Severity and Comorbidity as Predictors of CBT Outcome for Childhood Anxiety Disorders
A recent review supports the efficacy of Cognitive Behavioral Therapy (CBT) for Childhood Anxiety Disorders (CAD) and accords CBT the status of an empirically supported treatment (Cartwright-Hatton et al.
2004). However, a significant number of children (20 to 60 percent) that participate in research trials for CAD, do not show an adequate treatment response (Compton et al.
2002). Predictors of treatment response are of clinical and theoretical value (Rapee
2000) for identifying the mechanisms that facilitate or hinder treatment recovery. Two possible child predictors for treatment outcome for CAD are initial symptom severity and comorbidity.
In previous studies symptom severity has been associated with less favorable treatment outcomes in school-refusing youth, in which baseline school attendance represented severity (Layne et al.
2003). In another study the long-term outcome of child CBT for anxiety disorders was also predicted by severity as represented by the median split of the pretreatment scores on child-reported anxiety (Manassis et al.
2004). In a study of exposure-based CBT for phobic and anxiety disorders in youth mixed findings were reported: child-reported anxiety and depression severity predicted less favorable treatment outcome, but parent reported severity measures did not show any predictive value (Berman et al.
2000). In contrast, in a study of CBT for children with anxiety disorders parent reported child withdrawal symptoms predicted poor outcome while no associations were found with child-reported (e.g. anxiety and depression) severity measures (Southam-Gerow et al.
2001). Together, these results suggest that initial symptom severity is a good predictor of treatment outcome of CBT for CAD. However, we found no studies on the predictive value of measures of overall severity operationalized as total symptom count or total problem scores.
To date, most studies investigating the treatment outcome of CBT for CAD have not found an impact of diagnostic comorbidity on treatment recovery (Flannery-Schroeder et al.
2004; Kendall et al.
2001; Rapee
2003). One study found an association between comorbid depression and poor treatment response (Berman et al.
2000). Rapee (
2003) found no differences in treatment response at post-treatment, and negligible differences at 6 months follow-up between three groups of anxious children and adolescents; an anxiety disorder and no comorbid disorder group, a more than one anxiety disorder group and an anxiety disorder and comorbid disorder other than anxiety (mood disorder or externalizing disorder) group. At 6 months follow-up there was a slight increase of father-reported internalizing symptoms and mother-reported externalizing symptoms in the children with other comorbidity, whereas children with one or more anxiety disorders and no non-anxiety comorbid disorders still showed a decline in internalizing symptoms.
While studies suggest that CBT is equally effective for anxiety disordered children with or without comorbid disorders, it is premature to assume that a standard brief CBT program used in research trials will work as well for complex cases such as those that present themselves in non-research settings (Southam-Gerow et al.
2008). In addition, comorbidity has repeatedly been suggested to negatively impact treatment processes (e.g., Kennard et al.
2005). For clinical practice it is important to assess whether comorbidity is a clinically significant co-occurrence (Starcevic
2005) with possible unique effects on treatment outcome. To our knowledge research examining the unique impact of comorbidity on treatment outcome for childhood anxiety disorders above and beyond the impact of severity is scarce.
In the present study we use a measure of overall severity (i.e., the Total Problem score of the CBCL that has been validated as a measure indicating caseness, see Kasius et al. (
1997)). We further study the impact of both continuous and categorical outcome measures to examine the unique impact of comorbidity. Comorbidity and overall severity, though closely related, are for the purposes of this study viewed as distinct concepts, with comorbidity referring to the co-occurrence of two or more psychiatric disorders, and overall severity referring to the number of symptoms regardless of diagnostic status.
Two patterns of co-occurrence of psychiatric diagnoses are examined: total comorbidity, defined as any pattern of co-occurrence, and non-anxiety comorbidity, defined as the co-occurrence of one or more anxiety and one or more non-anxiety disorders. Total comorbidity reflects the broad definition of comorbidity as the co-occurrence of two or more psychiatric diagnoses (Starcevic
2005). Non-anxiety comorbidity originates from the proposal of Angold et al. (
1999) to make a distinction between two types of comorbidity that tend to have different implications: homotypic comorbidity (i.e., comorbidity between disorders within a diagnostic grouping, such as anxiety disorders) and heterotypic comorbidity (i.e., comorbidity between disorders from different diagnostic groupings). As the high level of comorbidity of different anxiety disorders may reflect the possible artificiality of the subdivision of anxiety disorders into many different syndromes (Caron and Rutter
1991), we decided to focus on non-anxiety comorbidity, i.e. the heterotypic comorbidity of one or more anxiety disorders and one or more non-anxiety disorders. Total comorbidity in contrast reflects the number of disorders regardless the nature of the comorbid disorder(s).
It is important when studying predictors of treatment outcome to effectively evaluate the nature and degree of change that has occurred as a result of therapy. Estimation of pre- to post-treatment change is often inferred by calculating differences between pre and post-treatment scores on primary outcome measures, e.g., by using a repeated measures design including time. A serious drawback of using pre-post difference scores is that measurement-error (error-based regression to the mean) is not taken into account (Hageman and Arrindell
1999). Hageman and Arrindell therefore proposed procedures to establish Reliable Change and clinically significant change. Furthermore, recovery usually reflects the clinical post-treatment symptom-status given the pretreatment symptom status; e.g., a disorder that was present before treatment, is present (i.e., no recovery) or absent (recovery) at post treatment. If continuous outcome measures are used to estimate recovery, then both pre-post change and a cut-off score (dividing ‘normal’ from ‘abnormal’ scores) for post-treatment should be used (e.g. recovery is defined as: a significant pre-post change
and a post-treatment score in the normal range). In recent years, it has become more common for treatment outcome researchers to report on clinically significant and meaningful change (i.e., Shortt et al.
2001; Silverman et al.
1999). Even these studies did not take measurement-error into account when using continuous measures in computing treatment recovery.
The purpose of the present study was to investigate the unique impact of pretreatment comorbidity on treatment outcome for childhood anxiety disorders above and beyond the impact of severity. The study focuses on the impact of total and non-anxious comorbidity and overall severity on outcome by addressing the following questions: (1) Does total and/or non-anxious comorbidity predict recovery above and beyond overall severity? (2) Does total and/or non-anxious comorbidity predict Reliable Change in self-reported anxiety and parent-reported internalizing symptoms above and beyond overall severity? (3) Does total and/or non-anxious comorbidity predict Reliable Change in non-anxiety symptoms (self-reported depressive symptoms and parent-reported externalizing symptoms) above and beyond overall severity?
Discussion
In the present study, children with a higher level of pre-treatment symptom severity were less likely to have recovered at post-treatment. Further, children with any comorbid disorder (total comorbidity) at pre-treatment were less likely to be free of a DSM-IV anxiety disorder at post-treatment. Pre-treatment non-anxiety comorbidity added to the prediction of recovery when recovery was assessed with child reported anxiety symptoms. Thus both increased symptom severity and having a nonanxiety comorbid disorder at pretreatment predicts recovery when outcome is assessed using self-reports of anxiety. Total comorbidity did not add to the prediction of recovery using child-reported anxiety nor parent-reported internalizing symptoms over and above the contribution of symptom severity.
Children with a higher level of pretreatment severity need greater decreases in symptoms to reach a subthreshold level of symptoms, therefore we also examined pre to posttreatment Reliable Change. Severity and comorbidity did not contribute to the prediction of Reliable Change when based on self-reported anxiety symptoms. Though children with a higher level of overall severity and non-anxiety comorbidity are less likely to show clinically significant recovery in terms of clinician rated DSM-IV diagnoses, they are equally likely to gain from the treatment when children are asked to report on anxiety symptoms. Conversely, severity predicted greater Reliable Change in parent reported internalizing and externalizing symptoms, and child reported depressive symptoms. Having a non-anxiety comorbidity added to this prediction when assessing parent-reported internalizing, externalizing and child-reported depressive symptoms, but in different ways. Non-anxiety comorbidity was the dominant predictor for Reliable Change in self-reported depressive symptoms, incorporating the predictive value of severity. In the predictions of Reliable Change of parent-reported internalizing and externalizing child symptoms, non-anxiety comorbidity could be classified as a classical suppressor variable. Severity is strongly associated with more improvement when irrelevant variance in common with non-anxiety comorbidity is removed, therefore researchers should consider removing the irrelevant variance of parent-reported pre-treatment overall severity when considering relations between non-anxious comorbidity and parent reported change in internalizing and externalizing problems.
The results indicate the importance of assessing recovery both in terms of treatment recovery and Reliable Change scores, as well as the investigation of treatment outcome from a multi-informant perspective. Similar to Doss and Weisz (
2006), we found higher initial severity to be predictive of both greater treatment gains (reliable change) and higher levels of remaining symptoms. In line with previous studies we found only a modest predictive value of total comorbidity on treatment outcome (i.e., Flannery-Schroeder et al.
2004; Kendall et al.
2001; Rapee
2003). However, the presence of a non-anxiety comorbid disorder at pretreatment added significantly to predictions of treatment recovery based on a clinical interview and child-reported anxiety symptoms and for Reliable Change on depressive, internalizing and externalizing symptoms.
The current findings may help identify those children that need additional treatment after a basic CBT program. Children with a higher level of overall severity might benefit from a stepped care approach (Bower and Gilbody
2005) in which additional treatment is necessary to reach the subthreshold level of symptoms. A generic program might be sufficient, as children with higher overall severity tend to show greater changes with such programs. If they also suffer from a non-anxiety comorbid disorder then they might benefit from a combined, modular or prescriptive treatment (Chorpita et al.
2004) in which non-anxiety problems are also targeted. Future studies on stepped care, modular or prescriptive treatment could evaluate strategies targeting anxiety as well as strategies targeting comorbid problems for these children.
There might be a positive spin-off of this generic anxiety-focused CBT treatment leading to a decrease in co-occurring depressive symptoms and externalizing symptoms. A greater change in depressive symptoms was associated with the presence of having another disorder at pretreatment. Similarly, another treatment outcome study also reported greater decreases in depressive scores in depressed adolescents with pretreatment comorbid anxiety disorders. These adolescents had more room for improvement as they reported significantly higher depression scores at intake (Rohde et al.
2001). We did find an effect of non-anxiety comorbid disorders on externalizing symptoms; non-anxiety comorbidity did have a negative impact on change in externalizing symptoms in anxious children when suppressor effects were taken into account. A recent study evaluated the effectiveness of an intervention for anxiety disorders and comorbid aggression (Levy et al.
2007). Children were treated with either a CBT program for anxiety only or a CBT intervention targeting both anxiety and comorbid aggression. Both interventions led to significant reductions in externalizing and internalizing parent reported problem behavior, and the combined treatment program did not show a higher effectiveness. Unfortunately, the study did not assess severity separately. Similar to Levy et al. we found no associations between the presence of non-anxiety comorbidity and reductions of internalizing and externalizing parent-reported problems with anxiety-focused CBT. However, we also investigated the combined prediction of comorbidity and overall severity and found significant suppressor effects, indicating that ‘pure’ non-anxiety comorbidity has a negative impact on reduction of internalizing and externalizing problems. In addition, there is sufficient evidence from meta-analyses that certain treatments are effective for certain types of problems, e.g. parent training for externalizing problems or exposure for phobia (Chambless and Ollendick
2001). Investigation of the combined impact of comorbidity and overall severity on the potency of treatments for various primary diagnoses may inform us how to enhance treatments for primary disorders as well as comorbid conditions.
Important assets of the present study are the multi-informant perspective on treatment outcome, assessment of changes not only in anxiety but also in anxiety-related and comorbid symptoms, use of a clinically meaningful method to define treatment recovery and computation of reliable pre to post-treatment changes.
For the present study, children with comorbid conditions other than anxiety were treated as one group, whereas the investigation of children with comorbid externalizing disorders versus comorbid affective disorders could also prove fruitful. Comorbidity of anxiety with an affective disorder or comorbidity with an externalizing disorder may be more common in community samples and therefore of clinical value to investigate. As only 17% of the children in the current study showed a comorbid disorder other than anxiety, the power did not permit a further splitting of this group. Moreover, the sample of children with a comorbid disorder other than anxiety (
n = 22) included 4 children with both a mood disorder and an externalizing disorder. Though the sample size in the present study is quite large, it was designed to investigate main effects and not designed for interaction effects. An adequate test of an interaction requires an even larger sample size than for detecting a simple main effect (Shoham-Salomon and Hannah
1991). These considerations point at the need for an adequately powered trial testing the mechanisms through which comorbidity might interact with treatment.
A further limitation of the present study is that we only assessed at post-treatment the presence or absence of anxiety disorders, and not the absence or presence of affective or externalizing disorders. Assessing comorbid diagnoses could give further insight into the impact of comorbidity on the treatment process. Kendall et al. (
2001) found that children with the continued presence of comorbidity were less likely to recover from their primary pretreatment diagnosis. Additionally, five children were on a consistent dose of medication for ADHD.It is not known whether the negative impact of comorbid conditions on anxiety and externalizing symptoms or the positive impact on depressive symptoms would have been stronger if children had not been on medication for ADHD. However, it was deemed unethical to withhold medication from children with ADHD for research purposes.
It can be argued that severity should not be investigated using a sole additive construct with symptoms of one sort counting the same as that of another, i.e., itching and suicidal ideation. However, differentiating between symptoms and prioritizing some above others would be difficult to calculate and not be representative of the severity construct. Future studies could incorporate an impairment measure such as the DSM global functioning scale in addition to parent reported overall severity.
In sum, severity predicted less favorable child, parent and clinician reported outcomes but greater pre- to post-treatment changes in parent-reported internalizing symptoms. Non-anxiety comorbidity added significantly to these predictions in a number of ways: as a separate predictor (in predicting recovery on ADIS), as predictor overlapping with severity (in predicting recovery on the MASC), as suppressor variable (in predicting Reliable Change on internalizing and externalizing CBCL-scales) and as dominant predictor (in predicting Reliable Change on the CDI). Future studies but also clinicians should take into account the potential impact of symptom severity on outcome. As severity and comorbid disorders only explain part of the variance in outcome a further understanding of valid predictors is essential to understand who does not benefit sufficiently from CBT for CAD. Replication of the current findings with severity and non-anxiety comorbidity as separate constructs are necessary to further our understanding on how symptoms and comorbid patterns of problem behavior change with anxiety focused CBT.