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.

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. 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. First-Line Treatments for OCD
Foa et. al 2005

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. Pediatric OCD Treatment Study
POTS Team, JAMA 2004

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. 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. POTS: CBT isn’t all created Equal
• Effect Sizes of Treatment Arms by Site

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. Options when SSRI Treatment
Doesn’t Work
• Cognitive Behavioral Therapy
• Try A Different SSRI
• Increase the SSRI dose
• Antipsychotic Augmentation

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. 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. Bloch et al. 2009
Bloch et al. 2009

14. Cost-Benefit of High-Dose SSRI
Bloch et al. 2009

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. 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. Antipsychotic Augmentation
-
-
+
+
-
+
+
+
-

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. NNT=1/0.22=4.6

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. 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. Potential Solutions
• Identify Moderators of Treatment Effects
• Identify Early Predictors of Treatment
Response
• Develop Novel Treatments that work better
and faster

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. 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. POTS – comorbid tics as moderator of
treatment outcome
Marsh JS, Bio Psychiatry (2007)

26. Antipsychotic Augmentation appears particularly effective in adults
with comorbid tics
NNT=1/.46=
2.3
NNT=1/.17=
5.9

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. 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. Hoarding as Predictor of Poor
Treatment Response

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. Further Opportunities: Time-Course of SSRI Response
Across the Lifespan
Adults
Children

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. 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. Adulthood Outcome in Pediatric
OCD

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. 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. Predictors of Long-term Outcome
• Early Age of Onset
• Inpatient Treatment

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. 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. OCD Severity at Adulthood Follow-up
24% Full OCD
55% Subthreshold
OCD
45%
31%
13%
11%
Minimal
Mild
Moderate
Severe
ç

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. Hypothesized Predictors of OCD
Persistence into Adulthood
OCD Persistence into adulthood
would be associated with :
• Comorbid Tic Symptoms
• Prominent Hoarding Symptoms

43. Comorbid Tics and Persistence of
OCD
ProportionofIndividualswithClinicallySignificantOCD
Years since OCD Diagnosis in Childhood
Bloch MH, Pediatrics, 2009

44. Clinical Course of Tourette
Syndrome
Leckman JF, Pediatrics 1998

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. OCD Symptom Dimensions and Persistence of OCD
symptoms into Adulthood
ProportionofIndividualswithClinicallySignificantOCD
Years since OCD Diagnosis in Childhood
Bloch MH, Pediatrics, 2009

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. 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. Childhood Basal Ganglia Volumes
• Hypothesis:
– Childhood Basal Ganglia volumes would
be associated with persistence of OCD
symptoms into adulthood?

50. Basal Ganglia Volumes

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. 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. 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. 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