Child Psychopharmacology, Effect Sizes, and the Big Bang

To the Editor: Dr. Wagner and colleagues reported on a randomized clinical trial for the treatment of depressed children and adolescents with citalopram. The standard of randomized clinical trial reporting has been described in the CONSORT statement (1); one of its recommendations is to describe the flow of the subjects in the study (number screened, proportion randomly assigned, etc.). Dr. Wagner and colleagues did not report the proportion of subjects who were excluded from the random assignment after the single-blind period. This information is critical because a placebo run-in period might help to “wash out” nonspecific responders, allowing sharper evaluation of treatment-specific effects as shown in some pharmacotherapy studies (2).

An additional concern is the elicitation method used for adverse events at a time when the safety of SSRIs in youth has been called into question (3). The adverse events were: “reported by patients or observed by investigators” (Wagner et al., p. 1080). The reliability of this practice is questionable because some adverse events, even very severe ones, could neither be reported by the patient nor observed by the investigator and would need to be specifically assessed (4).

Finally, it is somewhat surprising that the authors do not compare their results with those of another trial, involving 244 adolescents (13–18-year-olds), that showed no evidence of efficacy of citalopram compared to placebo and a higher level of self-harm (16 [12.9%] of 124 versus nine [7.5%] of 120) in the citalopram group compared to the placebo group (5). Although these data were not available to the public until December 2003, one would expect that the authors, some of whom are employed by the company that produces citalopram in the United States and financed the study, had access to this information.