A case series on drug induced hyponatremia: uncommon adverse effect of commonly used drugs

Older patients suffering from depression and psychosis have markedly increased since last decade. So, has the use of antidepressants and antipsychotics. The prevalence of hyponatremia due to these drugs is common in general as well as psychiatric practice. It may also lead to life threatening morbidity and mortality. Loss of renal function, polypharmacy, dementia and other conditions of advanced age can either exacerbate the severity of hyponatremia or mask its onset. In this case series, total four cases were reported of hyponatremia and drugs causing it were escitalopram, quetiapine, tianeptine and oxcarbazepine. Due to polypharmacy, a chance of hyponatremia was more in these patients. Patients received infusion of hypertonic saline with salt added diet to treat hyponatremia. Symptoms of hyponatremia were improved after the treatment. In all four cases, WHO and Naranjo’s causality assessment revealed ‘possible’ causal relationship with the prescribed drug. Prescribers should be aware of such adverse effect due to these drugs.

Effects of Tianeptine on Adult Rats Following Prenatal Stress

OBJECTIVE: Exposing a pregnant female to stress during the critical period of embryonic fetal brain development increases the risk of psychiatric disorders in the offspring. The objective of this study was to investigate the effect of antidepressant tianeptine on prenatally stressed (PNS) rats. METHODS: In this study, a repeated variable stress paradigm was applied to pregnant rats during the last week of gestation. To investigate the effects of antidepressant tianeptine on PNS rats, behavioral and protein expression analyses were performed. Forced swim test, open field test, and social interaction test were performed to determine changes in PNS rats compared to non-stressed offspring. Haloperidol was used as a positive control as an antipsychotic drug based on previous studies. RESULTS: Behavioral changes were restored after treatment with tianeptine or haloperidol. Western blot and immunohistochemical analyses of the prefrontal cortex revealed downregulation of several neurodevelopmental proteins in PNS rats. After treatment with tianeptine or haloperidol, their expression levels were increased. CONCLUSION: Downregulation of several proteins in PNS rats might have caused subsequent behavioral changes in PNS rats. After tianeptine or haloperidol treatment, behavioral changes in PNS rats were restored. Therefore, tianeptine might decrease incidence of prenatal stress related-psychiatric disorders such as depression and schizophrenia.

Effects of tianeptine on symptoms of fibromyalgia via BDNF signaling in a fibromyalgia animal model

Previous reports have suggested that physical and psychological stresses may trigger fibromyalgia (FM). Stress is an important risk factor in the development of depression and memory impairments. Antidepressants have been used to prevent stress-induced abnormal pain sensation. Among various antidepressants, tianeptine has been reported to be able to prevent neurodegeneration due to chronic stress and reverse decreases in hippocampal volume. To assess the possible effect of tianeptine on FM symptoms, we constructed a FM animal model induced by restraint stress with intermittent cold stress. All mice underwent nociceptive assays using electronic von Frey anesthesiometer and Hargreaves equipment. To assess the relationship between tianeptine and expression levels of brain-derived neurotrophic factor (BDNF), cAMP response element-binding protein (CREB), and phosphorylated cAMP response element-binding protein (p-CREB), western blotting and immunohistochemistry analyses were performed. In behavioral analysis, nociception tests showed that pain threshold was significantly decreased in the FM group compared to that in the control group. Western blot and immunohistochemical analyses of medial prefrontal cortex (mPFC) and hippocampus showed downregulation of BDNF and p-CREB proteins in the FM group compared to the control group. However, tianeptine recovered these changes in behavioral tests and protein level. Therefore, this FM animal model might be useful for investigating mechanisms linking BDNF-CREB pathway and pain. Our results suggest that tianeptine might potentially have therapeutic efficacy for FM.

Effect of Tianeptine on Depressed Tinnitus Patients

BACKGROUND AND OBJECTIVES: Tianeptine is a tricyclic antidepressant that has a novel pharmacological property: it increases the reuptake of 5-hydroxytryptamine. Recent studies have reported that the prevalence of depression is greater in patients with tinnitus than in control subjects who do not have tinnitus. The purpose of this study was to assess the efficacy of tianeptine for the relief of tinnitus, especially in patients with depressive mood. SUBJECTS AND METHODS: Among a total of 52 tinnitus patients, 15 had depressive mood. The depressed tinnitus patients were prescribed Stablon® 12.5 mg once daily for 1 month without any other drug. We assessed the severity of tinnitus, level of depression, and the quality of sleep in these patients by using the Tinnitus Handicap Inventory (THI), Beck Depression Inventory (BDI), and Pittsburgh Sleep Quality Index (PSQI). Hearing impairment and severity of tinnitus were measured with pure tone audiometry, speech audiometry, and tinnitograms. These evaluations were conducted before and after medication treatment. RESULTS: For the 15 depressed tinnitus patients, THI scores significantly correlated with BDI and PSQI scores prior to medication treatment. These results showed that the discomfort of tinnitus was closely related to depression and sleep disorder. After medication treatment, THI and BDI scores significantly decreased, indicating that tinnitus and depression improved. However, no significant alteration in PSQI score was observed, indicating that there was no improvement in sleep quality. CONCLUSIONS: In the treatment of depressed tinnitus patients, tianeptine might be an efficient drug to treat both tinnitus and depression. However, tianeptine is unlikely to improve the quality of sleep in these patients.

Effects of calcium channel blocker, nifedipine, on antidepressant activity of fl uvoxamine, venlafaxine and tianeptine in mice.

Background: Cardiovascular diseases are commonly associated with depression. Calcium channel blockers (CCBs) form commonly used group of drugs for the treatment of a number of cardiovascular diseases. Nifedipine, a CCB, has been shown to possess antidepressant activity and potentiate antidepressant activity of imipramine and sertraline, however, literature on its interaction with newer antidepressant drugs such as fl uvoxamine, venlafaxine and tianeptine is limited. Hence, the present study was undertaken. Methods: The study was carried out in albino mice in two phases. In Phase I, antidepressant activity of nifedipine, fl uvoxamine, venlafaxine and tianeptine were confi rmed after their single dose administration using forced swim test (FST) and tail suspension test (TST) and their minimum antidepressant doses were determined. In Phase II, the effect of nifedipine on antidepressant activity of fl uvoxamine, venlafaxine and tianeptine was studied by orally administering sub-antidepressant doses of these drugs for 28 days. FST and TST were carried out on 1st, 14th and 28th day of the study and change in immobility period was observed. Results: In Phase I, all the studied drugs exhibited dose dependent antidepressant activity in both FST and TST. Minimal antidepressant dose of nifedipine, fl uvoxamine, venlafaxine and tianeptine was observed as 10, 25, 25 and 10 mg/kg respectively. In Phase II, combinations of sub-antidepressant dose of nifedipine (5 mg/kg) with sub-antidepressant doses of fl uvoxamine (12.5 mg/kg), venlafaxine (12.5 mg/kg) and tianeptine (5 mg/kg) exhibited enhanced antidepressant activity when compared to the control group and individual drug groups after same duration of treatment. Conclusions: Nifedipine, fluvoxamine, venlafaxine and tianeptine possess antidepressant activity and nifedipine exhibits synergistic antidepressant activity with fl uvoxamine, venlafaxine and tianeptine.

Antiallodynic effects of intrathecal tianeptine in a neuropathic pain rat

BACKGROUND: Tianeptine is an antidepressant drug which is used for treating depression. Interestingly, the tianeptine has shown antinociceptive effects within a variety of nociceptions. The aim of this study is to investigate the antiallodynic effects of tianeptine in neuropathic pain rats and also determine the involvements of serotonergic, alpha-2 adrenergic and adenosine receptors at the spinal level. METHODS: Neuropathic pain was induced by ligation of left lumbar at 5th and 6th spinal nerves in male Sprague-Dawley rats. PE-10 catheters were placed into the thoracolumbar subarachnoid space for drug injections. Mechanical allodynia was evaluated by measuring the withdrawal threshold to von Frey filament when applying on the plantar surface of rats. The effects of intrathecal tianeptine were observed at 15, 30, 60, 90, 120, 150, 180 minutes after delivery. Antagonists for serotonergic (dihydroergocristine), alpha-2 adrenergic (yohimbine) and adenosine (CGS 15943) receptors were intrathecally administered 10 minutes prior to tianeptine in order to evaluate the involvement of both receptors. RESULTS: Intrathecal tianeptine increased dose-dependently at the withdrawal threshold in the ligated paw. Pretreatment with intrathecal dihydroergocristine, yohimbine and CGS 15943 antagonized the antiallodynic effects of tianeptine. CONCLUSIONS: These results suggested that intrathecal tianeptine attenuates the spinal nerve ligation induced tactile allodynia. Serotonergic, alpha-2 adrenergic and adenosine receptors are all involved in the antiallodynic effects of tianeptine at the spinal level.

NCAM140 and pCREB Expression after Tianeptine Treatment of SH-SY5Y Cells

OBJECTIVE: Antidepressants Modulate Neuronal Plasticity. Tianeptine, An Atypical Antidepressant, Might Be Involved In The Restoration Of Neuronal Plasticity; It Primarily Enhances The Synaptic Reuptake Of Serotonin. Ncam140 Is Involved In Neuronal Development Processes, Synaptogenesis And Synaptic Plasticity. We Investigated The Effect Of Tianeptine On The Expression Of Ncam140 And Its Downstream Signaling Molecule In The Human Neuroblastoma Cell Line Sh-sy5y. METHODS: NCAM protein expression was measured in human neuroblastoma SH-SY5Y cells that were cultivated in serum-free media and treated with 0, 10, or 20 microM tianeptine for 6, 24, or 72 hours. NCAM140 expression in the tianeptine treatment group was confirmed by Western blot, and quantified through measurement of band intensity by absorbance. CREB and pCREB expression was identified after treatment with 20 microM tianeptine for 6, 24, and 72 hours by Western blot. RESULTS: Compared to cells treated for 6 hours, cells treated with 0 or 10 microM tianeptine for 72 hours showed a significant increase in NCAM140 expression and cells treated with 20 microM tianeptine showed a significant increase after 24 and 72 hours. The pCREB level in cells treated with 20 microM tianeptine increased in time-dependent manner. CONCLUSION: Our findings indicated that the tianeptine antidepressant effect may occur by induction of NCAM140 expression and CREB phosphorylation.

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.

Effects of tianeptine and lithium on expression of pCREB in hippocampus of chronic stress depression rats / 中华行为医学与脑科学杂志

Objective To research the effects of tianeptine and lithium on expression of pCREB in hippocampus of chronic stress depression rats. Methods All the experimental rats were divided by random into : Group of depression,Group of tianeptine,Group of lithium and Group of control. The rats of Group of depression, Group of tianeptine and Group of lithium were applied stress for 21 days,and meanwhile Group of control had no stress. The rats of Group of tianeptine were fed with tianeptine (50 mg/kg) , Group of lithium were fed with lithium (60 mg/kg) , while another groups were fed with normal sodium of the same volume. The ethology examination was performed by using method of open-field and experiment of fluid consumption. The expression of pCREB was detected by Western-blotting method. Results After the chronic stress,the horizontal crossing numbers,the erection times,the modification times and the percentage of sacchar-consumption of the rats of Group of depression were 23.2±23.0;8. 1 ±7.2; 3.6 ±3.5 and (55.4 ±11.7)% respectively, which were less than Group of control (46.0±18.9;20.3±11.3;8.4±2.7 and (68.5 ±8.2)% ; P＜0.01). The horizontal crossing numbers(28. 1 ±23.0) ,the erection times(12. 1 ± 9.4) and the modification times(5.5 ±3.2) of Group of tianeptine are less than those of Group of control (P ＜ 0. 05), but no significant difference compared with Group of depression; the percentage of sacchar-consumption(62.7 ± 10.6) % ,Group of tianeptine was more than Group of depression (P＜ 0.05 ) , but no obvious difference with Group of control. The horizontal crossing numbers, the erection times, the modification times and the percentage of sacchar-consumption of Group of lithium were less than those of Group of control (P ＜ 0.05), more than those of Group of depression but no significant difference (P ＞ 0.05). In Westernblotting method,the level of pCREB in the hippocampus of Group of depression was less than that of Group of control (P＜ 0.01); that of Group of tianeptine was more than that of Group of depression (P ＜ 0.01) but no obvious difference with Group of control; that of Group of lithium was less than that of Group of control (P＜0. 01) and more than Group of depression (P＜0.01). Conclusion Tianeptine could reverse the reduction of expression of pCREB in hippocampus of chronic stress depression rats and lithium partly did it.

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.

Therapeutic Effect of Tianeptine on Elderly Depression and Hippocampal Volume Change / 대한정신약물학회지

OBJECTIVE: This research was performed to study the effect of tianeptine, a novel antidepressant, on elderly depressed patients, to compare the hippocampus size between a normal control group and the elderly depressed group, and to measure the change of hippocampal volume according to the treatment effect of tianeptine. The relationship between hippocampus size and severity of depression at baseline was also studied. METHODS: A group of elderly depressed patients and normal control subjects over 62 years old were recruited fifteen elderly depressed patients, all male, of average age 70 (range 62-80 years old) and 15 normal control subjects were recruited along with age and education duration matched. To investigate the effect of the antidepressant, Montgomery-Asberg Depression Rating Scale (MADRS), Hamilton Depression Rating Scale (HDRS) and Clinical Global Impression (CGI) scale were applied at baseline, and the 4th and 8th weeks. MRI was used to compare the volume of the hippocampus between the patients group and the control group, and to measure the hippocampal volume of the patients at baseline and after the 8-week treatment. RESULTS: For the elderly depressed patient group, tianeptine significantly reduced MADRS, HDRS and CGI (Ed-deleted part is unnecessary as this meaning is obvious from being in the `Results' section). There was no significant difference of hippocampal volume between the elderly depressed patients group and the normal control group, nor between the elderly depressed patients group at baseline and after the 8-week treatment. CONCLUSION: This study shows that tianeptine is a safe, effective and well-tolerated antidepressant for elderly depression. However, a change of hippocampal volume was not observed over the course of an 8-week, short-term therapy.

Effects of tianeptine on changes of MAP2 expression level in hippocampal CA3 pyramidal cell of rats in chronic stress / 中国药理学通报

Aim To investigate changes of MAP2 expression level in rat hippocampal pyramidal cells induced by chronic stress, and to explore effects of tianeptine on them. Methods 25 rats were divided randomly into three groups:Control group,Stress group and Stree-tianeptine group. The forced-swimming was performed to rats in stress group and stress-tianeptine. Using the immunohistochemistry and the computerized image technique, expression levels of phosphorated MAP2 and the number the Positive cells were assayed quantitatively in each group. Results Compared with control group (149.34?1.81), the phosphorated MAP2 average gray degree in pyramidal cells of stress group (144.99?4.40) was significantly lower, that of the stress-tianeptine group (148.84?2.73) was significantly higher than that of stress group; The number of phosphorated MAP2 positive cells in stress group (40.36?1.35) was significantly less compared withthat of control group (42.73?1.56); that of stress-tianeptine group (42.14?1.62) was significantly more than that of stress group. Conclusion It is suggested that tianeptine could inhibit the enhancement of phosphorated MAP2 expression in hippocampal pyramidal cells induced by chronic stress.

Comparison of Efficacy and Safety between Tianeptine and Sertraline in the Treatment of Patients with Depression / 신경정신의학

OBJECTIVE: This study was designed to evaluate the efficacy and safety of tianeptine and sertraline in the treatment of patients with depression. METHOD: The study was done on the patients with major depression diagnosed by DSM-IV, who had a Hamilton Rating Scale for Depression(HAM-D) score > OR =14 on the first 17 items of the HAM-D. A total of 40 patients were randomly assigned to tianeptine group and sertraline group. Tianeptine and sertraline were prescribed to each group. 6 weeks of each medication was carried out after 7 days of drug excretion period. Evaluation using 17 item HAM-D, Montgomery and {0c5}sberg Depression Rating Scale(MADRS), Clinical Global Impression Scale(CGI), and Covi Scale was done on the baseline and after 1 week, 2 weeks, 4 weeks, and 6 weeks. Regarding all side effects that had occurred during the period of our study such as their developed/disappeared time, severities, incidences, managements and results have been recorded. RESULTS: A total of 30 patients(tianeptine group 15;sertraline group 15) finished the 6 weeks of research. 37.5mg of the daily dose was regularly prescribed to the tianeptine group, the average amount of 64.0+/-22.5mg of the final daily dose was prescribed to the sertraline group. Total 17 item HAM-D scores, total points of MADRS and CGI showed significant decrease after 1 week in each treatment group and continous decrease after 2, 4 and 6 weeks;and no difference was found between tianeptine group and sertraline group in the antidepressant efficacy. Also there were no significant changes in vital sign, CBC, chemistry, and EKG in each treatment group. The common reported side effects of tianeptine were nausea(33.3%), epigastic distress(26.7%), dry mouth(20.0%), headache(13.3%) and those of sertraline were dry mouth(53.3%), headache(46.7%), nausea(33.3%), anorexia(33.3%). CONCLULSION: According to the results, tianeptine was effective in improvement of depressive symptoms and was well tolerated and safe in patients with depression.

Comparison of the effects of tianeptine, amitriptyline and placebo on daytime sleepiness, performance and nocturnal sleep in healthy young adults / 대한정신약물학회지

OBJECTIVES: Tianeptine, a novel tricyclic antidepressant, is known to increase the pre-synaptic uptake of serotonin while paradoxically having antidepressant and anxiolytic effects. The purpose of this study was to get information on the effects of tianeptine on daytime sleepiness, performance and nocturnal sleep in healthy, young, adult volunteers. METHODS: Twelve young healthy male volunteers visited the study center 1 day a week for 3 weeks. On each visit day, each subject received 1 of the 3 treatments with: tianeptine(12.5mg t.i.d.), amitriptyline(25mg b.i.d. and placebo at midday) or placebo(t.i.d.), in a double-blind, random latin square sequence, cross-over design. All the drugs and placebo were prepared in identical gelatin capsules. A battery of performance tests(digit cancellation, arithmatic addition, digit span, digit symbol substitution, word list memory), was carried out in the afternoons(at 1hr after the second dose). Subjective assessments of the daytime sleepiness and unwanted effects of drug were made, using a modified Epworth Sleepiness Scale and a modified Uscandinavian Kociety of Usypharmacology side-effects rating scale(UKU Scale), in late evenings (at 0.5 hr before the last dose). Sleep on the night of the treatment day was evaluated by a post-sleep questionnaire on rising the following morning. RESULTS: Compared to placebo, tianeptine showed no evidence of impairment on any performance test and did not affect the daytime alertness/drowsiness level and nocturnal sleep. Amitriptyline, however, produced considerable impairment of performance, associated with severe daytime sleepiness. Also, amitriptyline significantly affected nocturnal sleep by quicker induction, more restful maintenance and longer period relative to placebo. Adverse events were significantly more often and severe after amitriptyline than after tianeptine or placebo treatments. CONCLUSION: These results confirmed the previous observations that tianeptine is not accompanied by significant daytime sedation, nocturnal sleep change or performance impairment. And they also suggest that tianeptine could be a useful option for the depressive patient, in particular for the ambulatory out-patient or the elderly.

Effect of antidepressant on behavior and vascular endothelial cell growth factor in hippocampus of rat model of depression / 第三军医大学学报

ObjectiveTo study the mechanism by which antidepressant works on vascular endothelial cell growth factor(VEGF) in rat hippocampus of depression model.MethodsForty SD rats were randomly and equally divided into 5 groups: stress+fluoxetine,stress+tianeptine,stress,stress+normal sodium,blank matched control.We adopted separation and chronic unpredicted mild stress to establish depression in all rats except those in blank matched control group,and the behavior of all animals was evaluated by open-field and fluid consumption test.VEGF expression was detected by immunohistochemisty after intragastric administration respectively with fluoxetine,tianeptine or normal sodium for 30 d.ResultsVEGF expression in hippocampus was decreased in all stress groups compared with control group(P

Effect of antidepressant on astrocyte in the rat hippocampus of depression model / 重庆医科大学学报

Objective: To study the mechanism of antidepressant in the astrocyte in the rat hippocampus of depression model.Mehtods: The depression model of rat was produced by separation and chronic unpredicted mild stress.The behavior was measured by open-field and fliud consumption test.The number of astrocyte in hippocampus was assessed by GFAP immunohistochemisty after intragastric administration with fluoxetine,tianeptine and normal sodium for 30 days.Results: The number of astrocyte in hippocampus was decreased in stress group compared with normal group.After administration for 30 days,the number of astrocyte in hippocampus was increased in fluoxetine group and tianeptine group as compared with normal sodium group.Conclusions: Chronic antidepressant treatment significantly increases the astrocyte in the rat hippocampus of depression model.Astrocytes may be correlated with the pathophysiology of depression.