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Caroline M. Spencer - One of the best experts on this subject based on the ideXlab platform.

  • Tianeptine
    CNS Drugs, 2001
    Co-Authors: Antona J. Wagstaff, Douglas Ormrod, Caroline M. Spencer
    Abstract:

    Tianeptine is an antidepressant agent with a novel neurochemical profile. It increases serotonin (5-hydroxytryptamine; 5-HT) uptake in the brain (in contrast with most antidepressant agents) and reduces stress-induced atrophy of neuronal dendrites. Like the selective serotonin reuptake inhibitors (SSRIs) and in contrast with most tricyclic antidepressant agents, Tianeptine does not appear to be associated with adverse cognitive, psychomotor, sleep, cardiovascular or bodyweight effects and has a low propensity for abuse. Tianeptine has a comparatively favourable pharmacokinetic profile. It is not subject to first-pass hepatic metabolism, has high bioavailability and limited distribution, and is rapidly eliminated. While this offers advantages for Tianeptine over the tricyclic antidepressant agents in terms of dose titration, treatment changes and potential drug interactions, its rapid elimination makes adherence to dosage schedules more important. Tianeptine differs from most antidepressants in that it is not primarily metabolised by the hepatic cytochrome P450 system, indicating less likelihood of drug-drug interactions; this is of particular interest for elderly patients. Tianeptine, in dosages of 25 to 50 mg/day, has been investigated in patients with major depression, depressed bipolar disorder, dysthymia or adjustment disorder. It has equivalent antidepressant efficacy to several classical antidepressant agents (amitriptyline, clomipramine, imipramine, mianserin) and the SSRIs fluoxetine (in most patients), paroxetine and sertraline. Comparison with maprotiline indicated superior efficacy for Tianeptine but dothiepin appeared superior in another study. Extended treatment with Tianeptine decreases the incidence of relapse/ recurrence of depression. Tianeptine appears to be as effective as fluoxetine, sertraline, amitriptyline, clomipramine and mianserin and more effective than maprotiline in improving associated anxiety in patients with depressive disorders. Depression and anxiety symptoms in alcohol dependant patients also respond well to Tianeptine. The adverse effects associated with Tianeptine are similar in many respects to those of the SSRIs and minimal in comparison with the tricyclic antidepressants. The most common adverse effects are nausea, constipation, abdominal pain, headache, dizziness and changes in dreaming. Anticholinergic effects occur less often with Tianeptine than with tricyclic agents. Hepatoxicity is rare. The dosage should be decreased in elderly patients and those with severe renal failure, but adjustment is not necessary in patients with alcoholism or hepatic impairment, or those undergoing haemodialysis. Conclusions : The antidepressant efficacy and favourable tolerability and pharmacokinetic profiles of Tianeptine in patients with depression, including those with associated anxiety, have been proven; the data indicate that it may have additional potential in specific subgroups of depressed patients such as the elderly and those with chronic alcoholism. Pharmacodynamic Profile Tianeptine is an antidepressant drug with structural similarities to the tricyclic antidepressant agents but a novel neurochemical profile. The main difference between this and other antidepressant agents is its action on serotonin (5-hydroxytryptamine; 5-HT): Tianeptine increases serotonin uptake in the brain and platelets. The behavioural (in animal models) and physical (atrophy of neuronal dendrites) effects of stress on the hypothalamic-pituitary-adrenal axis are reduced by Tianeptine, and levels of noradrenaline (norepinephrine) and dopamine are indirectly increased in several regions of the brain. The main metabolite (MC_5; pentanoic acid) has some minor antidepressant activity. Clinical studies indicate that, unlike tricyclic antidepressant agents, Tianeptine is not associated with adverse effects on driving skills or cognitive function (such as sedation or impaired memory) and may have slight activating properties, particularly in aspects of attention. Similarly, there appear to be few effects on sleep in healthy volunteers or patients with concurrent depression and alcoholism after withdrawal of alcohol. Like the selective serotonin reuptake inhibitors (SSRIs) and in contrast with the tricyclic antidepressants, Tianeptine has a favourable cardiovascular profile in healthy volunteers and patients with depression, with and without concurrent alcoholism. Pharmacokinetic Profile The maximum plasma concentration (C_max) of Tianeptine was 0.3 mg/L, time to C_max (t_max) was 0.94 hours and bioavailability was 99% after a single oral dose of Tianeptine 12.5mg in healthy volunteers. The drug is not subject to first-pass hepatic metabolism. Food decreases C_max and prolongs t_max but does not affect the extent of absorption. Although the distribution of Tianeptine is rapid (distribution half-life 0.7 hours) protein binding is high (95%), resulting in alow volume of distribution (0.5 to 0.8 L/kg) in healthy volunteers. Tianeptine undergoes extensive extrarenal metabolism and has a short elimination half-life (t1/2β; 2.5 hours in healthy volunteers). The major metabolic pathway of Tianeptine is a 2-step β-oxidation process of the aliphatic chain, leading to the formation of 2 main metabolites MC_5 and MC_3 (propionic acid). MC_3 is the main metabolite of Tianeptine in urine and MC_5 is the main metabolite in plasma. Tianeptine does not undergo cytochrome P450—dependent biotransformation to any significant extent, thus reducing the risk of drug interactions. The pharmacokinetic profile of a single dose of Tianeptine in adults with depression appears similar to that in healthy adult volunteers, although the t_max and t12β were prolonged. Steady-state pharmacokinetics were achieved after 1 month of treatment with Tianeptine 37.5 mg/day and were maintained over 3 months. Most values were similar to those seen in depressed patients after a single dose, but the area under the concentration-time curve (AUC) was significantly greater after extended treatment (1.3 vs 1 mg/L · h; p < 0.03). The pharmacokinetic profile of oral Tianeptine was not significantly altered in patients with compromised renal function. However, the t1/2β and AUC of the MC_5 metabolite were increased compared with controls, suggesting a decreased clearance of this metabolite in patients with renal failure. Although bioavailability of Tianeptine remained high (85%) in elderly individuals, clearance was lower than that reported in younger individuals. The pharmacokinetic profile of Tianeptine is not altered in patients with alcoholic cirrhosis and depression. Therapeutic Efficacy The clinical antidepressant efficacy of Tianeptine 25 to 50 mg/day has been proven against placebo in patients aged 18 to 60 years with major depression (single episode or recurrent) or bipolar disorder (depressed) in 2 double-blind trials. Initial improvements were seen after 7 days, and improvement continued throughout the 6 weeks of study. Improvements from baseline on the Montgomery-Åsberg Depression Rating Scale (MÅDRS) were 44 and 54% with Tianeptine and 28 and 38% in placebo recipients (p < 0.05 and p < 0.01, respectively). Tianeptine 25 to 37.5 mg/day for 1.5 to 3 months had equivalent antidepressant efficacy to fluoxetine 20 mg/day in patients with major depression (single episode or recurrent), bipolar disorder (depressed) or dysthymic disorder in several studies. However, although equivalence was noted in several parameters in elderly patients receiving Tianeptine or fluoxetine in one study, reductions from baseline in the MÅDRS scores were statistically significantly greater in those receiving fluoxetine (62 vs 51% in fluoxetine and Tianeptine recipients, respectively, compared with 50 vs 51%, respectively, in a study in patients aged 18 to 65 years which used this assessment tool). The antidepressant efficacy of Tianeptine 37.5 mg/day (reduction in MÅDRS score of 56%) was equivalent to that of sertraline 50 mg/day (reduction of 54%) after 1.5 months in patients with major depression or bipolar disorder. A study published only in abstract form indicates that Tianeptine 37.5 mg/day has similar efficacy to paroxetine 20 mg/day for 3 months (reductions in MÅDRS scores of 62 and 61%, respectively). In comparative studies with tricyclic or tetracyclic antidepressant agents, the antidepressant efficacy of Tianeptine 25 to 50 mg/day (44 to 64% reduction in MÅDRS scores) was equivalent to that of amitriptyline 50 to 100 mg/day for 1 or 1.5 months (53 and 69%), clomipramine 100 to 200 mg/day for 6 months (55%), imipramine 100 to 200 mg/day for 1.5 months (41%) and mianserin 30 to 80 mg/day for 1.5 or 6 months (48 and 50%) in patients with major depression (single episode or recurrent), bipolar disorder (depressed), dysthymic disorder or adjustment disorder. Tianeptine 37.5 mg/day (56% reduction in MÅDRS score) was more effective than maprotiline 75 mg/day for 2 months (47%) in a study of perimenopausal women with anxio-depressive symptoms and less effective than dothiepin 150 to 225 mg/day for 1 month in a small study of patients with depressive disorders. The anxiolytic efficacy of Tianeptine was assessed in several comparative trials of patients with concurrent depression and anxiety. Tianeptine 25 to 50 mg/day appears to have equivalent anxiolytic efficacy to fluoxetine 20 mg/day for 1.5 to 3 months, sertraline 50 mg/day for 1.5 months, amitriptyline 50 to 100 mg/day for 1 to 1.5 months, clomipramine 100 to 200 mg/day for 6 months and mianserin 30 to 80 mg/day for 1.5 or 6 months. Superior anxiolytic efficacy was attributed to Tianeptine over maprotiline 75 mg/day for 2 months in a study of perimenopausal women with anxio-depressive symptoms. Tianeptine 25 to 50 mg/day is effective as long term treatment to prevent relapse or recurrence in patients with depression. It also appears to have potential for use in specific subgroups. The efficacy of Tianeptine 25 or 37.5 mg/day was equivalent to that of mianserin 30 mg/day and similar in some but not all parameters to that of fluoxetine 20 mg/day in elderly patients. Patients with chronic alcoholism often develop depression, especially on withdrawal of alcohol. Assessments of antidepressant and anxiolytic efficacy for Tianeptine 37.5 mg/day were equivalent to those for amitriptyline 75 mg/day over 1 to 2 months in this patient population. Improvements in quality-of-life scales with depressed Tianeptine recipients were similar to those in patients receiving mianserin or fluoxetine. Tolerability The adverse effect profile of Tianeptine appears to be similar in many respects to that of the SSRIs, in that cognitive, cardiovascular and bodyweight effects are minimal in comparison with the classical tricyclic antidepressant agents. In fact, in comparisons with placebo, the only symptom appearing significantly more often with Tianeptine was headache. In clinical trials, the most common adverse effects seen in patients with depressive disorders receiving Tianeptine were gastrointestinal (nausea, constipation, abdominal pain) or CNS (headache, dizziness, change in dreaming) disturbances, which decreased in frequency with continued treatment. Effects such as dry mouth, hot flushes, somnolence, vertigo, gastrointestinal disturbances, increased bodyweight, increased heart rate and tremor occurred significantly more often in patients receiving tri- or tetracyclic antidepressant agents than in those receiving Tianeptine. In studies comparing Tianeptine with fluoxetine, paroxetine or sertraline, in contrast, the incidence of most adverse effects was similar; nausea, tremor and palpitations tended to occur more often in fluoxetine recipients, and the incidence of dry mouth tended to be higher in Tianeptine recipients. Tianeptine has only rarely been associated with hepatoxicity. The favourable tolerability profile of Tianeptine has been confirmed in long term trials, and in elderly patients (including those with cardiovascular pathology before treatment initiation) and patients with alcoholism. The low incidence of anticholinergic and neurological effects associated with Tianeptine is of particular importance in these subgroups, who have increased sensitivity to the adverse effects of psychotropic drugs. Tianeptine has a wide therapeutic margin; overdosage has been associated with only minor transient adverse effects. Dosage and Administration The recommended dosage of Tianeptine in patients with depression is 37.5 mg/day orally in 3 divided doses, with meals. The dosage should be reduced in elderly patients and patients with severe renal failure, but dosage reduction is not required in patients with chronic alcoholism or hepatic impairment or those undergoing haemodialysis. The dosage of Tianeptine should be reduced over 1 to 2 weeks when discontinuing treatment, although there is little evidence of psychological or physical dependence on the drug. As with other antidepressants, Tianeptine is contraindicated in patients taking monoamine oxidase inhibitors.

  • Tianeptine: a review of its use in depressive disorders.
    CNS drugs, 2001
    Co-Authors: Antona J. Wagstaff, Douglas Ormrod, Caroline M. Spencer
    Abstract:

    UNLABELLED Tianeptine is an antidepressant agent with a novel neurochemical profile. It increases serotonin (5-hydroxytryptamine; 5-HT) uptake in the brain (in contrast with most antidepressant agents) and reduces stress-induced atrophy of neuronal dendrites. Like the selective serotonin reuptake inhibitors (SSRIs) and in contrast with most tricyclic antidepressant agents, Tianeptine does not appear to be associated with adverse cognitive, psychomotor, sleep, cardiovascular or bodyweight effects and has a low propensity for abuse. Tianeptine has a comparatively favourable pharmacokinetic profile. It is not subject to first-pass hepatic metabolism, has high bioavailability and limited distribution, and is rapidly eliminated. While this offers advantages for Tianeptine over the tricyclic antidepressant agents in terms of dose titration, treatment changes and potential drug interactions, its rapid elimination makes adherence to dosage schedules more important. Tianeptine differs from most antidepressants in that it is not primarily metabolised by the hepatic cytochrome P450 system, indicating less likelihood of drug-drug interactions; this is of particular interest for elderly patients. Tianeptine, in dosages of 25 to 50 mg/day, has been investigated in patients with major depression, depressed bipolar disorder, dysthymia or adjustment disorder. It has equivalent antidepressant efficacy to several classical antidepressant agents (amitriptyline, clomipramine, imipramine, mianserin) and the SSRIs fluoxetine (in most patients), paroxetine and sertraline. Comparison with maprotiline indicated superior efficacy for Tianeptine but dothiepin appeared superior in another study. Extended treatment with Tianeptine decreases the incidence of relapse/recurrence of depression. Tianeptine appears to be as effective as fluoxetine, sertraline, amitriptyline, clomipramine and mianserin and more effective than maprotiline in improving associated anxiety in patients with depressive disorders. Depression and anxiety symptoms in alcohol dependant patients also respond well to Tianeptine. The adverse effects associated with Tianeptine are similar in many respects to those of the SSRIs and minimal in comparison with the tricyclic antidepressants. The most common adverse effects are nausea, constipation, abdominal pain, headache, dizziness and changes in dreaming. Anticholinergic effects occur less often with Tianeptine than with tricyclic agents. Hepatoxicity is rare. The dosage should be decreased in elderly patients and those with severe renal failure, but adjustment is not necessary in patients with alcoholism or hepatic impairment, or those undergoing haemodialysis. CONCLUSIONS The antidepressant efficacy and favourable tolerability and pharmacokinetic profiles of Tianeptine in patients with depression, including those with associated anxiety, have been proven; the data indicate that it may have additional potential in specific subgroups of depressed patients such as the elderly and those with chronic alcoholism.

Antona J. Wagstaff - One of the best experts on this subject based on the ideXlab platform.

  • Tianeptine
    CNS Drugs, 2001
    Co-Authors: Antona J. Wagstaff, Douglas Ormrod, Caroline M. Spencer
    Abstract:

    Tianeptine is an antidepressant agent with a novel neurochemical profile. It increases serotonin (5-hydroxytryptamine; 5-HT) uptake in the brain (in contrast with most antidepressant agents) and reduces stress-induced atrophy of neuronal dendrites. Like the selective serotonin reuptake inhibitors (SSRIs) and in contrast with most tricyclic antidepressant agents, Tianeptine does not appear to be associated with adverse cognitive, psychomotor, sleep, cardiovascular or bodyweight effects and has a low propensity for abuse. Tianeptine has a comparatively favourable pharmacokinetic profile. It is not subject to first-pass hepatic metabolism, has high bioavailability and limited distribution, and is rapidly eliminated. While this offers advantages for Tianeptine over the tricyclic antidepressant agents in terms of dose titration, treatment changes and potential drug interactions, its rapid elimination makes adherence to dosage schedules more important. Tianeptine differs from most antidepressants in that it is not primarily metabolised by the hepatic cytochrome P450 system, indicating less likelihood of drug-drug interactions; this is of particular interest for elderly patients. Tianeptine, in dosages of 25 to 50 mg/day, has been investigated in patients with major depression, depressed bipolar disorder, dysthymia or adjustment disorder. It has equivalent antidepressant efficacy to several classical antidepressant agents (amitriptyline, clomipramine, imipramine, mianserin) and the SSRIs fluoxetine (in most patients), paroxetine and sertraline. Comparison with maprotiline indicated superior efficacy for Tianeptine but dothiepin appeared superior in another study. Extended treatment with Tianeptine decreases the incidence of relapse/ recurrence of depression. Tianeptine appears to be as effective as fluoxetine, sertraline, amitriptyline, clomipramine and mianserin and more effective than maprotiline in improving associated anxiety in patients with depressive disorders. Depression and anxiety symptoms in alcohol dependant patients also respond well to Tianeptine. The adverse effects associated with Tianeptine are similar in many respects to those of the SSRIs and minimal in comparison with the tricyclic antidepressants. The most common adverse effects are nausea, constipation, abdominal pain, headache, dizziness and changes in dreaming. Anticholinergic effects occur less often with Tianeptine than with tricyclic agents. Hepatoxicity is rare. The dosage should be decreased in elderly patients and those with severe renal failure, but adjustment is not necessary in patients with alcoholism or hepatic impairment, or those undergoing haemodialysis. Conclusions : The antidepressant efficacy and favourable tolerability and pharmacokinetic profiles of Tianeptine in patients with depression, including those with associated anxiety, have been proven; the data indicate that it may have additional potential in specific subgroups of depressed patients such as the elderly and those with chronic alcoholism. Pharmacodynamic Profile Tianeptine is an antidepressant drug with structural similarities to the tricyclic antidepressant agents but a novel neurochemical profile. The main difference between this and other antidepressant agents is its action on serotonin (5-hydroxytryptamine; 5-HT): Tianeptine increases serotonin uptake in the brain and platelets. The behavioural (in animal models) and physical (atrophy of neuronal dendrites) effects of stress on the hypothalamic-pituitary-adrenal axis are reduced by Tianeptine, and levels of noradrenaline (norepinephrine) and dopamine are indirectly increased in several regions of the brain. The main metabolite (MC_5; pentanoic acid) has some minor antidepressant activity. Clinical studies indicate that, unlike tricyclic antidepressant agents, Tianeptine is not associated with adverse effects on driving skills or cognitive function (such as sedation or impaired memory) and may have slight activating properties, particularly in aspects of attention. Similarly, there appear to be few effects on sleep in healthy volunteers or patients with concurrent depression and alcoholism after withdrawal of alcohol. Like the selective serotonin reuptake inhibitors (SSRIs) and in contrast with the tricyclic antidepressants, Tianeptine has a favourable cardiovascular profile in healthy volunteers and patients with depression, with and without concurrent alcoholism. Pharmacokinetic Profile The maximum plasma concentration (C_max) of Tianeptine was 0.3 mg/L, time to C_max (t_max) was 0.94 hours and bioavailability was 99% after a single oral dose of Tianeptine 12.5mg in healthy volunteers. The drug is not subject to first-pass hepatic metabolism. Food decreases C_max and prolongs t_max but does not affect the extent of absorption. Although the distribution of Tianeptine is rapid (distribution half-life 0.7 hours) protein binding is high (95%), resulting in alow volume of distribution (0.5 to 0.8 L/kg) in healthy volunteers. Tianeptine undergoes extensive extrarenal metabolism and has a short elimination half-life (t1/2β; 2.5 hours in healthy volunteers). The major metabolic pathway of Tianeptine is a 2-step β-oxidation process of the aliphatic chain, leading to the formation of 2 main metabolites MC_5 and MC_3 (propionic acid). MC_3 is the main metabolite of Tianeptine in urine and MC_5 is the main metabolite in plasma. Tianeptine does not undergo cytochrome P450—dependent biotransformation to any significant extent, thus reducing the risk of drug interactions. The pharmacokinetic profile of a single dose of Tianeptine in adults with depression appears similar to that in healthy adult volunteers, although the t_max and t12β were prolonged. Steady-state pharmacokinetics were achieved after 1 month of treatment with Tianeptine 37.5 mg/day and were maintained over 3 months. Most values were similar to those seen in depressed patients after a single dose, but the area under the concentration-time curve (AUC) was significantly greater after extended treatment (1.3 vs 1 mg/L · h; p < 0.03). The pharmacokinetic profile of oral Tianeptine was not significantly altered in patients with compromised renal function. However, the t1/2β and AUC of the MC_5 metabolite were increased compared with controls, suggesting a decreased clearance of this metabolite in patients with renal failure. Although bioavailability of Tianeptine remained high (85%) in elderly individuals, clearance was lower than that reported in younger individuals. The pharmacokinetic profile of Tianeptine is not altered in patients with alcoholic cirrhosis and depression. Therapeutic Efficacy The clinical antidepressant efficacy of Tianeptine 25 to 50 mg/day has been proven against placebo in patients aged 18 to 60 years with major depression (single episode or recurrent) or bipolar disorder (depressed) in 2 double-blind trials. Initial improvements were seen after 7 days, and improvement continued throughout the 6 weeks of study. Improvements from baseline on the Montgomery-Åsberg Depression Rating Scale (MÅDRS) were 44 and 54% with Tianeptine and 28 and 38% in placebo recipients (p < 0.05 and p < 0.01, respectively). Tianeptine 25 to 37.5 mg/day for 1.5 to 3 months had equivalent antidepressant efficacy to fluoxetine 20 mg/day in patients with major depression (single episode or recurrent), bipolar disorder (depressed) or dysthymic disorder in several studies. However, although equivalence was noted in several parameters in elderly patients receiving Tianeptine or fluoxetine in one study, reductions from baseline in the MÅDRS scores were statistically significantly greater in those receiving fluoxetine (62 vs 51% in fluoxetine and Tianeptine recipients, respectively, compared with 50 vs 51%, respectively, in a study in patients aged 18 to 65 years which used this assessment tool). The antidepressant efficacy of Tianeptine 37.5 mg/day (reduction in MÅDRS score of 56%) was equivalent to that of sertraline 50 mg/day (reduction of 54%) after 1.5 months in patients with major depression or bipolar disorder. A study published only in abstract form indicates that Tianeptine 37.5 mg/day has similar efficacy to paroxetine 20 mg/day for 3 months (reductions in MÅDRS scores of 62 and 61%, respectively). In comparative studies with tricyclic or tetracyclic antidepressant agents, the antidepressant efficacy of Tianeptine 25 to 50 mg/day (44 to 64% reduction in MÅDRS scores) was equivalent to that of amitriptyline 50 to 100 mg/day for 1 or 1.5 months (53 and 69%), clomipramine 100 to 200 mg/day for 6 months (55%), imipramine 100 to 200 mg/day for 1.5 months (41%) and mianserin 30 to 80 mg/day for 1.5 or 6 months (48 and 50%) in patients with major depression (single episode or recurrent), bipolar disorder (depressed), dysthymic disorder or adjustment disorder. Tianeptine 37.5 mg/day (56% reduction in MÅDRS score) was more effective than maprotiline 75 mg/day for 2 months (47%) in a study of perimenopausal women with anxio-depressive symptoms and less effective than dothiepin 150 to 225 mg/day for 1 month in a small study of patients with depressive disorders. The anxiolytic efficacy of Tianeptine was assessed in several comparative trials of patients with concurrent depression and anxiety. Tianeptine 25 to 50 mg/day appears to have equivalent anxiolytic efficacy to fluoxetine 20 mg/day for 1.5 to 3 months, sertraline 50 mg/day for 1.5 months, amitriptyline 50 to 100 mg/day for 1 to 1.5 months, clomipramine 100 to 200 mg/day for 6 months and mianserin 30 to 80 mg/day for 1.5 or 6 months. Superior anxiolytic efficacy was attributed to Tianeptine over maprotiline 75 mg/day for 2 months in a study of perimenopausal women with anxio-depressive symptoms. Tianeptine 25 to 50 mg/day is effective as long term treatment to prevent relapse or recurrence in patients with depression. It also appears to have potential for use in specific subgroups. The efficacy of Tianeptine 25 or 37.5 mg/day was equivalent to that of mianserin 30 mg/day and similar in some but not all parameters to that of fluoxetine 20 mg/day in elderly patients. Patients with chronic alcoholism often develop depression, especially on withdrawal of alcohol. Assessments of antidepressant and anxiolytic efficacy for Tianeptine 37.5 mg/day were equivalent to those for amitriptyline 75 mg/day over 1 to 2 months in this patient population. Improvements in quality-of-life scales with depressed Tianeptine recipients were similar to those in patients receiving mianserin or fluoxetine. Tolerability The adverse effect profile of Tianeptine appears to be similar in many respects to that of the SSRIs, in that cognitive, cardiovascular and bodyweight effects are minimal in comparison with the classical tricyclic antidepressant agents. In fact, in comparisons with placebo, the only symptom appearing significantly more often with Tianeptine was headache. In clinical trials, the most common adverse effects seen in patients with depressive disorders receiving Tianeptine were gastrointestinal (nausea, constipation, abdominal pain) or CNS (headache, dizziness, change in dreaming) disturbances, which decreased in frequency with continued treatment. Effects such as dry mouth, hot flushes, somnolence, vertigo, gastrointestinal disturbances, increased bodyweight, increased heart rate and tremor occurred significantly more often in patients receiving tri- or tetracyclic antidepressant agents than in those receiving Tianeptine. In studies comparing Tianeptine with fluoxetine, paroxetine or sertraline, in contrast, the incidence of most adverse effects was similar; nausea, tremor and palpitations tended to occur more often in fluoxetine recipients, and the incidence of dry mouth tended to be higher in Tianeptine recipients. Tianeptine has only rarely been associated with hepatoxicity. The favourable tolerability profile of Tianeptine has been confirmed in long term trials, and in elderly patients (including those with cardiovascular pathology before treatment initiation) and patients with alcoholism. The low incidence of anticholinergic and neurological effects associated with Tianeptine is of particular importance in these subgroups, who have increased sensitivity to the adverse effects of psychotropic drugs. Tianeptine has a wide therapeutic margin; overdosage has been associated with only minor transient adverse effects. Dosage and Administration The recommended dosage of Tianeptine in patients with depression is 37.5 mg/day orally in 3 divided doses, with meals. The dosage should be reduced in elderly patients and patients with severe renal failure, but dosage reduction is not required in patients with chronic alcoholism or hepatic impairment or those undergoing haemodialysis. The dosage of Tianeptine should be reduced over 1 to 2 weeks when discontinuing treatment, although there is little evidence of psychological or physical dependence on the drug. As with other antidepressants, Tianeptine is contraindicated in patients taking monoamine oxidase inhibitors.

  • Tianeptine: a review of its use in depressive disorders.
    CNS drugs, 2001
    Co-Authors: Antona J. Wagstaff, Douglas Ormrod, Caroline M. Spencer
    Abstract:

    UNLABELLED Tianeptine is an antidepressant agent with a novel neurochemical profile. It increases serotonin (5-hydroxytryptamine; 5-HT) uptake in the brain (in contrast with most antidepressant agents) and reduces stress-induced atrophy of neuronal dendrites. Like the selective serotonin reuptake inhibitors (SSRIs) and in contrast with most tricyclic antidepressant agents, Tianeptine does not appear to be associated with adverse cognitive, psychomotor, sleep, cardiovascular or bodyweight effects and has a low propensity for abuse. Tianeptine has a comparatively favourable pharmacokinetic profile. It is not subject to first-pass hepatic metabolism, has high bioavailability and limited distribution, and is rapidly eliminated. While this offers advantages for Tianeptine over the tricyclic antidepressant agents in terms of dose titration, treatment changes and potential drug interactions, its rapid elimination makes adherence to dosage schedules more important. Tianeptine differs from most antidepressants in that it is not primarily metabolised by the hepatic cytochrome P450 system, indicating less likelihood of drug-drug interactions; this is of particular interest for elderly patients. Tianeptine, in dosages of 25 to 50 mg/day, has been investigated in patients with major depression, depressed bipolar disorder, dysthymia or adjustment disorder. It has equivalent antidepressant efficacy to several classical antidepressant agents (amitriptyline, clomipramine, imipramine, mianserin) and the SSRIs fluoxetine (in most patients), paroxetine and sertraline. Comparison with maprotiline indicated superior efficacy for Tianeptine but dothiepin appeared superior in another study. Extended treatment with Tianeptine decreases the incidence of relapse/recurrence of depression. Tianeptine appears to be as effective as fluoxetine, sertraline, amitriptyline, clomipramine and mianserin and more effective than maprotiline in improving associated anxiety in patients with depressive disorders. Depression and anxiety symptoms in alcohol dependant patients also respond well to Tianeptine. The adverse effects associated with Tianeptine are similar in many respects to those of the SSRIs and minimal in comparison with the tricyclic antidepressants. The most common adverse effects are nausea, constipation, abdominal pain, headache, dizziness and changes in dreaming. Anticholinergic effects occur less often with Tianeptine than with tricyclic agents. Hepatoxicity is rare. The dosage should be decreased in elderly patients and those with severe renal failure, but adjustment is not necessary in patients with alcoholism or hepatic impairment, or those undergoing haemodialysis. CONCLUSIONS The antidepressant efficacy and favourable tolerability and pharmacokinetic profiles of Tianeptine in patients with depression, including those with associated anxiety, have been proven; the data indicate that it may have additional potential in specific subgroups of depressed patients such as the elderly and those with chronic alcoholism.

Benjamin Rolland - One of the best experts on this subject based on the ideXlab platform.

  • Neonatal Abstinence Syndrome Following Tianeptine Dependence During Pregnancy.
    Pediatrics, 2015
    Co-Authors: Camille Bence, Alexandre Bonord, Camille Rebillard, Pascal Vaast, Charlotte Alexandre, Renaud Jardri, Benjamin Rolland
    Abstract:

    Tianeptine, an atypical antidepressant, has been found to exhibit a potential for abuse. The use of therapeutic doses of Tianeptine during pregnancy has never raised safety concerns. However, the impact of Tianeptine abuse on the mother-child dyad has never been assessed. We report herein the case of a female patient who presented with dependence on Tianeptine, with the use of >650 mg of the drug per day. She had 2 successive pregnancies with similar doses. The state of dependence remained unidentified throughout the first pregnancy, but just after delivery, her full-term newborn exhibited unexpected neonatal abstinence syndrome (NAS). The NAS was successfully treated with morphine, although both the mother's and newborn's urine drug screen was negative. The causality of Tianeptine in inducing NAS was retrospectively assessed as "probable" by using a validated causality algorithm. During the second pregnancy, this patient sought addiction treatment and was admitted for residential detoxification treatment in her seventh month of pregnancy. Delivery occurred at full term with a low birth weight neonate. No further developmental insults or medical problems were subsequently identified in the 2 children. Maternal Tianeptine dependence during pregnancy may induce a type of NAS that mimics opiate NAS. This finding appears to be consistent with a recent finding of the agonist action of Tianeptine on the opiate μ-receptor.

Woong Mo Kim - One of the best experts on this subject based on the ideXlab platform.

  • Effects of Tianeptine on the development and maintenance of mechanical allodynia in a rat model of neuropathic pain.
    Neuroscience letters, 2016
    Co-Authors: Bong Ha Heo, Hyung Gon Lee, Jeong Il Choi, Myung Ha Yoon, Jae Yun Shin, Keun Suk Park, Woong Mo Kim
    Abstract:

    We validate the analgesic efficacy of Tianeptine by different administration routes and timing in a rat model of neuropathic pain. Neuropathic pain was induced by ligating the L5 and L6 spinal nerves in male Sprague-Dawley rats, and mechanical allodynia was assessed using von Frey filaments. The effects of orally administered Tianeptine and pretreatment with Tianeptine (intrathecally or intraperitoneally) on mechanical allodynia were assessed. Oral and preemptive intrathecal administration of Tianeptine significantly increased the paw withdrawal threshold but preemptive intraperitoneal administration did not. Nevertheless, intraperitoneal pretreatment of Tianeptine potentiated the antiallodynic effects of subsequently administered Tianeptine. These findings suggest that Tianeptine may be effective for preventing and treating neuropathic pain and that it can be used more widely in clinical pain practice.

  • Antiallodynic effect of Tianeptine via modulation of the 5-HT7 receptor of GABAergic interneurons in the spinal cord of neuropathic rats
    Neuroscience letters, 2015
    Co-Authors: Hai Lin, Woong Mo Kim, Bong Ha Heo, Yong-chul Kim, Myung Ha Yoon
    Abstract:

    Although Tianeptine, an atypical antidepressant has been reported to have antinociceptive effects, the mode of action is different from that of tricyclic antidepressants despite structural similarities. We examined the antiallodynic effect of intrathecal Tianeptine in neuropathic pain rats and determined the involvement of 5-hydroxytryptamine type 7 (5-HT7) receptor of the GABAergic interneurons in the spinal cord. Neuropathic pain was induced by spinal nerve ligation (SNL). After observation of the effect from intrathecal Tianeptine, a 5-HT7 receptor antagonist (SB-269970) was administered intrathecally 10 min before delivery of Tianeptine, to determine the contribution of spinal 5-HT7 receptor on the activity of Tianeptine. GAD expression and GABA concentrations were assessed. Intrathecal Tianeptine dose-dependently attenuated mechanical allodynia in SNL rats. Pre-treatment with intrathecal SB-269970 reversed the antiallodynic effect of Tianeptine. Both GAD65 expression and the GABA concentration in the spinal cord were decreased in neuropathic rats but were increased by Tianeptine. Additionally, 5-HT7 receptor and GAD65 were co-localized in the spinal cord. Intrathecal Tianeptine reduces neuropathic pain. 5-HT7 receptor of the GABAergic interneurons together with GAD65 plays a role in the activity of Tianeptine at the spinal cord level.

  • the antiallodynic effect of intrathecal Tianeptine is exerted by increased serotonin and norepinephrine in the spinal dorsal horn
    Neuroscience Letters, 2014
    Co-Authors: Hyung Gon Lee, Jeong Il Choi, Myung Ha Yoon, Hideaki Obata, Shigeru Saito, Woong Mo Kim
    Abstract:

    The purpose of this study was to validate the effects of Tianeptine on serotonergic and noradrenergic neurotransmission in a rat model of neuropathic pain. Neuropathic pain was induced by ligating the L5 and L6 spinal nerves in male Sprague-Dawley rats, and mechanical allodynia was assessed using von Frey filaments. The effects of intrathecally administered Tianeptine on mechanical allodynia were assessed. Dihydroergocristine or yohimbine, a serotonergic or α-2 adrenergic receptor antagonists, respectively, were intrathecally administered 10min before Tianeptine to investigate its mechanism of action. Additionally microdialysis studies were performed to measure the extracellular levels of serotonin (5-HT) and norepinephrine (NE) in the spinal dorsal horn following Tianeptine administration. Intrathecal Tianeptine significantly increased the paw withdrawal thresholds in a dose-dependent manner and the antiallodynic effect was antagonized by dihydroergocristine and yohimbine. Microdialysis studies revealed that Tianeptine increased the levels of 5-HT and NE in the spinal dorsal horn. These findings suggest that Tianeptine may be effective for the management of neuropathic pain and that its analgesic mechanism is exerted by increased levels of 5-HT and NE in the synaptic cleft at the spinal level.

  • The analgesic activity of intrathecal Tianeptine, an atypical antidepressant, in a rat model of inflammatory pain.
    Anesthesia and analgesia, 2012
    Co-Authors: Woong Mo Kim, Seong Heon Lee, Hye Jin Jeong, Hyung Gon Lee, Jeong Il Choi, Myung Ha Yoon
    Abstract:

    BACKGROUND Tianeptine is an atypical antidepressant that exhibits structural similarities to the tricyclic antidepressants but has distinct neurochemical properties. We evaluated the antinociceptive activity of Tianeptine and its mechanism of action regarding serotonergic and adrenergic transmission at the spinal level. METHODS The effects of intrathecally administered Tianeptine and DUP-697 (a cyclooxygenase-2 inhibitor) were examined on flinching behavior evoked by intraplantar formalin injection, and their interaction was characterized using isobolographic analysis. Dihydroergocristine, prazosin, or yohimbine-which are serotonergic, α-1, and α-2 adrenergic receptor antagonists, respectively-were intrathecally administered 10 minutes before Tianeptine to investigate its mechanism of action. RESULTS Intrathecally administered Tianeptine and DUP-697 reduced the flinching response evoked by formalin injection during phases 1 and 2 in an additive fashion. Prazosin and yohimbine attenuated the antinociceptive effect of intrathecal Tianeptine during both phases of the formalin test. Dihydroergocristine reversed the antinociception of Tianeptine during phase 2, but not during phase 1. CONCLUSIONS Intrathecally administered Tianeptine effectively relieved inflammatory pain in rats. The serotonergic system is related to the activity of Tianeptine for facilitated pain at the spinal level. Adrenergic transmission is also involved in Tianeptine-induced analgesia for both facilitated and acute pain. The combination of Tianeptine and cyclooxygenase-2 inhibitor may provide additional benefits for the management of inflammatory pain.

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  • Tianeptine
    CNS Drugs, 2001
    Co-Authors: Antona J. Wagstaff, Douglas Ormrod, Caroline M. Spencer
    Abstract:

    Tianeptine is an antidepressant agent with a novel neurochemical profile. It increases serotonin (5-hydroxytryptamine; 5-HT) uptake in the brain (in contrast with most antidepressant agents) and reduces stress-induced atrophy of neuronal dendrites. Like the selective serotonin reuptake inhibitors (SSRIs) and in contrast with most tricyclic antidepressant agents, Tianeptine does not appear to be associated with adverse cognitive, psychomotor, sleep, cardiovascular or bodyweight effects and has a low propensity for abuse. Tianeptine has a comparatively favourable pharmacokinetic profile. It is not subject to first-pass hepatic metabolism, has high bioavailability and limited distribution, and is rapidly eliminated. While this offers advantages for Tianeptine over the tricyclic antidepressant agents in terms of dose titration, treatment changes and potential drug interactions, its rapid elimination makes adherence to dosage schedules more important. Tianeptine differs from most antidepressants in that it is not primarily metabolised by the hepatic cytochrome P450 system, indicating less likelihood of drug-drug interactions; this is of particular interest for elderly patients. Tianeptine, in dosages of 25 to 50 mg/day, has been investigated in patients with major depression, depressed bipolar disorder, dysthymia or adjustment disorder. It has equivalent antidepressant efficacy to several classical antidepressant agents (amitriptyline, clomipramine, imipramine, mianserin) and the SSRIs fluoxetine (in most patients), paroxetine and sertraline. Comparison with maprotiline indicated superior efficacy for Tianeptine but dothiepin appeared superior in another study. Extended treatment with Tianeptine decreases the incidence of relapse/ recurrence of depression. Tianeptine appears to be as effective as fluoxetine, sertraline, amitriptyline, clomipramine and mianserin and more effective than maprotiline in improving associated anxiety in patients with depressive disorders. Depression and anxiety symptoms in alcohol dependant patients also respond well to Tianeptine. The adverse effects associated with Tianeptine are similar in many respects to those of the SSRIs and minimal in comparison with the tricyclic antidepressants. The most common adverse effects are nausea, constipation, abdominal pain, headache, dizziness and changes in dreaming. Anticholinergic effects occur less often with Tianeptine than with tricyclic agents. Hepatoxicity is rare. The dosage should be decreased in elderly patients and those with severe renal failure, but adjustment is not necessary in patients with alcoholism or hepatic impairment, or those undergoing haemodialysis. Conclusions : The antidepressant efficacy and favourable tolerability and pharmacokinetic profiles of Tianeptine in patients with depression, including those with associated anxiety, have been proven; the data indicate that it may have additional potential in specific subgroups of depressed patients such as the elderly and those with chronic alcoholism. Pharmacodynamic Profile Tianeptine is an antidepressant drug with structural similarities to the tricyclic antidepressant agents but a novel neurochemical profile. The main difference between this and other antidepressant agents is its action on serotonin (5-hydroxytryptamine; 5-HT): Tianeptine increases serotonin uptake in the brain and platelets. The behavioural (in animal models) and physical (atrophy of neuronal dendrites) effects of stress on the hypothalamic-pituitary-adrenal axis are reduced by Tianeptine, and levels of noradrenaline (norepinephrine) and dopamine are indirectly increased in several regions of the brain. The main metabolite (MC_5; pentanoic acid) has some minor antidepressant activity. Clinical studies indicate that, unlike tricyclic antidepressant agents, Tianeptine is not associated with adverse effects on driving skills or cognitive function (such as sedation or impaired memory) and may have slight activating properties, particularly in aspects of attention. Similarly, there appear to be few effects on sleep in healthy volunteers or patients with concurrent depression and alcoholism after withdrawal of alcohol. Like the selective serotonin reuptake inhibitors (SSRIs) and in contrast with the tricyclic antidepressants, Tianeptine has a favourable cardiovascular profile in healthy volunteers and patients with depression, with and without concurrent alcoholism. Pharmacokinetic Profile The maximum plasma concentration (C_max) of Tianeptine was 0.3 mg/L, time to C_max (t_max) was 0.94 hours and bioavailability was 99% after a single oral dose of Tianeptine 12.5mg in healthy volunteers. The drug is not subject to first-pass hepatic metabolism. Food decreases C_max and prolongs t_max but does not affect the extent of absorption. Although the distribution of Tianeptine is rapid (distribution half-life 0.7 hours) protein binding is high (95%), resulting in alow volume of distribution (0.5 to 0.8 L/kg) in healthy volunteers. Tianeptine undergoes extensive extrarenal metabolism and has a short elimination half-life (t1/2β; 2.5 hours in healthy volunteers). The major metabolic pathway of Tianeptine is a 2-step β-oxidation process of the aliphatic chain, leading to the formation of 2 main metabolites MC_5 and MC_3 (propionic acid). MC_3 is the main metabolite of Tianeptine in urine and MC_5 is the main metabolite in plasma. Tianeptine does not undergo cytochrome P450—dependent biotransformation to any significant extent, thus reducing the risk of drug interactions. The pharmacokinetic profile of a single dose of Tianeptine in adults with depression appears similar to that in healthy adult volunteers, although the t_max and t12β were prolonged. Steady-state pharmacokinetics were achieved after 1 month of treatment with Tianeptine 37.5 mg/day and were maintained over 3 months. Most values were similar to those seen in depressed patients after a single dose, but the area under the concentration-time curve (AUC) was significantly greater after extended treatment (1.3 vs 1 mg/L · h; p < 0.03). The pharmacokinetic profile of oral Tianeptine was not significantly altered in patients with compromised renal function. However, the t1/2β and AUC of the MC_5 metabolite were increased compared with controls, suggesting a decreased clearance of this metabolite in patients with renal failure. Although bioavailability of Tianeptine remained high (85%) in elderly individuals, clearance was lower than that reported in younger individuals. The pharmacokinetic profile of Tianeptine is not altered in patients with alcoholic cirrhosis and depression. Therapeutic Efficacy The clinical antidepressant efficacy of Tianeptine 25 to 50 mg/day has been proven against placebo in patients aged 18 to 60 years with major depression (single episode or recurrent) or bipolar disorder (depressed) in 2 double-blind trials. Initial improvements were seen after 7 days, and improvement continued throughout the 6 weeks of study. Improvements from baseline on the Montgomery-Åsberg Depression Rating Scale (MÅDRS) were 44 and 54% with Tianeptine and 28 and 38% in placebo recipients (p < 0.05 and p < 0.01, respectively). Tianeptine 25 to 37.5 mg/day for 1.5 to 3 months had equivalent antidepressant efficacy to fluoxetine 20 mg/day in patients with major depression (single episode or recurrent), bipolar disorder (depressed) or dysthymic disorder in several studies. However, although equivalence was noted in several parameters in elderly patients receiving Tianeptine or fluoxetine in one study, reductions from baseline in the MÅDRS scores were statistically significantly greater in those receiving fluoxetine (62 vs 51% in fluoxetine and Tianeptine recipients, respectively, compared with 50 vs 51%, respectively, in a study in patients aged 18 to 65 years which used this assessment tool). The antidepressant efficacy of Tianeptine 37.5 mg/day (reduction in MÅDRS score of 56%) was equivalent to that of sertraline 50 mg/day (reduction of 54%) after 1.5 months in patients with major depression or bipolar disorder. A study published only in abstract form indicates that Tianeptine 37.5 mg/day has similar efficacy to paroxetine 20 mg/day for 3 months (reductions in MÅDRS scores of 62 and 61%, respectively). In comparative studies with tricyclic or tetracyclic antidepressant agents, the antidepressant efficacy of Tianeptine 25 to 50 mg/day (44 to 64% reduction in MÅDRS scores) was equivalent to that of amitriptyline 50 to 100 mg/day for 1 or 1.5 months (53 and 69%), clomipramine 100 to 200 mg/day for 6 months (55%), imipramine 100 to 200 mg/day for 1.5 months (41%) and mianserin 30 to 80 mg/day for 1.5 or 6 months (48 and 50%) in patients with major depression (single episode or recurrent), bipolar disorder (depressed), dysthymic disorder or adjustment disorder. Tianeptine 37.5 mg/day (56% reduction in MÅDRS score) was more effective than maprotiline 75 mg/day for 2 months (47%) in a study of perimenopausal women with anxio-depressive symptoms and less effective than dothiepin 150 to 225 mg/day for 1 month in a small study of patients with depressive disorders. The anxiolytic efficacy of Tianeptine was assessed in several comparative trials of patients with concurrent depression and anxiety. Tianeptine 25 to 50 mg/day appears to have equivalent anxiolytic efficacy to fluoxetine 20 mg/day for 1.5 to 3 months, sertraline 50 mg/day for 1.5 months, amitriptyline 50 to 100 mg/day for 1 to 1.5 months, clomipramine 100 to 200 mg/day for 6 months and mianserin 30 to 80 mg/day for 1.5 or 6 months. Superior anxiolytic efficacy was attributed to Tianeptine over maprotiline 75 mg/day for 2 months in a study of perimenopausal women with anxio-depressive symptoms. Tianeptine 25 to 50 mg/day is effective as long term treatment to prevent relapse or recurrence in patients with depression. It also appears to have potential for use in specific subgroups. The efficacy of Tianeptine 25 or 37.5 mg/day was equivalent to that of mianserin 30 mg/day and similar in some but not all parameters to that of fluoxetine 20 mg/day in elderly patients. Patients with chronic alcoholism often develop depression, especially on withdrawal of alcohol. Assessments of antidepressant and anxiolytic efficacy for Tianeptine 37.5 mg/day were equivalent to those for amitriptyline 75 mg/day over 1 to 2 months in this patient population. Improvements in quality-of-life scales with depressed Tianeptine recipients were similar to those in patients receiving mianserin or fluoxetine. Tolerability The adverse effect profile of Tianeptine appears to be similar in many respects to that of the SSRIs, in that cognitive, cardiovascular and bodyweight effects are minimal in comparison with the classical tricyclic antidepressant agents. In fact, in comparisons with placebo, the only symptom appearing significantly more often with Tianeptine was headache. In clinical trials, the most common adverse effects seen in patients with depressive disorders receiving Tianeptine were gastrointestinal (nausea, constipation, abdominal pain) or CNS (headache, dizziness, change in dreaming) disturbances, which decreased in frequency with continued treatment. Effects such as dry mouth, hot flushes, somnolence, vertigo, gastrointestinal disturbances, increased bodyweight, increased heart rate and tremor occurred significantly more often in patients receiving tri- or tetracyclic antidepressant agents than in those receiving Tianeptine. In studies comparing Tianeptine with fluoxetine, paroxetine or sertraline, in contrast, the incidence of most adverse effects was similar; nausea, tremor and palpitations tended to occur more often in fluoxetine recipients, and the incidence of dry mouth tended to be higher in Tianeptine recipients. Tianeptine has only rarely been associated with hepatoxicity. The favourable tolerability profile of Tianeptine has been confirmed in long term trials, and in elderly patients (including those with cardiovascular pathology before treatment initiation) and patients with alcoholism. The low incidence of anticholinergic and neurological effects associated with Tianeptine is of particular importance in these subgroups, who have increased sensitivity to the adverse effects of psychotropic drugs. Tianeptine has a wide therapeutic margin; overdosage has been associated with only minor transient adverse effects. Dosage and Administration The recommended dosage of Tianeptine in patients with depression is 37.5 mg/day orally in 3 divided doses, with meals. The dosage should be reduced in elderly patients and patients with severe renal failure, but dosage reduction is not required in patients with chronic alcoholism or hepatic impairment or those undergoing haemodialysis. The dosage of Tianeptine should be reduced over 1 to 2 weeks when discontinuing treatment, although there is little evidence of psychological or physical dependence on the drug. As with other antidepressants, Tianeptine is contraindicated in patients taking monoamine oxidase inhibitors.

  • Tianeptine: a review of its use in depressive disorders.
    CNS drugs, 2001
    Co-Authors: Antona J. Wagstaff, Douglas Ormrod, Caroline M. Spencer
    Abstract:

    UNLABELLED Tianeptine is an antidepressant agent with a novel neurochemical profile. It increases serotonin (5-hydroxytryptamine; 5-HT) uptake in the brain (in contrast with most antidepressant agents) and reduces stress-induced atrophy of neuronal dendrites. Like the selective serotonin reuptake inhibitors (SSRIs) and in contrast with most tricyclic antidepressant agents, Tianeptine does not appear to be associated with adverse cognitive, psychomotor, sleep, cardiovascular or bodyweight effects and has a low propensity for abuse. Tianeptine has a comparatively favourable pharmacokinetic profile. It is not subject to first-pass hepatic metabolism, has high bioavailability and limited distribution, and is rapidly eliminated. While this offers advantages for Tianeptine over the tricyclic antidepressant agents in terms of dose titration, treatment changes and potential drug interactions, its rapid elimination makes adherence to dosage schedules more important. Tianeptine differs from most antidepressants in that it is not primarily metabolised by the hepatic cytochrome P450 system, indicating less likelihood of drug-drug interactions; this is of particular interest for elderly patients. Tianeptine, in dosages of 25 to 50 mg/day, has been investigated in patients with major depression, depressed bipolar disorder, dysthymia or adjustment disorder. It has equivalent antidepressant efficacy to several classical antidepressant agents (amitriptyline, clomipramine, imipramine, mianserin) and the SSRIs fluoxetine (in most patients), paroxetine and sertraline. Comparison with maprotiline indicated superior efficacy for Tianeptine but dothiepin appeared superior in another study. Extended treatment with Tianeptine decreases the incidence of relapse/recurrence of depression. Tianeptine appears to be as effective as fluoxetine, sertraline, amitriptyline, clomipramine and mianserin and more effective than maprotiline in improving associated anxiety in patients with depressive disorders. Depression and anxiety symptoms in alcohol dependant patients also respond well to Tianeptine. The adverse effects associated with Tianeptine are similar in many respects to those of the SSRIs and minimal in comparison with the tricyclic antidepressants. The most common adverse effects are nausea, constipation, abdominal pain, headache, dizziness and changes in dreaming. Anticholinergic effects occur less often with Tianeptine than with tricyclic agents. Hepatoxicity is rare. The dosage should be decreased in elderly patients and those with severe renal failure, but adjustment is not necessary in patients with alcoholism or hepatic impairment, or those undergoing haemodialysis. CONCLUSIONS The antidepressant efficacy and favourable tolerability and pharmacokinetic profiles of Tianeptine in patients with depression, including those with associated anxiety, have been proven; the data indicate that it may have additional potential in specific subgroups of depressed patients such as the elderly and those with chronic alcoholism.