Clues Revealed by Ketamine
Scott Mendelson in Herbal Treatment of Major Depression, 2019
The active form of the thyroid hormone, triiodothyronine, is often successful as an augmentation when antidepressants are ineffective.30 Among its effects on neurons in the brain are decreases in GSK-3β, increases in BDNF,31 and activation of mTOR.32 Lamotrigine can also be effective when added to an antidepressant in patients with treatment-resistant MDD.33 Lamotrigine increases BDNF, decreases activity of GSK-3β,34 and increases activity of mTOR.35 Tianeptine, an antidepressant that enhances serotonin reuptake, also induces many of the same neuronal changes as the SSRIs. Both tianeptine and fluoxetine inhibit activation of GSK-3β in cortical neurons of prenatally stressed mice.36 Both fluoxetine37 and tianeptine38 increase the activity of mTOR. Finally, both fluoxetine and tianeptine reverse stress and inflammation-induced decreases in neuronal BDNF.39
Intracellular Signaling Transduction Dysregulation in Depression and Possible Future Targets for Antidepressant Therapy:Beyond the Serotonin Hypothesis
Siegfried Kasper, Johan A. den Boer, J. M. Ad Sitsen in Handbook of Depression and Anxiety, 2003
Tianeptine is a novel antidepressant agent, both structurally (modified tricyclic) and in terms of its pharmacodynamic profile. Unlike other antidepressant agents, tianeptine stimulates the uptake of serotonin [132]. In patients with major depression without melancholia or psychotic features or with depressed bipolar disorder or dysthymic disorder, the antidepressant efficacy of short-term (4 weeks to 3 months) tianeptine therapy appears to be similar to that of amitriptyline, imipramine, and fluoxetine [28,133]. The hippocampus, most likely, is an important target for tianeptine’s therapeutic action. The human hippocampus undergoes atrophy in the aftermath of traumatic stress, recurrent depression, and Cushing’s syndrome [79,134–136]. Prolonged psychological stress in monkeys is associated with loss of hippocampal neurons [137], whereas repeated psychological stress in primitive primates and in rats causes hippocampal CA3 pyramidal neurons to undergo dendritic atrophy [138,139]. The atrophy is only seen in the apical dendritic tree and comprises a reduction in length and branching and must involve alterations in the apical dendritic cytoskeleton [140]. Three factors play a role in hippocampal damage. These include glucocorticoid hormones, which potentiate damage produced by other insults, endogenous excitatory amino acids, and serotonin [141,142]. Serotonin is released by stressors and plays a role in the actions of stress on nerve cells. It appears that stressors activate the release of excitatory amino acids from mossy fiber synapses and promote serotonin release and adrenal steroid secretion that concur to enhance the effect of stressful events in the hippocampus. Interestingly, tianeptine treatment prevents stress-induced atrophy of CA3 pyramidal neurons, whereas neither fluoxetine nor desipramine has such effects. Tianeptine treatment also prevents the stress-induced learning impairment. The molecular mechanisms by which tianeptine prevents stress-mediated dendritic atrophy is not yet fully understood, however [29].
An update on potential pharmacotherapies for cognitive impairment in bipolar disorder
Published in Expert Opinion on Pharmacotherapy, 2023
Danica E. Johnson, Roger S. McIntyre, Rodrigo B. Mansur, Joshua D. Rosenblat
Tianeptine is an atypical antidepressant that is being considered as an adjunctive maintenance treatment for BD that may have procognitive effects. It modulates glutamatergic synaptic neurotransmission [85] and increases serotonin uptake in the brain [86], which may underlie its ability to reverse hippocampal structural changes associated with impaired neural plasticity and cognitive impairment in preclinical models of depression [87]. One group evaluated the procognitive efficacy of tianeptine as an adjunctive maintenance treatment for BD [88]. They found that participants receiving tianeptine scored higher on measures of working memory, suggesting that tianeptine has a procognitive effect on this cognitive domain [88]. This preliminary evidence is an essential first step in elucidating whether tianeptine can be used as an adjunctive treatment to improve cognition in BD.
When an obscurity becomes trend: social-media descriptions of tianeptine use and associated atypical drug use
Published in The American Journal of Drug and Alcohol Abuse, 2021
Kirsten E. Smith, Jeffery M. Rogers, Justin C. Strickland, David H. Epstein
Because tianeptine was so often co-used with kratom, phenibut, and racetams, we examined mentions of positive, adverse, and withdrawal effects in the context of co-use (Figure 3). People who used kratom were more likely to report positive effects from tianeptine, OR = 2.72[1.27,5.82], p = .01, but also more likely to report withdrawal symptoms, OR = 5.48[2.16,13.94], p < .001. Racetam use was also associated with a greater odds of positive effects from tianeptine, OR = 3.74[1.53,9.13], p = .004, but not with withdrawal symptoms, OR = 0.68[0.15,3.09], p = .62. Phenibut use was associated with neither. None of the three co-used drugs showed a statistically significant relationship with odds of non-withdrawal adverse effects of tianeptine.
Characteristics of tianeptine effects reported to a poison control center: a growing threat to public health
Published in Clinical Toxicology, 2021
William Rushton, Brian Whitworth, Julie Brown, Michael Kurz, Jessica Rivera
Tianeptine toxicity in the United States remains unfamiliar to most practitioners. A 2017 poison center review describes nine cases of tianeptine toxicity. Two of the nine cases exhibited symptoms of acute tianeptine toxicity and both required intensive care unit (ICU) admission following naloxone administration. Five cases were notable for withdrawal syndromes with agitation being the most common symptom; of these, four patients required the use of benzodiazepines for management [7]. Another scientific abstract identified 13 cases of tianeptine toxicity over a 10-year study period in North Carolina; almost all of the cases were chronic ingestions and presentation involved a combination of tachycardia, agitation, anxiety, and hypertension. In this report, lorazepam was the most commonly utilized agent for stabilization [8].
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