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Adolescent Eating Disorders:Recent Advances in Treatment

Daniel Le Grange, PhD Benioff UCSF Professor in Children’s Health

Joint Director, Eating Disorders ProgramDepartments of Psychiatry and Pediatrics

I, Daniel Le Grange, PhD, have the following commercial relationship(s) to disclose:

The Training Institute for Child and Adolescent Eating Disorders, LLC (co-director), Guilford Press and Routledge (royalties).

Disclosures

11/9/2014 2

Acknowledgements

o National Institutes of Health

o Baker Foundation of Australia

o National Eating Disorders Association

o Eating Recovery Center (Insight Behavioral Health, LLC)

o Collaborators at The University of Chicago, Kings College, London, Mt Sinai School of Medicine, NY, University of Minnesota, MN, University of Melbourne, University of Sydney, Australia, and Stanford University.

Outline of Presentation

① Prevalence and Mortality

② Inpatient vs. Outpatient Treatment

③ Discussion Points

④ Further Reading

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Prevalence and Mortality

Part 1 Prevalence of Eating Disorders

Occurrence o Onset between ages 10 – 18 years; mean ~14 years of ageo Females outnumber males for both AN and BN (9:1)

Determinantso Gene/environment interaction effecto Neurobiology is poorly understoodo Personality traits and psychiatric co-morbidity o Medical conditions, e.g., GI and Endocrine disorderso Debunked theories on parenting styles

Lifetime Prevalence of EDs Among Females in the US (N= 10,123 Ages 13-18)

Swanson, Crow, Le Grange, Swendsen & Merikangas, Arch Gen Psychiatry, 2011

=7.7%

Other Lifetime Mental Disorders

Swanson, Crow, Le Grange, Swendsen & Merikangas, Arch Gen Psychiatry, 2011

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Lifetime Suicidality by ED Subtype

Suicide Ideation and Behavior (%)

AN BN BED SAN SBED No ED

Suicide Ideation 31.4a 53.0a 34.4a 30.0a 18.3a 11.2

Suicide Plan 2.3 25.9a 5.1 14.2a 5.1 3.6

Suicide Attempt 8.2 35.1a 15.1a 12.4 5.3 3.0

aSignificant differences between adolescents with ED subtype and adolescents without ED (p<.05)

Swanson, Crow, Le Grange, Swendsen & Merikangas, Arch Gen Psychiatry, 2011

Lifetime Service Use by ED Subtype

Service Sector (%) AN BN BED SAN SBED No ED

Mental Health 68.8a 60.9a 60.4a 54.3a 48.8a 28.6

General Pediatrics 26.9 49.2a 22.0 17.4 11.0 11.5

Human Service 40.0a 30.2a 17.7 29.2a 7.7 10.0

CAM 24.2a 13.8 3.6 7.7 8.4 7.5

Juvenile Justice 10.7 1.5 1.2a 15.5 5.2 5.1

School Service 40.4 45.4a 19.5 38.5a 43.8a 21.1

Any treatment 77.6a 88.2a 72.6a 70.5 64.2a 44.4

Treatment for ED 27.5 21.5 11.4 NA 3.4 NA

aSignificant differences between adolescents with ED subtype and adolescents without ED (p<.05)

Swanson, Crow, Le Grange, Swendsen & Merikangas, Arch Gen Psychiatry, 2011

How does this compare to other adolescent psychiatric disorders?

Lifetime prevalence for other psychiatric diagnoses:

o Major Depressive Episode – 9.3%

o Attention Deficit Hyperactivity Disorder – 11.8%

Park, Scott, Adams, Brindis, & Irwin, J Adolesc Health, In Press; Merikangas et al, Dialogues Clin Neurosci, 2009

What is the Incidence of EDs Compared to other Medical Diagnoses?

At peak onset (15-16 years of age), the incidence of eating disorders is:

o 5 x that of Type 1 DM.

o 10 x that of inflammatory bowel disease.

Patterson et al., Lancet, 2009; Loftus, Gastroenterology, 2004

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Mortality studies in ED

o Most mortality research in EDs have focused on AN

o Relatively few studies and most are modest in size o Sampling

o Diagnosis

o Follow-up

o Crude Mortality rate for all EDs is 6-8%

o Larger national registries available elsewhere (e.g., Canada, Northern Europe/Scandinavia)

Arcelus et al., JAMA Psychiatry, 2011; Crow et al., Am J Psychiatry, 2009; Keel et al., Arch Gen Psychiatry, 2003

Observed vs Expected Deaths after First Hospitalization for AN (N=6009)

Papadopolous, Ekbom, Brandt & Ekselius Br J Psychiatry 2009

Crow et al Am J Psychiatry 2009

SMR after Outpatient Care (US, N = 1,885 Females with an ED) What is the Mortality in Other Pediatric

Illnesses?

oPremature birth at 28 weeks gestation 8% mortality (Stoll et al., Pediatrics, 2010)

oMild to moderate congenital heart disease5 -10% mortality (Marino et al., Circulation, 2012)

oAcute lymphocytic leukemia 10% mortality (Hunger et al., J Clin Oncol, 2012)

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Summary (Part 1)o EDs are highly prevalent among the adolescent

population (females with lifetime prevalence >7%).

o Associated with serious medical complications, other psychiatric disorders, role impairment and suicidality.

o Elevated mortality risk for all EDs (both all-cause and suicide SMR are significantly elevated).

o The unmet treatment needs place these disorders as important public health concerns.

Treatment of Adolescent Eating Disorders

Part 2

Treatment Studies for AN and BN

AdultsAdults

BN (100+)

AN (10)

Treatment Studies for AN and BN

AdolescentsAdolescents

AN (9)

BN (2)

AdultsAdults

BN (100+)

AN (10)

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Treatment Studies for Adolescent EDs

Year

Treatment Studies for Adolescent EDs

Year

Treatment Studies for Adolescent EDs

Year

Treatment Studies for Adolescent EDs

Year

7

Number of Study Participants by End 2014 Number of Study Participants by end 2014

Evidence for the Treatment of Adolescent Eating Disorders

The predominant models for treating adolescent EDs are:

① Inpatient treatment for medically unstable patients.

② Inpatient treatment for weight restoration.

③ Outpatient psychosocial treatment.

① Medical Stabilization

The predominant models for treating adolescent EDs are:

o Inpatient treatment for medically unstable patients.o UCSF - Garber et al., J Adolesc Health (2013).

o Stanford - Goldner et al., J Adolesc Health (2013).

o SickKids - Katzman et al., J Adolesc Health (2013).

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Change in %MBMI by Day in Hospital

*

#

* *

*

*

**

# #

# Sign lower than Day 1; * Sign higher than Day 1 (p < 0.05); Garber, Michihata, Hetnal, Shafer & Moscicki, J Adolesc Health, 2012.

*

\\

\\

\\\\

# #

* *

# Sign lower than baseline (p<0.05); * Sign higher (p<0.05)

Garber, Maudlin, Michihata, Buckelew, Shafer & Moscicki, J Adolesc Health, 2013.

#

^

^

#

--- Dashed line represents average estimated energy needs, based on calculated Total Energy Expenditure # Calorie prescription was significantly greater in higher calorie group on Day 1 (p <0.000) ^ Calorie prescription was significantly greater in the higher calorie group upon discharge (p=0.043)

Comparing Increase in CaloriesConclusions

o Conventional wisdom of ‘start low, advance slow’ should be revisited.

o Recent studies show that ‘start high, advance fast’ might be more beneficial in terms weight gain, medical stability, and hospital days.

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② Inpatient Weight Restoration

The predominant models for treating adolescent AN are:

o Inpatient treatment if patient is medially unstable

o Inpatient weight restoration

Liverpool RCT(N=167)

o CAHMS 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 CAHMS 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 CAHMS 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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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 n=41

o WR n=41

o One year FU

Madden, Miskovic-Wheatley, Wallis, Kohn, Lock,

Le Grange, Jo, Clarke, Rhodes, Hay & Touyz,

Psychol Med, in press.

Westmead RCT(N=82)

o MS n=41

o WR 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 family-based treatment*.

o Significant cost savings will result from combining brief hospitalization with family-based treatment.

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German RCT (N=172)

o IP n=85

o DP n=87

o One year FU

Herpertz-Dahlman et al, LANCET, 2014

German RCT (N=172)

o IP n=85

o DP n=87

o One year FU

Herpertz-Dahlman et al, LANCET, 2014

17.818.1

15

20

BM

I

IP

DP

Reducing Need for Hospitalization

95% CI, −0·11 to 1·02; pnon-inferiority

<0·0001

Conclusions

o DP was non-inferior to IP with respect to the primary outcome, BMI at the 12-month follow-up.

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. Thus, DP might be a safe and less costly alternative to IP.

③ Psychosocial Treatments

The predominant models for treating adolescent AN are:

o Inpatient treatment if patient is medially unstable

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

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Outpatient Psychosocial Treatment

Adolescent Anorexia Nervosa

Summary of 9 published AN studies

o 7 of these involved a family-focused approach (FBT or BFST)

o 3 of these involved individual therapy (supportive, adolescent focused therapy, CBT)

o 3 involved inpatient treatment

o 0 of these involved any medication

o Evidence supports effectiveness of FBT, but more comparative efficacy data are limited

Family-Based Treatment Style

Parents in charge• Appropriate

control• Ultimately

relinquished

Parents in charge• Appropriate

control• Ultimately

relinquished

Therapist stance• Active –

mobilize anxiety

• Deference to parents

Therapist stance• Active –

mobilize anxiety

• Deference to parents

Adolescent Respect• Developmental

process• Traditional

treatment upside-down

Adolescent Respect• Developmental

process• Traditional

treatment upside-down

January 2010 47Prof Daniel Le Grange, ChicagoLe Grange et al, Int J Eating Disord 1992; Le Grange J Clin Psychol 1999

Family-Based Treatment Detail

Dose• 6-12 months

Dose• 6-12 months

Intensity• 10-20 sessions

Intensity• 10-20 sessions

Format• Conjoint• Separated

Format• Conjoint• Separated

January 2010 48Prof Daniel Le Grange, ChicagoLe Grange et al, Int J Eating Disord 1992

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Three Phases of FBT

• Parents in charge of weight restoration

Phase 1(Sessions 1-10)

Phase 1(Sessions 1-10)

• Parents hand control over eating back to the adolescent

Phase 2(Sessions 11-16)

Phase 2(Sessions 11-16)

• Discuss adolescent developmental issues

Phase 3(Sessions 17-20)

Phase 3(Sessions 17-20)

January 2010 49Prof Daniel Le Grange, ChicagoLock & Le Grange, Guildford Press, 2013

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.

Primary Outcome

Full remission, i.e., 95% EBW 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

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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)

Full and Partial Remission by Treatment

EOT 6mFU 12mFU EOT 6mFU 12mFU

Perc

enta

ge

AFT FBT

(p = .024, NNT = 4)

Full and Partial Remission by Treatment

EOT 6mFU 12mFU EOT 6mFU 12mFU

Perc

enta

ge

AFT FBT

RelapsePost-Treatment to 12-Month Follow-Up

*Fisher’s Exact p=.021

Relapse at 12mo FU

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What about the tempo of weight gain?

Time until >95%EBW

Le Grange, Accurso, Lock, Agras & Bryson, IJED, 2013.

Weight gain >4 lbs. by wk 4 correctly characterized:

Early Weight Gain and OutcomeFBT (N=65); FBT and AFT (N=121)

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.

How Much Weight in FBT before ROM? (N=84 w/ 2amenorrhea)

o Menses typically return at 95% EBW

o Menses resumed on average at session 13/20of FBT

Faust, Goldschmidt, Anderson, Glunz, Brown, Loeb, Katzman & Le Grange, J Eating Disord, 2013.

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What about hospital days?

Reducing Need for Hospitalization

p=.020

11/9/2014 62Lock, Le Grange, Agras, Moye, Bryson & Jo, Arch Gen Psychiatry, 2010.

Reducing Need for Hospitalization

o FBT was implemented in 2004 at Westmead Children’s Hospital, Sydney, reporting a 50% decrease in readmissions over the implementation period (Wallis et al., 2007).

o FBT was implemented in 2009 at RCH in Melbourne, reporting 56% decrease in admissions, 75% decrease in readmissions, and 51% decrease in overall hospital days (Hughes, Le Grange, Court et al., J Ped Child Care, 2013).

o The role of the pediatrician in FBT is unique, challenges to pediatricians trained in earlier ED treatment approaches, but effective support of the approach is critical to its success (Katzman, Peebles, Sawyer, Lock & Le Grange, J Adolesc Health, 2013).

How does this compare to inpatient refeeding?

o Strober et al. (1997)

o Steinhausen et al. (1993)

o Lay et al. (2002)

30% relapse within 15mo (highest risk up to 9mo)

27% re-adm => 56% 1+ further adm (re-adm mostly within 3 years)

23% re-adm => 78% afterfurther adm

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Effectiveness of a Specialist Family Focused Community Based Program for

Adolescent AN

76.6%

14.0%

6.6%3.1%

0%

20%

40%

60%

80%

100%

OP only ITP+OP ITP+IP+OP IP+OP

OP – Outpatient treatment (mainly FT-AN)ITP – Intensive day program IP – Psychiatric/ED admission

Type of Treatment (N=231)

Eisler et al., ICED (2014)

Outcome by mode of discharge (N=231)(Eisler et al., 2014)

68%

14%11%

7%

Planned discharged to GP

Discharge to CAMHS

Transferred to adult ED service

Declined/early drop out

More than 80% required no further treatment for an eating disorder

Outpatient Psychosocial Treatment

Adolescent Bulimia Nervosa

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Chicago RCTFBT-BN vs SPT

o N=80 adolescent BNo FBT-BN n = 41o SPT n = 39o 6 months of therapyo 6 month follow-up

Le Grange, Crosby, Rathuaz & Leventhal, Arch Gen Psych, 2007.

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Chicago RCTFBT-BN vs SPT

o N=80 adolescent BNo FBT-BN n = 41o SPT n = 39o 6 months of therapyo 6 month follow-up

Le Grange, Crosby, Rathuaz & Leventhal, Arch Gen Psych, 2007.

Conclusion

oFamily-based treatment showed a clinical andstatistical advantage over SPT at post-treatment and at 6-month follow-up.

Maudsley RCT

FT vs CBT-GSC

o N = 85 adolescent BN

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

o N = 85 adolescent BN

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.

Conclusion

oCBT 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.

Summary (Part 2) o Inpatient treatment for medical stabilization should

be brief with rapid refeeding.

o First-line in-patient psychiatric treatment does not provide advantages over out-patient management.

o FBT should be the first-line outpatient treatment for adolescents with AN when medically fit.

o Adolescents with BN should be treated on an outpatient basis, no treatment with proven efficacy.

o No medication studies.

① EDs are highly prevalent and associated with other psychiatric disorders, role impairment and suicidality.

② EDs are life-threatening and require urgent attention.

③ There are helpful treatments provided parents and providers act quickly.

④ Treatment should aim for full weight restoration in AN, and complete cessation of binge eating and purging in BN.

Discussion Points

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Madden, S., Miskovic-Wheatley, J., Wallis, A., Kohn, M., Lock, J., Le Grange, D., et al. (2014). A Randomized Controlled Trial of Inpatient Treatment for Anorexia Nervosa in Medically Unstable Adolescents. Psychol Med, 1-13 [Epub Ahead of Print].

Lock, J., Le Grange, D., Agras, S., Bryson, S., & Jo, B. (2010). Randomized clinical trial comparing family-based treatment to adolescent focused individual therapy for adolescents with anorexia nervosa. Arch Gen Psychiatry, 67, 1025-1032.

Le Grange, D., Crosby, R.D., Rathouz, P.J., & Leventhal, B.L. (2007). A randomized controlled comparison of family-based treatment and supportive psychotherapy for adolescent bulimia nervosa. Arch Gen Psychiatry, 64, 1049-1056.

Katzman, D., Peebles, R., Sawyer, S., Lock, J., & Le Grange, D. (2013). The role of the pediatrician in family-based treatment for adolescent eating disorders: Opportunities and challenges. J Adolesc Health, 53, 433-440.

Rosen, D. (2010). Clinical Report: Identification and management of eating disorders in children and adolescents. Pediatrics, 126, 1240-1253.

Further Information