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Fulltext Tianeptine dependence: a case report

Syed Nabil, Ng, Chong Guan, Rusdi Abd Rashid

Malaysian Journal of Psychiatry, 2018;27(1):0-0.
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Tianeptine is an atypical tricyclic antidepressant that is prescribed mainly for the treatment of depression and anxiety disorder. There have been scattered reported cases of tianeptine dependence and abuse in the literature. We report the case of a 32-year-old gentleman with resistant major depressive disorder that was initially successfully treated with Tianeptine. When his depression relapse due to work-related issue, he step-up his dosages without supervision. He developed tolerance and withdrawal to tianeptine making it difficult for him to stop without help. This case highlights the possibility of tianeptine abuse to its high tolerability and easy access for purchase.

Matched MeSH terms: Antidepressive Agents, Tricyclic
Cost-effectiveness of cyclic antidepressants in a developing country

Razali SM, Hasanah CI

Aust N Z J Psychiatry, 1999 Apr;33(2):283-4.
PMID: 10336231
Matched MeSH terms: Antidepressive Agents, Tricyclic/economics*; Antidepressive Agents, Tricyclic/therapeutic use*
Exploring the potential of tianeptine matrix tablets: Synthesis, physico-chemical characterization and acute toxicity studies

Salam NA, Naeem MA, Malik NS, Riaz M, Shahiq-Uz-Zaman -, Masood-Ur-Rehman -, et al.

Pak J Pharm Sci, 2020 Jan;33(1(Supplementary)):269-279.
PMID: 32122858

The main objective of the present study was to explore the potential of matrix tablets as extended release dosage form of tianeptine, using HMPC K100 as a polymer. HPMC K100 extended the release of the drug from formulation due to the gel-like structure. Direct compression method was adopted to compress the tablets using different concentrations of polymer. Tablets were evaluated for pre-compression and post-compression parameters. Drug release study showed that tablet extends the release of drug with the increasing concentration of polymer. Drug, polymers and tablets were analyzed and/or characterized for compatibility, degradation, thermal stability, amorphous or crystalline nature via FTIR, DSC, TGA, XRD studies. SEM study predicted that tablets had a uniform structure. HPMC K100 based tablets were similar to that of the reference product. Acute toxicity study conducted on Swiss albino mice showed that matrix tablets were safe and non-toxic, as no changes in physical activity and functions of organs were observed. Biochemical and histopathological study revealed lack of any kind of abnormality in liver and renal function. Moreover, necrotic changes were absent at organ level.

Matched MeSH terms: Antidepressive Agents, Tricyclic/chemical synthesis*; Antidepressive Agents, Tricyclic/toxicity*
Fulltext Employing mirtazapine to aid benzodiazepine withdrawal

Chandrasekaran PK

Singapore Med J, 2008 Jun;49(6):e166-7.
PMID: 18581012

Insomnia and depression are frequently encountered in patients during withdrawal from substances. While there are no approved medications for treating them, off-label attempts to address these phenomena with mirtazapine have shown some promising results. This case describes the use of mirtazapine as an aid in benzodiazepine withdrawal and its potential benefits in alleviating insomnia and depression in a 32-year-old man. It was found to ameliorate sleep myoclonus that was thought to be associated with his withdrawal syndrome. It is hoped this report will generate interest and stimulate further research in this area of psychopharmacology.

Matched MeSH terms: Antidepressive Agents, Tricyclic/therapeutic use*
Fulltext Efficacy of Tianeptine 25-50 mg in Elderly Patients With Recurrent Major Depressive Disorder: An 8-Week Placebo- and Escitalopram-Controlled Study

Emsley R, Ahokas A, Suarez A, Marinescu D, Dóci I, Lehtmets A, et al.

J Clin Psychiatry, 2018 07 03;79(4).
PMID: 29995359 DOI: 10.4088/JCP.17m11741

OBJECTIVE: The present placebo-controlled study evaluated the efficacy and safety of 8 weeks of treatment with tianeptine 25-50 mg/d in elderly patients suffering from major depressive disorder (MDD) according to DSM-IV-TR. Escitalopram 5-10 mg/d was used as an active comparator.
METHODS: Elderly outpatients aged at least 65 years with a primary diagnosis of moderate to severe episode of recurrent MDD were recruited by psychiatrists in 44 clinical centers in 10 countries from October 2013 to January 2016. Patients were randomly assigned to receive tianeptine (n = 105), placebo (n = 107), or escitalopram (n = 99) for 8 weeks. The primary outcome measure was the 17-item Hamilton Depression Rating Scale (HDRS₁₇) total score.
RESULTS: Tianeptine improved depressive symptoms, as evaluated by the HDRS₁₇ total score in terms of absolute change from baseline (week 0) to week 8 (placebo-tianeptine difference [SE] of 3.84 [0.85] points, P < .001, using a last-observation-carried-forward approach) and response to treatment (tianeptine: 46.7%; placebo: 34.0%, estimate [SE] = 12.70% [6.70], P = .06). A sensitivity analysis using a mixed model for repeated measures confirmed the main results on HDRS total score. The placebo-tianeptine difference (SE) was 0.66 (0.15) for Clinical Global Impressions-Severity of Illness (95% CI, 0.37 to 0.96; P < .001) and 0.57 (0.14) for Clinical Global Impressions- Improvement (95% CI, 0.30 to 0.83; P < .001). Positive results were also obtained with the active control escitalopram (HDRS₁₇ total score placebo-escitalopram difference of 4.09 ± 0.86 points, P < .001), therefore validating the sensitivity of the studied population. Tianeptine was well tolerated, with only minimal differences in tolerability from placebo.
CONCLUSIONS: The present study provides robust evidence that an 8-week treatment period with tianeptine 25-50 mg is efficacious and well tolerated in depressed patients aged 65 years or older.
TRIAL REGISTRATION: EudraCT identifier: 2012-005612-26.

Matched MeSH terms: Antidepressive Agents, Tricyclic/adverse effects; Antidepressive Agents, Tricyclic/therapeutic use
Fulltext Neuropsychiatric manifestation after a stroke: newly developed symptoms or side-effect of drug?

Tan EC, Aziz NA, Ahmad S

BMJ Case Rep, 2012;2012.
PMID: 22907854 DOI: 10.1136/bcr-2012-006518

A 55-year-old woman presented with sudden onset of left-sided body weakness and numbness, which was diagnosed as multifocal cerebral infarct with right thalamic bleed. She had concurrent hypertension, diabetes mellitus and chronic kidney disease. She suffered from central poststroke pain and reactive depression as poststroke complications, for which amitriptyline was prescribed. Unfortunately, she developed symptoms suggestive of mania and psychosis upon initiation of medications, which resolved upon withdrawal of amitriptyline. Amitriptyline is effective for treatment of poststroke pain and particularly useful in concomitant depression. Unexpectedly, this patient developed new psychopathologies after initiation of this medication. This case highlights the development of new psychopathologies that could be due to the antidepressant, underlying bipolar disorder or a complication of the stroke itself. Primary care providers need to actively enquire regarding neuropsychiatric symptoms because they can adversely affect the patient's quality of life as well as impede rehabilitation efforts.

Matched MeSH terms: Antidepressive Agents, Tricyclic/adverse effects*
Mirtazapine for anorexia nervosa with depression

Jaafar NR, Daud TI, Rahman FN, Baharudin A

Aust N Z J Psychiatry, 2007 Sep;41(9):768-9.
PMID: 17687663

To report the use of Mirtazapine in the treatment of anorexia nervosa with depression primarily regarding its propensity for weight gain.

Matched MeSH terms: Antidepressive Agents, Tricyclic/therapeutic use*
Fulltext Antidepressant Prescription Pattern in the Presence of Medical Co-morbidity: REAP-AD 2013 Study

Grover S, Avasthi A, Tripathi A, Tanra AJ, Chee KY, He YL, et al.

East Asian Arch Psychiatry, 2015 Sep;25(3):99-107.
PMID: 26429836

Objective: To evaluate the prescription pattern of antidepressants in patients with medical co-morbidity from major psychiatric centres in Asia.
Methods: The Research on Asian Psychotropic Prescription Pattern for Antidepressants (REAP-AD 2013) collected data from 42 psychiatric centres in 10 Asian countries and regions. Antidepressant prescriptions of 2320 patients with various psychiatric disorders were evaluated. Of these, 370 patients who had specified medical co-morbidities formed the study cohort.
Results: Escitalopram (20%) and mirtazapine (20%) were the most commonly prescribed antidepressants in patients with medical co-morbidity followed by sertraline (16%), trazodone (15%), and paroxetine (12%). Overall, more than half (52%; 247/476) of prescriptions comprised selective serotonin reuptake inhibitors. Slightly less than two-thirds (63%; n = 233) of patients received at least 1 selective serotonin reuptake inhibitor. In addition, 79% of patients were prescribed only 1 antidepressant. The mean number of antidepressants used per patient was 1.25 (standard deviation, 0.56). There were subtle differences in the most preferred antidepressant across medical illnesses such as diabetes mellitus, liver dysfunction, acid peptic disease, and cerebrovascular disease. Differences were also seen in prescription patterns across different countries.
Conclusion: Although selective serotonin reuptake inhibitors formed the bulk of antidepressant
prescriptions in the presence of medical co-morbidity, mirtazapine was also commonly used in the presence of medical co-morbidities. Specified medical morbidities do influence the selection of antidepressants.
Key words: Antidepressive agents; Asia; Comorbidity

Matched MeSH terms: Antidepressive Agents, Tricyclic/therapeutic use
Cytochrome P450 genotype-guided drug therapies: An update on current states

Dong AN, Tan BH, Pan Y, Ong CE

Clin Exp Pharmacol Physiol, 2018 10;45(10):991-1001.
PMID: 29858511 DOI: 10.1111/1440-1681.12978

Over the past 2 decades, knowledge of the role and clinical value of pharmacogenetic markers has expanded so that individualized pre-emptive therapy based on genetic background of patients could be within reach for clinical implementation. This is evidenced from the frequent updating of drug labels that incorporates pharmacogenetic information (where compelling data become available) by the regulatory agencies (such as the US FDA), and the periodical publication of guidelines of specific therapeutic recommendations based on the results of pharmacogenetic tests by the pharmacogenetics working groups or consortiums of professional bodies. Clinical relevance of the cytochrome P450 (CYP) polymorphism related to dose, effectiveness and/or toxicity of key drugs are presented in this review, including that of warfarin, clopidogrel, tricyclic antidepressants, and proton pump inhibitors. Prospect for routine clinical application of CYP genotyping before prescribing drugs is still currently unclear due to challenges and barriers associated with availability of well-defined and validated pharmacogenetic studies, the interpretation, result reporting and potential error of genotype testing, involvement of non-genetic factors, and other patient's demographic and disease conditions. Further studies to provide additional supporting clinical data and acceleration of pharmacogenetic testing standards and techniques should help improve the evidence base needed for clinical utility and hence move the implementation of genotype-guided therapy in clinical practice a step closer to reality.

Matched MeSH terms: Antidepressive Agents, Tricyclic
Fulltext Malaysian macroalga Padina australis Hauck attenuates high dose corticosterone-mediated oxidative damage in PC12 cells mimicking the effects of depression

Subermaniam K, Yow YY, Lim SH, Koh OH, Wong KH

Saudi J Biol Sci, 2020 Jun;27(6):1435-1445.
PMID: 32489279 DOI: 10.1016/j.sjbs.2020.04.042

Oxidative damage has been associated with the pathophysiology of depression. Macroalgae are equipped with antioxidant defense system to counteract the effects of free radicals. We explored the use of Malaysian Padina australis to attenuate high dose corticosterone-mediated oxidative damage in a cellular model mimicking depression. Fresh specimen of P. australis was freeze-dried and extracted sequentially with hexanes, ethyl acetate and ethanol. The extracts were screened for their phytochemical contents and antioxidant activities. Ethanol extract demonstrated the most potent antioxidant capacity and was selected for subsequent assays against high dose corticosterone of 600 µM-mediated oxidative damage in the rat pheochromocytoma (PC12) cells. The corticosterone reduced the cell viability, glutathione (GSH) level, aconitase activity, and mitochondrial membrane potential (MMP); and increased the lactate dehydrogenase (LDH) release, intracellular reactive oxygen species (ROS) level and apoptosis. However, the extent of oxidative damage was reversed by 0.25-0.5 mg/mL ethanol extract suggesting a possible role of P. australis-based antioxidants in the mitochondrial defense against constant ROS generation and regulation of antioxidant pathway. The effects were similar to that of desipramine, a tricyclic antidepressant. Our findings indicate that P. australis can be developed as a mitochondria-targeted antioxidant to mitigate antidepressant-like effects.

Matched MeSH terms: Antidepressive Agents, Tricyclic