A Feasibility Study of the Children's Medication Algorithm Project (CMAP) Algorithm for the Treatment of ADHD

The pharmacological treatment of attention-deficit/hyper-activity disorder (ADHD) is one of the most establishedand scientifically validated treatments in medicine (Greenhill,2001). Recently, the NIMH Collaborative MultisiteMultimodal Treatment Study of Children With ADHD(MTA) randomized more than 500 children with ADHDto four groups: community treatment, medication man-agement, intensive psychosocial intervention, and com-

bined medication management and psychosocial inter-vention (MTA Cooperative Group, 1999; Vitiello et al.,2001). After 14 months of treatment, those patients receiv-ing expert medication management had superior out-comes to those treated in the community. Only two thirdsof the community treatment group received medicationtreatment, and when stimulants were prescribed, the doseswere lower in the community treatment group relative tothe medication management group. While these findingssuggest that evidence-based medication management resultsin a better outcome than treatment as usual, it remains tobe seen whether such procedures from randomized clin-ical trials can be implemented in a real-world clinical set-ting. Furthermore, will clinicians without research experienceaccept and implement strategies designed to move knowl-edge from the “lab bench to the bedside”? Such questionsare at the heart of evidence-based medicine.

The Texas Department of Mental Health and MentalRetardation (TDMHMR) has long been interested in theimplementation of evidence-based algorithms for the treat-ment of high-prevalence psychiatric disorders. Algorithmsfor the treatment of affective disorders and schizophrenia

A Feasibility Study of the Children’s MedicationAlgorithm Project (CMAP) Algorithm for

the Treatment of ADHDSTEVEN R. PLISZKA, M.D., MOLLY LOPEZ, PH.D., M. LYNN CRISMON, PHARM.D., MARCIA G. TOPRAC, PH.D.,

CARROLL W. HUGHES, PH.D., GRAHAM J. EMSLIE, M.D., AND CHRISTINE BOEMER, B.A.

ABSTRACT

Objective: To determine whether an algorithm for the treatment of attention-deficit/hyperactivity disorder (ADHD) can

be implemented in a community mental health center. Method: Fifty child and adolescent patients at Texas community

mental health centers who met criteria for ADHD were treated according to an algorithm-based disease management pro-

gram for ADHD. Psychiatrists were trained in the use of the algorithm, and each subject underwent a baseline assess-

ment consisting of a structured interview and standardized rating scales. Subjects were monitored for 4 months. At the

end of treatment, the psychiatrists completed the Clinical Global Impression Scale (CGI) and the baseline rating scales

were repeated. The primary variables of interest were psychiatrist and family adherence to the algorithm. To examine

impact on treatment outcome, the CGI of the algorithm subjects was compared with CGIs based on chart reviews of 118

historical controls. Results: Psychiatrists implemented the major aspects of the algorithm, but the detailed tactics of the

algorithm (use of fixed titration of stimulants) were less well adhered to. Conclusions: An algorithm for the treatment of

ADHD can be implemented in a community mental health center. J. Am. Acad. Child Adolesc. Psychiatry, 2003,

42(3):279–287. Key Words: attention-deficit/hyperactivity disorder, treatment algorithms, Children’s Medication Algorithm

Project, evidence-based medicine, psychopharmacology.

J . AM. ACAD. CHILD ADOLESC. PSYCHIATRY, 42 :3 , MARCH 2003 279

Accepted September 23, 2002.Dr. Pliszka is Associate Professor of Psychiatry, University of Texas Health

Science Center at San Antonio; Dr. Lopez is a Research Psychologist, TexasDepartment of Mental Health and Mental Retardation (TDMHMR); Dr.Crismon is Professor of Pharmacy, University of Texas at Austin; Dr. Toprac isDirector of Research at TDMHMR; Drs. Emslie and Hughes are Professors ofPsychiatry and Ms. Boemer is Research Coordinator, University of Texas SouthwesternMedical School at Dallas.

The research was made possible by grants from the Meadows Foundation, theHogg Foundation for Mental Health, and the Houston Endowment.

Correspondence to Dr. Pliszka, Division of Child and Adolescent Psychiatry,University of Texas Health Science Center at San Antonio, 7703 Floyd CurlDrive, MC 7792, San Antonio, TX 78229-3900; e-mail: [email protected].

0890-8567/03/4203–0279�2003 by the American Academy of Childand Adolescent Psychiatry.

DOI: 10.1097/01.CHI.0000037028.04952.3B

in adults have been developed and widely implemented(Chiles et al., 1999; Crismon et al., 1999; Rush et al.,1999; Shon et al., 1999). In 1999, TDMHMR set out todevelop and test algorithms for the treatment of ADHDand major depressive disorder in children and adolescents.Two consensus conferences were held consisting of nationaland local experts, TDMHMR clinicians, and family rep-resentatives; algorithms and tactics for the treatment ofthese two disorders were developed (Hughes et al., 1999;Pliszka et al., 2000a,b). Several investigators from theMTA study served as national experts for the ADHD con-sensus conference; the design and results of the MTAstrongly influenced the design of the ADHD algorithm.We now report on our first attempt to implement thisalgorithm-based disease management program for ADHDin four community mental health centers in Texas. A fea-sibility study of this sort differs from a traditional ran-domized clinical trial in that it involves implementationof a treatment in a naturalistic setting by regular staff psy-chiatrists. The psychiatrists involved are not researchers,experienced in precisely carrying out a protocol. Rather,the physicians are educated in the algorithm, and one ofthe key questions is how well they (as well as the patientsand their families) adhere to and accept the algorithm.This study also sought to examine what practical prob-lems emerged during algorithm implementation. Finally,while this study will address whether algorithm imple-mentation leads to improvements in clinical outcomes, afinal answer to this question awaits a larger controlled trialof the algorithm and its tactics.

METHOD

Subjects

Subjects were 50 children aged 6 to 17 years who were being treatedat one of four community mental health centers in Texas. Eligiblechildren had a clinical diagnosis of ADHD made according to theusual practice of the center psychiatrist. Typically, the psychiatrist sawthe patient after an intake interview by a master’s-level clinician andhad access to the written note describing the chief complaint andsocial history. Most psychiatrists conducted an unstructured, open-ended clinical interview with parent and child; this assessment rangedin length from 1 to 1.5 hours. For this study, psychiatrists were askedto fill out an 18-item checklist of DSM-IV ADHD symptoms. Newpatients (those not on medication) and patients on medication requir-ing a reassessment because of poor response or tolerability were eli-gible for study. A finding of poor response to a prior medication wasbased on the parent’s report of the child showing no behavior changedespite adequate dosing. A child was also considered a nonresponderif side effects to a given medication were deemed excessive by the par-ent or psychiatrist. Those parents reporting lack of behavioral responsewere asked about the duration of treatment and the highest dose of

the medication used. Patients stable on their current medication (andthus likely to continue to take that medication throughout the 4-month period of the study) were not eligible. Exclusionary criteriaincluded a current diagnosis of mania, any psychotic disorder, schizo-phrenia, or mental retardation. Anxiety or depressive disorders wereexclusionary if they were believed to be the primary disorder requir-ing psychopharmacological intervention. Written informed consentwas obtained from the child’s parent/legal guardian; assent was obtainedfrom the child. Parents and children received gift certificates as com-pensation for time spent on research assessments. If a family discon-tinued their clinic treatment, they were still contacted and asked tocomplete the 4-month follow-up assessments. If a final 4-month assess-ment was not obtained, the measurement for each variable obtainedat the last clinic visit was carried forward for an intent-to-treat analy-sis. A bachelor’s-level clinical coordinator (CC) gathered all researchinstruments and provided psychoeducation (see “Other AlgorithmInterventions”). If research instruments could not be completed atthe time of the child’s clinic visit with the psychiatrist, an alternativetime was scheduled with the CC. The research was approved by theinstitutional review boards of the respective universities and, whereapplicable, at the community mental health centers.

Baseline Measures

The computerized Diagnostic Interview Schedule for Children(DISC) (Shaffer et al., 2000) was completed separately for each par-ent and child. The CC read each item from the computer screen tothe parent or child and recorded the response. The purpose of theDISC was not to assess the patient’s eligibility for entry into the study,but to provide a structured diagnostic assessment to compare withthe clinical diagnosis made by the psychiatrist. The parent filled outthe SNAP-IV (Swanson, 1992), an 80-item DSM-IV checklist. TheSNAP-IV items for ADHD and oppositional defiant disorder (ODD)specify a cutoff that distinguishes an abnormal degree of “inattentiveand hyperactive/impulsive” behavior from normal behavior in thesedomains. The other DSM-IV items on the SNAP-IV allow screeningfor other comorbid psychiatric disorders. The Conners Global Index-Parent (Conners, 1997), also obtained from the parent, is a 10-itemquestionnaire assessing those symptoms most responsive to short-term psychopharmacological treatment. The child’s teacher was askedto fill out the 10-item Conners Global Index-Teacher. To assess func-tioning, the Youth Outcome Questionnaire (YOQ) and the ChildAdolescent Functioning Assessment Scale (CAFAS) were obtained bythe CCs. The YOQ (Burlingame et al., 1996) is a 64-item parent-report measure of progress for children or adolescents receiving men-tal health treatment. The CAFAS (Hodges and Wong, 1997) is aclinician-rated measure of child or adolescent functioning. It wasadministered by CCs who were trained according to the CAFAS man-ual. It yields a total score as well as scores for subscales, which assessfunctioning with regard to school/work, home, community, think-ing, behavior toward others, moods/emotions, self-harmful behav-iors, and substance use. The child’s psychiatrist assessed the degree ofclinical severity using a modified Clinical Global Impression Scale-Severity (CGI-S). Severity was rated on a 10-point scale: 1 = symp-toms not present; 3 = mild symptoms, not clinically significant; 5 =moderate symptoms, clinically significant symptoms necessitatingintervention; 7 = severe symptoms; 9 = very severe symptoms; 10 =symptom severity requires immediate intervention, usually throughhospitalization or equivalent.

Algorithm-Based Treatment Protocol The algorithm for the treatmentof ADHD and its implementation has been previously described(Pliszka et al., 2000a,b). Briefly, the algorithm consisted of six stages,as shown in Figure 1 of Pliszka et al. (2000a). Stage 1 consists of the

PLISZKA ET AL.

280 J . AM. ACAD. CHILD ADOLESC. PSYCHIATRY, 42 :3 , MARCH 2003

use of one of the stimulant medications, methylphenidate (MPH) oramphetamine (AMP). Clinicians were free to use any form of amphet-amine (pure dextro [DEX] or mixed-salts amphetamine [MSA]); theycould also choose between an immediate-release form or a long-actingpreparation of the stimulant. Whichever stimulant medication waschosen, the clinician was requested to have the patient undergo a 4-week open trial of the medication, using a fixed titration schedule. Forinstance, if the chosen medication was MPH, the child was to receive5, 10, 15, and 20 mg of stimulant twice a day in weeks 1, 2, 3, and 4,respectively. The psychiatrist was free to use a long-acting formulationof MPH (Concerta� was the only long-acting form of stimulant avail-able at the time of the study). The total daily dose of short-acting MPHwas given as once-a-day dose of Concerta, using the standard conver-sion (5 mg t.i.d. = 18 mg/day, 10 mg t.i.d. = 36 mg/day, 15 mg t.i.d. =54 mg/day, 20 mg t.i.d. = 72 mg/day). The equivalent doses of AMPwere 2.5, 5, 7.5, and 10 mg. The order of the dosages was always inascending order and the highest dose was omitted for children weigh-ing less than 20 kg. Each week, a CC contacted the parent by tele-phone and obtained a 10-item Conners Global Index-Parent (Conners,1997). The CC also interviewed the parent regarding any side effectsthat the child might have experienced and sent a 10-item ConnersGlobal Index-Teacher to a designated teacher for rating the child’sweekly behavior in the classroom. The CC discussed the case with thechild’s psychiatrist; if no clinically significant side effects had occurred,the child’s stimulant dose was moved to the next titration level and theprocess was repeated. While the family or psychiatrist could decline tomove to the next dosage level, the intent of the algorithm was to haveeach child experience the full dose range of the stimulant. On the fifthweek, the child came for a clinic visit, during which the psychiatristreviewed the rating scales from all 4 weeks and the best dose from thetitration was chosen. The psychiatrist reviewed the rating scales, inter-viewed the child and parent, consulted with the CC, and then obtainedthe Clinical Global Impression Scale-Improvement (CGI-I). The CGI-I measures the degree of improvement from baseline and is rated ona 7-point scale. (The CGI-I is to be distinguished from the 10-pointCGI-S described earlier, which measures only severity). The anchorsof the CGI are as follows: 1 = very much improved, 2 = much improved,3 = minimally improved, 4 = no change, 5 = minimally worse, 6 =moderately worse, and 7 = severely worse. If the CGI was rated as a 1or 2, the child was considered a responder and the stimulant was usedfor long-term management. The psychiatrist could then do any fur-ther titration necessary (for instance, adding a third dose of immedi-ate-release MPH after school).

If the CGI-I was 3 or greater (indicating little or no improvement),the child proceeded to stage 2, which was the class of stimulant nottried in stage 1. If a child entered the study with a clear history ofnonresponse to either MPH or AMP, then he/she entered the studyat stage 2. Similarly, if the child’s history showed nonresponse to bothstimulants, he/she would enter at stage 3 (a trial of pemoline), and soon. Stages 4 through 6 consisted of a tricyclic antidepressant, bupro-pion, and finally an a-agonist. Details can be found in Pliszka et al.(2000b) and on the Web at http://www.mhmr.state.tx.us/centraloffice/medicaldirector/adhdpage.html.

Clinician Training

Each medical director of the participating clinics reviewed andapproved the project. Child and adolescent psychiatrists volunteeredto be part of the study; no clinician was required by state or localMHMR administration to participate, and no general psychiatristswere involved in treating children in these clinics. No overt or covertresistance was encountered from administration or psychiatrists, andnone of those asked to participate refused. A day-long conference was

held with participating psychiatrists, the authors, and the CCs. TheADHD algorithm was introduced to the psychiatrists, the tactics ofthe algorithm were described in detail, and the role of the CC wasdefined. Training was provided for both physicians and CCs in thepsychoeducational component of the treatment package. An exten-sive question-and-answer period followed. The procedures were wellaccepted by the psychiatrists; the chief concerns expressed related toabilities of families to make the required follow-up visits. Also notablewere concerns about handling children with more atypical presenta-tions. CCs at each of the sites had a regular telephone conference withthe research coordinator (C.B.), and all the psychiatrists and CCs hada monthly telephone conference with one of the three senior Children’sMedication Algorithm Project (CMAP) investigators. Problems withalgorithm implementation were discussed at these conferences; psy-chiatrists could seek answers to questions regarding operationaliza-tion of the algorithm tactics, as well as patient-specific consultation.These conferences served to enhance compliance with the algorithm.If the psychiatrist could not be present, the CC would present to theconsultants any issues the psychiatrist had raised. It must be empha-sized that psychiatrists were not mandated to strictly follow the algo-rithm; they were free to use their own clinical judgment in theirpsychopharmacological management of the subjects.

Other Algorithm Interventions

Other interventions were included with the algorithms in an attemptto enhance adherence. The CCs contacted patients and families on aregular basis and reminded them of clinic visits. They assisted physi-cians with clinical care and prompted them regarding use of the algo-rithms. They were also responsible for implementing an extensivepatient/family education program that was developed to complementthe CMAP algorithms. Thus the interventions comprised a diseasemanagement program, with the algorithms serving as the frameworkfor clinical decision making. The psychoeducational materials maybe viewed at http://www.mhmr.state.tx.us/centraloffice/medicaldirector/cmapadhded.html.

Outcome Measures

Subjects were monitored for 4 months. At 4 months, the CC per-formed an outcome assessment that consisted of the SNAP-IV, Connersscales, YOQ, and CAFAS. During an office visit at the 4-month mark,the child and adolescent psychiatrist completed the CGI, assessingboth the severity at endpoint and the degree of improvement relativeto baseline.

Historical Controls

To provide a comparison of the algorithm-treated group and thosewho experienced treatment as usual (TAU), a chart review was doneby the CCs on the charts of children aged 6 to 17 with a primary diag-nosis of ADHD. Four hundred charts of children treated by CMAPpsychiatrists in the year prior to algorithm implementation were ran-domly selected from the TDMHMR database. All charts of childrenmeeting criteria for a primary diagnosis of ADHD were reviewed.Exclusionary criteria were the same as for the algorithm group. Onehundred eighteen charts were reviewed. CCs extracted informationon age, gender, ethnicity, and comorbid diagnoses. They noted themedications prescribed and the number of visits attended for the 4-month period after the initial psychiatric evaluation. The baselineevaluation and progress notes were reviewed, and a CGI-S rating ofbaseline severity as well as a 4-month CGI-I rating of improvementwere done on the basis of this chart information.

CMAP: ADHD FEASIBILITY STUDY

J. AM. ACAD. CHILD ADOLESC. PSYCHIATRY, 42 :3 , MARCH 2003 281

RESULTS

Baseline Measures

Table 1 compares the algorithm patients with the his-torical controls. The groups were not different with regardto ethnicity or comorbid ODD/conduct disorder. In con-trast to many research studies, this sample had a high rep-resentation of minorities, consistent with their proportionin the community in which the centers were located. Thealgorithm group showed more severe symptoms at base-line relative to the TAU group (t69.5 = 4.18, p < .0001)and was older (t122 = –3.66, p = .0004). Age and baselineseverity were used as covariates in subsequent analysescomparing the algorithm and TAU groups. In terms ofthe parent DISC, 75.6% of the algorithm subjects whomet ADHD criteria by the psychiatrist’s clinical judg-ment also met DISC criteria for ADHD in the past month,while 84.4% of the subjects met past-year DISC criteriafor ADHD. The psychiatrist-generated DSM-IV check-list was used to examine the number of ADHD symp-toms identified by the psychiatrist in those subjects whodid not meet past-year DISC criteria for ADHD. Fourof these patients had greater than six inattention or hyper-activity/impulsivity symptoms on the psychiatrist check-list, suggesting the lack of a DISC diagnosis representeda false negative in these cases. Of the remaining two, onehad five hyperactive/impulsive symptoms and the otherhad four symptoms of inattention and four of hyperac-tivity. The psychiatrists nonetheless believed that the chil-dren showed sufficient impairment to warrant treatment.

Of the 50 algorithm subjects, 37 (74%) remained intreatment at 4 months. Of 118 charts of patients in the

TAU group with ADHD identified for review, 93 (78.8%)of these charts indicated that the patients were still in treat-ment at 4 months (c2 = 0.47, p = .50). In the algorithmgroups 49 (98%) started medications, compared with 114who were prescribed medication (96.6%) in the TAUgroup. Forty-five subjects (90%) completed baseline assess-ment, completed at least one stimulant titration, and hada follow-up beyond the titration. The psychiatrist com-pleted an end-of-treatment CGI on 46 (92%) of the algo-rithm subjects. The remaining four subjects either did notreturn for this measure or could not be scheduled withthe psychiatrist at the 4-month follow-up point.

Stage Progression

Figure 1 shows the progression of the subjects throughthe various stages (1 of the 50 subjects never started med-ication). Fourteen subjects started at stage 2 because ofa history of nonresponse to MPH. Three of these sub-jects could not tolerate MPH, and the remainder had aninadequate behavioral response (mean daily dose of MPH:22.5 ± 11.7 mg). Similarly, five subjects started stage 2with MPH because of a history of nonresponse to AMP.Two of these subjects did not tolerate AMP, and the otherthree did not have a behavioral response to AMP. Themean daily dose of AMP used was 18.3 ± 2.9 mg.

Thirty-nine (79.6%) subjects were managed success-fully on a single stimulant in either stage 1 or stage 2.Four patients should have progressed to pemoline, butthe psychiatrists instead did a trial of a third stimulantor did another trial of a stimulant that had previouslybeen judged unsuccessful. Two patients had clonidineadded to their DEX treatment. Thus six (12.2%) patients

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TABLE 1Comparison of Baseline Characteristics of Algorithm Subjects and Historical Controls

Treatment asAlgorithm Usual p

No. 50 118% Female 24 19 NSMean age (years) 8.28 (2.06) 9.69 (2.75) .0004% Hispanic 34 (n = 17) 28 (n = 33) NS% African American 22 (n = 11) 19 (n = 22) NS% ODD or CD 28 (n = 14) 42 (n = 49) .098Baseline severity 6.5 (1.1) 5.5 (1.5) .0001Remained in continuous treatment for 4 months, n (%) 37 (74) 93 (79) NSStarted medication for ADHD, n (%) 49 (98) 114 (96.6) NSCompleted baseline, titration, and at least one posttitration measure, n (%) 45 (90) NACGI performed by psychiatrist at follow-up, n (%) 46 (92) NA

Note: ODD = oppositional defiant disorder; CD = conduct disorder; ADHD = attention-deficit/hyperactivity disorder;CGI = Clinical Global Impression Scale; NS = not significant; NA = not applicable.

were managed “off algo.” One patient had risperidoneadded for aggression. Another patient experienced hal-lucinations during MPH treatment, and risperidone wasadded rather than discontinuing the MPH and movingto stage 2. Later, on reassessment, the psychiatrist deter-mined that the child met criteria for bipolar disorder. Asecond patient developed symptoms of “mood disorderNOS [not otherwise specified]” (irritability, aggression)while on MPH, and the psychiatrist added risperidoneand divalproex to combat these symptoms rather thanmoving to the next stage.

Stimulant Titration

A total of 55 stimulant titrations were undertaken dur-ing the study. Twenty (36.4%) of these trials involved allfour dosages in a fixed titration model as called for in the

algorithm. Three doses were used in 10 (18.2%) of thetitrations (mostly because of the low weight of the child),and only two doses were used in eight of the titrations(14.5%). Finally, 17 (30.9%) of the titrations used onlyone dose level. Thus the fixed titration methodology wasmodestly well received by families or the psychiatrists, inas-much as three or four titrations were used slightly morethan half of the time (54.5%). The most common reasongiven by the psychiatrist for why they did not use the fixedtitration was that families were resistant. If the family sawimprovement in their child’s behavior on the first dose ofthe titration, they did not wish to see any further escala-tion in dose. The mean highest dose of stimulant was 23.24mg/day for MPH and 21.54 mg/day for AMP.

The Conners Global Index-Parent was obtained atbaseline, up to four times during titration, at each med-



Fig. 1 Progression of subjects through the stages of the attention-deficit/hyperactivity disorder treatment algorithm. AMP = amphetamine; MPH = methylphenidate;MSA = mixed-salts amphetamine; DEX = dextroamphetamine; NOS = not otherwise specified.

ication visit, and at 4-month follow-up. During the titra-tion, 45 of the 50 parents returned at least one ratingscale. Given the number of titration dosages, 139 parentratings should have been obtained during titration; infact, parents completed 86 (61.9%) such scales. A dis-appointment was the inability to collect all but a hand-ful of Conners Global Index-Teacher ratings. Only 7teachers returned both a baseline and a titration scale,whereas 17 returned both a baseline and follow-up scale.The CCs reported that families often did not take therating forms to the school or that the teachers did notreturn them, particularly during the titration phase. TheCCs or parents reported that the teachers were frequentlyunresponsive to telephone calls. It is also possible that thepsychiatrists did not perceive any importance in the teacherratings, seeing them as just research paperwork. It wasclear that most psychiatrists in the centers did not rou-tinely obtain teachers’ ratings on their clinic patients withADHD. On the other hand, it may well be extremely dif-ficult to obtain multiple assessments from teachers over-whelmed by school duties.

CMAP psychiatrists completed 43 of the 53 end-of-titration CGIs, a very reasonable performance for clini-cians who were not highly familiar with research instruments.

Medication Use

Table 2 compares the medications prescribed at any timeduring the 4-month trial in the algorithm and TAU groups.The algorithm subjects were treated more often with MSArelative to the TAU group, which was more likely to receiveMPH (c2

2 = 15.8, p = .0004). The algorithm group was lesslikely to receive multiple psychotropic medications. Whereas32% of the TAU group received one or more nonstimu-

lant medications, only 14% of the algorithm group receivedone of these medications (c2

1 = 5.9, p = .015).

CGI Outcome

Figure 2 shows the comparison of the CGIs for the algo-rithm and TAU groups, controlling for baseline severityand age. Forty-six (using intent-to-treat sample) CGIs wereavailable for the algorithm group. The algorithm group

PLISZKA ET AL.


Fig. 2 Outcome at 4 months. A: The algorithm (ALGO) group had significantly greater improvement (lower CGI-Improvement scores)than the treatment as usual (TAU) group. B: The ALGO group showed a significantly greater decline in clinical severity scores (CGI-Severity)than the TAU group. CGI = Clinical Global Impression Scale; BSL = baseline.

TABLE 2Medication Use

Algorithm Treatment As Usual

Frequency FrequencyMedication (n) (%) (n) (%)

Mixed-salts amphetamine 31 45.59 29 16.29Bupropion 1 1.47 4 2.25Carbamazepine 1 0.56Clonazepam 1 0.56Clonidine 3 4.41 7 3.93Dextroamphetamine 8 11.76 18 10.11Diphenhydramine 1 1.47 3 1.69Divalproex 1 1.47 5 2.81Fluoxetine 4 2.25Fluvoxamine 1 0.56Guanfacine 1 0.56Hydroxyzine 1 0.56Imipramine 8 4.49Lithium 2 1.12Methylphenidate 18 26.47 70 39.33None 4 2.25Olanzapine 1 0.56Paroxetine 1 1.47 4 2.25Pemoline 3 1.69Risperidone 2 2.94 6 3.37Sertraline 2 1.12Trazodone 1 1.47 3 1.69

showed greater improvement on the CGI-I rating relativeto the TAU group (analysis of covariance, F3,160 = 9.99,p < .002), as well a greater decline in severity of illness at theendpoint (analysis of covariance, F3,160 = 13.56, p = .0003).

Other Outcome Measures

Table 3 shows the comparison of baseline and 4-monthfollow-up Conners scales (all 50 parent scales and the 17subjects whose teachers returned both baseline and follow-up studies), YOQ, CAFAS, and SNAP measures. Pairedt tests were used to examine the significance of these dif-ferences. The algorithm group showed significant changeon all these measures relative to baseline, indicating sig-nificant improvement in symptoms of ADHD and globalfunctioning. It should be noted that, despite improve-ment, both teacher and parent Conners ratings remainedin the impaired range.

DISCUSSION

To our knowledge, this was the first attempt to imple-ment and evaluate an evidence-based algorithm for thetreatment of ADHD into a community mental healthcenter environment. At a broad level, the algorithm waswell accepted and implemented by the psychiatrists.Stimulant medications were used as the drugs of firstchoice, and the psychiatrists attempted to use a fixed titra-tion strategy to expose patients to the full range of stim-ulant dosages. This was done in nearly half the cases. Allthe subjects responded to at least one of the commonlyprescribed stimulants, MSA, DEX, or MPH. That polyphar-macy was significantly reduced in the algorithm grouprelative to the TAU group strongly suggests that the algo-rithm impacted the psychiatrist’s decision making.Alternatively, that the psychiatrist knew his/her treatment

was being observed could also have had a “Hawthorne”effect. A number of issues arose with the feasibility of thealgorithm. Pemoline was included as stage 3 because ofthe extensive evidence for its efficacy as a treatment forADHD. The consensus conference was held in July 1998,but the more extensive requirements for liver monitor-ing during pemoline treatment appeared in June 1999.Had these requirements been known at the time of theconference, it is unlikely the panel would have includedpemoline in the algorithm. In constructing the algorithm,the consensus panel viewed MSA and DEX as inter-changeable, and thus they were included in the same stage.It is clear that most of the CMAP psychiatrists did notshare this view, but wished to attempt trials of both formsof AMP if one failed to improve symptoms. It is alsointeresting that when psychiatrists determined that a med-ication in a given stage was not improving symptoms,they would sometimes go back to a previous stage, usinga medication that was thought to have failed rather thanmoving forward to the next stage. This may not repre-sent a failure of the clinicians, however, but may indicatea need to modify the algorithm to allow such recyclingof stages to deal with this common clinical situation.

Because many patients had comorbid ODD and con-duct disorder, treatment of aggression became a signifi-cant concern. The consensus panel developed an algorithmfor the treatment of comorbid intermittent explosive dis-order (IED) (Pliszka et al., 2000a). It was not the intentof this feasibility study to examine that particular algo-rithm. None of the subjects had a diagnosis of IED atentry into the study, and informal discussion with the psy-chiatrists indicated that many of them were uncomfort-able with this diagnosis. As noted in the results, this ledto clinicians “winging it” when presented with aggressivebehavior. α-Agonists, mood stabilizers, and risperidonewere used in these situations, though not in the structuredmanner recommended by the IED algorithm. This wasnot the fault of the psychiatrists; rather the CMAP inves-tigators did not anticipate the degree to which aggressivesymptoms would occur in a sample of ADHD childrenwithout formally diagnosed IED. It was also clear thatthere is little consensus in our field regarding the diagno-sis of children with aggression and mood lability—in twocases diagnoses of bipolar disorder NOS and mood dis-order NOS were used to deal with this uncertainty.

Problems were encountered with the algorithm tac-tics. In particular, the MTA-style fixed titration modelproved difficult to implement fully in these community



TABLE 3Comparison of Baseline and Follow-up

Measures in Algorithm Group

Baseline Follow-up T p

YOQ (n = 45) 67.66 (27.55) 47.62 (26.69) 6.52 <.0001CAFAS (n = 45) 53.56 (25.77) 20.67 (17.63) 8.55 <.0001Conners Parent

(n = 50) 76.14 (9.84) 63.36 (11.86) 8.04 <.0001SNAP (n = 45) 2.04 (0.59) 1.24 (0.60) 7.40 <.0001Conners Teacher

(n = 17) 67.76 (12.45) 60.41 (11.81) 2.37 .0309

Note: YOQ = Youth Outcome Questionnaire; CAFAS = ChildAdolescent Functioning Assessment.

mental health centers. Resistance to upward titration ofdoses was encountered, and it was difficult to obtain reg-ular ratings from both teachers and parents. As a result,doses of medication were relatively low (particularly withregard to MPH). More AMP was used in the algorithmgroup relative to the historical controls, perhaps becauseof marketing of AMP products during the period of thestudy. Inasmuch as MPH is less potent than AMP, thefailure of psychiatrists to titrate to a higher dose of MPHmight have reduced its effectiveness relative to AMP. Itis interesting that 15 to 30 mg/day of any stimulant seemedto be an “instinctive” dose for most psychiatrists, and theywere most unlikely to push MPH to daily doses of 40 to60 mg. Complete remission of ADHD symptoms, regard-less of stimulant, was not obtained, at least as judged byparent and teacher Conners ratings. Thus the algorithmgroup more closely resembled the community treatmentgroup of the MTA study, where mean daily doses werelower and clinic visits less frequent than in the expertmedication management group (MTA Cooperative Group,1999). Given that optimal dosing of a stimulant is thoughtto be one of the primary reasons for the better outcomein the MTA medication management groups relative tothe community treatment group, more attention to thisaspect of the algorithm tactics is required. Alternativemeans of conveniently obtaining teacher ratings need tobe developed. These might include school visits by CCs,communicating by teachers with e-mail (at their schoolor home), or using Web-based instruments to allow teach-ers (with parental permission) to upload information tothe clinic. All of these raise interesting issues with regardto security and patient confidentiality.

Limitations

Data showing a greater degree of improvement in thealgorithm group relative to historical controls must beviewed with caution. CCs abstracting data from the chartswere not blind to group status, and chart review ratherthan direct assessment by a clinician was used to obtainthe CGIs in the TAU group. With the algorithm group,treating psychiatrists—rather than independent evalua-tors—completed the CGIs. This may have introduced abias, as the treating clinicians in the study may have judgedtheir own efforts as producing more improvement thanindependent observers might have. The finding that somany parent ratings on the Conners remained in theimpaired range is consistent with this fact. After the algo-rithms are modified to incorporate the experiences from

this study (e.g., removing pemoline), then randomizedclinical trials will be needed to determine whether theuse of the algorithm results in superior clinical outcome.

Psychiatrists received substantial administrative sup-port from the CCs that may have led them to receiveimportant clinical information which assisted them inthe child’s care. This support, rather than the algorithmper se, might have accounted for the better clinical out-come. Similarly, the patient education program may havehad a benefit separate from the effects of the algorithm.Future studies of the algorithm should attempt to parseout these effects.

Clinical Implications

Algorithms for the treatment of ADHD can be suc-cessfully implemented in community mental health cen-ters and appear to reduce polypharmacy in the treatmentof ADHD. However, significant variance from the algo-rithm recommendations did occur. This is particularly truewith regard to stimulant dosing and acquiring teacher rat-ings. We know from this study as well as the experiencesof others that implementation of guidelines is not easy(Davis et al., 1995; Rosenheck, 2001; Torrey et al., 2001).Processes must be put in place to make it easy for clini-cians to use algorithms and to provide them with feedbackregarding their performance. Computerized charting sys-tems, one method recommended to achieve this goal, havethe advantage of providing the clinician with immediate,nonintrusive feedback regarding decisions (Altshuler andRush, 1999). We also know that organization plays animportant role in implementing any new program. Rosenheck(2001) suggests that organizational factors may be moreimportant than individual clinician factors in implement-ing change and applying research evidence to practice.Thus future studies in this area need to examine methodsto implement organizational change as well as provide spe-cific interventions to influence behavior. Both cliniciansand teachers may need greater education regarding the useof more quantifiable measures of ADHD treatment.

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Documents

A Feasibility Study of the Children's Medication Algorithm Project (CMAP) Algorithm for the Treatment of ADHD