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Biomedicine & Pharmacotherapy =... May 2023Idiopathic pulmonary fibrosis (IPF) is a progressive and irreversible lung disease with a poor prognosis. There is currently no definitive cure for IPF. The present...
Idiopathic pulmonary fibrosis (IPF) is a progressive and irreversible lung disease with a poor prognosis. There is currently no definitive cure for IPF. The present study establishes a platform for the development of a novel therapeutic approach for the treatment of PF using the atypical antidepressant, mirtazapine. In the endotracheal bleomycin rat model, mirtazapine interfered with the activation of NLRP3 inflammasome via downregulating the NLRP3 on the gene and protein expression levels. Accordingly, the downstream mediators IL-1β and IL-18 were repressed. Such observation is potentially a direct result of the reported improvement in oxidative stress. Additionally, mirtazapine corrected the bleomycin-induced disparities in the levels of the fibrogenic mediators TGF-β, PDGF-BB, and TIMP-1, in consequence, the lung content of hydroxyproline and the expression of α-SMA were reduced. Besides, mirtazapine curbed the ICAM-1 and the chemotactic cytokines MCP-1 and CXCL4. This protective property of mirtazapine resulted in improving the BALF total and differential cell counts, diminishing LDH activity, and reducing the BALF total protein. Moreover, the inflammation and fibrosis scores were accordingly lower. To conclude, we reveal for the first time the efficacy of mirtazapine as a potential treatment for PF. The combination of social isolation, sleep problems, breathing difficulties, and fear of death can lead to psychological distress and depression in patients with IPF. Hence, mirtazapine is a promising treatment option that may improve the prognosis for IPF patients due to its antifibrotic effects, as well as its ability to alleviate depressive episodes.
Topics: Rats; Animals; Inflammasomes; Mirtazapine; Antidepressive Agents, Second-Generation; Bleomycin; NLR Family, Pyrin Domain-Containing 3 Protein; Lung; Fibrosis; Idiopathic Pulmonary Fibrosis; Antidepressive Agents
PubMed: 36934553
DOI: 10.1016/j.biopha.2023.114553 -
Acta Dermato-venereologica Aug 2017There is increasing evidence of clinically relevant anti-inflammatory effects of monoaminergic antidepressants. PubMed and Ovid databases were searched systematically... (Review)
Review
There is increasing evidence of clinically relevant anti-inflammatory effects of monoaminergic antidepressants. PubMed and Ovid databases were searched systematically for the use and efficacy of antidepressants in association with 5 common inflammatory skin disorders: chronic urticaria, psoriasis, atopic dermatitis, other eczema, and alopecia areata. From January 1984 to June 2016, publications included a total of 1,252 dermatological patients in 28 trials or case reports. These unambiguously reported a reduced burden of dermatological symptoms in relation to treatment with antidepressants. Several randomized controlled trials of first-generation antidepressants have been published, while studies of modern antidepressants are usually open-label, yet more informative, regarding patients' characteristics and study procedures. These overall positive findings may indicate a rationale, beyond treating comorbid psychiatric disorders, for the use of antidepressants in dermatology. Further research into modern tolerable antidepressants, including selective serotonin re-uptake inhibitors, mirtazapine and bupropion, is required.
Topics: Anti-Inflammatory Agents; Antidepressive Agents, Second-Generation; Dermatologic Agents; Dopamine Uptake Inhibitors; Humans; Selective Serotonin Reuptake Inhibitors; Skin Diseases; Treatment Outcome
PubMed: 28512664
DOI: 10.2340/00015555-2702 -
Psychiatria Polska Oct 2019To evaluate harmful interactions between antidepressants and medications used in treatment of cardiovascular disorders.
OBJECTIVES
To evaluate harmful interactions between antidepressants and medications used in treatment of cardiovascular disorders.
METHODS
The analysis of 66 cases of adverse reactions with a clinical picture indicating, to a degree that is probable or certain, that they were the result of the combination of antidepressant with cardiovascular medication.
RESULTS
The most common side effect (n = 25, 37.9%) was bradycardia (and other side effects of beta blockers) as a consequence of addition of metoprolol or propranolol to SSRI or bupropion. In one case combination of fluoxetine with propranolol resulted in cardiac arrest. We observed 8 cases of intensified side effects of amlodipine (swelling of lower limbs, headaches) after its combination with: fluoxetine, sertraline and paroxetine, and occurrence of myalgia, elevated aminotransferase levels, polyuria and hypotension after combination of lercanidipine with some of the SSRIs. We also found i.a. worsening of propafenone tolerance in combination with venlafaxine or bupropion, 2 cases of granulopenia associated with duloxetine-propafenone combination, 2 cases of hemorrhagic complications associated with the combination of vortioxetine-warfarin, 1 case of hyponatremia associated with the combination of vortioxetine and hydrochlorothiazide, as well as antagonizing clonidine's hypotensive effect by mirtazapine, and peripheral thrombosis following the combination of warfarin with trazodone.
CONCLUSIONS
Because of ahigh risk of interactions and related adverse effects, especially in older patients, each decision regarding combination of a particular antidepressant with a medication used in treatment of cardiovascular disorders should be preceded by a detailed analysis of safety and risk-benefit ratio, and also be associated with the search for the safest, alternative combinations of the above-mentioned medications.
Topics: Adult; Adverse Drug Reaction Reporting Systems; Antidepressive Agents; Arrhythmias, Cardiac; Cardiovascular Diseases; Depressive Disorder; Female; Heart Rate; Humans; Male; Middle Aged; Patient Safety; Risk Factors
PubMed: 31955180
DOI: 10.12740/PP/OnlineFirst/96286 -
Indian Journal of Ophthalmology Jun 2015Acute angle closure (AAC) is an ocular emergency with symptoms including blurred vision, eye pain, headache, nausea, vomiting and reddening of the eye those results from...
Acute angle closure (AAC) is an ocular emergency with symptoms including blurred vision, eye pain, headache, nausea, vomiting and reddening of the eye those results from increased intraocular pressure. This clinical condition can lead to permanent damage in vision, thus causing blindness by generating progressive and irreversible optic neuropathy if left untreated. There are several reasons of AAC, including several types of local and systemic medications; mainly sympathomimetics, cholinergics, anti-cholinergics, mydriatics, anti-histamines, antiepileptics like topiramate, tricyclic and tetracyclic antidepressants, serotonin reuptake inhibitors, antipsychotics, sulfa-based drugs and anticoagulants. Mirtazapine, a noradrenergic and specific serotonergic antidepressant, is an atypical antidepressant with a complex pharmacological profile. This case report describes a patient with major depressive disorder, who experienced AAC after the first dosage of mirtazapine treatment, and highlights the importance of close monitoring of individuals under antidepressant treatment particularly immediately after initiation of the drug.
Topics: Adult; Antidepressive Agents, Tricyclic; Depressive Disorder, Major; Female; Glaucoma, Angle-Closure; Gonioscopy; Humans; Intraocular Pressure; Mianserin; Mirtazapine
PubMed: 26265648
DOI: 10.4103/0301-4738.162612 -
Pharmaceuticals (Basel, Switzerland) May 2021Alzheimer's disease (AD; progressive neurodegenerative disorder) is associated with cognitive and functional impairment with accompanying neuropsychiatric symptoms. The... (Review)
Review
Alzheimer's disease (AD; progressive neurodegenerative disorder) is associated with cognitive and functional impairment with accompanying neuropsychiatric symptoms. The available pharmacological treatment is of a symptomatic nature and, as such, it does not modify the cause of AD. The currently used drugs to enhance cognition include an N-methyl-d-aspartate receptor antagonist (memantine) and cholinesterase inhibitors. The PUBMED, Medical Subject Heading and Clinical Trials databases were used for searching relevant data. Novel treatments are focused on already approved drugs for other conditions and also searching for innovative drugs encompassing investigational compounds. Among the approved drugs, we investigated, are intranasal insulin (and other antidiabetic drugs: liraglitude, pioglitazone and metformin), bexarotene (an anti-cancer drug and a retinoid X receptor agonist) or antidepressant drugs (citalopram, escitalopram, sertraline, mirtazapine). The latter, especially when combined with antipsychotics (for instance quetiapine or risperidone), were shown to reduce neuropsychiatric symptoms in AD patients. The former enhanced cognition. Procognitive effects may be also expected with dietary antioxidative and anti-inflammatory supplements-curcumin, myricetin, and resveratrol. Considering a close relationship between brain ischemia and AD, they may also reduce post-brain ischemia neurodegeneration. An investigational compound, CN-105 (a lipoprotein E agonist), has a very good profile in AD preclinical studies, and its clinical trial for postoperative dementia is starting soon.
PubMed: 34068096
DOI: 10.3390/ph14050458 -
International Journal of Health Sciences 2022Although there are numerous drugs available for the treatment of gastric ulcers (GU), these drugs are not always effective. Antidepressant medications have been used for...
OBJECTIVES
Although there are numerous drugs available for the treatment of gastric ulcers (GU), these drugs are not always effective. Antidepressant medications have been used for a variety of non-psychiatric indications, including antiulcer activity in various ulcer models. The purpose of this study was to compare the antiulcer effects of fluvoxamine and mirtazapine in two rat GU experimental models and to determine their relationship to antioxidant and antisecretory mechanisms.
MATERIALS AND METHODS
The antiulcer activities of various doses of fluvoxamine and mirtazapine on water immersion restraint stress (WIRS) and pyloric ligation-induced GU in rats have been studied against the positive control antiulcer drug famotidine. Various oxidative stress markers were evaluated.
RESULTS
Fluvoxamine and mirtazapine significantly protected against WIRS and pyloric ligation-induced gastric lesions, as evidenced by a dose-dependent decrease in ulcer index, myeloperoxidase (MPO) activity, lipid peroxidation, and an increase in prostaglandin E2, nitric oxide (NO), and reduced glutathione levels, as well as increased antioxidant enzyme activity. In the pyloric ligation model, fluvoxamine and mirtazapine improved GU more than famotidine. Furthermore, a 30 mg/kg dose of mirtazapine significantly improves both NO levels and MPO activity compared to famotidine.
CONCLUSIONS
The results highlighted the relationship in correlating the antiulcer effect of drugs from different antidepressant classes across two animal GU models, implying that antidepressants that affected both norepinephrine and serotonin levels (mirtazapine) had a more potent antiulcer effect in WIRS-induced gastric model than drugs that only affected serotonin levels (fluvoxamine).
PubMed: 35599943
DOI: No ID Found -
Drug Design, Development and Therapy 2017Gastroparesis symptoms can be severe and debilitating. Many patients do not respond to currently available treatments. Mirtazapine has been shown in case reports to...
INTRODUCTION
Gastroparesis symptoms can be severe and debilitating. Many patients do not respond to currently available treatments. Mirtazapine has been shown in case reports to reduce symptoms in gastroparesis.
AIM
To assess the efficacy and safety of mirtazapine in gastroparetic patients.
METHODS
Adults with gastroparesis and poorly controlled symptoms were eligible. Participants were prescribed mirtazapine 15 mg PO qhs. Questionnaires containing the gastrointestinal cardinal symptom index (GCSI) and the clinical patient grading assessment scale (CPGAS) were completed by patients' pretreatment, at 2 weeks, and at 4 weeks. Primary end point was nausea and vomiting response to mirtazapine using the GCSI. Secondary end point was nausea and vomiting severity assessment using the CPGAS. -values were calculated using the paired two-tailed Student's -test. Intention to treat analysis was used.
RESULTS
A total of 30 patients aged 19-86 years were enrolled. Of those, 24 patients (80%) completed 4 weeks of therapy. There were statistically significant improvements in nausea, vomiting, retching, and perceived loss of appetite at 2 and 4 weeks (all -values <0.05) compared with pretreatment. There was a statistically significant improvement in the CPGAS score at week 2 (=0.003) and week 4 (<0.001). Of the total patients, 14 (46.7%) experienced adverse effects from mirtazapine and due to this, 6 patients stopped therapy.
CONCLUSION
Mirtazapine significantly improved both nausea and vomiting in gastroparetics after 2 and 4 weeks of treatment. Side effects led to treatment self-cessation in a fifth of patients. From these data, we conclude that mirtazapine improves nausea and vomiting, among other symptoms, in patients with gastroparesis and might be useful in select patients.
Topics: Adult; Aged; Aged, 80 and over; Female; Gastroparesis; Humans; Male; Mianserin; Middle Aged; Mirtazapine; Young Adult
PubMed: 28408802
DOI: 10.2147/DDDT.S125743 -
Chonnam Medical Journal May 2018Randomized trials have shown that selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) have better safety profiles... (Review)
Review
Randomized trials have shown that selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) have better safety profiles than classical tricyclic antidepressants (TCAs). However, an increasing number of studies, including meta-analyses, naturalistic studies, and longer-term studies suggested that SSRIs and SNRIs are no less safe than TCAs. We focused on comparing the common side effects of TCAs with those of newer generation antidepressants including SSRIs, SNRIs, mirtazapine, and bupropion. The main purpose was to investigate safety profile differences among drug classes rather than the individual antidepressants, so studies containing comparison data on drug groups were prioritized. In terms of safety after overdose, the common belief on newer generation antidepressants having fewer side effects than TCAs appears to be true. TCAs were also associated with higher drop-out rates, lower tolerability, and higher cardiac side-effects. However, evidence regarding side effects including dry mouth, gastrointestinal side effects, hepatotoxicity, seizure, and weight has been inconsistent, some studies demonstrated the superiority of SSRIs and SNRIs over TCAs, while others found the opposite. Some other side effects such as sexual dysfunction, bleeding, and hyponatremia were more prominent with either SSRIs or SNRIs.
PubMed: 29854675
DOI: 10.4068/cmj.2018.54.2.101 -
Cureus Oct 2022Somatization refers to the condition in which psychological distress is shown in the form of somatic symptoms such as persistent headache, nausea, gastrointestinal... (Review)
Review
Somatization refers to the condition in which psychological distress is shown in the form of somatic symptoms such as persistent headache, nausea, gastrointestinal discomfort, etc. Various predisposing factors, including familial such as high expressed emotion, poor parental care, genetic, biological, and demographic which includes age and gender, cognitive such as learning disabilities, psychiatric such as depression, anxiety, post-traumatic stress disorder, social, etc., play an essential role in saturation of the disease. During the time of the COVID-19 pandemic, psychological distress increased in the patients infected with the coronavirus due to some the factors such as social distancing from loved ones, lack of physical exercise, loss of income, loneliness due to quarantine, etc. Therefore, management and treatment of the disorder became essential, especially in coronavirus-infected patients, as it may lead to an increase in complications of the disease. Many studies have been conducted to identify the proper way to manage the condition. Treatments include pharmacological therapy and psychosocial interventions. Pharmacological therapy includes using various antidepressants, hypnotics, and sedatives such as benzodiazepines. For the treatment, mirtazapine is a secure and reliable antidepressant. Another drug, trizolobenzodiazepine adinazolam, was also very useful in treating patients. In some randomized experiments, alprazolam significantly outperformed amitryptiline in reducing the symptoms. Psychosocial interventions include sessions such as cognitive behavioral therapy (CBT), mindfulness-based cognitive therapy, relaxation training, meditation, and psychological interventions such as enhancing multidimensional social help, modifying cognitive assessment, directing positive coping, and inspiring positive emotions.
PubMed: 36381919
DOI: 10.7759/cureus.30262 -
The International Journal of... May 2015Despite adequate treatment with antipsychotics, a substantial number of patients with schizophrenia demonstrate only suboptimal clinical outcome. To overcome this... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Despite adequate treatment with antipsychotics, a substantial number of patients with schizophrenia demonstrate only suboptimal clinical outcome. To overcome this challenge, various psychopharmacological combination strategies have been used, including antidepressants added to antipsychotics.
METHODS
To analyze the efficacy of add-on antidepressants for the treatment of negative, positive, cognitive, depressive, and antipsychotic-induced extrapyramidal symptoms in schizophrenia, published randomized controlled trials assessing the efficacy of adjunctive antidepressants in schizophrenia were reviewed using the following parameters: baseline clinical characteristics and number of patients, their on-going antipsychotic treatment, dosage of the add-on antidepressants, duration of the trial, efficacy measures, and outcomes.
RESULTS
There were 36 randomized controlled trials reported in 41 journal publications (n=1582). The antidepressants used were the selective serotonin reuptake inhibitors, duloxetine, imipramine, mianserin, mirtazapine, nefazodone, reboxetin, trazodone, and bupropion. Mirtazapine and mianserin showed somewhat consistent efficacy for negative symptoms and both seemed to enhance neurocognition. Trazodone and nefazodone appeared to improve the antipsychotics-induced extrapyramidal symptoms. Imipramine and duloxetine tended to improve depressive symptoms. No clear evidence supporting selective serotonin reuptake inhibitors' efficacy on any clinical domain of schizophrenia was found. Add-on antidepressants did not worsen psychosis.
CONCLUSIONS
Despite a substantial number of randomized controlled trials, the overall efficacy of add-on antidepressants in schizophrenia remains uncertain mainly due to methodological issues. Some differences in efficacy on several schizophrenia domains seem, however, to exist and to vary by the antidepressant subgroups--plausibly due to differences in the mechanisms of action. Antidepressants may not worsen the course of psychosis. Better designed, larger, and longer randomized controlled trials are needed.
Topics: Antidepressive Agents; Antipsychotic Agents; Drug Therapy, Combination; Humans; Outcome Assessment, Health Care; Randomized Controlled Trials as Topic; Schizophrenia; Selective Serotonin Reuptake Inhibitors
PubMed: 25991654
DOI: 10.1093/ijnp/pyv049