SSRIs tied to increased fat, lean mass in older teens with depression
Among older adolescents with depression, severity of the condition is associated with a reduction in weight over time, whereas treatment with selective serotonin reuptake inhibitors (SSRIs) counters such outcome, with differential effects across individual agents, a study has shown.
Following for a mean of 1.51 years a total of 264 medically healthy children (mean age 18.9 years; 60 percent female) who were unmedicated or within their first month of initiating an SSRI, the authors found that major depressive disorder (MDD) severity was inversely associated with body composition outcomes—particularly body mass index (BMI), fat mass index (FMI) and lean BMI z scores—as evaluated using whole-body dual-energy radiograph absorptiometry (DXA) scan. [Pediatrics 2017;doi:10.1542/peds.2016-3943]
On the other hand, cumulative SSRI treatment dose and duration were positively associated with BMI, FMI and lean BMI z scores. Of note, boys showed a greater increase in BMI and FMI z scores (p<0.01 and p<0.02, respectively) over a longer SSRI treatment period compared with girls.
“[The weight-increasing effect] was particularly true for citalopram, escitalopram and fluoxetine, which is notable given that fluoxetine and escitalopram are the only two drugs approved for treatment of major depressive disorder (MDD) in youth, with the latter being favoured in medically ill adolescents given its low propensity to cause drug-drug interactions,” the authors said.
Fluoxetine, in comparison, demonstrated a somewhat weaker effect on all body composition outcomes, including visceral fat mass. Sertraline was similar with no SSRI treatment.
No significant associations were found for generalized anxiety disorder (GAD) diagnosis and severity.
Of the children in the cohort, 124 had SSRI exposure while the remaining 137 were unmedicated. BMI was measured every 4 months, and DXA scans were performed every 8 months.
Obesity and MDD are bidirectionally associated, and the association has been attributed to dysregulation of the hypothalamo-pituitary-adrenal axis, other endocrinologic abnormalities, autonomic nervous system dysfunction, subclinical inflammation and lifestyle factors. Most psychotropic drugs are also implicated in weight gain. [Int J Obes 2014;38:906–911; Obes Rev 2016;17:235–249; Psychoneuroendocrinology 2013;38:209–218; J Clin Psychiatry 2015;76:e1619–e1621]
In the present study, the finding that SSRI use was positively associated with both fat and lean mass in a similar manner suggests that “over extended periods of use, SSRIs will cause an overall increase in BMI, comprising an increase in both fat and lean mass,” the authors said.
Importantly, the increase in fat and lean mass also comes with an increase in visceral fat, which is particularly detrimental to health and which may account for the elevated incidence of cardiovascular disease observed in patients with MDD, they explained.
The observed association between SSRIs and body composition outcomes cannot be attributed to lifestyle factors, such as physical activity or dietary factors, or to differences in body size (in the case of visceral fat), but rather to a “drug-induced increase in sympathetic nervous system activity, as has been shown recently in mice treated chronically with fluoxetine, although the same was not true for citalopram,” they added. [Am J Physiol Heart Circ Physiol 2015;309:H244–H258; Nat Med 2016;22:1170–1179]
The authors acknowledged that the current results should be interpreted in light of several limitations, including the potential of being underpowered to detect a significant effect of MDD or GAD independently of SSRI use.
“The reason for sex-related differences in the treatment effect on body composition warrants further investigation. Future research should also explore mechanisms as well as interventions to attenuate these treatment effects,” they said.