1 / 25

Antidepressants in Kids: Benefits of Treatment vs. Risk of Suicidal Behavior

Antidepressants in Kids: Benefits of Treatment vs. Risk of Suicidal Behavior. Gregory W. Dalack, MD April 26, 2007. Objectives. Review EBM Steps Develop a PICO question Brief Review of Literature Search technique Focus on one large meta-analysis Discuss study design

sereno
Download Presentation

Antidepressants in Kids: Benefits of Treatment vs. Risk of Suicidal Behavior

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Antidepressants in Kids: Benefits of Treatment vs. Risk of Suicidal Behavior Gregory W. Dalack, MD April 26, 2007

  2. Objectives • Review EBM Steps • Develop a PICO question • Brief Review of Literature Search technique • Focus on one large meta-analysis • Discuss study design • Quality of studies included • Models to pool results from multiple studies • Brief overview of results • Discuss Risk Differences • Number Needed to Treat • Number Needed to Harm • Implications for decision-making

  3. The Practice of EBM • Step 1: Ask– a structured, patient-focused question. Consider the PICO format (Patient/Population; Intervention; Comparison; Outcome). • Step 2: Acquire– do an efficient and effective literature search. • Step 3: Appraise– critically appraise the quality of the studies. • Step 4: Apply– the evidence to your specific patient. • Step 5: Assess– the result of the application of the evidence

  4. Good clinical questions • “Background” Questions • General knowledge • Two components • Root (who, what, when, where, why) • A disorder or aspect of a disorder • E.g., “What is the typical age of onset of bipolar disorder?” • “How do I decide to use a typical vs. atypical antipsychotic for agitation?”

  5. Good clinical questions • “Foreground” Questions • These ask for specific information about managing a patient with a disorder • They have 3-4 essential components • P • I • C • O

  6. Asking answerable clinical questions (CEBM- Oxford)

  7. P is a 14 year old boy who has been diagnosed by his pediatrician with depression. There is a family history of depressive illness and a completed suicide by a maternal uncle. P is withdrawn, gloomy and irritable at times, and often very dysphoric. He is not sleeping well and has had a difficult time attending and keeping up in school.

  8. The patient’s father, a nurse, and his mother, a lawyer, are anxious about their son’s condition and want some recommendations about medication treatment for depression. The pediatrician has sent them to you for a consultation. • What do you tell them? What recommendations do you make?

  9. The Well-Built, Patient-Oriented Clinical Question • P- Patient or population—Describe the most important characteristics of the patient • I- Intervention– Describe the main intervention • C- Comparison– Describe the main alternative being considered • O- Outcome– Describe what you are trying to trying to accomplish/improve/measure/etc.

  10. Search Strategy: the best terms come from P & I • P- Patient or population • I- Intervention • C- Comparison • O- Outcome

  11. Search Strategy: the best terms come from P & I • Let’s try PubMed • “Clinical Queries” • Search by Clinical Study Category • “Narrow” • Enter Search Terms

  12. Let’s pursue the first one • Meta-analysis • Clinical Response and Risk of Reported Suicidal Ideation and Suicide Attempts in Pediatric Antidepressant Treatment– JAMA 2007: 297:1683-1696 • Objective: To assess efficacy of antidepressants and risk of reported suicidal ideation/suicide attempt during antidepressant treatment of pediatric MDD, OCD, and non-OCD anxiety disorders

  13. Brief overview of methods • 27 Trials • MDD: 15 • OCD: 6 • Non-OCD Anxiety Disorders: 6 • Risk differences for response and for suicidal ideation/suicide attempt were estimated • Were these trials designed to assess response? • Were these trials designed to assess risk of SI/SA? • Quality Assessment

  14. Quality Assessment • Adequacy of Randomization • Study Entry Criteria • Outcome Measures • Therapeutic and Placebo procedures (e.g., flexible dosing, blinding of pills) • Statistical Analysis- to ITT or not to ITT • In this study, individual items “present” were summed and divided by # possible items to produce a score between 0-1

  15. Brief overview of methods • Outcome Measures • MDD: 8 weeks • OCD: 11 weeks • Non-OCD Anxiety Disorders: 11 weeks • Placebo run-in period- 17-47% of studies • Most (23/27) used flexible dosing schedule • Majority of studies (85%) were multi-site • Median quality score= 0.88—good quality • Most common weaknesses: • Failure to use ITT analyses • Ambiguity about Randomization and exclusionary processes

  16. Fixed Effects vs. Random Effects Model • Fixed Effects Model: assumes that for the studies combined in the meta-analysis there is a single true value; or, if all studies were infinitely large, they would yield the same estimate of the effect. Assumes there is only “within-study” variance and ignores “between-study” variance. • Random Effects Model: assumes that the studies included are a random sample of a population of studies addressing the question posed. Each study tends to estimate a different underlying true effect; the distribution of these is assumed to be normal around a mean value. It takes into account both within and between study variances.

  17. Brief overview of methods • Median treatment period • MDD: CGI in 8/15; Children’s Depression Rating Scale in 11/15 • OCD: all used change score in YBOCS; 3/6 also used > 25% decrease in Children’s YBOCS • Non-OCD Anxiety Disorders: CGI in all 6; Pediatric Anxiety Rating Scale in 2/6

  18. Definition of Terms • Absolute Risk Reduction: difference in the absolute risk (percentage of patients with specified [presumably good] outcome) in those exposed to the intervention vs. those unexposed • Absolute Risk Increase: difference in the absolute risk (percentage of patients with specified [presumably bad] outcome) in those exposed to the intervention vs. those unexposed • Number Needed to Treat: number of patients who need to be treated over a specific period to prevent 1 bad outcome • NNT= inverse of Absolute Risk Reduction • Number Needed to Harm: number of patients who need to be treated over a specific period before one adverse event of the treatment occurs • NNT= inverse of Absolute Risk Increase

  19. Results • MDD studies (13 trials, 2910 subjects) • Pooled absolute response rates: 61% (95% CI 58-63%) in AD treated subjects; 50% (95% CI 47%-53%) in Pbo treated subjects • Pooled risk difference of 11% (95% CI 7%-15%) • NNT= 10 (95% CI 7-15) • Pooled absolute rates of SI/SA: 3% (95% CI 2-4%) in AD treated subjects; 2% (95% CI 1%-2%) in Pbo treated subjects • Pooled risk difference of 1% (95% CI -0.1% to 2%) • NNH= 112 (note there were no suicides in any group)

  20. Results • OCD studies (6 trials, 705 subjects) • Pooled absolute response rates: 52% (95% CI 46-57%) in SSRI treated subjects; 32% (95% CI 27%-37%) in Pbo treated subjects • Pooled risk difference of 20% (95% CI 13-27%) • NNT= 6 (95% CI 4-8) • Pooled absolute rates of SI/SA: 1% (95% CI 0-2%) in SSRI treated subjects; 0.3% (95% CI -0.3-1%) in Pbo treated subjects • Pooled risk difference of 0.5% (95% CI -1% to 2%) • NNH= 200 (note there were no suicides in any group)

  21. Results • Non-OCD Anxiety Disorders (6 trials, 1136 subjects) • Pooled absolute response rates: 69% (95% CI 65-73%) in AD treated subjects; 39% (95% CI 35-43%) in Pbo treated subjects • Pooled risk difference of 37% (95% CI 23-52%) (large variance in risk differences across studies) • NNT= 3 (95% CI 2-5) • Pooled absolute rates of SI/SA: 1% (95% CI 0.2-2%) in AD treated subjects; 0.2% (95% CI -0.2-0.5%) in Pbo treated subjects • Pooled risk difference of 0.7% (95% CI -0.4% to 2%) • NNH= 143 (note there were no suicides in any group)

  22. Conclusions • Evidence of efficacy of AD for treatment of pediatric MDD, OCD and non-OCD anxiety • Strongest effect for non-OCD anxiety, intermediate for OCD and modest for MDD • Similar to previous (FDA) analysis, there was an overall increase in risk of SI/SA (but no completed suicides) associated with antidepressant treatment, but random-effects risk differences were all < 1% and lower than analyses using fixed-effect models. Risk differences were not statistically significant (CI’s included zero)

  23. Conclusions • Relative risk analysis not the focus here- relative risk analysis excludes studies in which there were no events in AD or Pbo groups. • Evidence of efficacy of AD vs. Pbo in MDD across several AD types. However, for children < 12 years old, only fluoxetine outperformed Pbo • Efficacy also inversely proportional to duration of disorder

  24. What to tell the parents? • NNTs of 3-10 balanced against NNH of 112-200 offer a favorable risk-to-benefit profile for AD in the treatment of MDD, OCD and non-OCD anxiety disorders. (N.B., the lack of completed suicides in any of this or other studies is an important factor in this risk-to benefit profile being viewed as favorable) • Quoting from the article: “…strength of evidence support the cautious and well-monitored use of antidepressant medications as one of the first-line treatment options…” • Also: “…the information presented in this report should allow for an informed evaluation of the potential benefits and risks of these medications vs. no treatment and provide a framework for their comparison with nondrug treatments as well.”

  25. References • Bridges JA et al. Clinical response and risk for reported suicidal ideation and suicide attempts in pediatric antidepressant treatment. JAMA 2007; 297:1683-1696 • Users’ Guides to the Medical Literature. Eds. Guyatt G, Rennie D. AMA Press, 2002

More Related