Research Day


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Introduction: Many substances with antidepressant effects exist worldwide. Since introduction of prescription antidepressants in the 1950s, research has focused on the monoamine and glutamate neurotransmitter systems. Recent developments suggest that the opioid system may play a role in the pathogenesis and treatment of depression. This case highlights a substance that activates both the opioid and monoamine systems to treat depression.

Case Presentation: A 33 year-old-male with history of depression presented to an outpatient psychiatric clinic for re-evaluation of his depression. He reported multiple ineffective antidepressant trials. He had learned of a medication, tianeptine, marketed to treat depression in Europe. Although not FDA approved in the USA, he was able to obtain the medicine through unregulated channels as a supplement/research chemical. In taking this substance, he found improvement in his symptoms, but as time progressed, he found himself developing a tolerance to tianeptine, needing higher and higher dose to maintain euthymia. After his initial depression resolved, his attempts to discontinue tianeptine resulted in withdrawal symptoms similar to opioid withdrawal. Consequently, he presented to us in search of alternative treatment for his depression.

Discussion: Abuse potential and other risks exist in using agents such as tianeptine long term for depression, however this raises the question of the role of the opioid system in treating depression. Similarly, ketamine trials have shown reduced effectiveness with naltrexone blockade of opioid receptors versus no blockade. Antidepressants acting on the opioid system, without producing tolerance and dependence, represent a novel target for future research efforts.

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