Specific Issues in
Pediatric OCD:
Treatment and
Adulthood Outcome
Michael H. Bloch M.D., M.S.
Assistant Director, Yale OCD...
Objectives
• Current State of Evidence-Based OCD
Treatment in Children and Adults
• Moderators of Treatment Effects in OCD...
First-Line Treatments for OCD
Foa et. al 2005
70%
62%
42%
8%
0%
10%
20%
30%
40%
50%
60%
70%
80%
Combination Treatment CBT Clomipramine Placebo
PercentRespondersXX
First...
Pediatric OCD Treatment Study
POTS Team, JAMA 2004
Figure 2. Weekly Adjusted Intent-to-Treat CY-BOCS Score, by Treatment Group Range of possible
scores for the Children’s Ya...
Short-Term Outcome in Pediatric-Onset
OCD
• Pediatric OCD Treatment Study
– After 12 weeks the likelihood of Clinical Remi...
POTS: CBT isn’t all created Equal
• Effect Sizes of Treatment Arms by Site
Take Home Points
• Few OCD patients get better without
Treatment
• First-Line Treatments for OCD work well in
both adults ...
Options when SSRI Treatment
Doesn’t Work
• Cognitive Behavioral Therapy
• Try A Different SSRI
• Increase the SSRI dose
• ...
Do Higher Doses of SSRIs improve
efficacy?
• APA Practice Guidelines currently
recommend the use of high doses of SSRIs
be...
Do Higher Doses of SSRIs improve
efficacy?
• Bloch et al. 2009
– Meta-analysis of 9 RCT (N=2297) comparing
multiple fixed-...
Bloch et al. 2009
Bloch et al. 2009
Cost-Benefit of High-Dose SSRI
Bloch et al. 2009
Take Home Points
• Higher doses of SSRIs are modestly more
effective
• Increased amount of side-effects as SSRI
doses are ...
Evidence Regarding SSRI Dose
Effects in Children with OCD
• NO fixed dose trials of SSRIs in pediatric OCD
• Generally SSR...
Antipsychotic Augmentation
-
-
+
+
-
+
+
+
-
Antipsychotic Augmentation
• Meta-analysis of 9 double-blind, RCT (N=278)
comparing antipsychotic augmentation to placebo
...
NNT=1/0.22=4.6
Take Home Point
• Antipsychotics are modestly effective for
treatment-refractory OCD.
• No difference in efficacy between ...
Issues in Clinical Treatment of
OCD across the lifespan
• Many Patients with OCD don’t improve with
first-line treatments
...
Potential Solutions
• Identify Moderators of Treatment Effects
• Identify Early Predictors of Treatment
Response
• Develop...
Searching for Moderators of
Treatment Effects
• Comorbid disorders – tics
• OCD Symptom Dimensions
– Two patients can have...
Tic-Related OCD
• Male-predominance
• Earlier age of onset
• Different obsessions and compulsions:
increased proportion in...
POTS – comorbid tics as moderator of
treatment outcome
Marsh JS, Bio Psychiatry (2007)
Antipsychotic Augmentation appears particularly effective in adults
with comorbid tics
NNT=1/.46=
2.3
NNT=1/.17=
5.9
OCD Symptom Dimensions
• 21 previous factor analytic studies in OCD using the
Y-BOCS (N=5,142)
• Previous studies reported...
OCD Symptom Dimensions
SYMMETRY
FORBIDDEN
THOUGHTS
CLEANING
HOARDING
FACTORSObsessions Compulsions
Symmetry
Aggressive
Sex...
Hoarding as Predictor of Poor
Treatment Response
Take Home Points: Moderators of
Treatment Response
• Roughly half of OCD Patients Respond to SSRIs.
• OCD Patients with Ho...
Further Opportunities: Time-Course of SSRI Response
Across the Lifespan
Adults
Children
The Challenge
• Roughly 25% of OCD patients do not
respond to available treatments
• A large portion of “clinical responde...
Directions for Future Treatment Research in OCD
across the lifespan
• Examining glutamate modulating agents in
treatment-r...
Adulthood Outcome in Pediatric
OCD
Unanswered Questions
• “Will my son have OCD for the rest of his
life?”
• “Since my son developed OCD in childhood is
he a...
Stewart et al. 2004
• Meta-analysis of 16 studies involving 521 children
with OCD.
– 41% persistence rate of full OCD
– 60...
Predictors of Long-term Outcome
• Early Age of Onset
• Inpatient Treatment
Study Design
AGE
8 12 16 2
0
Clinical Assessment
MRI
Neuropsychological
Testing
Follow-Up
Clinical
Assessment
Follow-up In...
Clinical Course of
OCD
Age of Onset=
8.0 +/- 2.5
Age of Worst-Ever=
11.3 +/- 2.4
Age of OCD Remission=
15.5 +/- 3.6 (N=20)
OCD Severity at Adulthood Follow-up
24% Full OCD
55% Subthreshold
OCD
45%
31%
13%
11%
Minimal
Mild
Moderate
Severe
ç
Medication Use Across Time
SRI Medication
Current use of
SRI, n=27
SRI use only in
childhood, n=14
60% of Children
remaine...
Hypothesized Predictors of OCD
Persistence into Adulthood
OCD Persistence into adulthood
would be associated with :
• Como...
Comorbid Tics and Persistence of
OCD
ProportionofIndividualswithClinicallySignificantOCD
Years since OCD Diagnosis in Chil...
Clinical Course of Tourette
Syndrome
Leckman JF, Pediatrics 1998
OCD Symptom Dimensions
SYMMETRY
FORBIDDEN
THOUGHTS
CLEANING
HOARDING
FACTORSObsessions Compulsions
Symmetry
Aggressive
Sex...
OCD Symptom Dimensions and Persistence of OCD
symptoms into Adulthood
ProportionofIndividualswithClinicallySignificantOCD
...
Neuropsychological Testing
• Poor Purdue Pegboard Performance was
associated with persistence of OCD
symptoms to young adu...
Motor Skills and Persistence of
Childhood Psychopathology
• Poor Purdue Pegboard performance
associated with increased adu...
Childhood Basal Ganglia Volumes
• Hypothesis:
– Childhood Basal Ganglia volumes would
be associated with persistence of OC...
Basal Ganglia Volumes
Results
• Larger putamen volumes were associated with
persistence of OCD symptoms.
– right putamen (HR=0.024, 95% CI: 0.00...
Take Home Points
• Like tic symptoms, OCD symptoms often get
much better in kids
• Hoarding symptoms are associated with a...
Directions for Future OCD
Research
• Longitudinal neuroimaging study examining
prognosis in childhood OCD
• Setting up a u...
Acknowledgements
• Kaitlyn E. Panza
• Angeli Landeros-
Weisenberger MD
• Suzanne Wasylink
• Eileen Billingslea
• Christoph...
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Dr. Michael H. Bloch - Simposio Internacional 'La enfermedad de la duda: el TOC'

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El 14 de noviembre de 2013, la Fundación Ramón Areces organizó y acogió en su sede un Simposio Internacional sobre 'La enfermedad de la duda: el TOC'. El Trastorno Obsesivo-Compulsivo (TOC) es un problema de salud pública, poco conocido, que afecta a un porcentaje de la población en torno a un 1-2% y que la Organización Mundial de la Salud ha situado entre las diez entidades que producen más discapacidad.

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  • Figure 2. Weekly Adjusted Intent-to-Treat CY-BOCS Score, by Treatment Group Range of possible scores for the Children’s Yale-Brown Obsessive-Complusive Scale (CY-BOCS) is 0-40. Error bars indicate SE. Mean (SE) scores adjusted for fixed effects for treatment, site, days since baseline (linear time trend), and all 2- and 3-way interactions.
  • CBT – recent AJP by Blair Simpson showing that skilled CBT effective in refractory patients
    Switching SSRI – after 1 failure about 25% response rate, 10% with 2 failures
  • 22% greater response rate on high dose compared to placebo. High > improvement than medium, low and placebo on Y-BOCS scores. NNT roughly 15.
  • No significant difference in droputs due to side-effects between conditions but higher rates of drop-outs due to side-effects in High and medium dose groups
  • 5 of 9 studies positive and 4 negative
  • Genetics – 5ht
  • Meta-analysis of these 22 studies involving over 5000 patients
    Dimensional structure was stable across methodology used in analysis, children vs. adults and ethncity
  • Meta-Analysis of Time-Course of SSRI response in children and adults with OCD compared to placebo.
    7 trials in children involving 725 participants, 17 trials involving 3700+ subjects in adults
    Large proportion of treatment benefits observed within the first month of treatment -- greater than 50% by week 4 and greater than 80% by week 6
    Logarithmic model – decreasing benefits of SSRIs compared to placebo over time – greatest incremental beenfits early
  • Meta-analysis of these 22 studies involving over 5000 patients
    Dimensional structure was stable across methodology used in analysis, children vs. adults and ethncity
  • Dr. Michael H. Bloch - Simposio Internacional 'La enfermedad de la duda: el TOC'

    1. 1. Specific Issues in Pediatric OCD: Treatment and Adulthood Outcome Michael H. Bloch M.D., M.S. Assistant Director, Yale OCD Clinic Assistant Professor, Yale Child Study Center Michael.bloch@yale.edu
    2. 2. Objectives • Current State of Evidence-Based OCD Treatment in Children and Adults • Moderators of Treatment Effects in OCD • Adulthood Outcome in Childhood OCD • Future Directions of Childhood OCD Research
    3. 3. First-Line Treatments for OCD Foa et. al 2005
    4. 4. 70% 62% 42% 8% 0% 10% 20% 30% 40% 50% 60% 70% 80% Combination Treatment CBT Clomipramine Placebo PercentRespondersXX First-Line OCD Treatments Combination Treatment: NNT=1/ARD=1/ (.7-.08)=1.6 CBT: NNT=1.9 Clomipramine: NNT=2.9 Foa et al., 2005 Number Needed to Treat (NNT) =the number of patients that need to be treated with an intervention for one to benefit compared to placebo.
    5. 5. Pediatric OCD Treatment Study POTS Team, JAMA 2004
    6. 6. Figure 2. Weekly Adjusted Intent-to-Treat CY-BOCS Score, by Treatment Group Range of possible scores for the Children’s Yale-Brown Obsessive-Complusive Scale (CY-BOCS) is 0-40. JAMA 2004;292:1969-1976 Copyright restrictions may apply.
    7. 7. Short-Term Outcome in Pediatric-Onset OCD • Pediatric OCD Treatment Study – After 12 weeks the likelihood of Clinical Remission in OCD is … – 3.6% for placebo – 21.4% for sertraline (NNT=5.6) – 39.3% for CBT (NNT=2.8) – 53.6% for Combination Treatment with CBT and sertaline (NNT=2.0) POTS Team, JAMA 2004
    8. 8. POTS: CBT isn’t all created Equal • Effect Sizes of Treatment Arms by Site
    9. 9. Take Home Points • Few OCD patients get better without Treatment • First-Line Treatments for OCD work well in both adults and children. • Skill of CBT therapist makes a DIFFERENCE • Treatments for OCD take a long time to work • A sizeable portion of OCD patients will not improve on first-line interventions
    10. 10. Options when SSRI Treatment Doesn’t Work • Cognitive Behavioral Therapy • Try A Different SSRI • Increase the SSRI dose • Antipsychotic Augmentation
    11. 11. Do Higher Doses of SSRIs improve efficacy? • APA Practice Guidelines currently recommend the use of high doses of SSRIs before starting alternative pharmacologic treatment for OCD. • Inclusion criteria for all clinical trials in refractory OCD requires that OCD patients have not achieved symptom relief on treatment with the MAXIMUM TOLERATED DOSE of at least 1 SSRI • Meta-analysis of fixed-dose antidepressant studies in depression failed to show an increased response rate with higher doses of antidepressants. (Bollini et al. 1999)
    12. 12. Do Higher Doses of SSRIs improve efficacy? • Bloch et al. 2009 – Meta-analysis of 9 RCT (N=2297) comparing multiple fixed-doses of SSRI to each other and placebo. – Goal determine if higher doses of SSRI treatment are more effective than lower doses.
    13. 13. Bloch et al. 2009 Bloch et al. 2009
    14. 14. Cost-Benefit of High-Dose SSRI Bloch et al. 2009
    15. 15. Take Home Points • Higher doses of SSRIs are modestly more effective • Increased amount of side-effects as SSRI doses are raised • Suggests 2 initial dosing strategies – Start at minimum recommend dose and wait – Titrate to maximum tolerated dose quickly
    16. 16. Evidence Regarding SSRI Dose Effects in Children with OCD • NO fixed dose trials of SSRIs in pediatric OCD • Generally SSRI trials in Pediatric OCD have used maximal recommended FDA dose as target.
    17. 17. Antipsychotic Augmentation - - + + - + + + -
    18. 18. Antipsychotic Augmentation • Meta-analysis of 9 double-blind, RCT (N=278) comparing antipsychotic augmentation to placebo in treatment-refractory OCD. • Response defined as a 35% reduction in Y-BOCS score. Bloch et al. 2007
    19. 19. NNT=1/0.22=4.6
    20. 20. Take Home Point • Antipsychotics are modestly effective for treatment-refractory OCD. • No difference in efficacy between agents • NNT=5 So if your patient does not get better on antipsychotic augmentation after 8 weeks then STOP IT. • No RCTs in pediatric OCD
    21. 21. Issues in Clinical Treatment of OCD across the lifespan • Many Patients with OCD don’t improve with first-line treatments • Takes a long-time to know if first-line treatments will be ineffective. • No data regarding efficacy of augmentation strategies in pediatric OCD • Dissemination of Effective First-Line Treatments
    22. 22. Potential Solutions • Identify Moderators of Treatment Effects • Identify Early Predictors of Treatment Response • Develop Novel Treatments that work better and faster
    23. 23. Searching for Moderators of Treatment Effects • Comorbid disorders – tics • OCD Symptom Dimensions – Two patients can have completely different symptoms but both still clearly have OCD. – Measuring this heterogeneity may increase power and explain differences in clinical and research studies of OCD.
    24. 24. Tic-Related OCD • Male-predominance • Earlier age of onset • Different obsessions and compulsions: increased proportion involving … – symmetry and exactness – touching and tapping rituals – obsessions involving fear of harm – obsessions surrounding sexual and violent imagery (Leckman, Anxiety 1997)
    25. 25. POTS – comorbid tics as moderator of treatment outcome Marsh JS, Bio Psychiatry (2007)
    26. 26. Antipsychotic Augmentation appears particularly effective in adults with comorbid tics NNT=1/.46= 2.3 NNT=1/.17= 5.9
    27. 27. OCD Symptom Dimensions • 21 previous factor analytic studies in OCD using the Y-BOCS (N=5,142) • Previous studies reported between 3-5 factors. • The relationship between many OCD symptom types remained unclear. • Due to statistical techniques involved in extracting factors, differences between study results get exaggerated • Differences between factor analysis results make it impossible to interpret the results of genetic, treatment and neuroimaging studies vis a vis symptom dimensions
    28. 28. OCD Symptom Dimensions SYMMETRY FORBIDDEN THOUGHTS CLEANING HOARDING FACTORSObsessions Compulsions Symmetry Aggressive Sexual Religious Somatic Contamination Hoarding Ordering Repeating Counting Checking Cleaning Hoarding Bloch et al. 2009
    29. 29. Hoarding as Predictor of Poor Treatment Response
    30. 30. Take Home Points: Moderators of Treatment Response • Roughly half of OCD Patients Respond to SSRIs. • OCD Patients with Hoarding Symptoms appear to have poor response to SSRI pharmacotherapy and possibly CBT. • OCD patients with comorbid tics appear to have improved response to antipsychotics but potentially worse response to SSRI. • No evidence on what to do in pediatric populations or that children are particularly different.
    31. 31. Further Opportunities: Time-Course of SSRI Response Across the Lifespan Adults Children
    32. 32. The Challenge • Roughly 25% of OCD patients do not respond to available treatments • A large portion of “clinical responders” have significant residual symptoms • Effective Treatments take a long time to work • No evidence base for interventions targeting pediatric OCD non-responders
    33. 33. Directions for Future Treatment Research in OCD across the lifespan • Examining glutamate modulating agents in treatment-refractory OCD – Ketamine in adults with OCD – N-acetylcysteine across the lifespan • Trials examining the efficacy of augmentation strategies in pediatric OCD – Antipsychotic augmentation? • Dose-response curve in pediatric OCD
    34. 34. Adulthood Outcome in Pediatric OCD
    35. 35. Unanswered Questions • “Will my son have OCD for the rest of his life?” • “Since my son developed OCD in childhood is he at risk for any other psychiatric conditions?” • “Is there any way to predict whether my son will continue to experience OCD in adulthood?”
    36. 36. Stewart et al. 2004 • Meta-analysis of 16 studies involving 521 children with OCD. – 41% persistence rate of full OCD – 60% persistence rate of at least subclinical OCD But … •95% CI was 32-51% for persistence rate of full OCD •95% CI was 46-74% for persistence rate for subclinical OC symptoms •Significant heterogeneity across the studies included in the meta-analysis Long-Term Outcome in OCD
    37. 37. Predictors of Long-term Outcome • Early Age of Onset • Inpatient Treatment
    38. 38. Study Design AGE 8 12 16 2 0 Clinical Assessment MRI Neuropsychological Testing Follow-Up Clinical Assessment Follow-up IntervalMean Childhood Age = 12.1 +/- 2.0 Mean Adult Age = 21.1 +/- 3.6 9 YEARS 62 eligible subjects with Pediatric-Onset OCD 46 participants (74%)
    39. 39. Clinical Course of OCD Age of Onset= 8.0 +/- 2.5 Age of Worst-Ever= 11.3 +/- 2.4 Age of OCD Remission= 15.5 +/- 3.6 (N=20)
    40. 40. OCD Severity at Adulthood Follow-up 24% Full OCD 55% Subthreshold OCD 45% 31% 13% 11% Minimal Mild Moderate Severe ç
    41. 41. Medication Use Across Time SRI Medication Current use of SRI, n=27 SRI use only in childhood, n=14 60% of Children remained on SRIs in adulthood No Hx of SRI Use, n=4
    42. 42. Hypothesized Predictors of OCD Persistence into Adulthood OCD Persistence into adulthood would be associated with : • Comorbid Tic Symptoms • Prominent Hoarding Symptoms
    43. 43. Comorbid Tics and Persistence of OCD ProportionofIndividualswithClinicallySignificantOCD Years since OCD Diagnosis in Childhood Bloch MH, Pediatrics, 2009
    44. 44. Clinical Course of Tourette Syndrome Leckman JF, Pediatrics 1998
    45. 45. OCD Symptom Dimensions SYMMETRY FORBIDDEN THOUGHTS CLEANING HOARDING FACTORSObsessions Compulsions Symmetry Aggressive Sexual Religious Somatic Contamination Hoarding Ordering Repeating Counting Checking Cleaning Hoarding SYMMETRY FORBIDDEN THOUGHTS CLEANING HOARDING FACTORSObsessions Compulsions Symmetry Aggressive Sexual Religious Somatic Contamination Hoarding Ordering Repeating Counting Checking Cleaning Hoarding Bloch et al.
    46. 46. OCD Symptom Dimensions and Persistence of OCD symptoms into Adulthood ProportionofIndividualswithClinicallySignificantOCD Years since OCD Diagnosis in Childhood Bloch MH, Pediatrics, 2009
    47. 47. Neuropsychological Testing • Poor Purdue Pegboard Performance was associated with persistence of OCD symptoms to young adulthood. – dominant-handed (HR=3.3, 95% CI: 1.1-10.6, p=0.04) – bimanual (HR=4.7, 95% CI: 1.2-17.5, p=0.02) • Full-scale intelligence and Rey-Osterreith Complex Figure Test performance were not associated with persistence of OCD symptoms.
    48. 48. Motor Skills and Persistence of Childhood Psychopathology • Poor Purdue Pegboard performance associated with increased adulthood tic severity in children with TS. Bloch MH et al. JCPP, 2006 • Increased neurological soft signs associated with persistence of internalizing (depression and anxiety) and externalizing symptoms. Pine DS et al., JAACAP 1993+1997
    49. 49. Childhood Basal Ganglia Volumes • Hypothesis: – Childhood Basal Ganglia volumes would be associated with persistence of OCD symptoms into adulthood?
    50. 50. Basal Ganglia Volumes
    51. 51. Results • Larger putamen volumes were associated with persistence of OCD symptoms. – right putamen (HR=0.024, 95% CI: 0.002-0.362, p=0.007) – left putamen (HR=0.037, 95% CI: 0.003-0.432, p=0.009) – bilateral putamen (HR=0.160, 95% CI:0.043-0.601, p=0.007) • Caudate and globus pallidus volumes were not associated with persistence of OCD symptoms. Neuroimaging Predictors of Adulthood Outcome
    52. 52. Take Home Points • Like tic symptoms, OCD symptoms often get much better in kids • Hoarding symptoms are associated with a poor long-term prognosis in pediatric-onset OCD. • Poor fine motor skills associated with the persistence of OCD, TS and many other child psychopathologies. • Larger putamen volumes associated with a childhood-onset OCD diagnosis and OCD persistence into adulthood.
    53. 53. Directions for Future OCD Research • Longitudinal neuroimaging study examining prognosis in childhood OCD • Setting up a useful clinical trials infrastructure in OCD treatment across the lifespan • Focus on dissemination of treatments to underserved areas.
    54. 54. Acknowledgements • Kaitlyn E. Panza • Angeli Landeros- Weisenberger MD • Suzanne Wasylink • Eileen Billingslea • Christopher Pittenger MD, PhD • James F. Leckman MD FUNDING • NIMH K23 • YCCI Scholar Award • AACAP Junior Investigator Award • NARSAD • Trichotillomania Learning Center • Rembrandt Foundation Patients and their families

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