1. High Intensity Comparators: Active Psychotherapy Denise E. Wilfley, Andrea E. Kass, & Rachel P. Kolko Department of Psychiatry Washington University School of Medicine Friday, June 24 th, 2011 R29MH051384; R01MH064153; K24MH070446; T32HL00745626

2. Disclosures Research Support – Shire Pharmaceuticals Advisory/Consultant – GlaxoSmithKline Consumer Healthcare – Minnesota Obesity Consortium – United Health Group, Childhood Obesity Initiative – Wellspring Healthy Living Academy

3. Competing Treatments: Going Head to Head

4. Overview Present an evolution of treatment research evaluating high-intensity, active comparators in contrast to IPT in the treatment of binge eating

5. Rationale for Selecting an Active Comparator To contrast two or more conceptually-competing interventions To evaluate the varied effects of different treatments – Short- and long-term efficacy To examine moderators and mediators of treatment outcome

6. RCT #1: Initial Efficacy Study Comparison of IPT, CBT, and WL Control Investigate whether IPT is as effective as CBT (“gold- standard”) for the treatment of recurrent binge eating Distinguish specificity between two models of symptom maintenance Test the applicability of results from a separate study team (Fairburn et al., 1991) in a different population Design: 56 women randomized to IPT, CBT, or WL control Wilfley et al. (1993 ), J Clin Consult Psychiatry

7. Comparison of IPT, CBT, and WL Control: Results Results support the efficacy of IPT for binge eating No differential active treatment effects Similar to previous findings (Fairburn et al., 1991) Wilfley et al. (1993 ), J Clin Consult Psychiatry WL vs. CBT: d = 0.82 WL vs. IPT: d = 1.47 CBT vs. IPT: d = 0.38 Group X Time Interaction: p<0.003

8. Lingering Questions from the Initial Efficacy Comparison Trial Is equivalency due to weak power (small sample size)? Were the assessment measures unreliable?

9. RCT #2: Large-Scale Comparison of IPT and CBT Compare short and long-term treatment effectiveness within a large sample (N=162) using state-of-the-art measures – Evaluate both treatment effectiveness and scope of outcome effects Assess mode specificity – Identify mechanisms of effect and predictors of outcome – Examine time course of changes in outcome – Will lead to more efficient and effective treatments and provide information about treatment matching Evaluate reliability of prior findings (Wilfley et al., 1993) Wilfley et al. (2002), Arch Gen Psychiatry

10. Large-Scale Comparison of IPT and CBT: Design Considerations Theory and empirical findings suggest IPT and CBT are ideal for comparison  ensure specificity of effects – Differ markedly on specific aspects (i.e., theories, assumptions, and procedures) – Comparable on many nonspecific elements (e.g., credibility to patients, duration, therapist attention) No WL control condition – CBT and IPT have demonstrated superiority to WL condition – No scientific, ethical, or clinical reason to include No placebo psychotherapy condition – Sufficient power to detect differences between CBT and IPT; less cost to implement Wilfley et al. (2002), Arch Gen Psychiatry

11. RCT #2: Large-Scale Comparison of IPT and CBT Wilfley et al. (2002), Arch Gen Psychiatry Recovery rates: –Equivalent Specificity of effects: –Differential time course for reductions in dietary restraint Treatment integrity: –100% rater accuracy for modality –Significantly differentiated treatment-specific indices Patient confidence in treatment: –Equivalent Dropout, compliance, or completion of follow-up: –Equivalent

12. RCT #3: Comparison of IPT, BWL, and CBT-GSH Research Question: Do patients with BED require specialty treatments? – Investigate the long-term effectiveness of three treatments for BED – Test differential efficacy across levels of negative affect (moderator) – Examine mechanisms of therapeutic change – Assess therapist and therapy variables Design: 205 women and men across three sites – Includes largest sample size to date, valid measurement of binge eating, and long-term follow-up – Evaluates generalizability by testing across sites Wilson, Wilfley, Agras, & Bryson (2010), Arch Gen Psychiatry

13. Rationale for the Treatment Approaches IPT: Specialty treatment – Addresses negative affect (moderator analysis) – May be highly acceptable to the majority of practicing therapists BWL: Nonspecialty treatment – Does not specifically target binge eating – More easily disseminable than IPT; requires less intensive training and therapeutic expertise CBT-GSH: Minimal treatment effectiveness comparison – Controls for many of the nonspecific influences that affect outcome – Less costly and more disseminable than BWL Wilson, Wilfley, Agras, & Bryson (2010), Arch Gen Psychiatry

14. Differential Treatment Outcomes for Dietary Restraint F(1,193) = 5.3 p=.006 BWL > GSH Wilson, Wilfley, Agras, & Bryson (2010), Arch Gen Psychiatry

15. RCT #3: Comparison of IPT, BWL, and CBT-GSH Recovery rates: – IPT and CBT-GSH > BWL Patient report of suitability: – IPT significantly more suitable Dropout: – IPT significantly lower rate Treatment Allegiances:* – No evidence of “allegiance bias” – no differential site X treatment effects – No individual therapist effects emerged in IPT or CBT-GSH Wilson, Wilfley, Agras, & Bryson (2010), Arch Gen Psychiatry *Wilson, Wilfley, Agras, & Bryson (2011), Clin Psychol Sci Prac BWL vs. CBT-GSH: OR = 2.3* BWL vs. IPT: OR = 2.6* CBT-GSH vs. IPT: OR = 1.2 *p<0.05

16. Moderators at 2-year Follow-up Global EDE, W(1) = 4.4, p <.036 Self-esteem, W(1) = 4.6, p < 0.032 Wilson, Wilfley, Agras, & Bryson (2010), Arch Gen Psychiatry

17. Remission Rates: Low Self-Esteem and Global Eating Pathology Wilson, Wilfley, Agras, & Bryson (2010), Arch Gen Psychiatry

18. Summary IPT is an efficacious treatment for binge eating disorder Using high-intensity comparators demonstrates treatment efficacy – Enhances ability to detect treatment matching and specificity of effects Important considerations: – Interpretation of effect sizes: likely to yield minimal differences – Rests on strict adherence to protocol

19. Future Directions Design considerations: – Tests of non-inferiority, equivalence, and superiority – Patient-centered outcome research Assessing for patient preference and satisfaction throughout treatment research process Dissemination and implementation science research