Embed Size (px)
Citation preview
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
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
The Status of Treatment Studies
Part 1
Treatment Studies for AN and BN
Adults
BN (100+)
AN (10)
Treatment Studies for AN and BN
Adolescents
AN (10)
BN (3)
Adults
BN (100+)
AN (10)
Treatment of Adolescent Anorexia Nervosa
Part 2
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.
① Inpatient Weight Restoration The predominant models for treating adolescent AN are:
o Inpatient weight restoration in a psychiatric setting
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.
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
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
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.
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.
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
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.
Six-Site German RCT (N=172)
o IP (n=85) o DP (n=87) o One year FU Herpertz-Dahlman et al, LANCET, 2014
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
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.
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.
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.
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
One of Two
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
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
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
Full and Partial Remission by Treatment
EOT 6mFU 12mFU EOT 6mFU 12mFU
Perc
enta
ge
AFT FBT
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
Time until above 95%EBW
Le Grange, Accurso, Lock, Agras & Bryson, IJED, 2013.
Time until above 95%mBMI
Le Grange, Accurso, Lock, Agras & Bryson, IJED, 2013.
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
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.
Time To Remission by Treatment from 1 Yr F/U
Le Grange, Lock, Accurso, Lock, Agras, Bryson & Jo, JAACAP, 2014.
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.
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.
A Comparison of Two Family Therapies for Adolescent AN
A Six Site Comparison
Agras et al., JAMA Psychiatry, 2014
Two of Two
%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)
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
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
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).
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
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.
② Weight for FBT/IPC compared to a sample of poor early responders
Lock, Le Grange, Agras, et al., Beh Res Therapy, 2015.
③ Moderator Effect on Remission Rate: Baseline YBC-ED
Le Grange, Lock, Agras, Moye, Bryson, Jo & Kraemer, Beh Res Therapy, 2012.
Moderator Effect on Remission Rate: Baseline YBC-ED
Le Grange, Lock, Agras, Moye, Bryson, Jo & Kraemer, Beh Res Therapy, 2012.
Moderator Effect on Remission Rate: Baseline EDE
Le Grange, Lock, Agras, Moye, Bryson, Jo & Kraemer, Beh Res Therapy, 2012.
Moderator Effect on Remission Rate: Baseline EDE
Le Grange, Lock, Agras, Moye, Bryson, Jo & Kraemer, Beh Res Therapy, 2012.
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).
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.
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.
Treatment of Adolescent Bulimia Nervosa
Part 4
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
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
Conclusion o Family-based treatment showed a clinical and
statistical advantage over SPT at post-treatment and at 6-month follow-up.
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.
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
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.
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.
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
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)
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.
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.
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.
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
Final Score
AN = 1 BN = 0
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.
