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Effect of tianeptine on cognitive functions in patients with depressive disorders during a 3-month observation

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The authors put forward the hypotheses that during a three-month treatment with tianeptine in patients with depressive disorders there is an improvement in the short-term memory, reaction time and attention. 20 patients suffering from depression, were included in the study. During the entire research period all patients were treated with monotherapy with tianeptine. Cognitive function measurements were performed using the Vienna Test System. Our study showed an improvement in the all the assessed functions: patients treated with tianeptine had better performance in tests measuring short term memory and learning processes as well as reaction time and attention. In conclusion, the study shows that tianeptine improves cognitive functions in depressed patients.
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... Also, various studies have shown that it is well tolerated 18 and no significant sedation, weight gain 19,20 or sexual side effects 21 , have been observed. It has been found to have positive cognitive effects 22 and anticonvulsant effects 23 24 . In addition, tianeptine offers the possibility of enhancing the outcomes of other antidepressants such as SSRIs when they are combined with it 25 , meaning that it is of particular interest regarding this population. ...
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The depressive disorder coexists in a high prevalence with a substance-related disorder, which is asso- ciated with a worst prognosis. The therapeutic interventions for this co-morbidity lack of the appropriate scientific sup- port. The existing evidence suggest that the currently avail- able anti-depressive drugs are of minor efficacy in this group of patients. An alternative would be the use of different drugs with distinctive neurobiological mechanism of action. The aim of this study was to describe the clinical develop- ment of a series of patients affected by this comorbidity un- der treatment with tianeptine under usual clinical practices.
... Tianeptine has been reported to, among other actions, enhance the reuptake of serotonin [22,23] and to have cognitive enhancing abilities [24,25]. Hence, we tested the impact of tianeptine on brain function during an inhibitory and sustained attention task in ASD. ...
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Background Autism spectrum disorder (ASD) is associated with deficits in executive functioning (EF), and these have been suggested to contribute to core as well as co-occurring psychiatric symptoms. The biological basis of these deficits is unknown but may include the serotonergic system, which is involved both in regulating EF in neurotypical populations and in the pathophysiology of ASD. We previously demonstrated that reducing serotonin by acute tryptophan depletion (ATD) shifts differences in brain function during performance of EF tasks towards control levels. However, ATD cannot be easily used in the clinic, and we therefore need to adopt alternative approaches to challenge the serotonin system. Hence, we investigated the role of the serotonergic modulator tianeptine on EF networks in ASD. Method We conducted a pharmacological magnetic resonance imaging study, using a randomized double-blind crossover design, to compare the effect of an acute dosage of 12.5 mg tianeptine and placebo on brain activation during two EF tasks (of response inhibition and sustained attention) in 38 adult males: 19 with ASD and 19 matched controls. Results Under placebo, compared to controls, individuals with ASD had atypical brain activation in response inhibition regions including the inferior frontal cortex, premotor regions and cerebellum. During sustained attention, individuals with ASD had decreased brain activation in the right middle temporal cortex, right cuneus and left precuneus. Most of the case–control differences in brain function observed under placebo conditions were abolished by tianeptine administration. Also, within ASD individuals, brain functional differences were shifted significantly towards control levels during response inhibition in the inferior frontal and premotor cortices. Limitations We conducted a pilot study using a single dose of tianeptine, and therefore, we cannot comment on long-term outcome. Conclusions Our findings provide the first evidence that tianeptine can shift atypical brain activation during EF in adults with ASD towards control levels. Future studies should investigate whether this shift in the biology of ASD is maintained after prolonged treatment with tianeptine and whether it improves clinical symptoms.
... Tianeptine has been reported to, among other actions, enhance reuptake of serotonin (22,23) and to have cognitive enhancing abilities (24,25). Hence, we tested the impact of tianeptine on brain function during an inhibitory and sustained attention tasks in ASD. ...
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Background: Autism spectrum disorder (ASD) is associated with deficits in executive functioning (EF), and these have been suggested to contribute to core as well as co-occuring psychiatric symptoms. The biological basis of these deficits is unknown but may include the serotonergic system, which is involved in both regulating EF in neurotypical populations and in the pathophysiology of ASD. We previously demonstrated that reducing serotonin by acute tryptophan depletion (ATD) shifts differences in brain function during performance of EF tasks towards control levels. However, ATD cannot be easily used in the clinic, and we therefore need to adopt alternative approaches to challenge the serotonin system. Hence, we investigated the role of the serotonergic modulator tianeptine on EF networks in ASD. Method: We conducted a pharmacological magnetic resonance imaging (phMRI) study, using a randomised double-blind crossover design, to compare the effect of an acute dosage of 12.5 mg tianeptine and placebo on brain activation during during two EF tasks (of response inhibition and sustained attention) in 38 adult males; 19 with ASD and 19 matched controls. Results: Under placebo, compared to controls, individuals with ASD had atypical brain activation in response inhibtion regions including the inferior frontal cortex, premotor regions and cerebellum. During sustained attention, individuals with ASD had decreased brain activation in the right middle temporal cortex, right cuneus and left precuneus. Most of the case-control differences in brain function observed under placebo conditions were abolished by tianeptine administration. Also, within ASD individuals, brain functional differences were shifted significantly towards control levels during response inhibition in the inferior frontal and premotor cortices. Limitations: We conducted a pilot study using a single dose of tianeptine and therefore we cannot comment on long-term outcome. Conclusions: Our findings provide the first evidence that tianeptine can shift atypical brain activation during EF in adults with ASD towards control levels. Future studies should investigate whether this shift in the biology of ASD is maintained after prolonged treatment with tianeptine, and if it improves clinical symptoms.
... Tianeptine has been reported to, among other actions, enhance reuptake of serotonin (22,23) and to have cognitive enhancing abilities (24,25). Hence, we tested the impact of tianeptine on brain function during an inhibitory and sustained attention tasks in ASD. ...
Preprint
Full-text available
Background Autism spectrum disorder (ASD) is associated with deficits in executive functioning (EF), and these have been suggested to contribute to core as well as co-occuring psychiatric symptoms. The biological basis of these deficits is unknown but may include the serotonergic system, which is involved in both regulating EF in neurotypical populations and in the pathophysiology of ASD. We previously demonstrated that reducing serotonin by acute tryptophan depletion (ATD) ‘normalizes’ differences in brain function during performance of EF tasks. However, ATD cannot be easily used in the clinic, and we therefore need to adopt alternative approaches to challenge the serotonin system. Hence, we investigated the role of the serotonergic modulator tianeptine on EF networks in ASD. Method We conducted a pharmacological magnetic resonance imaging (phMRI) study to compare the effect of an acute dosage of 12.5 mg tianeptine and placebo on brain activation during during two EF tasks (of response inhibition and sustained attention) in 38 adult males; 19 with ASD and 19 matched controls. ResultsUnder placebo, compared to controls, individuals with ASD had atypical brain activation in response inhibtion regions including inferior frontal cortex, premotor regions and cerebellum. During sustained attention, individuals with ASD had decreased brain activation in right middle temporal cortex, right cuneus and left precuneus. Most of the case-control differences in brain function observed under placebo conditions were abolished by tianeptine administration. Also, within ASD individuals, brain functional differences were ‘normalized’ during response inhibition in inferior frontal and premotor cortices.LimitationsOur sample only consisted of high functioning male adults. Therefore, our findings may not be generalizable to other autistic subgroups (e.g. children or women). Conclusions Our findings provide the first evidence that tianeptine can ‘normalize’ atypical brain activation during EF in adults with ASD. Future studies should investigate whether this shift in the biology of ASD is maintained after prolonged treatment with tianeptine; and if it improves clinical symptoms.
... The drug has been used as an antidepressant for over 30 years and its outstanding clinical tolerance is well known (48). In addition to its antidepressant effects, clinical benefit was demonstrated with tianeptine improving cognitive performance in cognitively impaired depressed patients (49,50). Of relevance, notwithstanding its effect in facilitating AMPA-R signalling, tianeptine was not found to increase seizure frequency when tested in epileptic patients (51). ...
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Mutations in the X-linked cyclin-dependent kinase-like 5 (CDKL5) gene cause a complex neurological disorder, characterised by infantile seizures, impairment of cognitive and motor skills, and autistic features. Loss of Cdkl5 in mice affects dendritic spine maturation and dynamics but the underlying molecular mechanisms are still far from fully understood. Here we show that Cdkl5 deficiency in primary hippocampal neurons leads to deranged expression of the alpha-amino-3-hydroxy-5-methyl-4-iso-xazole propionic acid receptors (AMPA-R). In particular, a dramatic reduction of expression of the GluA2 subunit occurs concomitantly with its hyper-phosphorylation on Serine 880 and increased ubiquitination. Consequently, Cdkl5 silencing skews the composition of membrane-inserted AMPA-Rs towards the GluA2-lacking calcium-permeable form. Such derangement is likely to contribute, at least in part, to the altered synaptic functions and cognitive impairment linked to loss of Cdkl5.Importantly, we find that tianeptine, a cognitive enhancer and antidepressant drug, known to recruit and stabilise AMPA-Rs at the synaptic sites, can normalise the expression of membrane inserted AMPA-Rs as well as the number of PSD-95 clusters, suggesting its therapeutic potential for patients with mutations in CDKL5.
... It shows a faster onset of therapeutic effects against some depressive symptoms (cognitive and anxiety symptoms) as compared to other antidepressants and more importantly is effective in patients resistant to SSRI therapy (Woo et al. 2013). In addition, this drug improves learning and increases long-term memory in rodents, exerts a vigilance-enhancing effect in laboratory animals and improves cognitive functions in depressed patients (Klasik et al. 2011;Jaffard et al. 1991;Zoladz et al. 2008). Tianeptine promotes neuroplasticity by increasing the expression of genes of neuroplasticity factors (Reagan et al. 2007;Wlaź et al. 2011;Kuipers et al. 2013), reverses synaptic plasticity, dendritic atrophy, memory impairment, and neuronal loss under conditions of stress (Zhang et al. 2013). ...
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Tianeptine is an atypical antidepressant with a unique mechanism of action and recently it has been also reported that its major metabolite, compound MC5, possesses pharmacological activity similar to that of the parent drug. The current study aims to investigate the pharmacokinetics (PK) of both tianeptine and MC5 after intravenous or intraperitoneal administration of the parent drug as well as the metabolic ratio of MC5 in rats. To achieve these goals an LC-MS/MS method using the small sample volume for the quantitation of tianeptine and its active metabolite MC5 in rat plasma and liver perfusate has been developed and validated. Following an intravenous administration of tianeptine pharmacokinetic parameters were calculated by non-compartmental analysis. The average tianeptine volume of distribution at steady state was 2.03 L/kg and the systemic clearance equaled 1.84 L/h/kg. The mean elimination half-lives of tianeptine and MC5 metabolite were 1.16 and 7.53 h, respectively. The hepatic clearance of tianeptine determined in the isolated rat liver perfusion studies was similar to the perfusate flow rate despite the low metabolic ratio of MC5. Mass spectrometric analysis of rat bile indicated that tianeptine and MC5 metabolite are eliminated with bile as glucuronide and glutamine conjugates. Bioavailability of tianeptine after its intraperitoneal administration was 69%. The PK model with a metabolite compartment developed in this study for both tianeptine and MC5 metabolite after two routes of administration may facilitate tianeptine dosage selection for the prospective pharmacological experiments.
... Bupropion has demonstrated to be as effective as SSRIs improving cognitive performance (Gorlyn et al., 2015;Herrera-Guzman et al., 2008;Soczynska et al., 2014), global function and work productivity (Soczynska et al., 2014). Tianeptine improved cognitive impairment in subjects with moderate to severe MDD (Klasik et al., 2011;Saiz-Ruiz et al., 1998) and, compared to SSRIs, it showed superiority over escitalopram (Jeon et al., 2014) but not over paroxetine (Nickel et al., 2003). As for the monoamine oxidase inhibitors (Roth et al., 1996) or tricyclic antidepressants (Bartfai et al., 1991), evidence remains unclear. ...
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Background Cognitive symptoms in Major Depressive Disorder (MDD) are persistent and commonly entail neurocognitive impairment and a decline in quality of life. This systematic review gathers the current scientific evidence on therapeutic strategies for neuropsychological impairment in MDD. Method A systematic search on PubMed, PsycINFO and Clinicaltrials.gov was carried out on December 2016 according to PRISMA using Boolean terms to identify interventions for the treatment of cognitive dysfunction in MDD. Only English-written articles providing original data and focusing in adults with MDD were included with no time restrictions. Results A total of 95 studies reporting data on 40 pharmacological and non-pharmacological interventions were included. Interventions were grouped into the following categories: 1) Pharmacological Therapies (antidepressants, stimulants, compounds acting on NMDA receptors, compounds acting on the cholinergic system, compounds showing anti-inflammatory or antioxidant properties, other mechanisms of action), 2) Physical Therapies and 3) Psychological Therapies, 4) Exercise. There are some promising compounds showing a positive impact on cognitive symptoms including vortioxetine, lisdexamfetamine or erythropoietin. Limitations The studies included showed significant methodological differences in heterogeneous samples. The lack of a standardized neuropsychological battery makes comparisons between studies difficult. Conclusion Current evidence is not sufficient to widely recommend the use of procognitive treatments in MDD although promising results are coming to light.
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