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ACG Case Reports Journal Oct 2019Gastroparesis is a chronic condition of delayed gastric emptying in the absence of mechanical outlet obstruction. We report a 47-year-old African American woman with...
Gastroparesis is a chronic condition of delayed gastric emptying in the absence of mechanical outlet obstruction. We report a 47-year-old African American woman with diabetic gastroparesis who presented with intractable nausea, vomiting, and decreased oral intake with electrolyte disturbances. The patient's symptoms were difficult to control with antiemetic and conventional prokinetic agents, and she was started on mirtazapine 15 mg nightly. She experienced an almost complete symptom relief and was able to tolerate solid food within 24-48 hours. We highlight the role of mirtazapine, a 5-HT agonist, as an effective therapy for refractory gastroparesis.
PubMed: 31832475
DOI: 10.14309/crj.0000000000000256 -
Pharmaceuticals (Basel, Switzerland) Sep 2021Mirtazapine belongs to the category of antidepressants clinically used mainly in major depressive disorder but also used in obsessive-compulsive disorders, generalized... (Review)
Review
Mirtazapine belongs to the category of antidepressants clinically used mainly in major depressive disorder but also used in obsessive-compulsive disorders, generalized anxiety, and sleep disturbances. This drug acts mainly by antagonizing the adrenergic α2, and the serotonergic 5-HT2 and 5-HT3 receptors. Neuropsychiatric symptoms, such as depression and agitation, are strongly associated with Alzheimer's disease, reducing the life quality of these patients. Thus, it is crucial to control depression in Alzheimer's patients. For this purpose, drugs such as mirtazapine are important in the control of anxiety, agitation, and other depressive symptoms in these patients. Indeed, despite some contradictory studies, evidence supports the role of mirtazapine in this regard. In this review, we will focus on depression in Alzheimer's disease, highlighting the role of mirtazapine in this context.
PubMed: 34577630
DOI: 10.3390/ph14090930 -
Annals of Indian Academy of Neurology 2023Depression and Alzheimer's disease (AD) are frequent interacting diseases in the elderly with a negative impact on the quality of life of patients and caregivers....
Depression and Alzheimer's disease (AD) are frequent interacting diseases in the elderly with a negative impact on the quality of life of patients and caregivers. Late-life depression may be regarded either as an early symptom of AD or a risk factor for AD, depending on the context. This review was focused on the latest developments in the fields of the neurobiological basis and treatment of depression in AD. We found that some plausible hypotheses are emerging to correlate with depression in AD, such as neuroinflammation and dysimmune regulation. It seems that depression is not related to amyloid deposition, but this issue is not completely resolved. The response to antidepressants is controversial according to the evidence from 10 small double-blind randomized placebo-controlled clinical trials with antidepressants in AD patients with depression: four with sertraline, one with three arms (sertraline, mirtazapine, placebo), one with fluoxetine, one with imipramine, one with clomipramine, one with escitalopram, and one with vortioxetine. The total number of treated patients completing the trials was 638. The main criterion of a positive response was a reduction in the scores of clinical scales for depression of at least 50%. The weighted OR (odds ratio) was calculated with the method of Mantel-Haenszel: 1.29; 95% CI: 0.77-2.16. No significant differences were found compared with placebo. Antidepressants did not have a meaningful negative influence on cognition, which was measured with the mini-mental state examination (MMSE) in 18 clinical trials. Alternatives other than drugs are also discussed. Although there have been important advances in this field, pathophysiology and treatment deserve further research.
PubMed: 37970263
DOI: 10.4103/aian.aian_326_23 -
Bioengineered Feb 2022Sepsis is mainly characterized by severe inflammation triggered by infection, and sepsis-associated encephalopathy (SAE) is defined as brain damage caused by sepsis....
Sepsis is mainly characterized by severe inflammation triggered by infection, and sepsis-associated encephalopathy (SAE) is defined as brain damage caused by sepsis. Disruption of the blood-brain barrier (BBB) triggered by injured brain microvascular endothelial cells (BMECs) and damaged tight junction (TJ) structure is closely associated with the pathogenesis of SAE. The present research proposed to evaluate the potential therapeutic effects of Mirtazapine, a central presynaptic α2 receptor antagonist, on LPS-induced BBB disruption. The mice were administered with normal saline and 10 mg/kg Mirtazapine for 8 consecutive days, and from day 6, the experiment group of mice received LPS for 2 days to induce SAE. We found that the increased BBB permeability, elevated concentrations of inflammatory factors in brain tissues, and downregulated zonula occludens -1 (ZO-1) were observed in LPS-stimulated mice, all of which were reversed by 10 mg/kg Mirtazapine. In the assay, bEnd.3 brain endothelial cells were treated with 1 μM LPS in the absence or presence of Mirtazapine (25, 50 μM). We found that LPS-treated cells had significantly declined transendothelial electrical resistance (TEER), increased monolayer permeability, elevated production of inflammatory factors, and downregulated ZO-1. However, 25 and 50 μM Mirtazapine ameliorated all these LPS- induced aberrations. Mirtazapine also mitigated the decreased level of NF-E2-related factor 2 (Nrf2) in LPS-challenged endothelial cells. The protective effect of Mirtazapine on endothelial permeability against LPS was significantly abolished by the knockdown of Nrf2. Collectively, we concluded that Mirtazapine exerted protective effects on LPS-induced endothelial cells hyperpermeability by upregulating Nrf2.
Topics: Animals; Blood-Brain Barrier; Capillary Permeability; Lipopolysaccharides; Male; Mice; Mirtazapine; Sepsis-Associated Encephalopathy; Tight Junctions
PubMed: 35081868
DOI: 10.1080/21655979.2021.2024962 -
Therapeutic Advances in... 2021Postpartum depression (PPD) is a common and serious mental health problem that is associated with maternal suffering and numerous negative consequences for offspring....
Postpartum depression (PPD) is a common and serious mental health problem that is associated with maternal suffering and numerous negative consequences for offspring. The benefit of breastfeeding for the infant and mother is well documented; therefore, the information about the risk-benefit of antidepressants, if used while mothers are breastfeeding, is necessary for the clinician's decision. The case series and systematic data on antidepressants in breastfeeding consist mainly of selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and mirtazapine, whereas information on newer antidepressants such as agomelatine in pregnant or lactating women is rare, especially the adverse effects on the infant of the mother with PPD treated with agomelatine. To add to the limited available data, we report the case of agomelatine treatment in a breastfeeding woman with PPD. In this case report, we took advantage of the short half-life of agomelatine to reduce the potential effect on infant in the treatment of a nursing woman with PPD. The results confirm the effectiveness of agomelatine in the treatment of PPD and demonstrate the safety in breastfeeding.
PubMed: 34158917
DOI: 10.1177/20451253211022172 -
Journal of Clinical Sleep Medicine :... Apr 2021Ivgy-May N. Residual daytime effects of esmirtazapine. 2021;17(4):865.
Ivgy-May N. Residual daytime effects of esmirtazapine. 2021;17(4):865.
Topics: Disease Progression; Double-Blind Method; Humans; Mirtazapine; Sleep Initiation and Maintenance Disorders
PubMed: 33432919
DOI: 10.5664/jcsm.9120 -
Therapeutic Advances in... Oct 2015To conduct a systematic review and meta-analysis of randomized placebo-controlled trials of mirtazapine for the treatment of antipsychotic-induced acute akathisia (AIAA). (Review)
Review
OBJECTIVE
To conduct a systematic review and meta-analysis of randomized placebo-controlled trials of mirtazapine for the treatment of antipsychotic-induced acute akathisia (AIAA).
METHODS
Studies were identified using online searches of PUBMED/MEDLINE and Cochrane database (CENTRAL), along with websites recording trial information such as www.clinicaltrials.gov, www.controlled-trials.com, and www.clinicalstudyresults.org. The study eligibility criteria were randomized, double-blind clinical trials comparing mirtazapine with placebo for AIAA with standardized rating for akathisia as outcome measure. The methodological quality of included trials was assessed using the Jadad Scale. Separate meta-analyses were undertaken for each outcome (response rate and complete remission) and treatment effects were expressed as Mantel-Haenszel risk ratio (RR). Fixed-effect meta-analysis was performed as heterogeneity was not significant. Number need to treat (NNT) as a measure of relative treatment effectiveness was calculated.
RESULTS
A systematic review of the literature revealed six studies that had assessed mirtazapine for the treatment of AIAA. Of these, two studies (n = 86) met the review inclusion criteria and were included in the final analysis. A meta-analysis was performed to see the effect size of response rate and complete remission. For response rate, RR was 6.67 [95% confidence interval (CI) 2.14-20.78], favoring mirtazapine compared with placebo, and the overall effect was significant (p = 0.001, NNT 4, 95% CI 2.6-8.6). For complete remission, RR was 6.20 (95% CI 1.74-22.08), favoring mirtazapine compared with placebo, and the overall effect was significant (p = 0.005, NNT 5, 95% CI 2.9-11.6).
CONCLUSIONS
Although limited to only two studies and small sample, existing data support the efficacy of mirtazapine for the treatment of AIAA, with one in four patients showing partial response and one in five patients showing complete remission.
PubMed: 26557987
DOI: 10.1177/2045125315601343 -
British Journal of Clinical Pharmacology Jan 2022Hypothyroxinaemia could be easily neglected if attention is paid only to patients with elevated thyroid-stimulating hormone. We aimed to assess the association between...
AIMS
Hypothyroxinaemia could be easily neglected if attention is paid only to patients with elevated thyroid-stimulating hormone. We aimed to assess the association between mirtazapine use and hypothyroxinaemia in patients affected by major depressive disorder.
METHODS
We conducted a retrospective cohort study in the Second Affiliated Hospital of Xinxiang Medical University between January 2016 and December 2018. Patients affected by major depression disorder and admitted to the hospital for treatment during the study period and who had thyroid tests at admission and after treatment were included. Mirtazapine use during hospitalization was the exposure measure and newly developed hypothyroxinaemia was as the primary outcome and structure parameters of thyroid homeostasis were the secondary outcomes of this study. Log-binomial model was used to estimate the association between mirtazapine use and hypothyroxinaemia, after adjusting for potential confounding factors.
RESULTS
A total of 220 eligible patients were included in the final analysis. The incidence of hypothyroxinaemia in patients who used mirtazapine was higher (37.5%) than those patients who did not use (19.7%). The relative risk of developing hypothyroxinaemia was 1.70 (95% confidence interval: 1.21-2.43) for mirtazapine use, after adjusting for confounding factors. The degree of reduction in thyroid feedback quantile-based index in mirtazapine group was significantly greater than that in nonmirtazapine group.
CONCLUSION
Mirtazapine use was associated with the increased risk of developing hypothyroxinaemia. The underlying mechanism may be involved the changed central set point of thyroid homeostasis, in which pituitary was in a possibly impaired sensitivity to the lower level of thyroid hormones.
Topics: Depressive Disorder, Major; Humans; Incidence; Mirtazapine; Retrospective Studies
PubMed: 34155670
DOI: 10.1111/bcp.14949 -
Bioengineered Jan 2022Mirtazapine is an antidepressant drug that has been proven to possess a cognitive enhancer efficiency. In this study, we evaluated the potential protective effects of...
Mirtazapine is an antidepressant drug that has been proven to possess a cognitive enhancer efficiency. In this study, we evaluated the potential protective effects of mirtazapine on BV2 microglia in response to isoflurane exposure. Our results show that mirtazapine attenuated isoflurane-induced expression of microglia-specific protein Iba1 in BV2 microglia. Mirtazapine prevented isoflurane-induced production of the pro-inflammatory factors interleukin (IL)-1β and IL-18 by inhibiting the activation of the nod-like receptor family protein 3 (NLRP3) inflammasome in BV2 microglia. The increased reactive oxygen species (ROS) production and elevated expression level of NADPH oxidase 4 (NOX4) in isoflurane-induced BV2 microglia were mitigated by mirtazapine. Isoflurane exposure reduced triggering receptor expressed on myeloid cells 2 (TREM2) expression in BV2 microglia, which was restored by mirtazapine. Moreover, silencing of TREM2 abolished the inhibitory effects of mirtazapine on ionized calcium-binding adapter molecule 1 (Iba1) expression and inflammation in BV2 microglia. From these results, we could infer that mirtazapine exerted a protective effect on BV2 microglia against isoflurane exposure-caused microglia activation, neuroinflammation, and oxidative stress via inducing TREM2 activation. Hence, mirtazapine might be a potential intervention strategy to prevent isoflurane exposure-caused cognitive dysfunction in clinical practice.
Topics: Animals; Anti-Inflammatory Agents; Cell Line; Interleukin-18; Interleukin-1beta; Isoflurane; Membrane Glycoproteins; Mice; Microglia; Mirtazapine; NLR Family, Pyrin Domain-Containing 3 Protein; Oxidative Stress; Reactive Oxygen Species; Receptors, Immunologic
PubMed: 34964706
DOI: 10.1080/21655979.2021.2009971 -
Atypical antidepressant mirtazapine inhibits 5-hydroxytryptamine3 receptor currents in NCB-20 cells.Journal of Pharmacological Sciences Feb 2023Mirtazapine, an atypical antidepressant, is known to enhance serotonergic transmission by inhibiting the 5-hydroxytryptamine (5-HT), 5-HT, and 5-HT receptors. However,...
Mirtazapine, an atypical antidepressant, is known to enhance serotonergic transmission by inhibiting the 5-hydroxytryptamine (5-HT), 5-HT, and 5-HT receptors. However, the mechanism of action on the 5-HT receptor remains unclear. We investigated the inhibitory mechanisms of mirtazapine on 5-HT receptors of NCB20 neuroblastoma cells using the whole-cell voltage-clamp method. Mirtazapine inhibited the 5-HT receptor currents in a concentration-dependent manner, and the inhibitory effect was influenced by the concentration of 5-HT. When mirtazapine was co-applied to 5-HT, the maximal response of the 5-HT receptor current was reduced and EC was increased, suggesting that mirtazapine might act as a non-competitive inhibitor. Inhibition of 5-HT current by mirtazapine was stronger in pre-application than in co-application, which suggests that mirtazapine might act as a closed state inhibitor. This finding was further supported by no use-dependency of the mirtazapine for 5-HT receptor inhibition. Finally, mirtazapine accelerated the desensitization and deactivation process in a concentration-dependent manner. The difference in recovery time showed that mirtazapine drastically influences the desensitization process than the deactivation process. These mechanistic characteristics of mirtazapine support the understanding of the relationship between the 5-HT receptor and atypical antidepressants.
Topics: Antidepressive Agents; Antidepressive Agents, Second-Generation; Cell Line, Tumor; Mirtazapine; Receptors, Serotonin, 5-HT3; Serotonin; Animals; Cricetinae; Cricetulus
PubMed: 36707180
DOI: 10.1016/j.jphs.2022.12.002