Major depressive disorder (MDD) is one of the most common psychiatric illnesses worldwide,
with reported prevalence rates ranging between 10% and 19%. Pharmacotherapy is a first-line
option for the management of MDD and, as a result, the use of antidepressants has increased 4 fold in
the last 20 years. Serotonin is the most commonly dysregulated neurotransmitter in the etiology of
MDD and this system is the primary focus of most medications used in the treatment of illness. Although
antidepressant use in adults increases the risk of developing new onset type 2 diabetes, the
mechanisms underlying this association are poorly defined. This review will focus on 1) the evidence
from human and animal studies suggesting a link between the use of antidepressants that target serotonin signaling (i.e.,
SSRIs, serotonin-norepinephrine reuptake inhibitors (SNRIs), serotonin antagonist and reuptake inhibitors (SARIs), and
noradrenergic and specific serotonergic antidepressants (NaSSAs)) and increased risk of diabetes, and 2) the mechanisms
by which alterations in serotonin signalling by antidepressants can affect glucose homeostasis.
Keywords: Antidepressants, insulin, noradrenergic and specific serotonergic antidepressants selective serotonin reuptake
inhibitors, serotonin-norepinephrine reuptake inhibitors, serotonin antagonist and reuptake inhibitors, type 2 diabetes.
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