Page 46 - Read Online

Page 4 of 11 Chávez-Castillo et al. Vessel Plus 2018;2:6 I http://dx.doi.org/10.20517/2574-1209.2018.02

Table 1. Comparison of the clinical effects of SSRIs in key metabolic variables
SSRIs Body weight Glycemia Serum Lipids Blood References
TAG HDL-C LDL-C TC pressure
Paroxetine Short-term: N Short-term: ↓ ↑ N ↑ ↑ N [59,67,68,75,80,81,85,
Long-term: ↑↑↑ Long-term: ↑↑↑ 88-90,94,96,99,101-104]
Fluoxetine Short-term: ↓ ↓ ↑↑ N ↑ ↑ N [58,59,64,65,67-70,78,85,
Long-term: N 90-92,94,96,99,105-107]
Fluvoxamine N ↑↑↑ SE SE SE ↑ SE [58,75,84,108-110]
Sertraline Short-term: ↓ ↓ ↑ N ↑ ↑ N [62,63,67,76,85,89,90,93,
Long-term: N 94,96,99,111]
Citalopram Short-term: ↑ N ↑↑ N ↑ ↑ N [58,68,71,79,84,85,90,92,
Long-term: ↑ 94,96,99,112]
Escitalopram Short-term: ↑ ↓ ↑ ↑ ↑ ↑ N [66,71,77,85,96,99,113,114]
Long-term: ↑
↑: increase; ↑↑: high increase; ↑↑↑: very high increase; ↓: decrease; N: neutral; SE: scarce evidence; TAG: triacylglycerides; HDL-C: high-
density lipoprotein cholesterol; LDL-C: low-density lipoprotein cholesterol; TC: total cholesterol; SSRI: selective serotonin reuptake
inhibitor

SSRI-ASSOCIATED CARDIOMETABOLIC RISK: CLINICAL EVIDENCE
Management of metabolic risk is a frequent clinical challenge when prescribing psychiatric medications .
[55]
However, in contrast to other psychotropic drug classes - which tend to behave more or less uniformly in regards
to metabolic risk , SSRIs appear to have more heterogeneous patterns [57,58] . The following sections summarize
[56]
key clinical evidence regarding the impact of SSRIs on each of the components of the MS [Tables 1 and 2].

Obesity
Historically, weight changes have been a hallmark in the side effect profile of most antidepressant classes [59-61] .
In the case of SSRIs, the specific agent used and the length of therapy may account for the very variable effects
these drugs appear to have on body weight . For example, in two multicenter, double-blind, randomized,
[59]
placebo-controlled clinical trials assessing sertraline therapy in 376 pediatric patients with major depressive
disorder (MDD) over 10 weeks, Wagner et al. found a mean weight loss of 0.38 kg in subjects treated with
[62]
sertraline. Croft et al. obtained similar outcomes in an 8-week case-control study, with an average weight loss
[63]
of 0.79 kg in patients treated with sertraline. Likewise, use of fluoxetine has been linked to short-term weight
loss, as reported by de Jonghe et al. in a randomized, double-blind 6-week study, where patients treated
[64]
with fluoxetine showed an average loss of 0.84 kg; as well as by Michelson et al. in a prospective, placebo-
[65]
controlled trial, where subjects on fluoxetine showed an average weight loss of 0.35 kg after 12 weeks. However,
escitalopram has been linked with a significant increase in waist circumference in the short term .
[66]
Nevertheless, the clinical value of these findings may be limited due to the short length of these studies, especially
when considering treatment guidelines for MDD suggest use of antidepressants for at least 6 months. Therefore,
in recent years, more studies have attempted to evaluate the long-term effect of SSRIs on weight [67-71] . In a similar
[67]
32-week study by Fava et al. with fluoxetine, sertraline and paroxetine, weight gain was significantly higher with
the latter. Mansoor et al. found a similar outcome, where citalopram and paroxetine were associated with long-
[68]
term weight gain, whereas fluoxetine and venlafaxine were not. Fluoxetine in particular is consistently reported
not to be linked with any major long-term weight changes [69,70] . In contrast, Calarge et al. found citalopram and
[71]
escitalopram are associated with significant changes in all body composition parameters, including visceral fat
mass, after 2 years in treatment for MDD and generalized anxiety disorder.

Notwithstanding this outline, some research has suggested patients with MDD are intrinsically more
susceptible to changes in body weight, and these shifts may occur independently of antidepressant use .
[72]
At any rate, at present, there is sufficient evidence to highlight long-term weight gain as a clinically relevant
effect for certain SSRIs, underlining the importance of patient-centric prescribing in psychopharmacology.