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Journal of Affective Disorders Oct 2023MicroRNAs (miRNAs) and circulating cell-free mitochondrial DNA (ccf-mtDNA) have attracted interest as biological markers of affective disorders. In response to stress,... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
MicroRNAs (miRNAs) and circulating cell-free mitochondrial DNA (ccf-mtDNA) have attracted interest as biological markers of affective disorders. In response to stress, it is known that miRNAs in mitochondria diffuse out of the cytoplasm alongside mtDNA; however, this process has not yet been identified. We hypothesized that miRNAs derived from specific cell nuclei cause mitochondrial damage and mtDNA fragmentation under MDD-associated stress conditions.
METHODS
A comprehensive analysis of the plasma miRNA levels and quantification of the plasma ccf-mtDNA copy number were performed in 69 patients with depression to determine correlations and identify genes and pathways interacting with miRNAs. The patients were randomly assigned to receive either selective serotonin reuptake inhibitors (SSRI) or mirtazapine. Their therapeutic efficacy over four weeks was evaluated in relation to miRNAs correlated with ccf-mtDNA copy number.
RESULTS
The expression levels of the five miRNAs showed a significant positive correlation with the ccf-mtDNA copy number after correcting for multiple testing. These miRNAs are involved in gene expression related to thyroid hormone synthesis, the Hippo signaling pathway, vasopressin-regulated water reabsorption, and lysine degradation. Of these five miRNAs, miR-6068 and miR-4708-3p were significantly associated with the SSRI and mirtazapine treatment outcomes, respectively.
LIMITATIONS
This study did not show comparison with a healthy group.
CONCLUSIONS
The expression levels of specific miRNAs were associated with ccf-mtDNA copy number in untreated depressed patients; moreover, these miRNAs were linked to antidepressant treatment outcomes. These findings are expected to lead to the elucidation of new pathological mechanism of depression.
Topics: Humans; MicroRNAs; DNA, Mitochondrial; Depressive Disorder, Major; Mirtazapine; Depression; Cell-Free Nucleic Acids; Mitochondria; Selective Serotonin Reuptake Inhibitors
PubMed: 37467797
DOI: 10.1016/j.jad.2023.07.073 -
MMW Fortschritte Der Medizin Dec 2018
Topics: Depressive Disorder, Treatment-Resistant; Humans; Mirtazapine; Primary Health Care; Selective Serotonin Reuptake Inhibitors; Serotonin and Noradrenaline Reuptake Inhibitors
PubMed: 30542867
DOI: 10.1007/s15006-018-1228-z -
Medicina Clinica Mar 2018
Topics: Aged, 80 and over; Antidepressive Agents; Causality; Depressive Disorder, Major; Female; Humans; Mirtazapine; Pancreatitis, Acute Necrotizing
PubMed: 28923677
DOI: 10.1016/j.medcli.2017.08.006 -
Rheumatology International Dec 2018Mirtazapine is commonly used to treat major depressive disorder. Due to its effects on multiple neurotransmitters, it has been investigated for possible benefits in... (Review)
Review
Mirtazapine is commonly used to treat major depressive disorder. Due to its effects on multiple neurotransmitters, it has been investigated for possible benefits in patients with fibromyalgia. The objective of this systematic review is to assess the efficacy and safety of mirtazapine in the treatment of patients with fibromyalgia. Pubmed (1946-May 2018), Embase (1947-May 2018), CENTRAL, and ClinicalTrials.gov were queried using the search term combination: fibromyalgia, pain, chronic pain, neuralgia, neuropathic pain, chronic widespread pain, or chronic pain syndrome and mirtazapine. Studies appropriate to the objective were evaluated, including three randomized, placebo-controlled trials and one open-label trial, investigating the effect of mirtazapine in patients with fibromyalgia. In patients with fibromyalgia, treatment with mirtazapine resulted in improvements in pain, sleep, and quality of life. Study durations ranged from 6 to 13 weeks and studies used varying dosing strategies for mirtazapine. Minor occurrences of somnolence, weight gain, nasopharyngitis, dry mouth, and increased appetite were reported with mirtazapine use. Based on the reviewed literature, mirtazapine appears to be a promising therapy to improve pain, sleep, and quality of life in patients with fibromyalgia. These benefits were demonstrated in patients that were treatment naïve and those that had failed previous therapies. Additional clinical evidence through larger and longer length trials would be of benefit to further define the role of mirtazapine for patients with fibromyalgia.
Topics: Fibromyalgia; Health Status; Humans; Mirtazapine; Neurotransmitter Agents; Pain Threshold; Quality of Life; Sleep; Treatment Outcome
PubMed: 29860538
DOI: 10.1007/s00296-018-4068-3 -
Current Problems in Dermatology 2016Psoriasis is a common chronic inflammatory skin disease observed in about 1-3% of the general population. About 60-90% of patients with psoriasis suffer from itching.... (Review)
Review
Psoriasis is a common chronic inflammatory skin disease observed in about 1-3% of the general population. About 60-90% of patients with psoriasis suffer from itching. Interestingly, in the past itch was not considered as an important symptom of psoriasis. Despite the high frequency of itch in psoriasis, the pathogenesis of this symptom is still not fully elucidated. Although most studies indicate neurogenic inflammation and the role of neuropeptides, other mediators may be important as well. The majority of psoriatic patients consider itch as the most bothersome symptom of the disease as it significantly alters daily functioning and psychosocial well-being. Patients with itch showed greater impairment of their health-related quality of life compared to those without itch, and the intensity of itch correlated with the degree of quality-of-life reduction. However, treatment options for itch in psoriasis are limited. Therapy of itch in patients with psoriasis should be directed toward the resolution of skin lesions, as disease remission usually is linked with itch relief. Recent studies have clearly pointed to an important role of apremilast and biologic agents in itch intensity reduction in subjects suffering from psoriasis. Other treatment modalities include antihistamines, especially with a sedative effect, narrowband ultraviolet B, and antidepressants (doxepin, mirtazapine, paroxetine). Support by family members and/or health professionals may also be of importance in helping psoriatic subjects cope with itch.
Topics: Adaptation, Psychological; Anti-Inflammatory Agents, Non-Steroidal; Antidepressive Agents; Doxepin; Histamine Antagonists; Humans; Mianserin; Mirtazapine; Paroxetine; Pruritus; Psoriasis; Social Support; Thalidomide; Ultraviolet Therapy
PubMed: 27578078
DOI: 10.1159/000446050 -
International Clinical... Jul 2022Mirtazapine has often been prescribed as add-on treatment for schizophrenia in patients with suboptimal response to conventional treatments. In this review, we evaluate... (Review)
Review
Mirtazapine has often been prescribed as add-on treatment for schizophrenia in patients with suboptimal response to conventional treatments. In this review, we evaluate the existing evidence for efficacy and effectiveness of add-on mirtazapine in schizophrenia and reappraise the practical and theoretical aspects of mirtazapine-antipsychotic combinations. In randomized controlled trials (RCTs), mirtazapine demonstrated favourable effects on negative and cognitive (although plausibly not depressive) symptoms, with no risk of psychotic exacerbation. Mirtazapine also may have a desirable effect on antipsychotic-induced sexual dysfunction, but seems not to alleviate extrapyramidal symptoms, at least if combined with second-generation antipsychotics. It is noteworthy that all published RCTs have been underpowered and relatively short in duration. In the only large pragmatic effectiveness study that provided analyses by add-on antidepressant, only mirtazapine was associated with both decreased rate of hospital admissions and number of in-patient days. Mirtazapine hardly affects the pharmacokinetics of antipsychotics. However, possible pharmacodynamic interactions (sedation and metabolic offence) should be borne in mind. The observed desired clinical effects of mirtazapine may be due to its specific receptor-blocking properties. Alternative theoretical explanations include its possible neuroprotective effect. Further well-designed RCTs and real-world effectiveness studies are needed to determine whether add-on mirtazapine should be recommended for difficult-to-treat schizophrenia.
Topics: Antidepressive Agents; Antipsychotic Agents; Humans; Mianserin; Mirtazapine; Schizophrenia
PubMed: 35357339
DOI: 10.1097/YIC.0000000000000404 -
The Cochrane Database of Systematic... Aug 2018Fibromyalgia is a clinically defined chronic condition of unknown etiology characterised by chronic widespread pain, sleep disturbance, cognitive dysfunction, and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Fibromyalgia is a clinically defined chronic condition of unknown etiology characterised by chronic widespread pain, sleep disturbance, cognitive dysfunction, and fatigue. Many patients report high disability levels and poor quality of life. Drug therapy aims to reduce key symptoms, especially pain, and improve quality of life. The tetracyclic antidepressant, mirtazapine, may help by increasing serotonin and noradrenaline in the central nervous system (CNS).
OBJECTIVES
To assess the efficacy, tolerability and safety of the tetracyclic antidepressant, mirtazapine, compared with placebo or other active drug(s) in the treatment of fibromyalgia in adults.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, SCOPUS, the US National Institutes of Health, and the World Health Organization (WHO) International Clinical Trials Registry Platform for published and ongoing trials, and examined reference lists of reviewed articles, to 9 July 2018.
SELECTION CRITERIA
Randomised controlled trials (RCTs) of any formulation of mirtazapine against placebo, or any other active treatment of fibromyalgia, in adults.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted study characteristics, outcomes of efficacy, tolerability and safety, examined issues of study quality, and assessed risk of bias, resolving discrepancies by discussion. Primary outcomes were participant-reported pain relief (at least 50% or 30% pain reduction), Patient Global Impression of Change (PGIC; much or very much improved), safety (serious adverse events), and tolerability (adverse event withdrawal). Other outcomes were health-related quality of life (HRQoL) improved by 20% or more, fatigue, sleep problems, mean pain intensity, negative mood and particular adverse events. We used a random-effects model to calculate risk difference (RD), standardised mean difference (SMD), and numbers needed to treat. We assessed the evidence using GRADE and created a 'Summary of findings' table.
MAIN RESULTS
Three studies with 606 participants compared mirtazapine with placebo (but not other drugs) over seven to 13 weeks. Two studies were at unclear or high risk of bias in six or seven of eight domains. We judged the evidence for all outcomes to be low- or very low-quality because of poor study quality, indirectness, imprecision, risk of publication bias, and sometimes low numbers of events.There was no difference between mirtazapine and placebo for any primary outcome: participant-reported pain relief of 50% or greater (22% versus 16%; RD 0.05, 95% confidence interval (CI) -0.01 to 0.12; three studies with 591 participants; low-quality evidence); no data available for PGIC; only a single serious adverse event for evaluation of safety (RD -0.00, 95% CI -0.01 to 0.02; three studies with 606 participants; very low-quality evidence); and tolerability as frequency of dropouts due to adverse events (3% versus 2%; RD 0.00, 95% CI -0.02 to 0.03; three studies with 606 participants; low-quality evidence).Mirtazapine showed a clinically-relevant benefit compared to placebo for some secondary outcomes: participant-reported pain relief of 30% or greater (47% versus 34%; RD 0.13, 95% CI 0.05 to 0.21; number needed to treat for an additional beneficial outcome (NNTB) 8, 95% CI 5 to 20; three studies with 591 participants; low-quality evidence); participant-reported mean pain intensity (SMD -0.29, 95% CI -0.46 to -0.13; three studies with 591 participants; low-quality evidence); and participant-reported sleep problems (SMD -0.23, 95% CI -0.39 to -0.06; three studies with 573 participants; low-quality evidence). There was no benefit for improvement of participant-reported improvement of HRQoL of 20% or greater (58% versus 50%; RD 0.08, 95% CI -0.01 to 0.16; three studies with 586 participants; low-quality evidence); participant-reported fatigue (SMD -0.02, 95% CI -0.19 to 0.16; two studies with 533 participants; low-quality evidence); participant-reported negative mood (SMD -0.67, 95% CI -1.44 to 0.10; three studies with 588 participants; low-quality evidence); or withdrawals due to lack of efficacy (1.5% versus 0.1%; RD 0.01, 95% CI -0.01 to 0.02; three studies with 605 participants; very low-quality evidence).There was no difference between mirtazapine and placebo for participants reporting any adverse event (76% versus 59%; RD 0.12, 95 CI -0.01 to 0.26; three studies with 606 participants; low-quality evidence). There was a clinically-relevant harm with mirtazapine compared to placebo: in the number of participants with somnolence (42% versus 14%; RD 0.24, 95% CI 0.18 to 0.30; number needed to treat for an additional harmful outcome (NNTH) 5, 95% CI 3 to 6; three studies with 606 participants; low-quality evidence); weight gain (19% versus 1%; RD 0.17, 95% CI 0.11 to 0.23; NNTH 6, 95% CI 5 to 10; three studies with 606 participants; low-quality evidence); and elevated alanine aminotransferase (13% versus 2%; RD 0.13, 95% CI 0.04 to 0.22; NNTH 8, 95% CI 5 to 25; two studies with 566 participants; low-quality evidence).
AUTHORS' CONCLUSIONS
Studies demonstrated no benefit of mirtazapine over placebo for pain relief of 50% or greater, PGIC, improvement of HRQoL of 20% or greater, or reduction of fatigue or negative mood. Clinically-relevant benefits were shown for pain relief of 30% or greater, reduction of mean pain intensity, and sleep problems. Somnolence, weight gain, and elevated alanine aminotransferase were more frequent with mirtazapine than placebo. The quality of evidence was low or very low, with two of three studies of questionable quality and issues over indirectness and risk of publication bias. On balance, any potential benefits of mirtazapine in fibromyalgia were outweighed by its potential harms, though, a small minority of people with fibromyalgia might experience substantial symptom relief without clinically-relevant adverse events.
Topics: Adult; Antidepressive Agents, Tricyclic; Fibromyalgia; Humans; Mianserin; Mirtazapine; Randomized Controlled Trials as Topic
PubMed: 30080242
DOI: 10.1002/14651858.CD012708.pub2 -
Internal Medicine (Tokyo, Japan) 2017A 40-year-old woman with bipolar disorder who was taking mirtazapine presented with mydriasis, abnormal diaphoresis, myoclonus and muscle rigidity after taking...
A 40-year-old woman with bipolar disorder who was taking mirtazapine presented with mydriasis, abnormal diaphoresis, myoclonus and muscle rigidity after taking metocloplamide. Her medical history, which included the use of serotonergic agents, and the presence of symptoms including myoclonus and muscle rigidity were consistent with a diagnosis of serotonin syndrome (SS) according to the Hunter criteria. The symptoms diminished following three days of treatment with oral lorazepam and cyproheptadine and a reduced dose of mirtazapine. Metoclopramide is frequently used to various gastric symptom. Metoclopramide is not widely known to induce SS. This potentially fatal condition should be avoided by exercising care in the use of drugs that have the potential to cause drug-drug interactions.
Topics: Adult; Antiemetics; Bipolar Disorder; Drug Interactions; Female; Humans; Metoclopramide; Mianserin; Mirtazapine; Serotonin Syndrome; Selective Serotonin Reuptake Inhibitors
PubMed: 28321081
DOI: 10.2169/internalmedicine.56.7727 -
European Neuropsychopharmacology : the... Jan 2016Depression is common in pregnancy and associated with increased risk of adverse effects for the neonate. Treatment and prevention options include antidepressant therapy.... (Review)
Review
Depression is common in pregnancy and associated with increased risk of adverse effects for the neonate. Treatment and prevention options include antidepressant therapy. The aim of this paper was to review the literature on safety of mirtazapine during pregnancy and lactation. In 31 papers a total of 390 cases of neonates exposed to mirtazapine during pregnancy or lactation have been described. There might be an association between mirtazapine and spontaneous abortion, however, this might be attributable to underlying psychiatric disease. An increased risk of major neonatal malformations associated with mirtazapine in pregnancy has not been reported. Although one study showed a nearly significant increase in occurrence of respiratory problems and hypoglycaemia, no indication of causality could be given. No other significant adverse effects on neonates were reported. Limited available data, four papers on 11 exposed neonates, suggest that use of mirtazapine during breastfeeding is safe due to a low relative infant dose. High plasma levels might be associated with increased body weight and sleep. However, the reported data are too scarce to come to a clear assessment of the risk of mirtazapine in lactation. No information is available on the use of mirtazapine in pregnancy and Poor Neonatal Adaptation Syndrome (PNAS) or neurobehavioral development at an age over one year. In conclusion, mirtazapine seems to be safe in pregnancy, especially regarding incidence of congenital malformations. There are not enough data available to come to a conclusion on the safety of mirtazapine during lactation.
Topics: Antidepressive Agents, Tricyclic; Breast Feeding; Depressive Disorder; Female; Humans; Lactation; Mianserin; Mirtazapine; Pregnancy; Pregnancy Complications; Prenatal Exposure Delayed Effects; Risk
PubMed: 26631373
DOI: 10.1016/j.euroneuro.2015.06.014 -
Drug and Alcohol Dependence Mar 2022Amphetamine-type stimulants continue to dominate the global drug markets. Despite this, no pharmacotherapy has been approved for treatment of amphetamine and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Amphetamine-type stimulants continue to dominate the global drug markets. Despite this, no pharmacotherapy has been approved for treatment of amphetamine and methamphetamine use disorder (AMD). We evaluate the efficacy of mirtazapine in the treatment of AMD, given emerging evidence that it may alleviate methamphetamine and amphetamine (MA/A) cravings and withdrawals.
METHODS
We searched five databases from inception until January 28, 2021 for studies with a comparator group evaluating mirtazapine for treatment of AMD. We collected data on reduction in MA/A use, treatment retention, sexual behaviors, depression symptoms, cravings and adverse events. We assessed certainty of evidence using GRADE. Where appropriate, we conducted fixed-effect meta-analyses weighted by inverse variance and calculated the absolute risk reduction.
RESULTS
Among the 206 studies screened, we included two parallel-arm placebo-controlled RCTs conducted among cis-gender men and transgender women (n = 180). We found that mirtazapine use likely results in a small reduction of methamphetamine use compared to placebo after 12-weeks (relative risk [RR]=0.81, 95% confidence interval [CI]: 0.63, 1.03; n = 133; moderate certainty evidence due to imprecision). We also found that the use of mirtazapine probably does not improve retention in treatment (RR=1.01, 95% CI: 0.91, 1.12; n = 180; moderate certainty evidence) or depression symptom severity (mean difference [MD]=0.45, 95% CI: -2.88, 3.78; n = 53; moderate certainty evidence). There were no serious adverse events.
CONCLUSIONS AND RELEVANCE
Mirtazapine probably results in a small reduction in continued methamphetamine use among cisgender men and transgender women with AMD, but probably does not improve patients' retention in treatment or depression symptom severity.
STUDY REGISTRATION
PROSPERO ID: CRD42021236806.
Topics: Central Nervous System Stimulants; Female; Humans; Male; Methamphetamine; Mirtazapine; Remission Induction; Substance-Related Disorders
PubMed: 35066460
DOI: 10.1016/j.drugalcdep.2022.109295