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.
Anxiety ; Depression ; Glutamic Acid ; Humans ; Neuronal Plasticity ; Thiazepines

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.
Depression ; Depressive Disorder, Major ; Evoked Potentials, Auditory ; Humans ; Serotonin ; Synaptic Transmission ; Thiazepines

AIMTo investigate the effects of omapatrilat (OMA) on endothelin-1-induced proliferation of cardiac fibroblasts (CFs).

METHODSIsolated and cultured CFs from neonatal Sprague-Dawley rats (SD) were randomly divided into 7 groups: (1) Control, (2) ET-1, (3) OMA, (4) ET-1 + OMA 10(-9) mol/L, (5) ET-1 + OMA 10(-8) mol/L, (6) ET-1 + OMA 10(-7) mol/L and (7) ET-1 + OMA 10(-6) mol/L. CFs were counted by MTT assay. Cell cycle distribution was determined with a flow cytometer (FCM). [3H]-Proline incorporation was evaluated by scintillation counting. Nitric oxide (NO) was measured by colorimetry.

RESULTS10(-7) mol/L ET-1 significantly increased A490 value and [3H]-Pro incorporation and decreased NO secretion compared with the control group (P < 0.01). 10(-9)-10(-6) mol/L OMA inhibited the effects of ET-1 on CFs in a concentration-dependent manner (P < 0.01 vs. ET-1). In the ET-1 group, the percentage of cells in the S phase was higher than control, which was inhibited by l0(-6) mol/L OMA (P < 0.01 vs. ET-1 and control).

CONCLUSIONOMA can restrain the proliferation and collagen synthesis of cardiac fibroblasts induced by endothelin-1, and this effect may be partially mediated by NO.

Animals ; Cell Proliferation ; drug effects ; Cells, Cultured ; Collagen ; biosynthesis ; Endothelin-1 ; pharmacology ; Fibroblasts ; cytology ; drug effects ; Myocytes, Cardiac ; cytology ; drug effects ; Nitric Oxide ; metabolism ; Pyridines ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Thiazepines ; pharmacology

OBJECTIVE: The aim of this study was to demonstrate changes of clinical benefit and subjective wellbeing after once-daily extended release quetiapine furmate (quetiapine XR) in patients with schizophrenia. METHODS: In a naturalistic, observational, and multicentric study, 1,494 patients with schizophrenia who switched to quetiapine XR (flexible dosing) due to insufficient efficacy or intolerance were recruited. Clinical Global Impressions-Clinical Benefit (CGI-CB), CGI-Severity (CGI-S), CGI-Improvement (CGI-I) and Subjective Wellbeing under Neuroleptic Treatment Scale (SWN-K) were assessed at baseline and after 8 weeks treatment. We also examined factors related to changes of CGI-CB and SWN-K scores using linear regression analysis. RESULTS: Among 1,494 patients, 1,342 patients (89.8%) completed this study and 1,204 patients (80.6%) without protocol violation were included in the analysis. The mean dose of quetiapine XR was 416.9+/-205.8 mg/day at the initiation and continuously increased to 591.6+/-228.3 mg/day until week 5. At the endpoint, the mean dose of quetiapine XR was 580.24+/-382.24 mg/day. Both CGI-CB and CGI-S scores were significantly decreased after 8 weeks (both p<0.0001) and 745 patients (61.9%) achieved clinical benefit. Mean CGI-I scores were 2.49+/-0.80 and the response rate defined as CGI-I< or =2 was 51.6%. Subjective wellbeing scores were increased after 8 weeks (p<0.0001). Improvements of CGI-CB and subjective wellbeing were associated with quetiapine XR dosages as well as age and baseline scores. CONCLUSION: After switching to quetiapine XR, 61.9% of patients with schizophrenia who had a history of unsatisfactory treatment (efficacy or tolerance) showed clinical benefit and subjective wellbeing was significantly increased. Regarding that dosages of quetiapine XR were associated with improvements of clinical benefit and subjective wellbeing, active treatment strategies with higher dosages of quetiapine XR could be suggested in the real field.
Dibenzothiazepines ; Humans ; Linear Models ; Schizophrenia ; Quetiapine Fumarate

The case of a 77-year-old man with Charles Bonnet syndrome was presented. This patient lost his vision due to glaucoma, and he subsequently developed complex visual hallucinations. No other psychotic symptoms (e.g., delusions, perceptual disturbances) and no evidence of cognitive impairment or neurological diseases were reported. The visual hallucinations disappeared after treatment with quetiapine, an atypical antipsychotic, without any side effects. The visual hallucinations reappeared after quetiapine was discontinued. Treatment with a small dose of quetiapine has been maintained to prevent the exacerbation of symptoms.
Aged ; Delusions ; Dibenzothiazepines ; Glaucoma ; Hallucinations ; Humans ; Vision, Ocular ; Quetiapine Fumarate

OBJECTIVES: The purpose of this study is to examine the efficacy and side effects of quetiapine and haloperidol for the treatment of symptoms of delirium. METHODS: One hundred and seven patients with delirium were recruited and randomly assigned to receive a flexible-dose regimen of quetiapine or haloperidol over 7days and seventy-seven patients completed the study(quetiapine group N=40, haloperidol group N=37). The severity of delirium was assessed by using Memorial Delirium Assessment Scale(MDAS) scores, the psychiatric and behavioral symptoms were assessed by Neurobehavioral Rating Scale(NRS) scores, and the cognitive status was measured by Mini-mental state examination Korean version(MMSE-K) scores. The side effects were measured by Drug Induced Extrapyramidal Symptoms Scale(DIEPSS) scores. RESULTS: MDAS scores significantly improved in both treatment groups. NRS scores also significantly improved in both treatment group, but the group-by-time effect approached significance, likely caused by the greater decrease in scores of the quetiapine group. MMSE-K scores significantly improved only in the quetiapine group. Side effects associated with treatment were not significant in either treatment groups. CONCLUSION: This study suggests that quetiapine is as efficacious as haloperidol in the treatment of delirium. In particular, quetiapine seems to improve psychiatric and behavioral problems of delirium and was more effective than haloperidol in cognitive improvement.
Behavioral Symptoms ; Delirium ; Dibenzothiazepines ; Haloperidol ; Humans ; Prospective Studies ; Quetiapine Fumarate

Hemiballism describes involuntary severe, violent, arrhythmic, rotatory and large amplitude movements of limb from proximal joint. We experienced an elderly stroke patient with hemiballism accompanied dysphagia that persisted for several months severity was evaluated by the Universidade Federal de Minas Gerais Sydenham's chorea rating scale (USCRS) and video fluoroscopic swallowing study (VFSS). In this case, we observed the improvement of hemiballism by conventional rehabilitation therapy and low dose quetiapine. Therefore, we recommend geriatrists considers vthese therapies in elderly patients with hemiballism.
Aged ; Chorea ; Deglutition ; Deglutition Disorders ; Dibenzothiazepines ; Dyskinesias ; Extremities ; Humans ; Joints ; Stroke ; Quetiapine Fumarate

OBJECTIVE: Recommended dosage of quetiapine for patients with schizophrenia is from 150 mg to 750 mg, which is based on randomized controlled study. But there are trends of increasing quetiapine dosage in clinical practice. Therefore, we evaluated the clinical aspect of schizophrenic patients who took quetiapine by naturalistic non-intervention study. METHODS: Schizophrenia outpatients in 88 mental hospitals were selected and 170 psychiatrists evaluated Clinical Global Impressions Scale for Severity (CGI-S) before starting quetiapine medication and CGI-S, Clinical Global Impressions Scale for Improvement (CGI-I), quetiapine dosage and medication compliance at 6 weeks after starting quetiapine medication. Overall efficacy and difference of efficacy between drug-naive patients and medication-switch patients were evaluated. We clustered the patients into 4 groups by using cluster analysis with three variables such as quetiapine dose at week 6, baseline CGI-S, and end-point CGI-S. We compared clinical aspect of each cluster with analysis of variance. RESULTS: 841 patients were enrolled. Efficacy of quetiapine was replicated, and improvement rate defined as CGI-I < or =2 was 55.9%. Drug-naive patients show more improvement in CGI-I than medication-switch patients, and efficacy for patients with insufficient treatment was also reported. Dosage for each clustered group was 25-350 mg, 400-500 mg, 600-700 mg and 750-1,500 mg. 750-1,500 mg group shows more decrease in CGI-S than 400-500 mg group and 600-700 mg group. CONCLUSION: This study suggests that there is a cluster of patients who take more benefits in reducing symptoms and show more compliance in high-dose quetiapine.
Cluster Analysis ; Compliance ; Dibenzothiazepines ; Hospitals, Psychiatric ; Humans ; Medication Adherence ; Outpatients ; Psychiatry ; Schizophrenia ; Quetiapine Fumarate

OBJECTIVE: Bipolar depression has a disabling course and its treatment represents a major challenge. Recently, a randomized, controlled trial of quetiapine monotherapy in patients with bipolar depression showed significant reductions in depressive symptomatology. The purpose of this study was to evaluate the efficacy of quetiapine in bipolar depression in the clinical setting. METHODS: This study was a multi-center, prospective, open-label, observational, 8-week evaluation of the efficacy of quetiapine in patients with bipolar depression. Patients with a DSM-IV-TR diagnosis of bipolar depression (bipolar I disorder, most recent episode depressed and bipolar II disorder, most recent episode depressed) were included and treated with quetiapine. The dose of quetiapine was flexible and concomitant mediations were permitted, by clinical judgment. Clinical improvements were rated with the Clinical Global Impression-Bipolar version (CGI-BP) and Montgomery-Asberg Depression Rating Scale (MADRS) at baseline, week 4, and week 8. RESULTS: A total of 1,193 patients were recruited and 46 (3.9%) patients were dropped from the study. The mean initial dose of quetiapine was 192.3+/-181.9 mg/day and the mean doses at weeks 4 and 8 were 315.2+/-229.7 mg/day and 337.1+/-229.9 mg/day, respectively. CGI-BP and MADRS were significantly improved at weeks 4 and 8, compared with baseline. In addition, improvements at week 8 were greater than at week 4. Subjectively, about 75% of the patients reported therapeutic compliance above 75% at weeks 4 and 8. Seven (0.6%) and four (0.3%) patients showed manic/hypomanic episodes at weeks 4 and 8, respectively. CONCLUSION: This study suggests that quetiapine improves depressive symptoms in bipolar depression, with minimal incidence of manic switching. We suggest that quetiapine could be an effective and safe option in treating bipolar depression.
Bipolar Disorder ; Compliance ; Depression ; Dibenzothiazepines ; Humans ; Incidence ; Judgment ; Prospective Studies ; Quetiapine Fumarate

Skin rash is one of the most common drug-induced side effects. Most of the lesions are usually self-limited and subsided by quitting causal drugs. However, generally, prescriptions involve intake of various drugs, so it is not easy to establish the cause. We report two cases of the patients who had experienced the skin rash in their first manic episode of bipolar I disorder while taking valproate and quetiapine. Their lesions had clearly subsided after quetiapine and valproate were stopped. In clinical practice, polypharmacy is an effective treatment strategy of bipolar disorder. Thus in case of prescribing various drugs, the close observation of drug-induced side effects is needed and drug interaction should be kept in mind.
Bipolar Disorder ; Dibenzothiazepines ; Drug Interactions ; Exanthema ; Humans ; Polypharmacy ; Prescriptions ; Skin ; Valproic Acid ; Quetiapine Fumarate