Neuroendocrine, biochemical and pharmacokinetic effects of a long-term treatment with the selective serotonin reuptake inhibitor (SSRI) citalopram in major depressive disorder

Background: Though manageable, major depressive disorder remains an underdiagnosed and undertreated condition. The objective of this study was to assess the effectiveness and safety of 8 weeks of treatment with the tricyclic antidepressant dosulepin hydrochloride in patients with depressive episodes not responsive to 4 consecutive weeks of treatment with a single selective serotonin reuptake inhibitor (SSRI).Methods: Patients diagnosed with depressive episode without psychotic symptoms (by ICD-10 diagnostic criteria for research), mini-mental state examination score of ≥24, and not responsive to four weeks of treatment with SSRIs (<50% reduction in depressive symptoms) were enrolled. The main outcome measures were mean change in the Hamilton depression, Hamilton anxiety, and insomnia severity index scores at Week 8 compared to baseline. Adverse events were recorded for safety assessment.Results: A total of 94 patients were enrolled, of which, 90 (95.7%) patients completed the study. Compared to baseline, 8 weeks of treatment significantly changed the HAM-D score by -12.7 (p<0.0001), HAM-A score by -8.3 (p<0.0001), and ISI score by -10.5 (p<0.0001). One patient reported anemia and was withdrawn from the study. Dry mouth and insomnia followed by headache, blurred vision, and drowsiness were the most commonly reported side effects as measured with the antidepressant side-effects checklist. Most side effects were of mild intensity and were related to study medication.Conclusions: Eight weeks of treatment with dosulepin hydrochloride resulted in significant and clinically relevant improvements in depression, anxiety, and insomnia symptoms in Indian patients with MDD.

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Interleukin-6 signaling pathway involved in major depressive disorder: selective serotonin reuptake inhibitor regulates IL-6 pathway

Turkish Journal of Biochemistry ◽

10.1515/tjb-2019-0010 ◽

2019 ◽

Vol 44 (6) ◽

pp. 831-839 ◽

Cited By ~ 1

Author(s):

Marziye Askari ◽

Leila Jahangard ◽

Alireza Zamani ◽

Mohammad Haghighi ◽

Iraj Salehi ◽

...

Keyword(s):

Major Depressive Disorder ◽

Depressive Disorder ◽

Selective Serotonin Reuptake Inhibitor ◽

Reuptake Inhibitor ◽

Serotonin Reuptake ◽

Selective Serotonin ◽

Serotonin Reuptake Inhibitor ◽

Major Depressive ◽

Ifn Γ ◽

Ssri Medication

Abstract Background Evidence indicates that pro-inflammatory Th17 and Th1 cells are involved in major depressive disorder (MDD) pathogenesis. Development of Th17 and Th1 are regulated by IL-6 and IFN-γ, respectively. In this study, the levels of IL-6 and IFN-γ, and mRNA expression of related signaling components and, Th17/Th1 transcription factors were investigated in MDD patients with/without selective serotonin reuptake inhibitor (SSRI) medication. Materials and methods Forty-six patients and 38 healthy controls (HCs) were recruited. Twenty patients were received the SSRI (sertraline 50–200 mg/day) for at least 1 year, and 26 patients were not received medication. Expression of IL-6R, IFN-γR, JAK1, JAK2, TYK2, STAT1, STAT3, T-bet and RORγt were assessed with Real-Time-PCR. Serum and supernatant levels of IL-6 and IFN-γ were determined using ELISA. Results and discussion The serum and supernatant levels of IL-6 were increased in patients without (SSRI−) compared with HCs, while its levels was reduced in SSRI+. Elevated expressions of IL-6R, STAT3 and RORγt were observed in SSRI− compared with HCs. Expressions of IL-6R, STAT3, RORγt and IFN-γR, were decreased in SSRI+ compared to SSRI− patients. Conclusion Increased IL-6 involved in MDD, and SSRI regulates IL-6 pathway and IL-6 production. MDD patients may benefit from IL-6/IL-6R targeted therapeutic intervention.

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Effect of selective serotonin reuptake inhibitor on prefrontal-striatal connectivity is dependent on the level of TNF-α in patients with major depressive disorder

Psychological Medicine ◽

10.1017/s0033291718003616 ◽

2018 ◽

Vol 49 (15) ◽

pp. 2608-2616 ◽

Cited By ~ 1

Author(s):

Kai Liu ◽

Xiaohua Zhao ◽

Xiaobing Lu ◽

Xiaoxia Zhu ◽

Hui Chen ◽

...

Keyword(s):

Major Depressive Disorder ◽

Depressive Disorder ◽

Selective Serotonin Reuptake Inhibitor ◽

Reuptake Inhibitor ◽

Serotonin Reuptake ◽

Selective Serotonin ◽

Major Depressive ◽

Tnf Α ◽

Α Level ◽

Ssri Treatment

AbstractBackgroundWe hypothesize that the tumor necrosis factor-α (TNF-α) may play a role in disturbing the effect of selective serotonin reuptake inhibitor (SSRI) on the striatal connectivity in patients with major depressive disorder (MDD).MethodsWe performed a longitudinal observation by combining resting-state functional magnetic resonance imaging (rs-fMRI) and biochemical analyses to identify the abnormal striatal connectivity in MDD patients, and to evaluate the effect of TNF-α level on these abnormal connectivities during SSRI treatment. Eighty-five rs-fMRI scans were collected from 25 MDD patients and 35 healthy controls, and the scans were repeated for all the patients before and after a 6-week SSRI treatment. Whole-brain voxel-wise functional connectivity (FC) was calculated by correlating the rs-fMRI time courses between each voxel and the striatal seeds (i.e. spherical regions placed at the striatums). The level of TNF-α in serum was evaluated by Milliplex assay. Factorial analysis was performed to assess the interaction effects of ‘TNF-α × treatment’ in the regions with between-group FC difference.ResultsCompared with controls, MDD patients showed significantly higher striatal FC in the medial prefrontal cortex (MPFC) and bilateral middle/superior temporal cortices before SSRI treatment (p < 0.001, uncorrected). Moreover, a significant interaction effect of ‘TNF-α × treatment’ was found in MPFC-striatum FC in MDD patients (p = 0.002), and the significance remained after adjusted for age, gender, head motion, and episode of disease.ConclusionThese findings provide evidence that treatment-related brain connectivity change is dependent on the TNF-α level in MDD patients, and the MPFC-striatum connectivities possibly serve as an important target in the brain.

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