le grange cap gr 2.9.16
TRANSCRIPT
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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
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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
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The Status of Treatment Studies
Part 1
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Treatment Studies for AN and BN
Adults
BN (100+)
AN (10)
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Treatment Studies for AN and BN
Adolescents
AN (10)
BN (3)
Adults
BN (100+)
AN (10)
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Treatment of Adolescent Anorexia Nervosa
Part 2
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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.
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① Inpatient Weight Restoration The predominant models for treating adolescent AN are:
o Inpatient weight restoration in a psychiatric setting
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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.
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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
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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
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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.
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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.
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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
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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.
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Six-Site German RCT (N=172)
o IP (n=85) o DP (n=87) o One year FU Herpertz-Dahlman et al, LANCET, 2014
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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
BM
I
IP
DP
Reducing Need for Hospitalization
95% CI, −0·∙11 to 1·∙02; pnon-inferiority
<0·∙0001
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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.
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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.
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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.
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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
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One of Two
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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
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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
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Full and Partial Remission by Treatment
EOT 6mFU 12mFU EOT 6mFU 12mFU
Perc
enta
ge
AFT FBT
p=.029, NNT=5
p= .024, NNT=4
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Full and Partial Remission by Treatment
EOT 6mFU 12mFU EOT 6mFU 12mFU
Perc
enta
ge
AFT FBT
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Full and Partial Remission by Treatment
EOT 6mFU 12mFU EOT 6mFU 12mFU
Perc
enta
ge
AFT FBT
p=.029, NNT=5
p= .024, NNT=4
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Time until above 95%EBW
Le Grange, Accurso, Lock, Agras & Bryson, IJED, 2013.
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Time until above 95%mBMI
Le Grange, Accurso, Lock, Agras & Bryson, IJED, 2013.
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Reducing Need for Hospitalization
15 (n=9)
37 (n=32)
0
20
40
60
80
Pe
rce
nta
ge
FBT
AFT
p=.020
3/11/16 30
Percent/(N) Hospitalized during Outpt Tx
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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.
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Time To Remission by Treatment from 1 Yr F/U
Le Grange, Lock, Accurso, Lock, Agras, Bryson & Jo, JAACAP, 2014.
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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.
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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.
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A Comparison of Two Family Therapies for Adolescent AN
A Six Site Comparison
Agras et al., JAMA Psychiatry, 2014
Two of Two
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%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)
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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
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Reducing Need for Hospitalization
8.3
21
0
5
10
15
20
25
30
Me
dia
n N
um
be
r o
f D
ay
s
FBT
SyFT
p=.020
38
Median Number of Days in Hospital
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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).
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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
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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.
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② Weight for FBT/IPC compared to a sample of poor early responders
Lock, Le Grange, Agras, et al., Beh Res Therapy, 2015.
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③ Moderator Effect on Remission Rate: Baseline YBC-ED
Le Grange, Lock, Agras, Moye, Bryson, Jo & Kraemer, Beh Res Therapy, 2012.
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Moderator Effect on Remission Rate: Baseline YBC-ED
Le Grange, Lock, Agras, Moye, Bryson, Jo & Kraemer, Beh Res Therapy, 2012.
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Moderator Effect on Remission Rate: Baseline EDE
Le Grange, Lock, Agras, Moye, Bryson, Jo & Kraemer, Beh Res Therapy, 2012.
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Moderator Effect on Remission Rate: Baseline EDE
Le Grange, Lock, Agras, Moye, Bryson, Jo & Kraemer, Beh Res Therapy, 2012.
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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).
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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.
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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.
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Treatment of Adolescent Bulimia Nervosa
Part 4
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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.
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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
0102030405060708090
100
Baseline Post-treatment 6 mo. Follow-up
Percent
FBT-BNSPT
p = .049p = .050
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Conclusion o Family-based treatment showed a clinical and
statistical advantage over SPT at post-treatment and at 6-month follow-up.
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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.
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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-GSC NS
NS
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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.
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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.
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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
Ab
sti
ne
nce R
ate
Time
FBT-‐BN observedFBT-‐BN estimatedCBT-‐A observedCBT-‐A estimated
Abstinence Rates
p=.040
p=.030 NS
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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
Abstine
nce Ra
te
FES conflict >= 2
CBT-‐A (n=34)
FBT-‐BN (n=27)
0.0
0.2
0.4
0.6
0.8
1.0
Baseline EOTAbstine
nce Ra
te
FES conflict < 2
CBT-‐A (n=24)
FBT-‐BN (n=24)
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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.
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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.
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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.
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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
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Final Score
AN = 1 BN = 0
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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.