters showed significant improvements in social behavior after treatment, all treatments were equally effective. For the social behavior outcome domain fail-safe N's range from 6.3 to 22. 4.5. Academic functioning The final selected sample consisted of seven studies, all with the child as informant. In the behavioral treatment condition the mean weighted effect-size was small (0.19) and effect-sizes of the individual studies were distributed homogeneously. In the medication treatment condition only four studies were present. Three studies (Klein & Abikoff, 1997; Brown et al., 1986; MTA Cooperative Group, 1999a) showed negative to small effect-sizes (0.24, −0.23, 0.13), and only one study (Hechtman et al., 2004), showed a large effect-size (1.04). The mean weighted effect-size was small, and effect-sizes were distributed heterogeneously. Finally, the combined treatment condition yielded small improvements and effect-sizes of the individual studies were distributed homogeneously. Methylphenidate and combined treatment showed no improvement on measures of academic functioning after treatment, and psychosocial treatments only showed a marginally significant effect of treatment. The three treatments were not statistically

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Table 3 Pearson correlations between treatment duration and individual effect-sizes of studies

PSY

MPH

ADHD-parent ADHD-teacher ODD/CD-teacher ADHD-parent ADHD-teacher ODD/CD-parent ODD/CD-teacher

All studies

Without lengthy studies a

0.14 0.34 0.38 −0.01 −0.05 0.05 −0.21

−0.02 0.12 0.01 −0.09 −0.24 −0.21 −0.17

Note: PSY = psychosocial treatment condition; MPH = methylphenidate treatment condition. ⁎p ≤ 0.05/⁎⁎p ≤ 0.01. a For PSY the MTA study (MTA Cooperative Group, 1999a) is excluded, for MPH both the MTA study and Abikoff et al.'s (2004a,b) study are excluded.

different. Since the mean weighted effect-sizes of all treatment conditions were already low, the fail-safe N's were low as well. It is unlikely that highly significant results are subject to the file-drawer problem, therefore it is unlikely that the file-drawer problem influences this overall effect-size. 4.6. Moderators of treatment outcome We investigated the effect of two moderators: (1) duration of treatment and (2) type of psychosocial treatment, i.e., behavioral versus cognitive-behavioral interventions. Pearson correlation coefficients were computed between moderators and effect-sizes in case of continuous variables, while for categorical variables the Q test was computed. A common misunderstanding is that the influence of moderators can only be examined if the effect-sizes are distributed heterogeneously (Rosenthal, 1995). Therefore we calculated correlations regardless of homogeneity. Moderators for only the methylphenidate and psychosocial treatment conditions in the ADHD and ODD/CD symptom domains were investigated (Table 3), since not enough studies were present in the other domains. Duration of treatment in the MTA study and the Abikoff et al.'s (2004a,b) study was substantially longer than the duration of treatment in other studies, which might have caused inflated correlations. Therefore, correlations were also computed without these two studies. On both the ADHD and ODD/CD outcome domain, there was no significant correlation between duration of treatment and effect-size, with and without the inclusion of the lengthier studies. Psychosocial treatment conditions were coded as “behavioral ” or “cognitive-behavioral”. Following e.g. Pelham and Murphy (1986) and Pelham et al. (1998) (1) clinical behavior therapy (e.g., behavioral parent training), (2) direct contingency management (e.g., behavioral classroom interventions), and (3) intensive packaged behavioral treatments (e.g., a combination of clinical behavior therapy and direct contingency management) were coded as “behavioral” treatments. Other treatments, using verbal self-instructions, social skills training, problem-solving strategies, cognitive modeling or self-reinforcement were coded as “cognitive-behavioral” (Whalen & Henker, 1991). Often several techniques were used in these cognitive-behavioral therapy, such as modeling, role-playing, response cost and token systems in therapy sessions and relaxation. In case a study mainly used both “behavioral” techniques and also provides some “cognitive-behavioral” techniques the study was coded as “behavioral”. There were no significant differences between the “behavioral” and “cognitive-behavioral” treatments on teacher rated effect-sizes in the ADHD (Q(1) = 0.73, p = 0.39) and ODD/CD domain (Q(1) = 1.51, p = 0.22). On the parent rated effect-sizes, however, the Q test reached significance (p = 0.09) between “behavioral” and “cognitive-behavioral” treatments (Q(1) = 2.70, p = 0.09) in the ADHD domain, in favor of the behavioral treatments. Since there was only one “cognitive-behavioral” study in the ODD/CD symptom domain, differences were not tested for this outcome domain. Overall the behavioral treatments showed higher effect-sizes than the cognitive-behavioral treatments, but this difference was never statistically different.

5. Discussion The present meta-analysis investigated the efficacy of short-acting methylphenidate, psychosocial treatments and their combination on ADHD and ODD/CD symptoms, social behavior and academic functioning in school-aged children with ADHD. Several databases were searched for studies published between 1985 and 2006 that employed a randomized controlled design, were conducted in outpatient settings and focused on 6 to12 year old children. Twentysix studies were retrieved that met these inclusion criteria.


795

With regard to ADHD symptoms, both methylphenidate and combined conditions were equally effective in symptom reduction, and very large improvements after treatment were reported. Although the mean weighted effectsize of the psychosocial treatment condition was moderate to large, this treatment modality was significantly less effective than the other two treatment modalities. For all treatments, no improvements in academic functioning were found, and all proved to be equally effective. Social behavior moderately improved after treatment in all treatment conditions, and no differences were noted between treatment conditions. Also, parent ratings of ODD/CD symptoms showed moderate to large gains after treatments, with no differences among treatment conditions. Teachers rated the methylphenidate and combined conditions as equally effective. The psychosocial treatment condition, however, was significantly less effective than the methylphenidate treatment condition as rated by the teachers. It is often assumed that behavioral and methylphenidate treatments have additive effects on the reduction of ADHD symptoms (e.g., Klein & Abikoff, 1997; Klein et al., 2004). The results of the present meta-analysis, however, do not suggest an additive effect of behavioral and methylphenidate treatments, as effect-sizes of combined treatments are comparable to the effect-sizes of methylphenidate treatments. It seems more likely that reciprocation between the two treatments has occurred, because the combined treatment has the same effect as the methylphenidate treatment condition. Possibly, this may be caused by which treatment is chosen as first line of treatment, and the dosing procedure used for titration of methylphenidate. For ADHD symptoms, the effects of methylphenidate are large and leave little room for improvement for psychosocial treatments. Most of the studies in our meta-analysis employing a combined treatment, first used optimal dosing procedures and then added psychosocial treatments, thus limiting the room for further improvement. Some within-subjects and laboratory studies, however, have shown that low doses of MPH (thus titrated to a lower than optimal dose) and behavioral treatments have additive effects on ADHD symptoms (e.g., Carlson et al., 1992; Pelham & Murphy, 1986), yielding a larger effect than either medication or behavioral intervention alone. Thus, if high doses of medication are used that effectively eliminate ADHD symptoms, incremental effects of behavioral interventions will not be detected (Pelham & Murphy, 1986; Pelham, 1999). Possibly with timing procedures, such as providing one treatment modality as a first line of treatment and then when there is room for improvement, providing another treatment modality, an additive effect of behavioral therapies to medication might be found (Pelham et al., 1993). One recent study using this stepped methodology in adults with ADHD, has shown a significant additional effect of psychosocial treatments next to methylphenidate (Safren et al., 2005). The finding that the combined and medication treatments do no differ on core ADHD symptoms is perhaps less surprising than the lack of difference in other areas of the child's functioning. Combined treatments are often suggested to enhance the effects of methylphenidate on ADHD-related symptoms, such as social behavior, oppositional symptoms and academic functioning (e.g., Klein et al., 2004; Wells et al., 2000). This, however, is not supported by the results of the present meta-analysis. For academic functioning, social behavior, and parent ratings of ODD/CD symptoms, comparable efficacy rates were found for methylphenidate, behavioral and combined treatments. Close inspection of the mean weighted effect-sizes, however, shows that efficacy rates of the combined conditions are largest on all outcome domains, although the difference with medication treatment is never statistically different. Only teacher rated ODD/CD symptoms show a negligible larger effect-size for the methylphenidate than for the combined treatment condition. In the MTA study, using success rates, a significantly higher success rate is reported for the combined treatment condition (67%) compared to the methylphenidate treatment condition (55%) (Swanson et al., 2001). But, what does the small, non-significant, incremental effect of the combined treatment condition in our metaanalysis mean for clinical decision-making? In most clinical trials all children are randomized to either medication or the combined treatment condition, regardless of individual differences. In clinical practice, however, the situation is different. Children are encountered who do not (fully) respond to methylphenidate. This room for improvement urges the need to offer psychological treatments. For these children the addition of psychosocial treatments clearly may improve outcome (Taylor, 1999). Informant agreement is important issue in ADHD research, since informant agreement on ratings of ADHD symptoms has been low (e.g., Mitsis, McKay, Schulz, Newcorn, & Halperin, 2000; Van der Oord, Prins, Oosterlaan, & Emmelkamp, 2006). Some authors suggest that parent's ratings are less informative for assessing ADHD symptoms than teachers' ratings (Loeber, Green, & Lahey, 1990). A recent study (Biederman, Faraone, Monuteaux, & Grossbard,

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2004) compared the ability of parents and teachers to document change in ADHD symptoms after sustained release stimulant treatment. Comparison of effect-sizes of parents and teachers indicated that parents were as sensitive as teachers to detect changes in ADHD symptoms. A meta-analysis on the efficacy of short-acting methylphenidate, reported larger effects for teachers than for parents (Schachter et al., 2001), which is not surprising since short-acting methylphenidate often does not cover home situations. Also in his review of meta-analysis of methylphenidate, Conners (2002) has found higher effect-sizes for teachers than for parents on rating scales. In our meta-analysis we also found larger effect-sizes for teachers than for parents with methylphenidate treatment on all outcome domains. Combined treatment showed a larger effect-size for teachers in the social behavior outcome domain and no differences between raters in the ADHD and ODD/CD symptom domains. In both cases, however, the confidence intervals were very large. Psychosocial treatment showed no significant differences between raters on all outcome domains. Possibly psychosocial treatments promote generalization across a variety of situations. It has been suggested that the effectiveness of psychosocial treatments depends on the duration of treatment (Barkley, 2002; Pelham et al., 1998; Wells et al., 2000). Moderator analysis showed, however, that duration of psychosocial treatment was not related to efficacy of treatment of ADHD symptoms. Furthermore, the lengthy intervention of the MTA study was equally effective as the other treatments reviewed here. However, none of the longterm behavioral treatments were as long as the medication treatments. In the MTA study, for example, the behavioral treatment was faded out at post-test. Still, the effectiveness of more lengthy psychosocial treatments needs to be explored. In contrast to our finding that there was no relationship between efficacy of methylphenidate and the duration of treatment, one meta-analysis (Schachter et al., 2001) has reported a positive relation between length of treatment and effect-sizes. Schachter et al. (2001) reported this positive relation between time of treatment and efficacy in short-term studies, utilizing within-subjects designs. In studies beyond four weeks, however, these authors were unable to demonstrate a relation between time of treatment and efficacy. Our meta-analysis mostly included methylphenidate studies with a duration beyond 4 weeks, which implies that this lack of effect may be related to differences in methodology. It has been commonly stated in the psychosocial literature of ADHD, that cognitive-behavioral interventions are not effective and do not meet the criteria for empirically supported treatments (e.g. Pelham et al., 1998; Task Force on Promotion and Dissemination of Psychological Procedures, 1995). Alternatively, behavioral treatments such as contingency management, clinical behavior therapy and intensive multimodal packages, however, are considered to meet the criteria of empirically supported treatments and are labeled “well established” (Pelham et al., 1998; Task Force on Promotion and Dissemination of Psychological Procedures, 1995). Inspection of effect-sizes of both cognitivebehavioral and behavioral treatments in the present meta-analysis, however, shows that effect-sizes ADHD and ODD/ CD symptoms are not statistically different. Although the difference between the effect-size of cognitive-behavioral treatments and behavioral treatments does not reach significance, the effect-sizes of cognitive-behavioral treatments are moderate and the effect-sizes of behavioral treatments are large (Cohen, 1988). However, note that only a few studies were available to make this comparison. The problem is that cognitive-behavioral treatments often differ in content. For example, cognitive-behavioral treatments may or may not include cognitive modeling, role-playing, relaxation, selfreinforcement, in-session response cost and token-reward systems, social skills training, problem-solving training or self-instruction training (Whalen & Henker, 1991). In our meta-analyses 7 out of 9 studies applying cognitivebehavioral techniques mainly intended for the children to learn problem-solving techniques using several of these techniques. The studies differed in their content and amount of techniques to teach the child these abilities. Two studies were mainly focused on social skills training. Possibly the broad range of effect-sizes in cognitive-behavioral treatments can be explained by this variability in treatments. 6. Strengths and limitations The studies examined in our meta-analysis often suffered from low statistical power, due to a small number of participants and multiple outcome measures. Meta-analysis enhances power by combining the results of all underpowered studies, and therefore yields statistically better informed conclusions than a narrative review. This may explain the difference in the results from this meta-analysis and the results of previous narrative reviews, in which an additional effect of psychosocial interventions next to methylphenidate is often suggested, especially on ADHD-related symptoms (e.g. Barkley, 2002; Farmer et al., 2002; Pelham et al., 1998).


797

As stated by other authors (e.g., Pelham, Fabiano, & Massetti, 2005) another major difficulty in ADHD research is the number of dependent measures used to assess ADHD symptoms, increasing method variance in a meta-analysis. In our meta-analysis we encountered as many as 13 different measures to assess ADHD. Most widely used is the Conners ratings scale, of which several versions exist (Conners, 1998). To decrease possible method variance, we choose the most used version of this instrument as a major outcome measure (i.e. Conners HI index). However, operationalization of ADHD symptoms with this measure is limited (Schachter et al., 2001). Another important issue is that the MTA study, with its large sample size, contributes most weight to the mean weighted effect-size. Especially in the combined treatment this is most prominent, since combined treatments are relatively understudied. The treatments of the MTA study were designed to have maximum impact (Wells et al., 2000), therefore the mean weighted effect-sizes in this meta-analysis are surely no underestimation of treatment effects. This makes the lack of difference between the combined and methylphenidate treatments even more striking. Due to the limited number of retrieved, methodologically sound studies, several analyses were not possible. Since only 60% of the studies reported comorbidity rates, assessment of the effects of comorbidity were not possible. Also, assessment of the long-term efficacy of treatments was not possible. Research has shown that the positive effects of methylphenidate cease as soon as the medication is discontinued (Abikoff et al., 2004b). Also, the addition of psychosocial treatments indeed may have limited short-term additional value, but it may prevent relapse over time in treated ADHD children and their families (Pelham et al., 1993). Further, the efficacy of treatment on other ADHDrelated symptoms was not assessed. Possibly on other domains of functioning, such as anxiety, depression or parenting practices, different results would have been encountered. Finally, it is important to remember our search parameters for the generalizability of our results. Only studies that were published since 1985 were included, that used between subject designs, were conducted in an outpatient setting, included children between 6 and 12 years old, and used short-acting formulations of methylphenidate. Also, singlecase studies and within-subjects designs were excluded in this study. Some studies using within-subjects designs and single-case study designs do find for example combined treatment to be superior to methylphenidate treatment alone (Carlson et al., 1992; Waschbusch, Kipp, & Pelham, 1998). Inclusion of these single-case studies may have caused different and inflated results, especially for the combined treatment. Also, due to the exclusion of studies using longterm formulations of stimulants the effects in terms of parent reports may have been underestimated compared to teacher reports. Very few studies were available for the combined condition, and inclusion of combined studies before 1985 might have changed the results of our meta-analysis. To address this issue, the literature before 1985 was reviewed and only one combined study (Firestone, Kelly, Goodman, & Davey, 1981) was found that met our inclusion criteria. Analyses were rerun, including this older combined study, and the same results were reported (data available from first author). One could argue that single-case studies should be included in our meta-analysis, since a large amount of the behavioral and combined treatment studies use a single-case methodology. However, a thorough inspection of the available reviews on treatments for ADHD showed much larger effect-sizes (2 to 3 times larger) for single-case studies then for between-group designs (see DuPaul & Eckert, 1997; Pelham & Fabiano, in press). Since there was such a large difference in effect-sizes in between-subject and single-subject designs, only between-subject designs were included. Prior meta-analyses and reviews often have also included between-subject methodology only. However, it should be kept in mind, that including single-case designs could have inflated results for behavioral and combined treatments. It should be kept in mind that within group effect-sizes are often larger than between-group effect-sizes, thus for example the reported methylphenidate effect-sizes are larger than the effect-sizes often found in between-group calculation. However, we believe in this study that within group effect-sizes are appropriate. One major criticism of meta-analyses, is that it compares “apples and oranges” (Gliner, Morgan, & Harmon, 2003). Since the control groups encountered in our literature retrieval were very different in nature (varying from intervention control, attention control to waitlist control), the control groups were incomparable and calculation of between-group effect-sizes would have yielded results that would have been difficult to interpret, if not misleading. 6.1. Clinical implications This meta-analysis suggests that in school-aged children with ADHD, psychosocial treatments do not enhance the effects of methylphenidate treatments in terms of ADHD and ODD/CD symptoms, social behavior and academic functioning. However, the effect-sizes were change scores, calculated using pre–post-effect-sizes and standard

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deviations of one treatment condition, and were not calculated with using a comparison of a control group and a treatment group. Therefore a moderate effect-size of, for example, the cognitive-behavioral treatment, may merely indicate improvement over time. However, as a comparison we computed mean weight effect-sizes of the three studies that included a no treatment control, thus the improvement over time without any intervention. These weight effectsizes are very low (0.10 for teachers, and 0.12 for parents). Thus without intervention small improvement over time is expected. Furthermore, only 25% of the studies included in our meta-analysis compared the treatment effects of behavioral, methylphenidate or combined treatments within their study. It should be noted, however, that the results of this study, should not be interpreted as a lack of efficacy of psychosocial treatments. Psychosocial treatments alone are just as effective as the other two treatments in terms of the improvement of social behavior and in reducing ODD/CD symptoms. For the reduction of ADHD core symptoms, however, both methylphenidate and combined treatments are more effective, than psychosocial treatments alone, which also yield substantial effects. Psychosocial treatment, methylphenidate and their combination are not effective in improving academic functioning. This study shows preliminary evidence that time of treatment is not related to shortterm treatment-efficacy. However, lengthier psychosocial treatments need to be conducted to further examine this issue. References ⁎Abikoff, H., Hechtman, L., Klein, R. G., Gallagher, R., Fleiss, K., Etcovitch, J., et al. (2004a). Social functioning in children with ADHD treated with long-term methylphenidate and multimodal psychosocial treatment. 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