Response to Chadi A. Calarge re: “Effects of Long-Term Sertraline Use on Pediatric Growth and Development: The Sertraline Pediatric Registry for the Evaluation of Safety (SPRITES)”

To the Editor:

In a letter to the editor written by Calarge (2023), the authors raised concern originating from studies they conducted that demonstrated a deleterious effect of selective serotonin reuptake inhibitors on height in boys at Tanner Stages 3 and 4. The authors of the letter requested a similar evaluation to estimate the treatment effect of sertraline use on height based on sexual maturation using data collected in the Sertraline Pediatric Registry for the Evaluation of Safety (SPRITES) (Kolitsopoulos et al., 2023).

The study that was completed by Calarge et al. (2018) appears to have used Tanner Stage at baseline. Therefore, we estimated the treatment effect on the change in standardized height at each visit and Tanner Stage, defined in the analysis as Tanner Stage at Baseline. This analysis also accounted for treatment with psychostimulants or antipsychotics previous to baseline. As a sensitivity, we also explored the treatment effect by defining Tanner Stage for each study visit, and for the previous study visits.

Results of the analyses conducted in male patients are presented in Tables 1 to 2, and Figure 1. Table 1 provides the p-value from the statistical test to assess whether the treatment effect on standardized height depends on Tanner Stage. The resulting p-value is 0.31, which is not statistically significant. Table 2 reports the estimated treatment effects (and 95% confidence intervals) by baseline Tanner Stage and study visit. Estimated treatment effects consist of the change of the gain in standardized height from baseline based on a 5 mg/day increase in sertraline dose. Across study visit and Tanner Stage, the effect estimates range from −0.05 to 0.03. The two empty cells are representative of the few boys with Tanner Stage 5 at baseline, of whom none completed the months 30 and 36 visits due to loss to follow-up/drop-out. Figure 1 illustrates these findings in a Forest Plot of the estimated treatment effects by study visit and Tanner Stage. Both Table 2 and Figure 1 show that the treatment effect estimates are fairly consistent across study visit and Tanner Stage. Similar results were seen when Tanner Stage was defined for each study visit and for the previous study visit.

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FIG. 1.

Forest Plot of Estimated Treatment Effects by Baseline Tanner Stage and Study Visit, SPRITES.

To summarize, we observed no differences in the treatment effect on the gain in standardized height by Tanner Stage or study visit. Thus, in our exploration, there is insufficient evidence to conclude that the treatment effect (impact of sertraline exposure on the gain in standardized height) depends on the Tanner Stage the participant had at baseline.