Background: Tianeptine is an atypical antidepressant marketed as Stablon since
the late 1980's. While chemically very similar to tricyclic antidepressants, tianeptine was
thought to have the apparently paradoxical mechanism of action of enhancing serotonin
reuptake. However, recent data highlight a multimodal pharmacology for tianeptine including
actions at glutamatergic synapses (inhibiting NMDA receptors and an indirect effect on AMPA
receptors) coupled with agonist effects at mu opioid receptors (µ-receptors).
Objective: We have reviewed clinical and preclinical data for tianeptine to provide a comprehensive
study of its pharmacology.
Results: Clinical trials show that tianeptine is at least as efficacious as first-line antidepressant
treatments, with improved tolerability as it is significantly less prone to disrupting the
patient's normal functionality. Tianeptine appears more efficacious in males than females,
although these gender-specific differences may be accounted for by pharmacokinetics. Preclinical
data suggest that the ability to stabilise glutamatergic neurotransmission may underlie
tianeptine's ability to improve cognitive function and anxiety-related symptoms. Alternatively,
µ-receptor activation of the mTOR signalling pathway could lead tianeptine to be a fastacting
antidepressant. Agonist actions at µ-receptors could also explain the potential abuse liability
and dependence issues seen with high dose tianeptine.
Conclusion: Tianeptine itself is off patent, but it still holds much promise as an experimental
tool yielding valuable insights into the molecular mechanisms underlying depression.