Predictors of Treatment Response in Anxious-Depressed Adolescents With School Refusal

There is a growing recognition of the need to improve ourcapacity to effectively treat anxiety disorders in childrenand adolescents as they are the most prevalent psychiatricdisorders of childhood and adolescence (Bernstein andBorchardt, 1991; Dadds and Barrett, 2001) and have sig-nificant impact on functioning (e.g., Pine et al., 1998).Furthermore, the long-term outcomes of anxiety disordersin adolescence include later risk of additional anxiety dis-orders, major depression, illicit drug use, and reduced like-

lihood of attending college (Woodward and Fergusson,2001). While great strides have been made in developingefficacious cognitive-behavioral therapy (CBT) (e.g.,Barrett et al., 1996; Flannery-Schroeder and Kendall, 2000;Silverman et al., 1999) and pharmacological (ResearchUnit on Pediatric Psychopharmacology Anxiety StudyGroup, 2001; Rynn et al., 2001) interventions for chil-dren and adolescents with anxiety, few studies have attemptedto identify the predictors of treatment response and, to ourknowledge, none have specifically focused on predictorsof treatment response in adolescents with school refusal.

Studies evaluating predictors of treatment responsehave been published for other childhood disorders, includ-ing depression (Brent et al., 1998; Clarke et al., 1992;Jayson et al., 1998) and externalizing behavior problems(Kazdin and Crowley, 1997; Webster-Stratton andHammond, 1990). To date, only two studies have beenpublished that were specifically designed to evaluate pre-dictors of outcome to CBT in children with anxiety dis-orders (Berman et al., 2000; Southam-Gerow et al., 2001).The Berman and colleagues (2000) study included 106participants aged 6 to 17 years with a phobic or anxiety

Predictors of Treatment Response in Anxious-DepressedAdolescents With School Refusal

ANN E. LAYNE, PH.D., GAIL A. BERNSTEIN, M.D., ELIZABETH A. EGAN, PH.D., AND MATT G. KUSHNER, PH.D.

ABSTRACT

Objective: To identify predictors of treatment response to 8 weeks of cognitive-behavioral therapy (CBT) among anx-

ious-depressed adolescents with school refusal, half of whom received imipramine plus CBT and half of whom received

placebo plus CBT. Method: A hierarchical multiple regression analysis was used to evaluate the following variables as

potential predictors of treatment response as measured by school attendance at the end of treatment: baseline severity

(school attendance at baseline), drug group (imipramine versus placebo), presence of separation anxiety disorder (SAD),

and presence of avoidant disorder (AD). Results: Baseline attendance, CBT plus imipramine, SAD, and AD were significant

predictors of treatment response and accounted for 51% of the variance in outcome. Specifically, a higher rate of atten-

dance at baseline and receiving imipramine predicted a better response to treatment whereas the presence of SAD and

AD predicted a poorer response to treatment. The relationship between sociodemographic variables and treatment out-

come was also evaluated. Age and socioeconomic status were unrelated to school attendance after treatment. Males

had significantly higher rates of attendance after treatment than females. Conclusions: Adolescents with school refusal

are a heterogeneous population and require individualized treatment planning. Variables such as diagnosis and sever-

ity at the start of treatment should be taken into consideration when planning treatment. J. Am. Acad. Child Adolesc.

Psychiatry, 2003, 42(3):319–326. Key Words: school refusal, treatment, adolescents.

J . AM. ACAD. CHILD ADOLESC. PSYCHIATRY, 42 :3 , MARCH 2003 319

Accepted September 10, 2002.Dr. Layne is Postdoctoral Fellow, Dr. Bernstein is Professor and Head of the

Program in Child and Adolescent Anxiety and Mood Disorders, and Dr. Egan isStatistician in the Division of Child and Adolescent Psychiatry, and Dr. Kushneris Associate Professor, Department of Psychiatry, University of Minnesota MedicalSchool, Minneapolis.

Presented at the Annual Meeting of the American Academy of Child andAdolescent Psychiatry, San Francisco, October 2002.

Supported in part by NIMH grant R29 MH46534 to Dr. Bernstein. Theauthors acknowledge Cynthia G. Last, Ph.D., for her input to early discussions regard-ing content of the manuscript.

Reprint requests to Dr. Layne, Division of Child and Adolescent Psychiatry,F256/2B West, 2450 Riverside Avenue, Minneapolis, MN 55454.

0890-8567/03/4203–0319�2003 by the American Academy of Childand Adolescent Psychiatry.

DOI: 10.1097/01.CHI.0000037026.04952.96

disorder who received 10 to 12 weeks of exposure-basedtreatment. The results indicated that significant predic-tors of poor response to treatment were comorbid depres-sion diagnosis, elevated score on the Children’s DepressionInventory, high trait anxiety score on the Stait-Trait AnxietyInventory for Children, and psychological symptoms inthe parent (elevated scores on the Obsessive-Compulsive,Psychoticism, Depression, Hostility, and Paranoia scalesof the Symptom Checklist-90; elevated scores on the BeckDepression Inventory and Fear Questionnaire). However,the authors note that parental pathology was less predic-tive with older versus younger children and with thosewho received group instead of individual treatment. Thefollowing variables were not predictive of treatmentresponse: age, gender, ethnicity, family income, primaryanxiety diagnosis, total number of diagnoses, comorbidanxiety or externalizing disorders, parental ratings of sever-ity of the child’s disorder, or treatment modality (groupversus individual).

Southam-Gerow and colleagues (2001) evaluatedresponse to 12 weeks of individual CBT in 135 partici-pants, aged 7 to 15 years, with a primary anxiety disor-der. Poor treatment response was predicted by (1) higherlevels of internalizing problems, (2) higher levels of mater-nal depression, and (3) older youth age. Externalizingsymptoms, number of comorbid disorders, and demo-graphic variables were not predictive of treatment response.

Kendall and colleagues (2001) evaluated whether pre-treatment comorbidity (i.e., comorbid anxiety disorderor comorbid externalizing behavior disorder) was pre-dictive of CBT outcome in children with a primary anx-iety disorder. Participants (N = 173) received 16 to 20weeks of therapy. The results indicated that althoughindividuals with comorbid anxiety and/or externalizingdisorders displayed more severe internalizing symptomsat pretreatment than did the group without comorbiddiagnoses, comorbidity at pretreatment was not associ-ated with differences in treatment outcome. The find-ings are consistent with previous research that hasdemonstrated no significant relationship between num-ber of comorbid diagnoses and treatment outcome (e.g.,Jayson et al., 1998; Kendall et al., 1997; Shortt et al.,2001; Southam-Gerow et al., 2001).

Despite the lack of predictive validity of comorbidityin general, several studies have reported that children withcomorbid anxiety and major depressive disorders presentwith greater symptom severity (Bernstein, 1991; Lastet al., 1996), have a poorer response to treatment

(Berman et al., 2000; Brent et al., 1998; Clarke et al.,1992), and have more anxiety disorders (Masi et al., 1999).Similar results have also been reported for adults withanxiety and comorbid depression (Brown et al., 1995;Rief et al., 2000). In response to their finding that comor-bid depression was a significant predictor of treatmentfailure but comorbidity for other anxiety disorders wasnot, Berman and colleagues (2000) refer to the tripartitemodel of depression (Clark et al.,1994) which proposesthat the structure of affect is composed of three factors:a general negative affective feature (present in anxiety anddepression), elevated levels of physiological arousal (relatedto anxiety), and low levels of positive affect (e.g., lowinterest; related to depression.) Thus additional anxietydiagnoses would not add additional factors while a diag-nosis of depression would introduce an additional fac-tor. This model, along with the above-cited research,suggests that children with comorbid anxiety and depres-sive disorders warrant special consideration when the pre-dictors of treatment response are being investigated.

Study Objectives

The present study was designed to evaluate predictorsof treatment response in a sample of school-refusing ado-lescents with comorbid anxiety and major depressive dis-orders who received CBT. The study is innovative in thatall participants had both anxiety and depressive disorders,and treatments included CBT plus imipramine versus CBTplus placebo. Although there has been little previous researchevaluating predictors of treatment response among ado-lescents with school refusal or among adolescents with anx-iety and comorbid depression, selection of variables forevaluation as predictors was guided by related research.

The variables included for evaluation were severity ofschool refusal at baseline (measured by rate of schoolattendance), presence/absence of active drug therapy incombination with CBT, the presence/absence of separa-tion anxiety disorder (SAD), and presence/absence ofavoidant disorder (AD). Based on much of the researchcited above, as well as additional studies (Kendall et al.,1997; Shortt et al., 2001; Treadwell et al., 1995), sociode-mographic variables were not expected to significantlypredict treatment response and were therefore not includedin the conceptual model under evaluation.

It was expected that individuals with more severe schoolrefusal measured by lower rate of school attendance atbaseline would have a poorer response to CBT comparedwith individuals with less severe school refusal at base-

LAYNE ET AL.

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

line. Last et al. (1998) reported that participants withhigher school attendance at session 1 were significantlymore likely to have completely improved by the end ofa CBT treatment for school refusal. Furthermore, mea-sures of baseline symptom severity in general have pre-dicted treatment response in a number of studies withanxious (e.g., Southam-Gerow et al., 2001) and depressed(e.g., Clarke et al., 1992; Jayson et al., 1998) participants.Our earlier work indicated that the combined effect ofimipramine plus CBT results in greater improvementthan with placebo plus CBT (Bernstein et al., 2000) andshould therefore emerge as a significant predictor in thepresent analysis. It was expected that the presence of SADand AD would be predictive of poorer response to treat-ment. Individuals with SAD and AD are likely to havegreater difficulty attending school than those with moregeneralized anxiety based on the nature of the disorders(i.e., excessive anxiety about separation from home andfrom attachment figures and persistent and excessiveavoidance of contact with strangers, respectively) (AmericanPsychiatric Association, 1987, 1994). The hypothesisregarding SAD is also supported by previous research thatfound that in adolescents with major depression, con-current SAD was associated with poorer response to phar-macological treatment (Ryan et al., 1986).

METHOD

Participants

The original sample has been described in detail previously(Bernstein et al., 2000). The total sample included 63 adolescents;however, only 41 participants were included in the present analysis.Participants without baseline attendance data and participants whodid not complete the study were omitted. Over the course of the treat-ment study, 25% (n = 16) of the total sample (N = 63) dropped out.Previously reported results indicate that participants who droppedout of the study did not differ significantly from those who completedthe study across demographic variables, school attendance, and symp-tom severity (Bernstein et al., 2000). The resulting sample included23 females and 18 males aged 12 to 18 (mean = 14.7 years) who par-ticipated in a randomized controlled study of imipramine versusplacebo in combination with CBT for school refusal. The ethnic back-ground of the sample was 92.7% white (n = 38) and 7.3% AfricanAmerican (n = 3). Socioeconomic status was determined using theHollingshead Two Factor Index (Hollingshead, 1957): 2.4% (n = 1)class I, 14.6% (n = 6) class II, 41.5% (n = 17) class III, 36.6% (n =15) class IV, and 4.9% (n = 2) class V (1–V, with I highest).

Inclusion criteria included the following: (1) at least 20% of schooldays missed in the 4 weeks prior to the initial assessment; (2) post-pubertal (Tanner stages III–IV) (Marshall and Tanner, 1969, 1970)based on physical examination; (3) diagnosis of one or more anxietydisorders and major depressive disorder based on the DiagnosticInterview for Children and Adolescents-Revised-Parent Version (DICA-R-P) and/or Adolescent Version (DICA-R-A) (Reich and Welner,

1990) or the Diagnostic Interview Schedule for Children Version 2.3,Parent (DISC-P) and/or Child (DISC-C) versions (Shaffer et al.,1996) for anxiety disorders not covered in the DICA-R (i.e., socialphobia, panic disorder, agoraphobia); and (4) score of ≥5 on theAnxiety subscale of the Anxiety Rating for Children-Revised (ARC-R) (Bernstein et al., 1996) and a score of ≥35 on the Children’sDepression Rating Scale-Revised (CDRS-R) (Poznanski et al., 1984).Exclusionary diagnoses were attention-deficit/hyperactivity disorder(ADHD), conduct disorder, bipolar affective disorder (in participantor first-degree relative), eating disorder, psychosis, substance abusedisorder, or mental retardation.

Procedure

Written informed consent for participation was obtained for par-ticipants and their parent(s). Participants meeting criteria for inclu-sion underwent a 1-week single-blind placebo washout period. Noparticipants met exclusionary criteria after this period. Participantswere then randomly assigned to one of two treatment conditions: 8weeks of imipramine plus CBT or 8 weeks of placebo plus CBT.Twenty-one participants received imipramine and 20 received placebo.The individual CBT program was a manual-based school reentry pro-gram developed by Cynthia Last, Ph.D. (Last et al., 1998). The ther-apy was administered by two doctoral-level therapists and a master’s-leveltherapist. Treatment consisted of eight sessions 45 to 60 minutes inlength conducted primarily with the adolescent. Participants werealso seen weekly by a psychiatrist blind to treatment condition for thepurpose of monitoring side effects and compliance and assessing globalimprovement. For additional information refer to Bernstein and col-leagues (2000).

Assessment Measures

The DICA-R (Reich and Welner, 1990) parent and child inter-views were used to assess psychiatric disorders according to DSM-III-R criteria. The measure has demonstrated interrater reliability (κcoefficients ranged from 0.76 to 1.00) and has been shown to be effec-tive for use in general population samples (Welner et al., 1987).

The DISC (Shaffer et al., 1996) parent and child interviews wereadded in the 2nd year of the study to assess anxiety disorders (basedon DSM-III-R) not included in the DICA-R (i.e., social phobia, panicdisorder, agoraphobia). The DISC has acceptable psychometric prop-erties including test-retest reliability (intraclass correlation coefficientsranged from 0.66 to 1.00) (Shaffer et al., 1993), internal consistency(Shaffer et al., 1996), and criterion validity (Schwab-Stone et al., 1996).

The ARC-R (Bernstein et al., 1996) was used as a clinician-ratedmeasure of anxiety symptoms. The ARC-R has been demonstratedto have reliability and validity including high test-retest reliability,interrater reliability, and internal consistency (Bernstein et al., 1996).

The CDRS-R (Poznanski et al., 1984) was used as a clinician-ratedmeasure of depression. The CDRS-R has demonstrated adequate test-retest reliability, discriminant validity, and concurrent validity(Poznanski et al., 1984).

Baseline attendance data were gathered during the 1-week placebowashout period. Weekly rates of school attendance were based on thenumber of hours attended each week divided by the number of pos-sible hours of school attendance, multiplied by 100. Attendance datawere gathered by parents and recorded weekly on the provided forms.Attendance data were verified by school records.

Statistical Analysis

To test the main hypotheses, a hierarchical multiple regressionanalysis was performed on the four variables of interest in the fol-

PREDICTORS OF TREATMENT RESPONSE


lowing order: step 1, baseline school attendance; step 2, drug group,presence/absence of SAD, presence/absence of AD; and step 3, alltwo-way interactions between drug group, SAD, and AD. Baselineschool attendance was entered first to control for pretreatment dif-ferences in severity. All main effects were entered on the next step,followed by an exploration of two-way interactions. It was expectedthat step 2 of the regression would offer the best solution; step 3 wasincluded post hoc for exploratory purposes only. The unique contri-bution of each significant variable was calculated by entering thatvariable last after all other variables had been entered. Unique con-tributions reflect the change in R 2 and reflect the amount of variancein the dependent variable for which the variable of interest accounts.Rate of school attendance at week 8 was used as the outcome variable(number of hours attended each week divided by the number of pos-sible hours of school attendance, multiplied by 100). Post hoc analy-ses included zero-order correlation analyses and t tests to determinewhether demographic variables were related to treatment outcome.Analyses were based on participants who completed the study andhad baseline attendance data (n = 41).

RESULTS

Sample Characteristics

Participants met criteria for one or more of the fol-lowing anxiety disorders: SAD (34%, n = 14), AD (51%,n = 21), posttraumatic stress disorder (5%, n = 2), over-anxious disorder (OAD) (90%, n = 37), simple phobia(83%, n = 34), social phobia (68%, n = 23), agorapho-bia (47%, n = 16), and panic disorder (6%, n = 2). Thepercentage rates of the latter three diagnoses were basedon participants who received the DISC (n = 34). All par-ticipants met criteria for major depressive disorder. Forty-six percent (n = 19) of the sample met criteria for dysthymia,in addition to major depression. Forty-four percent ofthe sample met criteria for oppositional defiant disorder(n = 18). The mean rate of baseline school attendancewas 40.4%.

Main Analyses

As expected, step 2 of the regression offered the mostparsimonious model (R 2 = 0.51, F4,40 = 9.487, p < .001)(Table 1). The inclusion of treatment by diagnosis inter-action terms in step 3 did not improve the model. Baselineattendance (p = .016), CBT plus imipramine (p = .003),SAD (p = .010), and AD (p = .036) were significant pre-dictors of treatment response. Specifically, lower rates ofattendance at baseline, receiving placebo, presence ofSAD, and presence of AD predicted a poorer responseto treatment. The interactions between treatment andSAD and AD were not significant.

The predictor variables selected for inclusion in the regres-sion model accounted for 51% of the variance (step 2 of

model). When the unique contribution of each predictorvariable was calculated, baseline attendance accounted for14% of the variance, as did drug group (imipramine ver-sus placebo) (14%), followed by SAD (10%), and AD (6%).

Post hoc analyses included zero-order correlations anda t test to determine whether demographic variables weresignificantly related to treatment outcome (i.e., atten-dance at week 8). Because 38 of the 41 participants werewhite, the relationship between ethnicity and treatmentoutcome was not evaluated. Contrary to expectations,males had significantly higher rates of attendance at week8 than did females (t39 = –2.07, p = .045). Results indi-cate that age (r = –0.04, p = .77) and socioeconomic sta-tus (r = –0.12, p = .48) were not significantly correlatedwith attendance at the end of treatment.

Although gender was not hypothesized to emerge as asignificant predictor of treatment outcome, analysis indi-cates that at week 8 males have significantly higher ratesof attendance than females. Therefore, additional posthoc analyses were conducted to determine whether themodel presented above would be improved by addinggender as a potential predictor of outcome. Steps 1 and2 were entered as they were in the main analysis. Genderwas entered as a third step; the interaction terms betweentreatment and SAD/AD were entered as a fourth step.Results indicate that gender did not emerge as a signifi-cant predictor of attendance at week 8 and the inclusion

LAYNE ET AL.


TABLE 1Summary of Hierarchical Regression Analysis for Variables

Predicting School Attendance at Treatment End

Variable B SE B β

Step 1Baseline attendance 0.36 0.14 .37*

Step 2Baseline attendance 0.31 0.12 .32*Drug group 14.89 4.71 .39**Separation anxiety disorder –13.08 4.82 –.33*Avoidant disorder –9.85 4.52 –.26*

Step 3Baseline attendance 0.32 0.12 .33*Drug group 12.70 5.03 .33*Separation anxiety disorder –13.04 4.83 –.33*Avoidant disorder –10.20 4.54 –.27*Treatment � SAD –6.35 4.80 –.17Treatment � AD –0.29 4.57 –.01

Note: R2 = 0.14 for step 1, Δ R2 = 0.38 for step 2 (p < .001), Δ R2 =0.03 for step 3 (p = .40). SAD = separation anxiety disorder; AD =avoidant disorder.

* p < .05; ** p < .01.

of gender did not significantly improve the model (Fchange = 2.627, p = .11).

DISCUSSION

As predicted, baseline severity, drug group (imipramineversus placebo), SAD, and AD all emerged as significantpredictors of response to CBT. Poor treatment responsewas predicted by (1) lower rates of school attendance atbaseline, (2) receiving placebo instead of imipramine, (3)having a diagnosis of SAD, and (4) having a diagnosis ofAD. Together, these variables accounted for a consider-able amount of the treatment response variance (51%).The strongest predictors of treatment outcome were base-line attendance and drug group. Contrary to expecta-tions and to previous research, males had higher rates ofattendance after treatment than females. Age and socio-economic status were not related to treatment response.

The finding that lower rates of school attendance priorto CBT predict poorer treatment response is not sur-prising and is consistent with previous findings. The resultsuggests that case severity should be taken into accountwhen planning treatment. It is possible that the moresevere cases will require a stronger, more aggressive treat-ment plan. Southam-Gerow et al. (2001) suggested thatfor more severe cases, the strength of treatment may needto be increased by adding more sessions, more boostersessions, and/or additional adjunctive interventions (e.g.,social skills training, family therapy).

The addition of a pharmacological component (i.e.,imipramine) to the CBT protocol resulted in significantlygreater likelihood of having a positive response to treat-ment. The medication may have served to reduce depres-sive symptoms that interfere with school attendance (e.g.,sleeping too much, feelings of hopelessness, anhedonia).In a previous report regarding this sample, it was notedthat while all participants demonstrated significantlydecreased levels of depression after treatment, depressiondecreased at a significantly faster rate for participants whoreceived CBT plus imipramine (Bernstein et al., 2000).It is possible that the addition of medication enabled par-ticipants to be more actively engaged in CBT and com-pliant with between-session activities such as exposure.

In addition to baseline severity and drug group, SADand AD also emerged as significant predictors of treat-ment response. SAD accounted for 10% of the varianceand AD accounted for 6%. The finding that adolescentswith SAD were less likely to have a positive response to

treatment is inconsistent with results from a CBT treat-ment study of children with school refusal. Last andHansen (personal communication, 2001) reported thatchildren whose primary diagnosis was SAD had greaterimprovement in school attendance at the end of treat-ment compared with children with other anxiety diag-noses. It is possible that SAD in adolescence presents adifferent and more complex set of challenges than SADin childhood. Southam-Gerow and colleagues (2001, p.432) state, “it is possible that highly anxious older youthmay be more non-normative, developmentally speaking,and the problems associated with these disorders maycause more interference for older youth as they navigatethe challenges associated with adolescence.”

Adolescents with SAD are, in fact, nonnormative giventhat SAD is more prevalent in childhood (Last et al., 1987)and that the prevalence of SAD decreases with increasingage, whereas the prevalence of OAD increases with age(Westenberg et al., 1999). In addition, SAD has beenshown to have an earlier age of onset than other anxietydisorders (Last et al., 1987). Therefore, it is also possiblethat adolescents with SAD have been struggling with theiranxiety for a longer period of time than adolescents whoseanxiety disorders have a later age of onset. Furthermore,Westenberg et al. (1999) found that the age difference forOAD and SAD (i.e., children with SAD are younger com-pared with those with OAD) could be attributed to dif-ferences in psychosocial maturity. They found that levelof ego development, based on Loevinger’s (1976, 1993)theory of ego development, was the strongest predictorof having either SAD or OAD, with participants withdiagnosed OAD having a more developed ego comparedto those with SAD. These findings support the notionthat adolescents with SAD are more developmentally non-normative than younger children with SAD and there-fore present greater challenges at the time of treatment.

A poorer response to treatment was also predicted bythe presence of AD. In the revision of DSM-III-R (AmericanPsychiatric Association, 1987) to DSM-IV (AmericanPsychiatric Association, 1994), AD was eliminated givenits similarity to social phobia. Research comparing ADand social phobia has supported this change in DSM clas-sification. Francis and colleagues (1992) found no sig-nificant differences between youths with AD and socialphobia with regard to self-reported depression and fear,gender, race, and comorbid psychiatric diagnoses.

A number of studies have evaluated the presentationand treatment of children and adolescents with social



phobia (Beidel et al., 1999, 2000; Masia et al., 2001;Spence et al., 2000). Recent research has shown that com-pared with nonanxious children, children with social pho-bia have greater deficits in social skills and social competence(Beidel et al., 1999; Spence et al., 1999). The results ofresearch evaluating childhood social phobia indicate thattreatment should include social skills training and increasedsocial opportunities in addition to traditional CBT inter-ventions such as exposure, cognitive restructuring, andanxiety reduction techniques (Spence et al., 2000). Theauthors state, “exposure to social situations and the chal-lenging of negative cognitions is unlikely to be effectiveif the child continues to exhibit social skills deficits”(Spence et al., 2000, p. 714).

Despite having similar rates of attendance at baseline,a comparison of rates of attendance at week 8 for malesand females revealed that males had a significantly higherrate of attendance. However, gender did not emerge as asignificant predictor of outcome when added to the modelpresented above. The finding indicates that once the effectsof baseline severity, drug group, and the presence/absenceof SAD and AD on posttreatment attendance have beenaccounted for, the consideration of gender does not sig-nificantly improve one’s ability to predict outcome. Previousstudies have identified no relationship between genderand treatment outcome (Berman et al., 2000; Kendallet al., 1997; Shortt et al., 2001; Southam-Gerow et al.,2001; Treadwell et al., 1995).

Limitations

A major limitation of the study was having a samplesize too small to permit extensive evaluation of predic-tors, as well as assessment of potential mediators andmoderators of treatment response. The sample size requiredus to adopt a conservative approach to statistical analy-ses. A larger sample size would have permitted analysesthat may have resulted in additional predictors, as wellas interactions emerging as significant. Another limita-tion is not conducting a diagnostic interview at the endof treatment.

In addition, at present, selective serotonin reuptakeinhibitors (SSRIs) are the first line of treatment for pedi-atric anxiety and mood disorders. It is not known whetherthe same findings would result if an SSRI was used insteadof imipramine. Therefore, there are limitations on thegeneralizability of the findings to other classes of anti-depressant medication. Another threat to the generaliz-ability of the findings are the exclusionary criteria used

(i.e., exclusion of participants with ADHD, conduct dis-order, substance abuse, eating disorder, psychosis, bipo-lar disorder). It is possible that the presence of additionalcomorbidity would result in different findings.

Clinical Implications

Although preliminary, the results presented above havesome implications for mental health professionals treat-ing adolescents with school refusal. Because adolescentspresenting with more severe school refusal, SAD, and/orAD had a poorer response to the treatment administeredin the present study, such clinical characteristics may sug-gest the need for adjunctive treatments and/or modifica-tion to traditional CBT interventions for school refusal.While the results of the present study do not allow us toknow which modifications are best for which problems,a multimodal approach that includes both CBT andimipramine predicts a better response to treatment in ado-lescent school refusers with anxiety and depression com-pared with CBT and placebo. It is important to note thatblood levels were closely monitored to determine whetherparticipants received a therapeutic dose (see Bernsteinet al., 2000, for specific dosing information). The bene-fits of imipramine are likely to be limited when the doseis subtherapeutic. Overall, the findings indicate that ado-lescents with school refusal are a heterogeneous group andshould benefit from individualized treatment planningthat takes into consideration diagnoses and severity.

Future Directions

The results of this study suggest a number of direc-tions for future research, including identifying mediatorsand moderators of CBT response among adolescents withschool refusal (i.e., When is CBT alone versus CBT plusmedication indicated? When is a longer course of ther-apy indicated?), effective treatment components for ado-lescents with SAD, and which adjunctive treatments areindicated for adolescents with social phobia and schoolrefusal (e.g., social skills training). Given that severityemerged as a significant predictor of outcome, futurestudies should make efforts to identify indicators of sever-ity. Specifically, when should school refusal be consideredmild versus severe? Based on recent findings regardingelevated rates of anxiety and depressive disorders in par-ents of school refusers (Martin et al., 1999), investiga-tion of the relationship between parental psychopathologyand treatment outcome in adolescent school refusal isindicated. Of interest, Berman et al. (2000) found that

LAYNE ET AL.


parental pathology was less predictive of child function-ing after treatment in older versus younger children andadolescents with anxiety disorders. Several treatment out-come studies with anxious youths have found that addinga parent training component to the treatment resulted insuperior benefit compared with CBT without a parent-ing component (Barrett et al., 1996; Mendlowitz et al.,1999). Additional research is needed to determine whetherCBT outcome for adolescent school refusers could bestrengthened by including a parent training component.

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Predictors of Treatment Response in Anxious-Depressed Adolescents With School Refusal

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