Adolescents with major depressive disorder (MDD) were more likely to lose weight, but treatment with some SSRIs was associated with weight gain, based on data from a longitudinal study of 264 participants published online June 16 in Pediatrics.
MDD was associated with decrease in body mass index (BMI), fat mass index (FMI), and lean BMI (LBMI) z scores after controlling for factors including age, sex, physical activity, dietary intake, and length of study participation. However, dosage and duration of treatment with SSRIs were associated with increases in BMI, FMI, and LBMI z scores (Pediatrics. 2017. doi: 10.1542/peds.2016-3943).
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The participants were part of a 2-year prospective study on the skeletal impact of SSRI use in older adolescents, and the average length of study participation was 1.5 years. After a baseline visit, they had follow-up visits, at which they completed the Inventory of Depressive Symptomatology (IDS), the Beck Depression Inventory (BDI-II), the Beck Anxiety Inventory (BAI), and the modified version of the Physical Activity Questionnaire for Adolescents, every four months. In addition, height, weight, and grip strength were measured. Body composition was measured using the BMI z score, FMI z score, LBMI z score, and visceral fat (Vfat) score.
Depression and anxiety, based on IDS and BAI scores, were inversely associated with changes in BMI z scores, and longer SSRI use was associated with increased BMI z scores. These changes remained significant when IDS scores and cumulative SSRI doses were included in the analysis.
In addition, use and duration of SSRIs each were significantly associated with increased FMI and LBMI scores after adjusting for standard confounding variables. SSRI use was associated with increased visceral fat mass, but the change was not significant.
When the researchers examined differences among individual drugs, they found that citalopram and escitalopram, but not sertraline, were associated with significant increases in both adiposity and lean mass. Fluoxetine showed a smaller, but still significant, effect.
SSRI use also impacted height over the study period (P less than .05), and fluoxetine had the greatest effect. Depression (IDS score) had no significant impact on height.
No significant differences appeared in the impact of SSRI use according to gender for LBMI, height z scores, or VFat. However, males had a significantly greater increase in BMI and FMI z scores, compared with females, over a longer period of SSRI use, a finding that deserves additional study, Dr. Calarge and associates noted.
The results were limited by several factors including the relatively small sample size, the use of self-reports, and the challenges of accurately documenting medication use, the researchers said.
Fat and lean mass were measured separately in this study, and, “to our surprise, SSRI use was positively associated with both outcome variables in a similar manner,” Dr. Calarge and associates noted. “When we specifically focused on VFat, the association with SSRI use remained positive, albeit weaker. This suggests that, over extended periods of use, SSRIs will cause an overall increase in BMI, comprising an increase in both fat and lean mass. Importantly, this is also associated with an increase in VFat, which is particularly detrimental to health,” and may contribute to the higher incidence of cardiovascular disease in MDD patients, they added. Future research should explore mechanisms of action and interventions to address treatment effects.
The researchers had no relevant financial disclosures. The study was funded by the National Institutes of Health, the National Institute of Mental Health, and the National Center for Research Resources.