FBT is the most effective treatment for adolescent anorexia nervosa based on evidence from multiple randomized controlled trials: 1) FBT leads to faster weight gain and symptom improvement compared to alternative therapies like adolescent focused therapy. 2) FBT reduces the need for hospitalization more than alternatives. 3) For bulimia nervosa, FBT and family therapy may lead to better outcomes than individual therapies like CBT at post-treatment and follow-up, though alternatives can also be effective.

1. Treatment of Adolescent Bulimia Nervosa vs.
Anorexia Nervosa: Which is Ahead?
Daniel Le Grange, PhD
Benioff UCSF Professor in Children’s Health
Eating Disorders Director
Department of Psychiatry
University of California, San Francisco, CA
CAP Grand Rounds February 2016

2. Outline of Presentation
① The Status of Treatment Studies
② Evidence-Based Treatment for AN
③ Workings of Efficacious Treatments
④ Evidence-Based Treatment for BN
⑤ Discussion Points

3. The Status of Treatment Studies
Part 1

4. Treatment Studies for AN and BN
Adults
BN
(100+)
AN (10)

5. Treatment Studies for AN and BN
Adolescents
AN (10)
BN (3)
Adults
BN
(100+)
AN (10)

6. Treatment of Adolescent
Anorexia Nervosa
Part 2

7. Evidence for the Treatment of
Adolescent Eating Disorders
The predominant models for treating adolescent AN
are:
① Inpatient treatment for weight restoration in
psychiatric setting.
② Outpatient psychosocial treatment.

8. ① Inpatient Weight Restoration
The predominant models for treating adolescent AN are:
o Inpatient weight restoration in a psychiatric setting

9. Liverpool RCT
(N=167)
o CAMHS (n=55)
o Specialized Outpt (n=55)
o Inpt treatment (n=57)
o One and two year FU
Gowers, Clark, Roberts, Griffiths, Edwards,
Bryan, Smethurst, Byford & Barrett, Br J Psych,
2007.

10. Liverpool RCT
(N=167)
o CAMHS n=55
o Specialized Outpt n=55
o Inpt treatment n=57
o One and two year FU
Gowers, Clark, Roberts, Griffiths, Edwards,
Bryan, Smethurst, Byford & Barrett, Br J Psych,
2007.
One Yr FU
0
25
50
75
100
Good Interm Poor
CAHMS
SOP
INPT

11. Liverpool RCT
(N=167)
o CAMHS (n=55)
o Specialized Outpt (n=55)
o Inpt treatment (n=57)
o One and two year FU
Gowers, Clark, Roberts, Griffiths, Edwards,
Bryan, Smethurst, Byford & Barrett, Br J Psych,
2007.
One Yr FU
0
25
50
75
100
Good Interm Poor
CAHMS
SOP
INPT
Two Yr FU
0
25
50
75
100
Good Interm Poor
CAHMS
SOP
INPT

12. Conclusions
o First-line in-patient psychiatric treatment
does not provide advantages over out-
patient management.
o Out-patient treatment failures do very
poorly on transfer to in-patient facilities.

13. Westmead RCT
(N=82)
o MS then FBT (n=41)
o WR then FBT (n=41)
o One year FU
Madden, Miskovic-Wheatley, Wallis, Kohn, Lock,
Le Grange, Jo, Clarke, Rhodes, Hay & Touyz,
Psychol Med, 2014.

14. Westmead RCT
(N=82)
o MS then FBT (n=41)
o WR then FBT (n=41)
o One year FU
Madden, Miskovic-Wheatley, Wallis, Kohn, Lock,
Le Grange, Jo, Clarke, Rhodes, Hay & Touyz,
Psychol Med, 2014.
Reducing Need for Hospitalization
p=.046

15. Conclusions
o Outcomes were similar with either MS or WR
when inpatient treatment is combined with
outpatient FBT.
o Significant cost savings will result from
combining brief hospitalization with FBT.

16. Six-Site German RCT
(N=172)
o IP (n=85)
o DP (n=87)
o One year FU
Herpertz-Dahlman et al, LANCET, 2014

17. Six-Site German RCT
(N=172)
o IP (n=85)
o DP (n=87)
o One-year follow-up
Herpertz-Dahlman et al, LANCET, 2014
17.8
18.1
15
20
BMI
IP
DP
Reducing Need for Hospitalization
95% CI, −0·∙11 to 1·∙02; p
non-inferiority
<0·∙0001

18. Conclusions
o DP after short inpatient care in adolescent non-
chronic AN seems no less effective than IP for
weight restoration and maintenance during the
1st yr after admission and at 12-month F/U.
o DP might be a safe and less costly alternative
to IP.

19. Summary for Inpatient TX
o First-line in-patient psychiatric treatment does not
provide advantages over day-patient or out-
patient management.
o Weight restoration at home is successful once
medical stabilization has been achieved.

20. ② Psychosocial Treatments for AN
The predominant models for treating adolescent AN are:
o Inpatient weight restoration
o Outpatient psychosocial treatment
o Family-Based Treatment (FBT) is family focused and aims
at symptom management by parents early in treatment.
o Adolescent Focused Therapy (AFT) is an individual
therapy and aims to promote self-efficacy, self-esteem,
and self-management of eating problems.
o Systemic Family Therapy (SyFT) places the focus on the
family system to draw on their existing strengths.

21. Summary of the 10 published RCTs for AN*
o 8 involved family-focused approaches (FBT, BFST or
SyFT).
o 3 involved individual therapy (CBT, supportive, or
adolescent focused therapy).
o 3 involved inpatient treatment.
o 0 involved any medication.
* Highlight the two latest psychosocial RCTs

22. One of Two

23. Family-Based Treatment vs. Adolescent
Focused Therapy for Adolescent
Anorexia Nervosa
A multisite comparison
Lock, Le Grange, Agras, Moye, Bryson & Jo, Arch Gen Psychiatry, 2010;
Le Grange, Lock, Agras, Moye, Bryson, Jo & Kraemer, Beh Res Therapy, 2012;
Le Grange, Lock, Accurso, Agras, Bryson & Jo, J Am Acad Child Adolesc Psychiatry, 2014
One of Two

24. Primary Outcome
Remission is 95% mBMI for height and age according
to CDC norms + EDE within 1SD of community norms
o Approximates weight needed for return to full
physical health in young adolescents and addresses
growth, bone health, and hormonal function
o EDE threshold is in the normal range for community
sample and addresses minimization common in
adolescent AN

25. Full and Partial Remission by Treatment
EOT 6mFU 12mFU EOT 6mFU 12mFU
Percentage
AFT FBT
p=.029, NNT=5
p= .024, NNT=4

26. Full and Partial Remission by Treatment
EOT 6mFU 12mFU EOT 6mFU 12mFU
Percentage
AFT FBT

27. Full and Partial Remission by Treatment
EOT 6mFU 12mFU EOT 6mFU 12mFU
Percentage
AFT FBT
p=.029, NNT=5
p= .024, NNT=4

28. Time until above 95%EBW
Le Grange, Accurso, Lock, Agras & Bryson, IJED, 2013.

29. Time until above 95%mBMI
Le Grange, Accurso, Lock, Agras & Bryson, IJED, 2013.

30. Reducing Need for Hospitalization
15
(n=9)
37
(n=32)
0
20
40
60
80
Percentage
FBT
AFT
p=.020
3/11/16 30
Percent/(N) Hospitalized during Outpt Tx

31. o Only 2 participants who were remitted at
1yr FU relapsed at 4yr FU.
o One fourth not remitted at 1yr FU achieved
remission at long-term FU.
Long-Term Follow-Up
Le Grange, Lock, Accurso, Agras, Moye, Bryson, & Jo, JAACAP, 2014.

32. Time To Remission
by Treatment from 1 Yr F/U
Le Grange, Lock, Accurso, Lock, Agras, Bryson & Jo, JAACAP, 2014.

33. o Only 2 participants remitted at 1yr FU
relapsed at 4yr FU.
o One fourth not remitted at 1yr FU achieved
remission at long-term FU.
o About one third of participants were remitted
at long-term FU, irrespective of treatment.
Long-Term Follow-Up
Le Grange, Lock, Accurso, Agras, Moye, Bryson, & Jo, JAACAP, 2014.

34. Conclusions
o FBT is more efficient than AFT in facilitating
Remission at 6- and 12-month follow-up.
o FBT brings about faster weight gain early in
treatment with fewer hospital days.
o Remission rates stable at 4-yr follow-up, but
AFT ‘catches up’ with FBT.

35. A Comparison of Two Family Therapies
for Adolescent AN
A Six Site Comparison
Agras et al., JAMA Psychiatry, 2014
Two of Two

36. %IBW
Agras et al., JAMA Psychiatry, 2014
o FBT (n=82)
o SyFT (n=82)
o One Year Follow-up
RIAN RCT
Six Sites
(N = 164)

37. 75
80
85
90
95
100
0
36
88
FBT
SFT
Months
%IBW
Agras et al., JAMA Psychiatry, 2014
o FBT (n=82)
o SyFT (n=82)
o One Year Follow-up
RIAN RCT
Six Sites
(N = 164)
% mBMI

38. Reducing Need for Hospitalization
8.3
21
0
5
10
15
20
25
30
MedianNumberofDays
FBT
SyFT
p=.020
38
Median Number of Days in Hospital

39. Conclusions
o No differences on %mBMI, eating disorder
symptoms, or comorbid psychiatric symptoms.
o FBT brings about faster weight gain early in
treatment (1st 8/52, p=.003), with fewer
hospital days.
o FBT lower mean treatment costs (FT +
hospitalization at EOT) per patient (FBT=
$8963; SyFT=$18,005).

40. Treatment of Adolescent
Anorexia Nervosa
Part 3
Workings of Effective Treatment
① Predictors of Outcome
② Adapting FBT
③ Moderator Effect on Outcome
④ Reducing the need for Hospitalization

41. Weight gain >2 kgs. by wk 4 correctly characterized:
① Early Weight Gain and Outcome
(N>400 in FBT and AFT)
o 79% of responders [AUC = .814 (p<.001)]
o 71% of non-responders [AUC = .811 (p<.001)]
Doyle, Le Grange, Celio-Doyle, Loeb & Crosby, IJED, 2009; Le Grange, Accurso, Lock, Agras & Bryson, IJED, 2013;
Lock et al., JAACAP, 2005; Madden et al., IJED, 2015.

42. ② Weight for FBT/IPC compared to a
sample of poor early responders
Lock, Le Grange, Agras, et al., Beh Res Therapy, 2015.

43. ③ Moderator Effect on Remission Rate:
Baseline YBC-ED
Le Grange, Lock, Agras, Moye, Bryson, Jo & Kraemer, Beh Res Therapy, 2012.

44. Moderator Effect on Remission Rate:
Baseline YBC-ED
Le Grange, Lock, Agras, Moye, Bryson, Jo & Kraemer, Beh Res Therapy, 2012.

45. Moderator Effect on Remission Rate:
Baseline EDE
Le Grange, Lock, Agras, Moye, Bryson, Jo & Kraemer, Beh Res Therapy, 2012.

46. Moderator Effect on Remission Rate:
Baseline EDE
Le Grange, Lock, Agras, Moye, Bryson, Jo & Kraemer, Beh Res Therapy, 2012.

47. ④ Reducing Need for Hospitalization
o Westmead Children’s Hospital, Sydney (2004) - reporting a
50% decrease in readmissions over the implementation
period (Wallis et al., Int J Adolesc Med Health, 2007).
o RCH in Melbourne (2009) - reporting 56% decrease in
admissions, 75% decrease in readmissions, 51% decrease in
overall hospital days (Hughes, Le Grange, Court et al., J Ped Child
Care, 2013).

48. Conclusions
o Early weight gain predicts outcome at end-
of-treatment.
o Adapting FBT for early non-responders
seems to improve outcomes for this subgroup.
o Subgroups for whom FBT is particularly
helpful have been identified.
o Family involvement underscored in good
outcomes, leading to reduced hospitalization.

49. Summary of Outpatient TX
o FBT should be the first-line outpatient treatment for
adolescents with AN when medically fit.
o FBT seems particularly effective at reducing the
need for hospitalization.
o Improved understanding of the workings of FBT.
o AFT and SyFT are feasible treatment alternatives.

50. Treatment of Adolescent
Bulimia Nervosa
Part 4

51. 51
Chicago RCT
FBT-BN vs SPT
(N = 80)
o FBT-BN (n=41)
o SPT (n=39)
o 6 months of therapy
o 6 month follow-up
Le Grange, Crosby, Rathuaz & Leventhal, Arch Gen
Psych, 2007.

52. 52
Chicago RCT
FBT-BN vs SPT
(N = 80)
o FBT-BN (n=41)
o SPT (n=39)
o 6 months of therapy
o 6 month follow-up
Le Grange, Crosby, Rathuaz & Leventhal, Arch Gen
Psych, 2007.
Remission
0
10
20
30
40
50
60
70
80
90
100
Baseline Post-treatment 6 mo. Follow-up
Percent
FBT-BN
SPT
p = .049
p = .050

53. Conclusion
o Family-based treatment showed a clinical and
statistical advantage over SPT at post-treatment
and at 6-month follow-up.

54. Maudsley RCT
FT vs CBT-GSC
(N = 85)
o Family Therapy (n=41)
o CBT-GSC (n=44)
o 6 months of therapy
o 6 month follow-up
Schmidt, Lee, Beecham, et al., Am J Psych,
2007.

55. Maudsley RCT
FT vs CBT-GSC
(N = 85)
o Family Therapy (n=41)
o CBT-GSC (n=44)
o 6 months of therapy
o 6 month follow-up
Schmidt, Lee, Beecham, et al., Am J Psych,
2007.
0
25
50
75
100
Baseline EOT 6 Mo FU
Remission
FBT
CBT-
GSCNS
NS

56. Conclusion
o CBT guided self-care has the slight advantage
of offering a more rapid reduction of bingeing,
lower cost, and greater acceptability for
adolescents with bulimia nervosa.

57. Chicago/Stanford RCT
FT-BN vs. CBT-A
(N = 110)
o FBT-BN (n=52)
o CBT-A (n=58)
o 6 months of therapy
o 6 and 12 month follow-up
Le Grange, Lock, Agras et al., J Am Acad Child
Adolesc Psychiatry, 2015.

58. Chicago/Stanford RCT
FT-BN vs. CBT-A
(N = 110)
o FBT-BN (n=52)
o CBT-A (n=58)
o 6 months of therapy
o 6 and 12 month follow-up
Le Grange, Lock, Agras et al., J Am Acad Child
Adolesc Psychiatry, 2015.
0.0
0.1
0.2
0.3
0.4
0.5
0.6
Baseline EOT 6m
FU 12m
FU
AbstinenceRate
Time
FBT-­‐BN
observed
FBT-­‐BN
estimated
CBT-­‐A
observed
CBT-­‐A
estimated
Abstinence Rates
p=.040
p=.030
NS

59. Moderator Effect on Remission Rate
FES Conflict
Le Grange, Lock, Agras, et al., JAACAP, 2015.
0.0
0.2
0.4
0.6
0.8
1.0
Baseline EOT
Abstinence
Rate
FES
conflict
>=
2
CBT-­‐A
(n=34)
FBT-­‐BN
(n=27)
0.0
0.2
0.4
0.6
0.8
1.0
Baseline EOT
Abstinence
Rate
FES
conflict
<
2
CBT-­‐A
(n=24)
FBT-­‐BN
(n=24)

60. Conclusion
o FBT-BN is superior to CBT-A at end-of-
treatment and at 6-month follow-up.
o No statistically significant difference between
the two treatments at 12-month follow-up.
o FBT works faster at symptom remission and
benefits are maintained over time.
o Some progress in terms of treatment
moderators.

61. Summary for Adol BN
o FBT is a strong candidate as first-line outpatient
treatment for adolescents with BN.
o CBT seems a feasible alternative should the family
be unavailable.
o Little data on how these treatments work.

62. Overall Conclusions
o First-line inpt psychiatric treatment for AN does not
provide advantages over outpt management.
o FBT should be the first-line outpatient treatment for
adolescents with AN when medically stable.
o Utilizing families in the treatment of adolescents
with BN looks promising.

63. ① Parent Focused Treatment vs. FBT – Melbourne/
UCSF.
② Dissemination Study – Stanford/UCSF.
③ Effectiveness Study – Minnesota/UCSF.
④ Telemedicine – Chicago/UCSF.
⑤ FBT vs. FBT/IPC+ Pending.
Looking Ahead

64. Final Score
AN = 1
BN = 0

65. Acknowledgements
o National Institutes of Health
o Baker Foundation of Australia
o National Eating Disorders Association
o Children’s Hospitals and Clinics of Minnesota
o Collaborators at Kings College, London, Mt Sinai School of
Medicine, NY, University of Minnesota, MN, NRI Fargo,
ND, University of Melbourne, University of Sydney,
Australia, and Stanford University.