Using a Large Electronic Health Record Database to Characterize SSRI's Effect on Height Growth

PROJECT SUMMARY
The pubertal growth spurt is a hallmark of adolescence, which is a time of increasing vulnerability to
depressive and anxiety disorders, a fact reflected in the widespread use of antidepressants, particularly selective
serotonin reuptake inhibitors (SSRIs). In fact, antidepressants comprise the second to third most prescribed
medication class in this age group.
We and others have found that SSRIs are associated with height growth suppression in adolescents. This
was particularly true in boys undergoing puberty. To build on these findings, we recently completed another
study (R21HD097776) of children and adolescents undergoing puberty and starting treatment with one of two
commonly prescribed SSRIs, sertraline, and fluoxetine. We again found that, over the 6-month follow-up period,
the higher the SSRI dose, the more significant height growth suppression was. In fact, SSRI use reduced growth
by about 50% of that observed in unmedicated participants. Notably, sertraline was associated with the most
significant deleterious effect on height. Moreover, the higher the SSRI dose, the lower the serum concentration
level of insulin growth factor 1), the principal marker of growth hormone neurosecretory function.
To better capture the implications of these findings at a large scale, we here propose to use 12 years of data
from a very large electronic health record database and state-of-the-art Super-Imposition by Translation And
Rotation (SITAR) growth curve analyses to determine 1) the effect of SSRIs on height growth, 2) the moderating
role of the magnitude of SSRI exposure and its timing in relation to the growth spurt on height growth
suppression, and 3) whether differences between the most prescribed SSRIs exist. This work will allow us to
determine whether SSRI discontinuation normalizes height growth, leaving adult height unaffected.
In sum, the proposed study will be the first to investigate the magnitude of height growth suppression induced
by SSRIs, its clinical predictors, and its long-term sequelae, shedding light on a currently little-recognized side
effect of a widely and increasingly used medication class. The information will be critical to inform clinical decision
making.

Grant Number: 1R56HD116951-01
NIH Institute/Center: NIH
Principal Investigator: Hua Chen