Specific Issues in Pediatric OCD: Treatment and Adulthood Outcome

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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

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 First-Line OCD Treatments 80% 70% Foa et al., % 62% 60% 50% 42% Number 40% Needed to Treat (NNT) =the number of patients that need Percent Responders to 30% be treated with an intervention for one to benefit compared to placebo. 20% 8% 10% 0% Combination Treatment CBT Clomipramine Placebo Combination Treatment: NNT=1/ARD=1/(.7-.08)=1.6 CBT: NNT=1.9 Clomipramine: NNT=2.9

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 JAMA 2004;292: 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

$Inclusion criteria for all clinical trials in refractory OCD requires that OCD patients have not achieved symptom relief on treatment with the MAXIMUM TOLERATED DOSE of at least 1 SSRI Meta-analysis$

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 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 SSRI Dose Response Relationship Absolute Response Difference (%) Response Rate Y-BOCS Score Change in Y-BOCS Rating 0 PLACEBO LOW MEDIUM HIGH 0 Dose Bloch et al. 2009

14 Cost-Benefit of High-Dose SSRI SSRI Dose Tolerability Relationship Absolute Risk Difference of Dropout (%) All Cause Side Effects PLACEBO LOW MEDIUM HIGH Dose 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

$to placebo in treatment-refractory OCD. Response defined as a 35% reduction in Y-BOCS score. Bloch et al.$

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

$Take Home Point Antipsychotics are modestly effective for treatment-refractory OCD.$

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

first-line treatments will be ineffective.

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

symptoms but both still clearly have OCD.

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 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

$Directions for Future Treatment Research in OCD across the lifespan Examining glutamate modulating agents in treatment-refractory OCD Ketamine in adults with OCD$

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 Long-Term Outcome in OCD Stewart et al But Meta-analysis of 16 studies involving 521 children with OCD. 95% CI was 32-51% for persistence rate of full 41% OCDpersistence rate of full OCD 60% persistence rate of at least subclinical OCD 95% CI was 46-74% for persistence rate for subclinical OC symptoms Significant heterogeneity across the studies included in the meta-analysis

37 Predictors of Long-term Outcome Early Age of Onset

Study Design Clinical Assessment MRI Neuropsychological Testing Mean Childhood Age = 12.1 +/- 2.

38 Study Design Clinical Assessment MRI Neuropsychological Testing Mean Childhood Age = /- 2.0 Follow-up Interval 9 YEARS Follow-Up Clinical Assessment Mean Adult Age = / eligible subjects with Pediatric-Onset OCD 46 participants (74%) AGE 0

Clinical Course of OCD Age of Worst-Ever= 11.3 +/- 2.

39 Clinical Course of OCD Age of Worst-Ever= /- 2.4 Age of Onset= 8.0 +/- 2.5 Age of OCD Remission= /- 3.6 (N=20)

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

41 Medication Use Across Time 60% of Children remained on SRIs in adulthood SRI Medication No Hx of SRI Use, n=4 Current use of SRI, n=27 SRI use only in childhood, n=14

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

43 Bloch MH, Pediatrics, 2009 Comorbid Tics and Persistence of OCD

44 Clinical Course of Tourette Syndrome Leckman JF, Pediatrics 1998

45 OCD Symptom Dimensions Bloch et al.

46 OCD Symptom Dimensions and Persistence of OCD symptoms into Adulthood Bloch MH, Pediatrics, 2009

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.

47 Neuropsychological Testing Poor Purdue Pegboard Performance was associated with persistence of OCD symptoms to young adulthood. dominant-handed (HR=3.3, 95% CI: , p=0.04) bimanual (HR=4.7, 95% CI: , 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

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

50 Basal Ganglia Volumes

Neuroimaging Predictors of Results Adulthood Outcome Larger putamen volumes were associated with persistence of OCD symptoms. right putamen (HR=0.024, 95% CI: 0.002-0.362, p=0.

51 Neuroimaging Predictors of Results Adulthood Outcome Larger putamen volumes were associated with persistence of OCD symptoms. right putamen (HR=0.024, 95% CI: , p=0.007) left putamen (HR=0.037, 95% CI: , p=0.009) bilateral putamen (HR=0.160, 95% CI: , p=0.007) Caudate and globus pallidus volumes were not associated with persistence of OCD symptoms.

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.

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.

clinical trials infrastructure in OCD treatment across the

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

An Update on the Treatment of Obsessive Compulsive Disorder In Children and Adolescents

An Update on the Treatment of Obsessive Compulsive Disorder In Children and Adolescents Kyle Williams, MD, PhD Director, Pediatric Neuropsychiatry and Immunology Program Massachusetts General Hospital