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Peds Ocd
 

Peds Ocd

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    Peds Ocd Peds Ocd Presentation Transcript

    • Pharmacotherapy for Pediatric OCD A Systematic Review
    • Objectives
      • Review randomized placebo-controlled trials in pediatric OCD
      • Discuss a published meta-analysis of SSRIs in pediatric OCD
    • Method
      • OVID Medline 1950 to December 2007:
        • Child [MeSH] or Adolescent [MeSH] or pediatric [keyword] or paediatric [keyword]
        • AND
        • Obsessive-Compulsive Disorder [MeSH]
      • Resulted in 2453 hits
    • Inclusion Criteria
      • Randomized placebo-controlled trial
      • Subjects aged 0-18 with DSM diagnosis of Obsessive-Compulsive disorder
      • Intervention is pharmacological
      • English language
      • Parallel or Cross-over design
    • Exclusion Criteria
      • Less than 30 subjects for parallel design, less than 15 for cross-over
      • Principal diagnosis of Tourette’s Disorder or Developmental Disorder
    • Child Yale-Brown Obsessive Compulsive Scale
      • C-YBOCS:
        • 10 item scale, range of 0-4
          • Obsessions and Compulsions
          • Time occupied, Interference, Distress, Personal Control, Resistance
        • Range of scale 0-40
        • 8-15 is mild, 16-23 moderate, >24 severe
    • Clomipramine (Anafranil)
    • Clomipramine
      • DeVeaugh et al, 1992
      • Subjects: 10-17 years
      • CMI started at 25mg/d, titrated up to 75mg/d by second week, then titrated to 200mg/d (or 3mg/kg/d)
      • N=60, 31 had CMI vs. 29 PBO
      • Duration: 2 weeks of PBO lead-in, then 8 week trial
    • Clomipramine
    • Clomipramine
      • One year open-label extension: 25/47 of subjects continuing to use CMI
    • Clomipramine Tremor Fatigue Dizziness Somnolence Dry Mouth 2.3% 32.6% 9.1% 34.8% 13.6% 41.3% 11.4% 45.7% 15.9% 63.0% PBO (N=29) CMI (N=31)
    • Clomipramine 0 1 subj. Hepatic Enzyme Inc. 2.3% 13.0% Dyspepsia 2.3% 21.7% Anorexia 2.3% 21.7% Constipation PBO (N=29) CMI (N=31)
    • Clomipramine
      • Limits:
        • Side effects of CMI compromises blinding
        • Small sample size
        • No mention of suicidal ideation
        • Sponsored by Ciba-Geigy
    • Fluoxetine (Prozac)
    • Fluoxetine (1)
      • Geller et al, 2001
      • Subjects: 7-17
      • FLX started at 10mg/d, titrated up to 20-60mg/d
      • N=103, 71 had FLX vs. 32 PBO
      • Duration: 13 weeks
    • Fluoxetine (1)
    • Fluoxetine (1)
      • Effect Size = 0.5
      • Mean dose of FLX was 24.6mg
      • Effects comparable between children and adolescents
    • Fluoxetine (1)
      • No adverse effect that was significantly different from placebo
      • Diarrhea and Hyperkinesia found more in Fluoxetine group
    • Fluoxetine (1)
      • Limits:
        • Many subjects dropped out
          • 31% of FLX, 37.5% of PBO
          • No difference in reasons for drop out
        • Sponsored by Eli Lilly
    • Fluoxetine (2)
      • Liebowitz et al, 2002
      • Subjects: 6-18 years old
      • FLX 20mg/d titrated up to 80mg/d
      • N=43, 21 had FLX, 22 had PBO
      • Duration: 8 weeks + 8 weeks of maintenance for responders
    • Fluoxetine (2)
    • Fluoxetine (2)
      • Significant difference only in maintenance extension
      • Mean dose of FLX 64.8mg/d
    • Fluoxetine (2) 4.5% 33.3% Muscle Ache 0% 28.6% Nightmares 4.5% 38.1% Drowsiness 4.5% 33.3% Weight loss 0% 19% Palpitations PBO (N=22) FLX (N=21)
    • Fluoxetine (2)
      • Significance only found on post-hoc analysis of extension group
      • Sponsored by Eli Lilly and NIMH
    • Paroxetine (Paxil)
    • Paroxetine
      • Geller et al, 2004
      • Subjects: 7-17
      • PRX:started at 10mg/d, titrated up to 50mg/d
      • N=203: 98 had PRX, 105 had PBO
      • Duration: 10 weeks
    • Paroxetine
    • Paroxetine
      • Stronger effect in more severe OCD
      • Stronger effect in younger age
      • Mean dose: 20mg/d for children, 26.8mg/d for adolescents
    • Paroxetine 2% 8% Diarrhea 1% 9% Hostility 1% 9% Decreased appetite 3% 10% Trauma (?) 6% 12% Hyperkinesia PBO N=105 PRX N=98
    • Paroxetine 0 1 subj. Suicidal Ideation (?situation) 1% 5% Neurosis (?) 2% 5% Agitation 2% 6% Vomiting 1% 8% Asthenia PBO N=105 PRX N=98
    • Paroxetine
      • Limits:
        • High drop out rate (in children only)
          • 33% of PRX vs. 24% of PBO
        • Sponsored by GlaxoSmithKline
    • Fluvoxamine (Luvox)
    • Fluvoxamine
      • Riddle et al, 2001
      • Subjects: 8-17 years old
      • FLV started at 25mg qhs, titrated up to 100mg bid (200mg/d)
      • N=120, 57 had FLV, 63 had PBO
      • Duration: 10 weeks
    • Fluvoxamine
    • Fluvoxamine
      • Higher response in younger age
      • Statistically significant differences between groups as early as week 1
      • Mean dose was 165mg/d
    • Fluvoxamine 15.9% 26.3% Asthenia (mean onset ~20d) 9.5% 29.8% Insomnia (mean onset at 45d) PBO N=63 FLV N=57
    • Fluvoxamine
      • Limits:
        • Many dropouts:
          • 33% of FLV vs. 43% of PBO
        • Sponsored by Solvay
    • Sertraline (Zoloft)
    • Sertraline (1)
      • March et al 1998
      • Subjects: 6-17
      • Sertraline started at 25mg/d, titrated up to 50-200mg
      • N=187: 92 had SRT, 95 had PBO
      • Duration: 1 week PBO lead-in, 12 week trial
    • Sertraline (1)
    • Sertraline (1)
      • Mean dose of SRT was 167mg/d
    • Sertraline (1) 0% 7% Tremor 2% 13% Agitation 7% 17% Nausea 13% 37% Insomnia PBO N=95 SRT N=92
    • Sertraline (1)
      • Limits:
        • 12/92 withdrew from SRT due to adverse events vs. 3/95 in PBO
        • Sponsored by Pfizer
    • Sertraline (2)
      • Pediatric OCD Treatment Study (POTS), 2004
      • Subjects: 7-17
      • Sertraline: 25mg/d up to 200mg/d
      • N=112: 28 had SRT+CBT, 28 had CBT, 28 had SRT, 28 had PBO
    • Sertraline (2)
    • Sertraline (2)
    • Sertraline (2)
      • Effect size compared to placebo:
        • Combined: 1.4 (NNT = 2)
        • CBT: 0.97 (NNT = 3)
        • Sertraline: 0.67 (NNT = 6)
    • Sertraline (2) 2% 21% Stomach ache 4% 21% Nausea 4% 12% Motor Overactivity 0% 7% Enuresis 4% 10% Diarrhea 0% 16% Decreased appetite PBO, N=28 SRT, N=56
    • Sertraline (2)
      • Limits:
        • Those assigned to CBT or combined group not blinded at all - expectancy effects
        • Sponsored by NIMH and Pfizer
    •  
    • Meta-analysis
      • Geller et al, 2003
      • 12 randomized controlled-trials
      • Included smaller studies, withdrawl design, cross-over design and active-comparator trials
    • Meta-analysis
      • On CYBOCS: overall effect size of 0.47, statistically significant
      • No evidence of publication bias
      • Clomipramine had significantly more effect than SSRIs
      • SSRIs equal amongst each other
      • Fail-safe N of 973
    • Conclusions
      • Serotonin reuptake inhibitors are effective for pediatric OCD
      • Moderate effect size
      • Response rates: 30-60%
      • Common adverse events: insomnia, hyperkinesia, asthenia, diarrhea, nausea, weight loss
    • Future research
      • Dosing
      • Length of treatment
      • Treatment resistant cases
      • CMI > SSRIs?
      • Safety: suicidal ideation, sexual side effects
    • References
      • DeVeaugh-Geiss, J., Moroz, G., Biederman, J., Cantwell, D., Fontaine, R., Greist, J.H., Reichler, R., Katz, R., Landau, P., Clomipramine Hydrochloride in Childhood and Adolescent Obsessive-Compulsive Disorder - a Multicenter Trial. J.Am. Acad. Child Adolesc. Psychiatry , 31:1, January 1992. 45-49
    • References
      • Geller, D., Hoog, S.L., Heiligenstein, J.H., Ricardi, R.K., Tamura, R., Kluszynski, S., Jacobson, J.G. Fluoxetine Treatment for Obsessive-Compulsive Disorder in Children and Adolescents: A Placebo-Controlled Clinical Trial. J. Am. Acad. Child Adolesc. Psychiatry , 40:7, July 2001, 773-779
    • References
      • Liebowitz, M.R., Turner, S.M., Piacentini, J., Beidel, D.C., Clarvit, S.R., Davies, S.O., Graae, F., Jaffer, M., Lin, S., Sallee, F.R., Schmidt, A., Simpson, H.B. Fluoxetine in Children and Adolescents with OCD: A Placebo-Controlled Trial. J. Am. Acad Child Adolesc Psychiatry 41:12, December, 2002, 1431-1438
    • References
      • Geller, D., Wagner, K., Emslie, G., Murphy, T., Carpenter, D.J., Wetherhold, E., Perera, P., Machin, A.,Gardiner, C. Paroxetine Treatment in Children and Adolescents with Obsessive-Compulsive Disorder: A Randomized, Multicenter, Double-Blind, Placebo-controlled Trial, J. Am. Acad. Child Adolesc. Psychiatry , 43:11, November 2004, 1387-1396
    • References
      • Riddle, M. A., Reeve, E. , Yaryura-Tobia, J.A., Yang, H., Claghorn, J.L., Gaffney, G., Greist, J.H., Holland, D.H., McConville, B.J., Pigott, T., Walkup, J.T., Fluvoxamine for Children and Adolescents with Obsessive-Compulsive Disorder: A Randomized, Controlled, Multicenter Trial, J.Am. Acad. Child Adolesc. Psychiatry , 40:2, February 2001, 222-229
    • References
      • March, J.S., Biederman, J., Wolkow, R., Safferman, A., Mardekian, J., Cook, E.H., Cutler, N.R., Dominguez, R., Ferguson, J., Muller, B., Riesenberg, R., Rosenthal, M., Sallee, F., Steiner, H, Wagner, K. Sertraline in Children and Adolescents with Obsessive-Compulsive Disorder. JAMA , 280: 20, November 1998, 1752-1756
    • References
      • Pediatric OCD Study Team: March, J., Foa, E. et al. Cognitive-Behavior Therapy, Sertraline and Their Combination for Children and Adolescents with Obsessive-Compulsive Disorder, JAMA , 292:16, October 2004, 1969-1976
    • References
      • Geller, D., Biederman, J., Stewart, S.E., Mullin, B., Martin, A., Spencer, T., Faraone, S., Which SSRI? A Meta-analysis of Pharmacotherapy Trials in Pediatric Obsessive-Compulsive Disorder, Am. J. Psychiatry 160:11, November 2003, 1919-1928
    • Credits
      • Principal Investigator, Producer, Music and Narration: Darren Courtney, M.D., B.Sc.
      • Supervisor: Dr. Clare Gray
      • Technical Support: Dr. Michael Cheng
      • Children’s Hospital of Eastern Ontario