Deconstructing pediatric depression trials: an analysis of the effects of expectancy and therapeutic contact.

Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
Journal of the American Academy of Child and Adolescent Psychiatry (Impact Factor: 6.97). 08/2011; 50(8):782-95. DOI: 10.1016/j.jaac.2011.04.004
Source: PubMed

ABSTRACT This study investigated how study type, mean patient age, and amount of contact with research staff affected response rates to medication and placebo in acute antidepressant trials for pediatric depression.
Data were extracted from nine open, four active comparator, and 18 placebo-controlled studies of antidepressants for children and adolescents with depressive disorders. A multilevel meta-analysis examined how study characteristics affected response rates to antidepressants and placebo.
The primary finding was a main effect of study type across patient age and contact amount, such that the odds of medication response were greater in open versus placebo-controlled studies (odds ratio 1.87, 95% confidence interval 1.17-2.99, p = .012) and comparator studies (odds ratio 2.01, 95% confidence interval 1.16-3.48, p = .015) but were not significantly different between comparator and placebo-controlled studies. No significant main effects of patient age or amount of contact with research staff were found for analyses of response rates to medication and placebo. Response to placebo in placebo-controlled trials did significantly increase with the amount of therapeutic contact in older patients (age by contact; odds ratio 1.08, 95% confidence interval 1.01-1.15, p = .038).
Although patient expectancy strongly influences response rates to medication and placebo in depressed adults, it appears to be less important in the treatment of children and adolescents with depression. Attempts to limit placebo response and improve the efficiency of antidepressant trials for pediatric depression should focus on other causes of placebo response apart from expectancy.

  • [Show abstract] [Hide abstract]
    ABSTRACT: We investigated how the number of follow-up visits affects response rates and dropout among patients in antidepressant trials for major depressive disorder (MDD). MEDLINE, PsycINFO, and PubMed were searched to identify trials contrasting antidepressants to placebo or active comparator in adults with depression. The index terms depression-drug therapy, depressive disorder-drug therapy, and antidepressant agents, in addition to the classes and individual generic names of all antidepressants, were combined using the "or" operator. Results were limited to (1) English-language articles, (2) publication year 1985 or later, (3) age group ≥ 18 years, and (4) publication types including clinical trials, controlled clinical trials, meta-analysis, multicenter study, randomized controlled trial, or review. Included articles reported trials of approved antidepressant medications for MDD in outpatients aged 18-65 years, were 6-12 weeks in duration, and had response rates specified using a standardized measure. Trials were excluded for enrolling inpatients, pregnant women, psychotic subjects, or those with treatment-resistant depression. These criteria allowed 9,189 articles identified in the literature review to be narrowed to 111 reports. Demographic characteristics, the number of study visits planned in each treatment cell, duration of active treatment, attrition rates, and response rates to medication and placebo were entered into a database. In a multilevel meta-analysis, active medication versus placebo (OR = 1.96, P < .001), active comparator versus placebo-controlled study design (OR = 1.82, P < .001), and longer versus shorter duration (OR = 1.87, P < .001) were associated with significantly increased odds of treatment response. After controlling for these variables, the number of study visits did not significantly influence response rates (OR = 0.97, P = .877). The odds of dropout were significantly decreased for active comparator versus placebo-controlled trials (OR = 0.67, P = .002) and longer versus shorter duration trials (OR = 0.54, P = .035), while increasing numbers of study visits significantly increased the odds of participant dropout (OR = 2.77, P < .001). Visit schedules that are much more frequent than are commonly practiced in the community treatment of depression may increase the expense of clinical trials and make them less generalizable to standard clinical treatment.
    The Journal of Clinical Psychiatry 07/2013; 74(7):703-15. · 5.81 Impact Factor
  • Source
    Journal of Psychology and Psychotherapy. 01/2014; 4:158-167.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Just like children are not small adults, pediatric studies are not just subgroup-adult studies. Clinical pharmacology aims to predict these effects based on drug, population and/or patient-specific pharmacokinetics (concentration-time profiles) and -dynamics (concentration-effect profile). The most essential characteristics of childhood are growth and maturation. Both phenomena are most prominent during infancy making the claim that "an infant is not just a small child" as relevant compared to the paradigm that "a child is not just a small adult". From a clinical pharmacology perspective, the consequence of such a dynamic setting is extensive variability throughout childhood in both the pharmacokinetics and pharmacodynamics. Trial design probably has impact on recruitment to an even greater extent compared to adult studies. In general, if a study is designed well, with a clear clinical question with which parents and children can identify, they are likely to consider participation. Open communication with all stakeholders involved will most likely result in ethically correct, practically feasible, scientifically sound, and economical reasonable studies to provide children with the appropriate treatment. From an academic perspective, feasibility, relevance, applicability and costs of clinical pharmacological studies in children can be significantly improved by new sampling concepts (e.g., saliva, urine, dried spot blood) and the systematic introduction of already known information into the trial design through model based pediatric drug development, that mainly affect feasibility of pharmacokinetic studies. In contrast, for the pharmacodynamic part of pediatric studies, development and validation of population specific biomarkers or robust outcome variables is urgently needed.
    World journal of clinical pediatrics. 08/2012; 1(2):3-7.

Full-text (2 Sources)

Available from
May 22, 2014