Posted by Shawn. T. on August 1, 2002, at 4:38:09
Perhaps my neurobiological critique of SSRI's was not all that comprehensible to some. I believe that tianeptine, a selective serotonin reuptake enhancer, illustrates my point nicely. I am a firm believer in the inadequacy of SSRI and TCA antidepressant treatments. I sometimes wonder about the US health care system; my world often seems to be quite an irrational place.
http://users.skynet.be/crc.mh/fibromyalgia.html
-I still don't get fibromyalgia, so I'll just post that link.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8668756&dopt=Abstract
"There is little awareness in the United States and other English-speaking countries of a number of novel antidepressant drugs that have recently
been developed and marketed in France."http://www.pnas.org/cgi/content/full/98/22/12796
"The results of this study show that chronic psychosocial stress decreases the in vivo concentrations of cerebral metabolites, the proliferation rate of the granule precursor cells in the dentate gyrus. Both of these alterations can be prevented by treating the stressed animals with the antidepressant tianeptine, which also increased hippocampal volume above the nonsignificant decrease found in stressed animals."
"As revealed by in vivo measurements of brain metabolites with quantitative proton MRS, stress-induced metabolic changes were prevented by tianeptine. These findings rely on the ability to determine in vivo metabolite concentrations rather than ratios thereof. In fact, concomitant reductions of NAA, Cho, and Cr would have escaped detection if the study had been based on mere alterations of metabolite ratios. This approach might explain why the use of metabolite ratios in clinical proton MRS studies of depressed subjects led to conflicting results in frontal cortex and basal ganglia."
"The present data show that stress-induced alterations in brain metabolism, hippocampal volume, and cell proliferation are counteracted by tianeptine treatment that started 7 days after the onset of psychosocial stress. Thus, these findings provide experimental evidence for recent theories that impairments of brain structural plasticity are important features of depressive illness and suggest that pharmacological treatments should be sought to reverse structural changes in brain."
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1356358&dopt=Abstract
"Single high doses, post-restraint, of 8-OH-DPAT, gepirone (5-HT agonists), and tianeptine normalised open field activity, whereas desipramine, chlordiazepoxide, and diazepam did not. It is of considerable interest that tianeptine decreased the availability of 5-HT to receptors."
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1389026&dopt=Abstract
"Tianeptine does not induce sleep disorders, anticholinergic effects, or modifications of cardiovascular variables or biological parameters (renal, haematological, or hepatic). After the end of treatment, the only signs of withdrawal have been some disturbances of sleep."
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1407480&dopt=Abstract
"With regard to the clinical tolerance of tianeptine, somatic complaints were rarely reported and adverse events necessitating premature termination of treatment (4.8% of included patients) were without clinical severity. Cardiovascular, haematologic, hepatic and biochemical safety were verified. No signs of dependence and no specific withdrawal symptoms were found after discontinuation of treatment."
"There was a significant decrease in the Montgomery-Asberg Depression Rating Scale score in both groups (from 28.9 at baseline to 11 at endpoint in the tianeptine group, and from 29.6 to 11.6 in the paroxetine group) after 3 months of treatment."
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8149980&dopt=Abstract
"The effects of acute and chronic administration of tianeptine, a novel antidepressant agent, on the hypothalamo-pituitary-adrenal axis were studied in the adult male rat. A single injection of tianeptine did not alter the activity of the hypothalamo-pituitary-adrenal axis. In contrast, chronic administration of tianeptine (10 mg/kg twice a day for 15 days) induced a significant decrease in the concentration of corticotropin-releasing factor (CRF) in the hypothalamus and adrenocorticotropin (ACTH) in the anterior lobe of the pituitary. Chronic tianeptine treatment did not modify CRF levels in the cerebral cortex and hippocampus, and did not alter alpha-melanocyte-stimulating hormone and beta-endorphin levels in the neurointermediate lobe of the pituitary. Using the in situ hybridization technique, we observed that chronic dministration of tianeptine did not modify CRF mRNA levels in the paraventricular nucleus of the hypothalamus. The effect of chronic tianeptine treatment on the neuroendocrine response to stress was also
investigated. Tube restraint stress for 30 min induced a significant depletion of hypothalamic CRF and a substantial increase of plasma ACTH and corticosterone. Tianeptine abolished the stress-induced reduction of hypothalamic CRF concentration and markedly reduced the stress-induced increase in plasma ACTH and corticosterone levels. Taken together, these results suggest that tianeptine acts primarily at the level of the hypothalamus: (1) in unstressed rats, tianeptine reduces hypothalamic CRF and pituitary ACTH contents; (2) in stressed animals, tianeptine attenuates the activation of the hypothalamo-pituitary-adrenal axis."http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7510316&dopt=Abstract
"However, long-term treatment does not result in a decreased plasma 5-HT, as might be expected from the acute effects of the drug."
"Results showed that post-training tianeptine injection enhanced memory consolidation in an autoshaping Pavlovian/instrumental learning task,
which has been useful to detect changes on memory formation elicited by drugs or aging."http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1389024&dopt=Abstract
"Seven subjects who attempted suicide by tianeptine overdose had favourable outcomes, in spite of also taking other psychotropic drugs or alcohol. No evidence of tolerance or withdrawal symptoms was seen after treatment was stopped. These results suggest that tianeptine has the potential to provide safe antidepressant activity in both the acute and chronic phases of treatment."
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1340807&dopt=Abstract
"In term of safety, tianeptine is equivalent to a placebo if we consider somatic complaints expressed by the patients, global improvement evaluated by the patient and the investigator, weight and blood pressure."
"Acute inescapable stress dramatically affects the inducibility of plasticity at glutamatergic synapses in the intact hippocampus. The present study examined the involvement of serotonergic mechanisms in mediating and modulating the block of long-term potentiation (LTP) in the CA1 area of anesthetized rats after exposure to an elevated platform stress. Fluoxetine and fenfluramine, agents that raise hippocampal extracellular 5-HT concentration, blocked the induction of LTP in nonstressed animals, thus mimicking the effect of stress. In contrast, (+/-)-tianeptine, a drug that decreases 5-HT levels, had no effect on LTP induction in nonstressed animals. Remarkably, (+/-) administration of tianeptine after the stress rapidly overcame the block of LTP induction without affecting baseline excitatory transmission."
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1389022&dopt=Abstract
"New concepts point to a special role of the hippocampus, a nexus of cognition and emotion, in the feedback actions of adrenal steroids during the diurnal rhythm, and in response to stress."
"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."
"Extended treatment with tianeptine decreases the incidence of relapse/recurrence of depression."
"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."
"Chronic, but not acute, treatment with tianeptine attenuated the behavioral signs of sickness behavior induced by peripheral, but not central, LPS or IL-1beta. CONCLUSIONS: This work, which is the first in vivo study assessing the effect of an antidepressant on centrally induced immune activation, shows a clear dissociation between peripheral and central cytokine effects, and suggests a peripheral site of action of tianeptine. It also provides the first evidence that the protective effects of classical antidepressants on LPS-induced sickness behavior extend to an atypical antidepressant, and that the protective effect of antidepressants also applies to IL-1beta."
"The study revealed an equal efficiency of the drug in comorbid depressive, anxious and autonomic disorders as well as a good tolerance."
"Nowadays, we talk more and more often about sexual disorders, and depression in one of the possible etiologies of them. Depression could lead to sexual disorders or induce them indirectly. Paradoxically, depression treatments, such as tricyclic antidepressant or SSRI could induce this kind of disorder. Tianeptine, the only molecule representative of this pharmacological class, has proved its good acceptability on the libido, as shown by the results of a meta-analysis. The respect of the sexual function is essential to obtain a good observance of the antidepressant treatment."
"Results confirmed that stress [in rats] produced CA3 dendritic atrophy and tianeptine prevented it."
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8319748&dopt=Abstract
"The effects of various doses of tianeptine on extracellular concentrations of dopamine were studied in the frontal cortex and nucleus accumbens of the rat. At 5 and 10 mg/kg intraperitoneally, tianeptine raised extracellular dopamine in the nucleus accumbens but only the higher dose caused a significant increase in the frontal cortex."
"Both repeated stress and corticosterone administration induce remodeling of apical dendrites of hippocampal CA3 pyramidal neurons. Circulating glucocorticoids are involved in the mechanism that produces atrophy, along with excitatory amino acids and serotonin (5-hydroxytryptamine, 5-HT). We used 5-HT-related antidepressants and a benzodiazepine in order to explore indirectly the role of serotonin and GABA(A)-benzodiazepine receptors in the stress-induced structural changes visualized by the Golgi impregnation of the rat hippocampus. The 5-HT reuptake enhancer (+/-)-tianeptine prevented the dendritic atrophy caused by repeated restraint stress in a non-stereoselective fashion and two 5-HT reuptake antagonists, fluoxetine and fluvoxamine, failed to block dendritic atrophy. Tianeptine also functions as a therapeutic tool since it reversed the already established hippocampal atrophy caused by treatment with corticosterone for 3 weeks."
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9807972&dopt=Abstract
"Studies have shown that levels of free serotonin in plasma are increased in symptomatic patients with asthma. In addition, the concentration of free serotonin in symptomatic patients with asthma correlates positively with clinical status and negatively with pulmonary function. Thus, reducing the concentration of free serotonin in plasma might be useful in treating patients with asthma. We studied the effectiveness of tianeptine in treating patients with asthma. Tianeptine is the only drug known to be able to reduce levels of free serotonin in plasma and to enhance uptake by platelets. In this study, 69 children with asthma were assigned in randomized fashion to receive tianeptine and/or placebo in a double-blind crossover trial that lasted 52 weeks. Tianeptine provoked a dramatic and sudden decrease in both clinical rating and free serotonin plasma levels and an increase in pulmonary function."
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9617981&dopt=Abstract
"Responders had a lower pretreatment platelet 5-HT (530 +/- 36 vs. 664 +/- 50 ng/10(9) platelets, p < 0.03; N = 44 and 39, respectively). Patients with a platelet 5-HT concentration above 800 ng/10(9) platelets had a lower response rate than those below this value (p < 0.003). This difference was maximal in the subgroup of patients treated with 5-HT uptake inhibitors (N = 49). In this subgroup, the response rates of patients with 5-HT concentrations below and above the cutoff point were, respectively, 70% and 17% (p < 0.001). A pretreatment platelet 5-HT value above 800 ng/10(9) platelets had a predictive value for a negative response of 92%. These results suggest the presence of biochemical differences in the peripheral serotonergic system between melancholic and nonmelancholic patients. The inverse relationship between the pretreatment platelet 5-HT content and clinical response may be useful in the investigation of the relationship between the 5-HT system and antidepressant response."
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9608604&dopt=Abstract
"1.Depression is frequent in the elderly but difficult both to diagnose and treat due to a number of distinctive features. 2. Tianeptine is a novel antidepressant with a reverse mode of action to that of the selective serotonin reuptake inhibitors yet with proven efficacy and safety. 3. 63 elderly patients (mean age:68.8 years; range:65-80 years) with depressive symptoms (major depression:55.6%; dysthymia: 44.4%) were included in a 3-month open multicenter study with tianeptine (25 mg daily). 4. 43 patients (68.2%) completed the study. There were no drop-outs due to side-effects. Total Montgomery and Asberg Depression Rating Scale scores were significantly decreased (p < 0.01) on day 14, with a response rate of 76.7%. 5. Improvements were also observed in anxiety and cognitive performance. Side-effects were seen in only 11.7% of patients, with no changes in laboratory or ancillary safety parameters. Tianeptine is thus effective and well tolerated in this category of patient."
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9405961&dopt=Abstract
"Altogether, tianeptine was shown to be an effective and safe medication for the treatment of major depressive episodes."
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9405958&dopt=Abstract
"Tianeptine treatment (10 mg/kg/day) prevented the stress-induced atrophy of dendrites of CA3 pycamidal neurons, whereas neither fluoxetine (10
mg/kg/day) nor desipramine (10 mg/kg/day) had any effect. Tianeptine treatment also prevented the stress-induced impairment of radial maze learning. Because corticosterone- and stress-induced atrophy of CA3 dendrites is also blocked by phenytoin, an inhibitor of excitatory amino
acid release and actions, these results suggest that serotonin released by stress or corticosterone may interact pre- or post-synaptically with glutamate released by stress or corticosterone, and that the final common path may involve interactive effects between serotonin and glutamate receptors on the dendrites of CA3 neurons innervated by mossy fibers from the dentate gyrus."http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9172969&dopt=Abstract
"These data support the use of tianeptine in the long term treatment of unipolar major recurrent depression. Relapses and recurrences were 2 to 3
times less frequent with tianeptine as compared to placebo. Furthermore, prolonged treatment with tianeptine appeared to be very well tolerated."http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9018020&dopt=Abstract
"The results confirmed the efficacy of tianeptine (mean dosage: 37.5 mg/day) in the treatment of Major Depression and Bipolar Disorder, Depressed, with or without melancholia, compared to placebo. Tianeptine's acceptability did not differ from that of placebo. For adverse events, a higher incidence of headaches was found with tianeptine."
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8930312&dopt=Abstract
"After tianeptine injection the 5-HIAA signal increased by about 60%."
"Administration of sertraline or clomipramine reduced the 5-HIAA signal by about 30-50%."
-I will explain the importance of these differences sometime else.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8685201&dopt=Abstract
"These findings reconfirm the antidepressive efficacy, acceptability and safety of tianeptine. They also confirm the anxiolytic aspect associated with the antidepressive effect of tianeptine without any sedative effect. Tianeptine is particularly well indicated in the treatment of depression in elderly or very elderly subjects."
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7774514&dopt=Abstract
"Progressive therapeutic improvements have been observed with up to 1 year of tianeptine treatment, and long term therapy may reduce the rate of relapse or recurrence. Tianeptine is effective in the treatment of depression in elderly and post-alcohol-withdrawal patient subgroups. Tianeptine was more effective in reducing psychic anxiety than placebo in patients with major depression or depressed bipolar disorder with or without melancholia. The overall anxiolytic properties of tianeptine in patients with coexisting depression and anxiety appear to be similar to those of amitriptyline, imipramine and fluoxetine and may be superior to those of maprotiline, although submaximal dosages of amitriptyline and maprotiline were used."
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8180832&dopt=Abstract
"Restraint stress, 6 h/day for 21 days, caused an impairment, during acquisition, of the performance of a spatial memory task, the eight-arm radial maze. The impairment was reversible, temporally limited and blocked by phenytoin, a blocker of excitatory amino acid action, or tianeptine, an antidepressant, which lowers extracellular serotonin."
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7800169&dopt=Abstract
"Three hundred in- and outpatients suffering from depressive disorder, as diagnosed using DSM-III criteria were treated for 6 weeks under double-blind conditions in a multicenter controlled study of tianeptine vs. amitriptyline. Both groups presented steady improvement of depressive
syndrome from day 7 up to the end of the treatment, as shown by all evaluation scales: HDRS, SAD, CGI. Furthermore, anxiety linked to the depressive syndrome decreased equally in both groups, as shown by the HARS measurements. In addition to the improvement of mood, the tianeptine-treated patients presented less somatic complaints and side effects when compared to the reference antidepressant. These results confirm previous findings that tianeptine is an effective antidepressant with a lower side effect profile than amitriptyline."http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8243560&dopt=Abstract
"The evidence that treatments reducing extrasynaptic 5-HT, by increasing its reuptake (tianeptine) or reducing its release (buspirone) in innervated regions are able to modify the stress-induced decrease in 5-HT uptake, further confirms the importance of serotonin in the mechanisms mediating neurochemical responses to stress."
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8415473&dopt=Abstract
"This study was conducted to evaluate the effectiveness and acceptability of Tianeptine (T) versus Maprotiline (M) in the management of anxiodepressive disorders in menopausal and premenopausal women."
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1630590&dopt=Abstract
"The results show that tianeptine increased the extracellular concentrations of dopamine more in the nucleus accumbens than in striatum. The effect on the output of DA in the nucleus accumbens could be involved in the antidepressant activity of tianeptine."
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1389023&dopt=Abstract
"On iontophoretic injection into CA1 pyramidal cells, tianeptine shortens the period of neuronal hypoactivity caused by GABA or 5-HT, whereas other tricyclics prolong it, and it enhances attention, learning, and memory in laboratory animals, while classical tricyclics have opposite effects. However, the relationships between these effects of tianeptine in animal experiments and their relevance to clinical findings remain to be determined."
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1580922&dopt=Abstract
"The effect on ethanol intake of the selective 5-HT uptake enhancer tianeptine was examined in rats and compared with that of fluoxetine, a specific 5-HT uptake inhibitor. Both treatments significantly decreased ethanol intake (54% by tianeptine and 57% by fluoxetine). Fluoxetine also decreased food intake whereas tianeptine did not."
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1836619&dopt=Abstract
"The three other studies were performed as open, long-term trials (up to one-year treatment) in large populations of patients (more than 3,300 patients). The findings show that tianeptine does not modify heart rate, blood pressure, conduction or ventricular function. Tianeptine was well tolerated in depressed patients and induced no significant changes at the current dosage in treatment periods from three-months to one-year even in elderly patients, patients with cardiovascular abnormalities or alcoholic patients. Fewer cases of orthostatic hypotension were observed than with other antidepressants. Suicide attempts with tianeptine overdosage did not lead to death due to cardiovascular complications."
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1836617&dopt=Abstract
"An open multicenter study of the efficacy and acceptability of tianeptine, a new antidepressant structurally related to tricyclic antidepressants, was conducted by 36 gerontologists. There were 228 patients in the study; 140 were treated for one year. The patients' overall MADRS score started to decrease on day 14 and continued to decline to month 3. An improvement in depression was again observed near the end of the treatment period from month 9 to month 12. This pattern of improvement was also found with the HARS, the first item on the CGI scale and the Zung self-evaluation scale. These findings demonstrate the beneficial effect of long-term treatment in depressed elderly patients. Ten patients (4.4 percent) dropped out because of side effects: mainly drowsiness, anxiety or gastrointestinal disorders. The benefit/risk ratio (CGI, item 3), an expression of treatment effectiveness and acceptability, was very satisfactory even in these elderly patients. Regularly performed laboratory tests and clinical examinations (including weight and blood pressure) revealed no significant changes. Finally, somatic disorders, essentially cardiovascular and neurological diseases often ocurring in depressed patients, remained remarkably quiescent throughout the entire treatment period."
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1836611&dopt=Abstract
"But glucocorticoids can compromise immune defence systems leading to nerve cell destruction in the hippocampus. Certain types of stress can also lead to loss of neurons in the hippocampus, one of the most stress susceptible regions. Tianeptine decreases morning hypersecretion of glucocorticoids induced by a contention (1 hour) stress. Moreover, tianeptine inhibits the decrease in the number of type I glucocorticoid receptors induced by isolation stress. Tianeptine inhibits the increase in the tryrosine hydroxylase messenger RNA, also induced by isolation stress. Finally, tianeptine tends to increase dendrite ramifications of the hippocampus' pyramidal neurons (CA3) in isolated rats, thus counteracting the effect of isolation stress."
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3322802&dopt=Abstract
"During this study in subjects particularly predisposed to the abuse of psychoactive drugs, tianeptine has not induced anything suggesting the possibility of drug abuse or tolerance."
el fin.
poster:Shawn. T.
thread:114758
URL: http://www.dr-bob.org/babble/20020731/msgs/114758.html