After describing the scientific and regulatory context for the large number of antidepressant trials in the late 1990s and early 2000s, Walkup noted several key differences between the implementation of industry-supported antidepressant trials in children and adolescents and those funded by the National Institute of Mental Health (NIMH).
He wrote, “The confluence of pressure [in industry-sponsored antidepressant trials] to recruit a large number of participants in a tight time frame, large numbers of sites with small Ns per site, site investigators with unknown pediatric depression or clinical trial experience …, and the inclusion of prepubertal children may have resulted in the inclusion of participants with all forms of unhappiness”—all factors that could contribute to high placebo response rates and low active medication response rates. “The results of the industry-sponsored studies were relatively consistent, with response rates of active drug in the 55%–65% range and placebo response rates in the 50%–60% range. The positive outcomes demonstrated an approximate 8% difference between groups,” he stated.
In contrast to the industry-sponsored trials, Walkup noted that the NIMH studies were “characterized by many methodological strengths, lower placebo response rates (30%−35%), and meaningful between-group differences (25%−30%) that support antidepressant efficacy.”
Walkup suggested that instead of concluding that industry antidepressant trials with high placebo response rates (50%-60%) and small between-group differences (~10%) failed to demonstrate efficacy, such trials should be considered failed trials due to substantial methodological problems—and, as such, should not be included in meta-analyses of efficacy. Such trials “may provide valuable information about safety and tolerability,” he wrote, “but not about efficacy.”
In a related editorial, Daniel S. Pine, M.D., of the NIMH Intramural Research Program and Robert Freedman, M.D., of the University of Colorado Denver Health Sciences Center wrote, “Clearly, SSRIs can have adverse effects on behavior in children and adolescents. Moreover, even in government-funded studies of the highest quality, the magnitude of the clinical effect in major depression is not large. Nevertheless, Walkup reminds us that the efficacy data clearly do support the use of SSRIs in pediatric major depression, anxiety disorders, and OCD and that the benefits outweigh the risks in many clinical scenarios.”
For related information, see the Psychiatric News PsychoPharm article “How Effective Are Antidepressants in Youth?”
Clarification: It was reported in yesterday’s Alert that the American Health Care Act would repeal coverage of “essential health benefits” required in plans under the ACA. In fact, the bill calls for the repeal of coverage of essential health benefits in the Medicaid expansion plans but not in the exchange plans for the individual and small group markets.