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Tianeptine and Kratom

1 Objectives Explain the history and origins of Tianeptine Describe the adverse effects of Kratom use

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Tianeptine

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4 Tianeptine

Marketed as: •Stablon •Coaxil

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Marketed in 15 European counties and 66 countries world wide

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Online marketing- different “Boost working memory” “Improve mental clarify”

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History •Discovered and patented in 1960s by the French society of medical research, but for many decades mechanism of action was unknown

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Metabolism- β oxidation of side chain • 66% eliminated by kidneys • ½ life 2.5 hours • No adjustments in liver failure

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Toxicity •Respiratory depression – death •Considered initially a rare, if not unheard of problem, as abuse of this medication was felt to be < 0.3%

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Mechanism of Action •First reported mechanism of action was felt to be increased serotonin reuptake which was opposite of SSRI

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In 2014 the article, “The atypical antidepressant and neurorestorative agent tianeptine is a μ- opioid receptor agonist” showed: • Mu activation was likely the initial molecular event • Possible effects to delta receptor also • Indirectly modulates glutamate (excitatory)

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“Our data are also in agreement with growing evidence regarding the importance of the opioid system in depression, anxiety and stress-related disorders.”

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Tianeptine, an atypical pharmacological approach to depression

“A noteworthy fact is that tianeptine, despite its affinity for these receptors, did not cause tolerance, as it does not lose its efficacy after continued treatment, or physical dependence, as after suppression or administration of naloxone no withdrawal syndrome was observed. These two characteristics clearly differentiate tianeptine from the other opioids, such as morphine.”

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Conflicts of Interest • C. Alamo has collaborated in studies on training and information through presentations at scientific events for healthcare workers sponsored by Adamed, Exeltis, Janssen, Lundbeck, Normon, Otsuka, Pfizer, Sevier, Zambon. • P. García-García works in the Medical Department of Exeltis Healthcare S.L. • The other authors have no conflict of interests to declare.

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Tianeptine: Why has it not been classified as a narcotic in Spain?

“In short, tianeptine is a drug new to Spain, but it is one that has raised numerous issues elsewhere for years. Compared to other antidepressants, it does not present any advantages with respect to either efficacy or convenience.”

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Tianeptine, antidepressant with positive benefit/risk

Summary of letter= Calabozo does not know what he talking about

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Reddit- the source of all knowledge • Tianeptine sodium- shorter acting 2.5 hours • Tianeptine sulfate- longer acting 7.5 hours

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“Incredible mood enhancer” 10-15 mg “Immediate antidepressant effect” “Did not feel impaired”

“Sedation” 50-60 mg “Impaired my ability to drive”

“Nodded off” 85-90 mg “Vivid dreams”

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Another post: “Tolerance is quick. Kills your ability to feel any other opioids, kills effectives of Kratom 100%”

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Low dose- recommended doses • Nausea • Constipation • Headache • Dizziness

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High dose- when misused • May mimic opioid OD- Naloxone effective • Tolerance common • NAS after delivery

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Withdrawal •Really indistinguishable from opioids

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Use of Buprenorphine- Naloxone in the Treatment of Tianeptine Use Disorder

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Kratom

25 Kratom

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• DEA - Mitragyna speciose (Rubiaceae family) • Indigenous to Thailand, Malaysia, Myanmar, Papua New Guinea, others

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History • Tree indigenous to Asia • Used in religious practices and by workers for mild stimulation • Member of the coffee family • At times in history used to help taper people off of opioids

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• Formulations • Leaves • Powder • Pills • Leaves • Liquid extract/tinctures • Route • Drink • Chew leaves • Smoke • Ingest pills

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•Adverse Effects • Dry mouth •Hepatic injury • Nausea •QT prolongation • Weight loss •Tolerance • Constipation •Withdrawal • Seizure

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•Withdrawal •Similar to opioid withdrawal •Starts at about 6-12 hours •Lasts about 2-3 days

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• Gassaway MM, Rives ML, Kruegel AC, Javitch JA, Sames D. The atypical antidepressant and neurorestorative agent tianeptine is a μ-opioid receptor agonist. Transl Psychiatry. 2014;4(7):e411. Published 2014 Jul 15. doi:10.1038/tp.2014.30 • Alamo C, Garcia-Garcia P, Lopez-Munoz F, Zaragoza C. Tianeptine, an atypical pharmacological approach to depression. Journal of Psychiatry and Mental Health, 2019-07-01, Volume 12, Issue 3, Pages 170-186, Copyright © 2019 Calabozo B, Molina V, Uribe F. Tianeptine: Why has it not been classified as a narcotic in Spain? Journal of Psychiatry and Mental Health, 2016-07-01, Volume 9, Issue 3, Pages 176-177, Copyright © 2016 Garcia-Garcia P. Tianeptine, antidepressant with positive benefit/risk. Journal of Psychiatry and Mental Health, 2016-10-01, Volume 9, Issue 4, Pages 234- 235, Copyright © 2016 Trowbridge P,Walley AY. Use of buprenorphine-naloxone in the treatment of tianeptine use disorder. J Addict Med. 2019 Jul/Aug; 13(4):331-333.

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