Moderators and mediators of remission in family-based treatment and adolescent focused therapy for anorexia nervosa

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Abstract

Few of the limited randomized controlled trails (RCTs) for adolescent anorexia nervosa (AN) have explored the effects of moderators and mediators on outcome. This study aimed to identify treatment moderators and mediators of remission at end of treatment (EOT) and 6- and 12-month follow-up (FU) for adolescents with AN (N = 121) who participated in a multi-center RCT of family-based treatment (FBT) and individual adolescent focused therapy (AFT). Mixed effects modeling were utilized and included all available outcome data at all time points. Remission was defined as ≥95% IBW plus within 1SD of the Eating Disorder Examination (EDE) norms. Eating related obsessionality (Yale-Brown-Cornell Eating Disorder Total Scale) and eating disorder specific psychopathology (EDE-Global) emerged as moderators at EOT. Subjects with higher baseline scores on these measures benefited more from FBT than AFT. AN type emerged as a moderator at FU with binge-eating/purging type responding less well than restricting type. No mediators of treatment outcome were identified. Prior hospitalization, older age and duration of illness were identified as non-specific predictors of outcome. Taken together, these results indicate that patients with more severe eating related psychopathology have better outcomes in a behaviorally targeted family treatment (FBT) than an individually focused approach (AFT).

Highlights

► Eating related obsessionality and eating disorder specific psychopathology are moderators of treatment outcome. ► FBT is indicated when levels of eating psychopathology are high, while FBT or AFT seem useful when levels are low. ► Scores from the EDE-Global or YBC-ED can be utilized to identify patients in high vs. low eating psychopathology groups.

Introduction

There are six published randomized controlled trials (RCTs) examining treatments for adolescent anorexia nervosa (AN); however, few of these have examined the effects of moderators and mediators on outcome. In the most recent published RCT for this patient population, the relative efficacy of family-based treatment (FBT) was compared to individual adolescent focused therapy (AFT) (Lock et al., 2010). In this RCT, adolescents with AN were randomly assigned to receive FBT or AFT over a 12-month treatment period and assessed at the end of treatment (EOT) and at 6-months and 12-months after treatment was completed. This study demonstrated that FBT was superior to AFT in terms of weight change, as assessed using body mass index (BMI) percentile (Hebebrand, Himmelmann, Hesecker, Schaefer, & Remschmidt, 1996) and change on the Eating Disorder Examination (EDE) (Cooper, Cooper, & Fairburn, 1989), at EOT. FBT was also superior to AFT in terms of full remission rates at 6 and 12-month follow-up.

While RCTs provide an evaluation of the relative efficacy of treatments, clinical practice can be informed and our understanding of how treatments work can be enhanced by an examination of predictors/moderators and mediators of outcome (Kraemer, Wilson, Fairburn, & Agras, 2002). Non-specific predictors are fixed (e.g., sex) or variable factors (e.g., weight) that precede treatment outcome, are unrelated to the treatment received, and have a main effect on outcome (i.e., a non-specific predictor has the same effect on the outcome regardless of the treatment status). Moderators are fixed or variable pre-randomization characteristics that modify the effect of treatment on outcome (i.e., interaction effect) and identify for whom treatments may work (i.e., a moderator has a different effect on the outcome depending on the treatment status). Mediators of outcome are variables that act after treatment has begun but before treatment changes occur and indicate the mechanisms through which a treatment might achieve its aims (Kraemer et al., 2006, Kraemer et al., 2008, Kraemer et al., 2002, Wilson et al., 2002). When moderators are identified, different factors may mediate treatment outcome in subgroups defined by the moderators. Identifying moderators and mediators serves a dual purpose because it informs clinical practice, that is, which treatment is best for which patient, whereas mediators may suggest ways to enhance the effectiveness of treatments.

Not surprisingly, given the few RCTs that have examined treatment for adolescent AN, data about moderators and mediators of treatment outcome are exceedingly limited. In the only RCT to embark on a preliminary exploration of moderators of treatment outcome for this patient population, receiving either short or long term FBT (Lock, Agras, Bryson, & Kraemer, 2005), two possible moderators were observed. For weight change, patients with high levels of eating related obsessionality, using the Yale-Brown-Cornell-Eating Disorder Scales (YBC-ED) (Mazure, Halmi, Sunday, Romano, & Einhorn, 1994), did significantly better with a longer rather than a shorter course of FBT. Similarly, non-intact families (single parent, divorced) did better with longer treatment in terms of improvements in eating disorder specific psychopathology as measured by the EDE (Cooper et al., 1989). Exploring predictors of dropout and remission, the same group (Lock, Couturier, Bryson & Agras, 2006) found co-morbid psychiatric disorder and longer treatment to predict dropout, while co-morbid psychiatric disorder, being older, and problematic family behaviors were associated with lower rates of remission.

Earlier studies imply that parental criticism, as measured by Expressed Emotion (EE), may play a role in moderating treatment outcome (Eisler et al., 2000, Le Grange et al., 1992). Families with higher levels of parental criticism toward the affected offspring did better in separated FBT (patient and parents seen separately) than in conjoint FBT. Moreover, it has been shown that high levels of parental criticism is a predictor of dropout in FBT (Szmukler, Eisler, Russell & Dare, 1985), while more recently it is argued that parental warmth may be associated with good treatment outcome in FBT (Le Grange, Reinecke-Hoste, Lock & Bryson, 2011).

An examination of treatment response in the broader eating disorder literature is equally limited and has yielded inconsistent findings. While outcome predictors for cognitive behavioral treatment for adults with bulimia nervosa (BN) have been examined (Agras et al., 2000, Fairburn et al., 2004), only one study explored moderators and mediators of outcome in FBT for adolescents with BN (Le Grange et al., 2008, Lock et al., 2008). Contrary to the examination of FBT for adolescent AN, participants with less severe eating disorder psychopathology (EDE global score), receiving FBT for BN, were more likely than those receiving individual supportive psychotherapy to be partially remitted at follow-up.

In the present study we examine moderators, mediators and predictors of remission for participants in the RCT of FBT vs. AFT that was described above. Based on prior findings in the adolescent AN literature we advanced two hypotheses at the exploratory level. First, patients with high levels of eating related obsessionality, as measured by the YBC-ED, will have better outcomes in FBT rather than AFT. Second, families with higher levels of parental criticism, as measured by EE, will fare better in AFT as opposed to FBT. For the remainder though, we chose to investigate several variables as possible moderators and the procedure was therefore an exploratory analysis and findings should be regarded as hypothesis generating.

Section snippets

Design

This two-site study (The University of Chicago and Stanford University) describes a RCT to explore moderators, mediators and predictors of outcome. The main outcome findings comparing FBT with AFT for adolescents with AN were published elsewhere (Lock, Le Grange, Agras, et al., 2010). Randomization was performed separately for each site by a biostatistician in the Data Coordinating Center (DCC) at Stanford University. One-hundred twenty-one participants were randomly assigned to either FBT (n

Results

Detailed descriptions of participant baseline characteristics were published elsewhere (Lock et al., 2010). To summarize, participants had a mean age of 14.4 (SD 1.6) years, 82%IBW, and BMI of 16.1 (SD 1.1). Ninety-one percent of the sample was female and most had AN for less than one year (mean = 11.3 months, SD 8.6). A quarter (26%; N = 31) of participants had a co-morbid psychiatric disorder with 17% of the total sample (N = 20) taking psychotropic medications for these conditions at

Discussion

We examined moderators and mediators of remission in a sample of 121 adolescents with AN who participated in an RCT comparing FBT and AFT. Among 17 pre-randomization variables examined, eating related obsessionality (YBC-ED-Total), and eating disorder specific psychopathology (EDE-Global) emerged as moderators of remission at EOT. These results underscore that eating related obsessionality moderates treatment outcome in AN, as has been suggested previously albeit in a more modest study (Lock

Limitations

There are important limitations to this study. All adolescents and their families were treatment seeking, randomized to one of two study therapies, and medically stable for outpatient treatment (at or above 75% IBW at baseline) with low levels of comorbidity (25%), all of which restrict the generalizability of our findings. Investigators and centers known for work using family treatment for eating disorders conducted the study and we cannot rule out that this may have lead to biased

Conclusions

This study identified two important clinical features of AN, i.e., eating related obsessionality and eating disorder specific psychopathology, as moderators at EOT. Given the high correlation between these two indictors of eating disorder psychopathology, we consider this to be essentially one moderator at EOT. While YBC-Total and EDE-Global did not continue to moderate outcome at follow-up, should not mean that moderation does not exist. Larger sample sizes and more sensitive outcome measures,

Acknowledgments

This research was supported by National Institute of Mental Health grants R01-MH-070620 (Dr Le Grange) and R01-MH-070621, K24 MH-074467 (Dr. Lock). Drs. Le Grange and Lock receive royalties from Guilford Press and consultant fees from the Training Institute for Child and Adolescent Eating Disorders, LLC. Drs. Lock and Agras receive Royalties from Oxford University Press.

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