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Cancers Jul 2023This study compared mirtazapine with megestrol in the management of cancer-related anorexia-cachexia syndrome in patients with advanced cancer. A randomized,...
Mirtazapine versus Megestrol in the Treatment of Anorexia-Cachexia Syndrome in Patients with Advanced Cancer: A Randomized, Double-Blind, Controlled Phase II Clinical Trial.
This study compared mirtazapine with megestrol in the management of cancer-related anorexia-cachexia syndrome in patients with advanced cancer. A randomized, double-blind, controlled clinical trial involving patients with advanced cancer and anorexia-cachexia syndrome was performed. Participants received mirtazapine 30 mg/day or megestrol 320 mg/day for eight weeks. The primary endpoint was the effect of mirtazapine on weight gain and the secondary endpoints were its effect on appetite, muscle strength, physical performance, body composition, adverse events, and medication adherence. Linear regression model with mixed effects was applied and a significance level of 5% was adopted. Fifty-two patients were randomized. Mean age was 65.8 ± 8.4 years. There was weight gain in 52% of the participants in the megestrol group and in 38% in the mirtazapine group after four weeks ( = 0.040). Appetite improved in 92% of the participants in the megestrol group and in 56% in the mirtazapine group after eight weeks ( = 0.007). In the sub-analysis by sex, women showed improvement in appetite ( < 0.001) and weight gain ( < 0.005) in the mirtazapine group, which was not observed in men. Mirtazapine appears to be inferior to megestrol in weight and appetite improvement. However, there may be a difference in the therapeutic response between sexes.
PubMed: 37509249
DOI: 10.3390/cancers15143588 -
American Family Physician Jul 2015One in 11 U.S. adults currently meets diagnostic criteria for major depressive disorder, and a similar number report that they have taken an antidepressant medication in... (Review)
Review
One in 11 U.S. adults currently meets diagnostic criteria for major depressive disorder, and a similar number report that they have taken an antidepressant medication in the past 30 days. In the primary care population, medications are modestly superior to placebo in achieving remission, with a number needed to treat of seven or eight for selective serotonin reuptake inhibitors and seven to 16 for tricyclic antidepressants. The benefit of antidepressants over placebo is more pronounced in patients with severe depression. Second-generation antidepressants are generally considered first-line therapy. Specific therapy choice should be based on cost, patient preference, and adverse effect profile. About two-thirds of patients receiving second-generation antidepressants experience at least one adverse effect during treatment. Nausea and vomiting are the most common reasons for discontinuation of therapy. The optimal treatment duration is unclear, but clinical guidelines suggest four to 12 months for an initial episode of major depression. Patients with recurrent depression may benefit from prolonged treatment. High-quality evidence is lacking on the benefits and harms of antidepressant use in pregnancy. It is unclear whether selective serotonin reuptake inhibitor use in breastfeeding mothers causes adverse effects in their infants, but sertraline and paroxetine transfer to breast milk in lower concentrations than other antidepressants. Consensus guidelines recommend a "start low, go slow" approach to antidepressant therapy in older persons; preferred medications include citalopram, escitalopram, sertraline, mirtazapine, and venlafaxine.
Topics: Adult; Antidepressive Agents; Depression; Depressive Disorder, Major; Drug Administration Schedule; Humans; Serotonin and Noradrenaline Reuptake Inhibitors; Treatment Outcome
PubMed: 26176368
DOI: No ID Found -
Cureus Jun 2021The clinical presentations of neuroleptic malignant syndrome (NMS) and malignant catatonia (MC) are similar, posing a diagnostic challenge. Here, we present a...
The clinical presentations of neuroleptic malignant syndrome (NMS) and malignant catatonia (MC) are similar, posing a diagnostic challenge. Here, we present a 58-year-old Caucasian male who presented to the emergency department with an altered mental state, fever, tachycardia, and rigidity. Labs were remarkable for elevated creatine phosphokinase (CPK) and leukocytosis. The patient was on a regimen of clozapine and cariprazine to manage schizophrenia, lorazepam to treat catatonia, and mirtazapine to treat insomnia and appetite stimulation. The patient was initially diagnosed with NMS after common metabolic, infectious, and substance-induced etiologies were ruled out. Within 72 hours of receiving dantrolene and lorazepam, the patient's fever, tachycardia, and other laboratory abnormalities resolved. However, when the patient's rigidity, waxy flexibility, mutism, and stupor persisted, the diagnosis was reconsidered and changed to MC. Our case discusses the overlapping clinical presentations of NMS and MC, demonstrating a diagnostic challenge.
PubMed: 34306883
DOI: 10.7759/cureus.15818 -
Journal of the American Association For... Sep 2022Inappetence is a welfare concern in rabbits (, as it can lead to potentially fatal gastrointestinal stasis. In other species, inappetence is commonly treated with...
Inappetence is a welfare concern in rabbits (, as it can lead to potentially fatal gastrointestinal stasis. In other species, inappetence is commonly treated with appetite stimulants; however, few published studies have evaluated the efficacy of appetite stimulants in rabbits. We performed 2 studies to evaluate the effects of capromorelin and mirtazapine on appetite in New Zealand White (NZW) rabbits. In the first study, healthy rabbits ( = 9) were evaluated using a randomized crossover design and 9 treatments: capromorelin 4 mg/kg oral (PO) once a day (SID), capromorelin 8 mg/kg PO SID, saline control PO SID, capromorelin 4 mg/kg PO twice a day (BID), capromorelin 8 mg/kg PO BID, saline control PO BID, mirtazapine 0.5 mg/kg transdermal (TD) SID, mirtazapine 1 mg/kg TD SID, and saline control TD SID for 3 d with a 1-wk washout period between treatments. Treatment efficacy was assessed by measuring daily feed intake and fecal output and by weighing rabbits twice a week. Overall, feed intake and fecal output were higher for all treatments as compared with controls, except for fecal output in the capromorelin 4 mg/kg and 8 mg/kg PO SID groups. Feed intake and fecal output were significantly higher with mirtazapine as compared with capromorelin. Body weight and erythema/petechia of the pinnae were greater in the mirtazapine 1 mg/kg TD SID group than in the control group. A second study evaluated rabbits that had undergone surgery (castration, = 7) and then received one of 3 treatments: capromorelin 8 mg/kg PO BID, mirtazapine 1 mg/kg TD SID, or saline PO BID for 3 d postoperatively. Feed intake and fecal output in the postoperative mirtazapine group were not significantly different from those of the capromorelin and control groups. Due to its superior efficacy as compared with capromorelin in healthy NZW rabbits, we recommend considering mirtazapine as a treatment for inappetence in NZW rabbits.
Topics: Animals; Rabbits; Appetite; Appetite Stimulants; Mirtazapine; Piperidines; Pyrazoles
PubMed: 35981857
DOI: 10.30802/AALAS-JAALAS-22-000003 -
PloS One 2022Hormonal fluctuations, such as the perinatal period, may increase susceptibility of women to depression, which in turn exert a negative impact on child's...
Hormonal fluctuations, such as the perinatal period, may increase susceptibility of women to depression, which in turn exert a negative impact on child's neurodevelopment, becoming a risk factor in development of neuropsychiatric disorders. Moreover, the use of antidepressants during this critical period presents a serious health concern for both the mother and the child, due to the consequences of treatment in terms of the reliability and safety for the proper neurodevelopment of the organism being not well known. Atypical antidepressants, such as mirtazapine, that targets both serotonergic and noradrenergic systems in the central nervous system (CNS), represent a novel focus of research due to its unique pharmacological profile. The aim of this work was to study the effects of maternal depression and/or perinatal antidepressant mirtazapine treatment on the neurobehavioral development of the offspring. Pre-gestationally chronically stressed or non-stressed Wistar rat dams were treated with either mirtazapine (10 mg/kg/day) or vehicle during pregnancy and lactation followed by analysis of offspring's behavior at juvenile and adolescent age. We found mirtazapine induced significant alterations of nursing behavior. In offspring, pregestational stress (PS) had an anxiogenic effect on adolescent males (p≤0.05) and increased their active behavior in forced swim test (p≤0.01). Interaction between pregestational stress and mirtazapine treatment variously induced anxiolytic changes of juvenile (p≤0.05) and adolescent (p≤0.05) females and impairment of spatial memory (p≤0.01) in adolescent females as well. Hippocampal density of synaptophysin, pre-synaptic protein marker, was decreased mainly by mirtazapine treatment. In conclusion, our results show mirtazapine induced significant alterations in maternal behavior and several sex- and age-dependent changes in neurobehavioral development of offspring caused by both prenatal mirtazapine treatment and/or chronic pregestational stress.
Topics: Mirtazapine
PubMed: 35113878
DOI: 10.1371/journal.pone.0255546 -
Annals of General Psychiatry Nov 2023Factors influencing antidepressant treatment discontinuation are poorly understood. In the present study, we aimed to estimate the prevalence of antidepressant treatment...
BACKGROUND
Factors influencing antidepressant treatment discontinuation are poorly understood. In the present study, we aimed to estimate the prevalence of antidepressant treatment discontinuation and identify demographic characteristics, psychiatric comorbidities, and specific side effects associated with treatment discontinuation.
METHODS
We leveraged data from the Australian Genetics of Depression Study (AGDS; N = 20,941) to perform a retrospective cohort study on antidepressant treatment discontinuation. Participants were eligible if they were over 18 years of age, had taken antidepressants in the past 4 years, and provided informed consent.
RESULTS
Among the ten antidepressants studied, the highest discontinuation rates were observed for Mirtazapine (57.3%) and Amitriptyline (51.6%). Discontinuation rates were comparable across sexes except for Mirtazapine, for which women were more likely to discontinue. The two most common side effects, reduced sexual function and weight gain, were not associated with increased odds of treatment discontinuation. Anxiety, agitation, suicidal thoughts, vomiting, and rashes were associated with higher odds for treatment discontinuation, as were lifetime diagnoses of PTSD, ADHD, and a higher neuroticism score. Educational attainment showed a negative (protective) association with discontinuation across medications.
CONCLUSIONS
Our study suggests that not all side effects contribute equally to discontinuation. Common side effects such as reduced sexual function and weight gain may not necessarily increase the risk of treatment discontinuation. Side effects linked to discontinuation can be divided into two groups, psychopathology related and allergy/intolerance.
PubMed: 38001492
DOI: 10.1186/s12991-023-00480-z -
Iranian Journal of Pharmaceutical... 2020We evaluated and compared the efficacy and safety of mirtazapine (MTZ) with olanzapine (OLP) for preventing chemotherapy-induced nausea and vomiting (CINV) following...
We evaluated and compared the efficacy and safety of mirtazapine (MTZ) with olanzapine (OLP) for preventing chemotherapy-induced nausea and vomiting (CINV) following anthracycline plus cyclophosphamide (AC) regimen. Eligible participants were chemotherapy-naive early-stage breast cancer patients who were scheduled to undergo adjuvant AC. The patients were randomized to take oral MTZ or OLP in combination with aprepitant (A), dexamethasone (D), and granisetron (G), (ADG). The endpoints included rates of complete response (CR), complete control (CC), total control (TC), and adverse events during the acute, delayed, and overall phases in the two cycles of chemotherapy. The influence of CINV on the quality of life (QoL) was evaluated on day 6 of chemotherapy. Of 82 patients, 60 were randomized. In the first cycle, CR rates in cycle 1 were 83.3% and 76.6% during the acute period, 80% and 86.6% during the delayed period, and 66.6% and 63.3% during the overall period, for the ADG-M and ADG-O, respectively. High efficacy of both groups was maintained over 2 cycles. More patients in the ADG-M group noted minimal or no impact of CINV on daily life in cycle 2 (89.7% 67.9%; 0.044). Incidence of somnolence and fatigue was more frequent with the olanzapine group. In this study, there was no substantial difference between mirtazapine and olanzapine in preventing CINV. Further large randomized trials are essential to demonstrate the anti-emetic effect of mirtazapine in chemotherapy.
PubMed: 33680044
DOI: 10.22037/ijpr.2020.113955.14584 -
Journal of Physiology and Pharmacology... Oct 2021Recent studies suggest that impaired glutathione synthesis and dopaminergic transmission are important factors in the pathophysiology of schizophrenia. Moreover, some...
Repeated co-treatment with mirtazapine and aripiprazole reversed the schizophrenia-like behaviors and increased the brain-derived neurotrophic factor mRNA expression in the adult Sprague-Dawley rats exposed to glutathione deficit during early postnatal brain development.
Recent studies suggest that impaired glutathione synthesis and dopaminergic transmission are important factors in the pathophysiology of schizophrenia. Moreover, some studies have suggested that antidepressants are able to increase the activity of atypical antipsychotics which may efficiently improve the treatment of negative and some cognitive symptoms of schizophrenia. In the present study, we investigated the influence of repeated co-treated with mirtazapine and aripiprazole on the schizophrenia-like behavior and brain-derived neurotrophic factor (BDNF) mRNA expression in adult rats exposed to glutathione deficit during early postnatal development. Between the postnatal days p5-p16, male pups were treated with the inhibitor of glutathione synthesis, BSO (L-buthionine-(S,R)-sulfoximine) and the dopamine uptake inhibitor, GBR 12909 alone or in combination. Mirtazapine and aripiprazole were given repeatedly, once daily for 21 days before the tests. The behavioral and biochemical tests were performed in p90-92 rats. BSO given alone and in combination with GBR 12909 induced deficits in the studied behavioral tests and decreased the expression of BDNF mRNA. Repeated aripiprazole administration at a higher dose reversed these behavioral deficits. Co-treatment with an ineffective dose of aripiprazole and mirtazapine also abolished the behavioral deficits and biochemical changes, especially in the hippocampus in these rats. The present study indicated that the inhibition of glutathione synthesis in early postnatal development induced long-term deficits corresponding to schizophrenia-like behavior and decreased the BDNF mRNA expression in adult rats, and these behavioural and biochemical deficits were reversed by repeated treatment with a higher dose of aripiprazole and also by co-treatment with an ineffective dose of aripiprazole and mirtazapine. The above data suggest that this neurodevelopment rat model of schizophrenia-induced by glutathione deficit evoked by repeated treatment with BSO alone and together with GBR 12909 in early postnatal life may be useful for studies on the pathomechanism of schizophrenia.
Topics: Animals; Aripiprazole; Brain; Brain-Derived Neurotrophic Factor; Glutathione; Male; Mirtazapine; RNA, Messenger; Rats; Rats, Sprague-Dawley; Schizophrenia
PubMed: 35158332
DOI: 10.26402/jpp.2021.5.05 -
Gastroenterology and Hepatology From... 2023In the current clinical trial study, the potency of mirtazapine and nortriptyline was compared in patients with Functional Dyspepsia (FD) who had anxiety or depression.
AIM
In the current clinical trial study, the potency of mirtazapine and nortriptyline was compared in patients with Functional Dyspepsia (FD) who had anxiety or depression.
BACKGROUND
FD usually accompanies other psychosocial disorders. According to previous studies, among these disorders, anxiety and depression have the most correlation.
METHODS
This randomized clinical trial was organized in Taleghani hospital (Tehran, Iran). In two parallel groups, 42 patients were treated for 12 weeks, with 22 patients receiving 7.5 mg of mirtazapine and 20 patients receiving 25 mg of nortriptyline per day. To gain robust results, the patients with a positive history of antidepressant therapy, organic diseases, alcohol abuse, pregnancy, and major psychiatric disorders were excluded from the study. The subjects were examined by three questionnaires, including Nepean and Hamilton questionnaires. The patients were asked to answer the questions three times during the study: once before the onset of the treatment, second during the treatment, and third at the end of the treatment.
RESULTS
Based on Gastrointestinal (GI) manifestations, mirtazapine, in comparison to nortriptyline could significantly suppress the signs and symptoms of FD, including epigastric pains (P=0.02), belching (P=0.004), and bloating (P=0.01). Although the results from the use of mirtazapine compared to the use of nortriptyline (P=0.002) showed a lower mean depression score on the Hamilton questionnaire, no significant differences were found between the effects of these drugs on the anxiety scale of patients (P=0.091).
CONCLUSION
Mirtazapine is more effective for GI symptoms related to gastric emptying. Considering the level of anxiety, mirtazapine, compared to nortriptyline, revealed better outcomes in FD patients suffering from depression.
PubMed: 37070114
DOI: 10.22037/ghfbb.v16i1.2513 -
The Cochrane Database of Systematic... May 2023Harmful alcohol use is defined as unhealthy alcohol use that results in adverse physical, psychological, social, or societal consequences and is among the leading risk... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Harmful alcohol use is defined as unhealthy alcohol use that results in adverse physical, psychological, social, or societal consequences and is among the leading risk factors for disease, disability and premature mortality globally. The burden of harmful alcohol use is increasing in low- and middle-income countries (LMICs) and there remains a large unmet need for indicated prevention and treatment interventions to reduce harmful alcohol use in these settings. Evidence regarding which interventions are effective and feasible for addressing harmful and other patterns of unhealthy alcohol use in LMICs is limited, which contributes to this gap in services.
OBJECTIVES
To assess the efficacy and safety of psychosocial and pharmacologic treatment and indicated prevention interventions compared with control conditions (wait list, placebo, no treatment, standard care, or active control condition) aimed at reducing harmful alcohol use in LMICs.
SEARCH METHODS
We searched for randomized controlled trials (RCTs) indexed in the Cochrane Drugs and Alcohol Group (CDAG) Specialized Register, the Cochrane Clinical Register of Controlled Trials (CENTRAL) in the Cochrane Library, PubMed, Embase, PsycINFO, CINAHL, and the Latin American and Caribbean Health Sciences Literature (LILACS) through 12 December 2021. We searched clinicaltrials.gov, the World Health Organization International Clinical Trials Registry Platform, Web of Science, and Opengrey database to identify unpublished or ongoing studies. We searched the reference lists of included studies and relevant review articles for eligible studies.
SELECTION CRITERIA
All RCTs comparing an indicated prevention or treatment intervention (pharmacologic or psychosocial) versus a control condition for people with harmful alcohol use in LMICs were included.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane.
MAIN RESULTS
We included 66 RCTs with 17,626 participants. Sixty-two of these trials contributed to the meta-analysis. Sixty-three studies were conducted in middle-income countries (MICs), and the remaining three studies were conducted in low-income countries (LICs). Twenty-five trials exclusively enrolled participants with alcohol use disorder. The remaining 51 trials enrolled participants with harmful alcohol use, some of which included both cases of alcohol use disorder and people reporting hazardous alcohol use patterns that did not meet criteria for disorder. Fifty-two RCTs assessed the efficacy of psychosocial interventions; 27 were brief interventions primarily based on motivational interviewing and were compared to brief advice, information, or assessment only. We are uncertain whether a reduction in harmful alcohol use is attributable to brief interventions given the high levels of heterogeneity among included studies (Studies reporting continuous outcomes: Tau² = 0.15, Q =139.64, df =16, P<.001, I² = 89%, 3913 participants, 17 trials, very low certainty; Studies reporting dichotomous outcomes: Tau²=0.18, Q=58.26, df=3, P<.001, I² =95%, 1349 participants, 4 trials, very low certainty). The other types of psychosocial interventions included a range of therapeutic approaches such as behavioral risk reduction, cognitive-behavioral therapy, contingency management, rational emotive therapy, and relapse prevention. These interventions were most commonly compared to usual care involving varying combinations of psychoeducation, counseling, and pharmacotherapy. We are uncertain whether a reduction in harmful alcohol use is attributable to psychosocial treatments due to high levels of heterogeneity among included studies (Heterogeneity: Tau² = 1.15; Q = 444.32, df = 11, P<.001; I²=98%, 2106 participants, 12 trials, very low certainty). Eight trials compared combined pharmacologic and psychosocial interventions with placebo, psychosocial intervention alone, or another pharmacologic treatment. The active pharmacologic study conditions included disulfiram, naltrexone, ondansetron, or topiramate. The psychosocial components of these interventions included counseling, encouragement to attend Alcoholics Anonymous, motivational interviewing, brief cognitive-behavioral therapy, or other psychotherapy (not specified). Analysis of studies comparing a combined pharmacologic and psychosocial intervention to psychosocial intervention alone found that the combined approach may be associated with a greater reduction in harmful alcohol use (standardized mean difference (standardized mean difference (SMD))=-0.43, 95% confidence interval (CI): -0.61 to -0.24; 475 participants; 4 trials; low certainty). Four trials compared pharmacologic intervention alone with placebo and three with another pharmacotherapy. Drugs assessed were: acamprosate, amitriptyline, baclofen disulfiram, gabapentin, mirtazapine, and naltrexone. None of these trials evaluated the primary clinical outcome of interest, harmful alcohol use. Thirty-one trials reported rates of retention in the intervention. Meta-analyses revealed that rates of retention between study conditions did not differ in any of the comparisons (pharmacologic risk ratio (RR) = 1.13, 95% CI: 0.89 to 1.44, 247 participants, 3 trials, low certainty; pharmacologic in addition to psychosocial intervention: RR = 1.15, 95% CI: 0.95 to 1.40, 363 participants, 3 trials, moderate certainty). Due to high levels of heterogeneity, we did not calculate pooled estimates comparing retention in brief (Heterogeneity: Tau² = 0.00; Q = 172.59, df = 11, P<.001; I = 94%; 5380 participants; 12 trials, very low certainty) or other psychosocial interventions (Heterogeneity: Tau² = 0.01; Q = 34.07, df = 8, P<.001; I = 77%; 1664 participants; 9 trials, very low certainty). Two pharmacologic trials and three combined pharmacologic and psychosocial trials reported on side effects. These studies found more side effects attributable to amitriptyline relative to mirtazapine, naltrexone and topiramate relative to placebo, yet no differences in side effects between placebo and either acamprosate or ondansetron. Across all intervention types there was substantial risk of bias. Primary threats to validity included lack of blinding and differential/high rates of attrition.
AUTHORS' CONCLUSIONS
In LMICs there is low-certainty evidence supporting the efficacy of combined psychosocial and pharmacologic interventions on reducing harmful alcohol use relative to psychosocial interventions alone. There is insufficient evidence to determine the efficacy of pharmacologic or psychosocial interventions on reducing harmful alcohol use largely due to the substantial heterogeneity in outcomes, comparisons, and interventions that precluded pooling of these data in meta-analyses. The majority of studies are brief interventions, primarily among men, and using measures that have not been validated in the target population. Confidence in these results is reduced by the risk of bias and significant heterogeneity among studies as well as the heterogeneity of results on different outcome measures within studies. More evidence on the efficacy of pharmacologic interventions, specific types of psychosocial interventions are needed to increase the certainty of these results.
Topics: Humans; Male; Acamprosate; Alcoholism; Amitriptyline; Developing Countries; Disulfiram; Mirtazapine; Naltrexone; Ondansetron; Topiramate
PubMed: 37158538
DOI: 10.1002/14651858.CD013350.pub2