Usefulness of LDAEP to Predict Tolerability to SSRIs in Major Depressive Disorder: A Case Report

We report here a patient with major depressive disorder who experienced severe adverse effects after the administration of SSRIs (serotonin selective reuptake inhibitors) without improvement of his depressive symptoms. These adverse effects disappeared and his depressive symptoms improved after discontinuation of the SSRIs and the administration of tianeptine. The patient exhibited a low value for the loudness dependent of auditory evoked potentials (LDAEP) -0.14 at baseline, which means that his central serotonergic neurotransmission was already highly active. We assumed that it was this high serotonergic activity that rendered him unresponsive to SSRIs, and brought on him the adverse effects, and that the tianeptine was effective due to the lack of serotonin reuptake inhibitory action. Thus, we suggest that LDAEP can be used to predict an individual patient's tolerability and clinical response to SSRIs in major depression.

Is Tianeptine in a Class of Its Own?: Pharmacological Profiles and Clinical Use of Tianeptine / 대한정신약물학회지

Tianeptine is an antidepressant effective in reducing depressive symptoms and combined anxiety symptoms. Tianeptine has drawn much attention, because this compound challenges traditional monoaminergic hypothesis of depression. The involvement of glutamate in the mechanism of action of tianeptine is consistent with glutamate hypothesis of depression which demonstrating the key function of glutamate in the mechanism of altered neuroplasticity that underlies the symptoms of depression. This article reviews the evidence of tianeptine's mechanism of action with a focus on the glutamatergic system in an attempt to provide a possible explanation for the observed beneficial clinical profile of tianeptine in patients with depression.

Effects of omapatrilat on endothelin-1-induced proliferation and synthesis of cardiac fibroblasts / 中国应用生理学杂志

<p><b>AIM</b>To investigate the effects of omapatrilat (OMA) on endothelin-1-induced proliferation of cardiac fibroblasts (CFs).</p><p><b>METHODS</b>Isolated and cultured CFs from neonatal Sprague-Dawley rats (SD) were randomly divided into 7 groups: (1) Control, (2) ET-1, (3) OMA, (4) ET-1 + OMA 10(-9) mol/L, (5) ET-1 + OMA 10(-8) mol/L, (6) ET-1 + OMA 10(-7) mol/L and (7) ET-1 + OMA 10(-6) mol/L. CFs were counted by MTT assay. Cell cycle distribution was determined with a flow cytometer (FCM). [3H]-Proline incorporation was evaluated by scintillation counting. Nitric oxide (NO) was measured by colorimetry.</p><p><b>RESULTS</b>10(-7) mol/L ET-1 significantly increased A490 value and [3H]-Pro incorporation and decreased NO secretion compared with the control group (P < 0.01). 10(-9)-10(-6) mol/L OMA inhibited the effects of ET-1 on CFs in a concentration-dependent manner (P < 0.01 vs. ET-1). In the ET-1 group, the percentage of cells in the S phase was higher than control, which was inhibited by l0(-6) mol/L OMA (P < 0.01 vs. ET-1 and control).</p><p><b>CONCLUSION</b>OMA can restrain the proliferation and collagen synthesis of cardiac fibroblasts induced by endothelin-1, and this effect may be partially mediated by NO.</p>

Treatment of depression with the serotonin reuptake enhancer tianeptine in the primary care setting of India.

Despite the availability of several antidepressants, low patient compliance with medication, mainly due to adverse effects remains a major problem. The aim of this study was to evaluate the efficacy and compliance of tianeptine, a selective serotonin reuptake enhancer (SSRE), for the treatment of major depression in primary care setting of India. In a prospective observational multicentric study, 320 outpatients with major depression were treated with tianeptine 12.5 mg thrice daily for 60 days. Outcome measures were change in Hamilton depression rating scale (HDRS) score, frequency of side-effects, and compliance with medication. After treatment, mean HDRS score decreased from 10.9 +/- 3.2 at baseline to 6.9 +/- 2.7 at day 60 (p < 0.01), with more than half the patients showing > 50% improvement in HDRS score. No patient withdrew due to side-effects, which were reported in 23 patients (7.2%). Mean compliance with the medication was 91%. This study demonstrates the efficacy and acceptability of tianeptine in the management of major depression in Indian clinical practice.

Evaluation of cognitive function of fluoxetine, sertraline and tianeptine in isolation and chronic unpredictable mild stress-induced depressive Wistar rats.

Depressive illness is generally associated with cognitive impairment. Serotonergic selective antidepressant drugs, fluoxetine (FLX), sertraline (SER) and tianeptine (TIA), are claimed to have less or no effect on cholinergic system, the key system involved in memory. In the present study, these drugs were evaluated for their influence on cognitive behavior in both depressive and non-depressive animals. Depression was induced by two models, (i) 60 days social isolation of litter; and ii) by applying chronic unpredictable mild stress for 21 days. Depression in the rats was confirmed by behavioral despair test. Transfer latency on elevated plus maze and inflexion ratio in passive avoidance step through behavior were employed to assess learning and memory. The results indicated that administration of fluoxetine; sertraline and tianeptine attenuated the cognitive deficits observed in depressive rats. In non-depressive rats these drugs produced retention deficit, which was found to be parameter and model dependent. Data suggested that, FLX and SER (SSRI's) effectively attenuated the isolation-induced depression and cognitive deficit, whereas TIA (SSRE) produced better effect in stress-induced depressive conditions. It was concluded that behavioral profiles of fluoxetine, sertraline and tianeptine on cognition were model and parameter dependent.

Treatment of major depression and anxiety with the selective serotonin re-uptake enhancer tianeptine in the outpatient psychiatric care setting of India.

In the outpatient psychiatric care setting, patients with major depression and anxiety comply poorly with traditional tricyclic antidepressants and specific serotonin re-uptake inhibitor treatment. The purpose of this study was to examine whether the low drop out rate reported with tianeptine in randomised studies is also reflected in daily outpatient psychiatric practice. In a six-week prospective multicentre study, treatment with tianeptine (12.5mg thrice daily) in 314 patients with major depression and anxiety, drawn from 25 randomly selected outpatient psychiatric practices across India was assessed. Outcome measures were frequency of drop outs due to side-effects and change in depression and anxiety rating scale scores. Intention to treat analysis showed that 7 patients (2.3%) discontinued treatment due to side-effects. Patients with an improvement of at least 50% from baseline on Montgomery Asberg Depression Rating Scale (MADRS) increased from 18.5% at week 3 to 53.0% at week 6; on the Hamilton Anxiety Rating Scale (HARS), patient responders likewise increased from 22.6% at three weeks to 52.2% at six weeks. When used in the setting of day to day outpatient psychiatric practice, tianeptine is a well-tolerated and effective antidepressant. It could serve as a useful alternative, and improve the present low compliance with treatment in patients with major depression and anxiety.