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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 -
Therapeutic Advances in... 2023This review presents a comprehensive guide for optimizing medication management in older adults with depression within an outpatient setting. Medication optimization... (Review)
Review
This review presents a comprehensive guide for optimizing medication management in older adults with depression within an outpatient setting. Medication optimization involves tailoring the antidepressant strategy to the individual, ensuring the administration of appropriate medications at optimal dosages. In the case of older adults, this process necessitates not only adjusting or changing antidepressants but also addressing the concurrent use of inappropriate medications, many of which have cognitive side effects. This review outlines various strategies for medication optimization in late-life depression: (1) Utilizing the full dose range of a medication to maximize therapeutic benefits and strive for remission. (2) Transitioning to alternative classes (such as a serotonin and norepinephrine reuptake inhibitor [SNRI], bupropion, or mirtazapine) when first-line treatment with selective serotonin reuptake inhibitors [SSRIs] proves inadequate. (3) Exploring augmentation strategies like aripiprazole for treatment-resistant depression. (4) Implementing measurement-based care to help adjust treatment. (5) Sustaining an effective antidepressant strategy for at least 1 year following depression remission, with longer durations for recurrent episodes or severe presentations. (6) Safely discontinuing anticholinergic medications and benzodiazepines by employing a tapering method when necessary, coupled with counseling about the benefits of stopping them. Additionally, this article explores favorable medications for depression, as well as alternatives for managing anxiety, insomnia, allergy, overactive bladder, psychosis, and muscle spasm in order to avoid potent anticholinergics and benzodiazepines.
PubMed: 38022834
DOI: 10.1177/20451253231212327 -
Tzu Chi Medical Journal 2020Mirtazapine (MTZ) is an atypical antidepressant approved by the FDA, which mechanism of action involves the antagonism of alpha-2, H1, 5-HT2A, 5-HT2C, and 5-HT3... (Review)
Review
Mirtazapine (MTZ) is an atypical antidepressant approved by the FDA, which mechanism of action involves the antagonism of alpha-2, H1, 5-HT2A, 5-HT2C, and 5-HT3 receptors. In this context, the aim of this literature review is to evaluate the clinical epidemiological profile, pathological mechanisms, and management of MTZ-associated movement disorders (MDs). Relevant reports of six databases were identified and assessed by two reviewers without language restriction. Fifty-two reports containing 179 cases from 20 countries were assessed. The mean age was 57 year (range, 17-85). The majority of the individuals were female (60%) and of European origin. The mean time from MTZ start to symptom onset was 7.54 days; the time from management to MD improvement was within one week in 82.60% of the individuals. The MDs associated with MTZ were 69 restless legs syndrome (RLS), 35 tremors, 10 akathisia (AKT), 9 periodic limb MD, 6 dystonia, 4 rapid eye movement sleep behavior disorders, 3 dyskinesia, 2 parkinsonism, and 1 tic, and in the group not clearly identified, 18 restlessness, 15 hyperkinesis, and 1 extrapyramidal symptom. In the literature, the majority of the reports lack important information about the neurological examination. The management should be the MTZ withdrawal, except in RLS that other options are possible. In AKT, the MTZ should not be rechallenge, and if available, the prescription of a benzodiazepine may reduce recovery time.
PubMed: 33163376
DOI: 10.4103/tcmj.tcmj_13_20 -
Scientific Reports Nov 2020Mirtazapine, a noradrenergic and specific serotonergic antidepressant (NaSSA), is known to activate serotonin (5-HT) 1A receptor. Our recent study demonstrated that...
Mirtazapine, a noradrenergic and specific serotonergic antidepressant (NaSSA), is known to activate serotonin (5-HT) 1A receptor. Our recent study demonstrated that stimulation of astrocytic 5-HT1A receptors promoted astrocyte proliferation and upregulated antioxidative property in astrocytes to protect dopaminergic neurons against oxidative stress. Here, we evaluated the neuroprotective effects of mirtazapine against dopaminergic neurodegeneration in models of Parkinson's disease (PD). Mirtazapine administration attenuated the loss of dopaminergic neurons in the substantia nigra and increased the expression of the antioxidative molecule metallothionein (MT) in the striatal astrocytes of 6-hydroxydopamine (6-OHDA)-injected parkinsonian mice via 5-HT1A receptors. Mirtazapine protected dopaminergic neurons against 6-OHDA-induced neurotoxicity in mesencephalic neuron and striatal astrocyte cocultures, but not in enriched neuronal cultures. Mirtazapine-treated neuron-conditioned medium (Mir-NCM) induced astrocyte proliferation and upregulated MT expression via 5-HT1A receptors on astrocytes. Furthermore, treatment with medium from Mir-NCM-treated astrocytes protected dopaminergic neurons against 6-OHDA neurotoxicity, and these effects were attenuated by treatment with a MT-1/2-specific antibody or 5-HT1A antagonist. Our study suggests that mirtazapine could be an effective disease-modifying drug for PD and highlights that astrocytic 5-HT1A receptors may be a novel target for the treatment of PD.
Topics: Animals; Antioxidants; Astrocytes; Cells, Cultured; Dopamine; Dopaminergic Neurons; Female; Male; Metallothionein; Mice; Mice, Inbred ICR; Mirtazapine; Neuroprotection; Neuroprotective Agents; Oxidative Stress; Oxidopamine; Parkinson Disease; Pregnancy; Rats, Sprague-Dawley; Receptor, Serotonin, 5-HT1A; Substantia Nigra
PubMed: 33244123
DOI: 10.1038/s41598-020-77652-4 -
Health Technology Assessment... Oct 2023Agitation is common and impacts negatively on people with dementia and carers. Non-drug patient-centred care is first-line treatment, but we need other treatment when... (Randomized Controlled Trial)
Randomized Controlled Trial
A pragmatic, multicentre, double-blind, placebo-controlled randomised trial to assess the safety, clinical and cost-effectiveness of mirtazapine and carbamazepine in people with Alzheimer's disease and agitated behaviours: the HTA-SYMBAD trial.
BACKGROUND
Agitation is common and impacts negatively on people with dementia and carers. Non-drug patient-centred care is first-line treatment, but we need other treatment when this fails. Current evidence is sparse on safer and effective alternatives to antipsychotics.
OBJECTIVES
To assess clinical and cost-effectiveness and safety of mirtazapine and carbamazepine in treating agitation in dementia.
DESIGN
Pragmatic, phase III, multicentre, double-blind, superiority, randomised, placebo-controlled trial of the clinical effectiveness of mirtazapine over 12 weeks (carbamazepine arm discontinued).
SETTING
Twenty-six UK secondary care centres.
PARTICIPANTS
probable or possible Alzheimer's disease, agitation unresponsive to non-drug treatment, Cohen-Mansfield Agitation Inventory score ≥ 45.
INTERVENTIONS
Mirtazapine (target 45 mg), carbamazepine (target 300 mg) and placebo.
OUTCOME MEASURES
Cohen-Mansfield Agitation Inventory score 12 weeks post randomisation. incremental cost per six-point difference in Cohen-Mansfield Agitation Inventory score at 12 weeks, from health and social care system perspective. Data from participants and informants at baseline, 6 and 12 weeks. Long-term follow-up Cohen-Mansfield Agitation Inventory data collected by telephone from informants at 6 and 12 months.
RANDOMISATION AND BLINDING
Participants allocated 1 : 1 : 1 ratio (to discontinuation of the carbamazepine arm, 1 : 1 thereafter) to receive placebo or carbamazepine or mirtazapine, with treatment as usual. Random allocation was block stratified by centre and residence type with random block lengths of three or six (after discontinuation of carbamazepine, two or four). Double-blind, with drug and placebo identically encapsulated. Referring clinicians, participants, trial management team and research workers who did assessments were masked to group allocation.
RESULTS
Two hundred and forty-four participants recruited and randomised (102 mirtazapine, 102 placebo, 40 carbamazepine). The carbamazepine arm was discontinued due to slow overall recruitment; carbamazepine/placebo analyses are therefore statistically underpowered and not detailed in the abstract. placebo-mirtazapine (-1.74, 95% confidence interval -7.17 to 3.69; = 0.53). The number of controls with adverse events (65/102, 64%) was similar to the mirtazapine group (67/102, 66%). However, there were more deaths in the mirtazapine group ( = 7) by week 16 than in the control group ( = 1). Post hoc analysis suggests this was of marginal statistical significance ( = 0.065); this difference did not persist at 6- and 12-month assessments. At 12 weeks, the costs of unpaid care by the dyadic carer were significantly higher in the mirtazapine than placebo group [difference: £1120 (95% confidence interval £56 to £2184)]. In the cost-effectiveness analyses, mean raw and adjusted outcome scores and costs of the complete cases samples showed no differences between groups.
LIMITATIONS
Our study has four important potential limitations: (1) we dropped the proposed carbamazepine group; (2) the trial was not powered to investigate a mortality difference between the groups; (3) recruitment beyond February 2020, was constrained by the COVID-19 pandemic; and (4) generalisability is limited by recruitment of participants from old-age psychiatry services and care homes.
CONCLUSIONS
The data suggest mirtazapine is not clinically or cost-effective (compared to placebo) for agitation in dementia. There is little reason to recommend mirtazapine for people with dementia with agitation.
FUTURE WORK
Effective and cost-effective management strategies for agitation in dementia are needed where non-pharmacological approaches are unsuccessful.
STUDY REGISTRATION
This trial is registered as ISRCTN17411897/NCT03031184.
FUNDING
This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in ; Vol. 27, No. 23. See the NIHR Journals Library website for further project information.
Topics: Humans; Alzheimer Disease; Carbamazepine; Cost-Benefit Analysis; Mirtazapine; Pandemics; Quality of Life; Technology Assessment, Biomedical
PubMed: 37929672
DOI: 10.3310/VPDT7105 -
Current Neuropharmacology 2023People with epilepsy (PWE) are more likely to develop depression and both these complex chronic diseases greatly affect health-related quality of life (QOL). This... (Review)
Review
People with epilepsy (PWE) are more likely to develop depression and both these complex chronic diseases greatly affect health-related quality of life (QOL). This comorbidity contributes to the deterioration of the QOL further than increasing the severity of epilepsy worsening prognosis. Strong scientific evidence suggests the presence of shared pathogenic mechanisms. The correct identification and management of these factors are crucial in order to improve patients' QOL. This review article discusses recent original research on the most common pathogenic mechanisms of depression in PWE and highlights the effects of antidepressant drugs (ADs) against seizures in PWE and animal models of seizures and epilepsy. Newer ADs, such as selective serotonin reuptake inhibitors (SRRI) or serotonin-noradrenaline reuptake inhibitors (SNRI), particularly sertraline, citalopram, mirtazapine, reboxetine, paroxetine, fluoxetine, escitalopram, fluvoxamine, venlafaxine, duloxetine may lead to improvements in epilepsy severity whereas the use of older tricyclic antidepressant (TCAs) can increase the occurrence of seizures. Most of the data demonstrate the acute effects of ADs in animal models of epilepsy while there is a limited number of studies about the chronic antidepressant effects in epilepsy and epileptogenesis or on clinical efficacy. Much longer treatments are needed in order to validate the effectiveness of these new alternatives in the treatment and the development of epilepsy, while further clinical studies with appropriate protocols are warranted in order to understand the real potential contribution of these drugs in the management of PWE (besides their effects on mood).
Topics: Animals; Quality of Life; Antidepressive Agents; Selective Serotonin Reuptake Inhibitors; Epilepsy; Seizures
PubMed: 35761500
DOI: 10.2174/1570159X20666220627160048 -
Acta Psychiatrica Scandinavica Jun 2022To investigate the association between mirtazapine exposure in pregnancy and risk of specific adverse pregnancy outcomes.
OBJECTIVE
To investigate the association between mirtazapine exposure in pregnancy and risk of specific adverse pregnancy outcomes.
METHODS
A register-based nationwide cohort study was conducted including all registered pregnancies in Denmark from 1997 to 2016. Mirtazapine-exposed pregnancies were compared with mirtazapine unexposed pregnancies in a 1:4 ratio matched according to propensity scores. Outcomes were major congenital malformations analyzed using log binomial models, and spontaneous abortion, stillbirth and neonatal death analyzed using Cox proportional hazard regression.
RESULTS
From a source population of 1,650,649 pregnancies, the propensity score-matched cohort included 4475 pregnancies (895 mirtazapine exposed) in the analysis of major congenital malformations. The analyses of spontaneous abortion included 9 500 pregnancies (1900 mirtazapine exposed), and for the analyses of stillbirths and neonatal deaths 9725 (1 945 mirtazapine-exposed) and 4485 pregnancies (897 mirtazapine-exposed) were included, respectively. Thirty-one (3.5%) children were diagnosed with major congenital malformation among the mirtazapine exposed compared with 152 (4.3%) among the unexposed pregnancies (OR=0.81, 95% CI 0.55-1.20). Spontaneous abortion occurred in 237 (12.5%) of the mirtazapine exposed compared with 931 (12.3%) of the unexposed pregnancies (HR = 1.04%, 95% CI 0.91-1.20). The analyses revealed no increased risk of stillbirth (HR = 0.88%, 95% CI 0.34-2.29) or neonatal death (HR = 0.60%, 95% CI 0.18-2.02).
CONCLUSIONS
In this nationwide Danish register study, mirtazapine exposure in pregnancy was not associated with major congenital malformations, spontaneous abortion, stillbirth, or neonatal death. Clinicians and patients can be reassured that mirtazapine is safe in pregnancy.
Topics: Abortion, Spontaneous; Child; Cohort Studies; Female; Humans; Infant, Newborn; Mirtazapine; Perinatal Death; Pregnancy; Stillbirth
PubMed: 35320582
DOI: 10.1111/acps.13431 -
Substance Abuse and Rehabilitation 2017The cannabis withdrawal syndrome (CWS) is a criterion of cannabis use disorders (CUDs) () and cannabis dependence (International Classification of Diseases [ICD]-10).... (Review)
Review
The cannabis withdrawal syndrome (CWS) is a criterion of cannabis use disorders (CUDs) () and cannabis dependence (International Classification of Diseases [ICD]-10). Several lines of evidence from animal and human studies indicate that cessation from long-term and regular cannabis use precipitates a specific withdrawal syndrome with mainly mood and behavioral symptoms of light to moderate intensity, which can usually be treated in an outpatient setting. Regular cannabis intake is related to a desensitization and downregulation of human brain cannabinoid 1 (CB1) receptors. This starts to reverse within the first 2 days of abstinence and the receptors return to normal functioning within 4 weeks of abstinence, which could constitute a neurobiological time frame for the duration of CWS, not taking into account cellular and synaptic long-term neuroplasticity elicited by long-term cannabis use before cessation, for example, being possibly responsible for cannabis craving. The CWS severity is dependent on the amount of cannabis used pre-cessation, gender, and heritable and several environmental factors. Therefore, naturalistic severity of CWS highly varies. Women reported a stronger CWS than men including physical symptoms, such as nausea and stomach pain. Comorbidity with mental or somatic disorders, severe CUD, and low social functioning may require an inpatient treatment (preferably qualified detox) and post-acute rehabilitation. There are promising results with gabapentin and delta-9-tetrahydrocannabinol analogs in the treatment of CWS. Mirtazapine can be beneficial to treat CWS insomnia. According to small studies, venlafaxine can worsen the CWS, whereas other antidepressants, atomoxetine, lithium, buspirone, and divalproex had no relevant effect. Certainly, further research is required with respect to the impact of the CWS treatment setting on long-term CUD prognosis and with respect to psychopharmacological or behavioral approaches, such as aerobic exercise therapy or psychoeducation, in the treatment of CWS. The up-to-date ICD-11 Beta Draft is recommended to be expanded by physical CWS symptoms, the specification of CWS intensity and duration as well as gender effects.
PubMed: 28490916
DOI: 10.2147/SAR.S109576 -
The Cochrane Database of Systematic... May 2018Many individuals who have a diagnosis of schizophrenia experience a range of distressing and debilitating symptoms. These can include positive symptoms (such as... (Review)
Review
BACKGROUND
Many individuals who have a diagnosis of schizophrenia experience a range of distressing and debilitating symptoms. These can include positive symptoms (such as delusions, hallucinations, disorganised speech), cognitive symptoms (such as trouble focusing or paying attention or using information to make decisions), and negative symptoms (such as diminished emotional expression, avolition, alogia, and anhedonia). Antipsychotic drugs are often only partially effective, particularly in treating negative symptoms, indicating the need for additional treatment. Mirtazapine is an antidepressant drug that when taken in addition to an antipsychotic may offer some benefit for negative symptoms.
OBJECTIVES
To systematically assess the effects of mirtazapine as adjunct treatment for people with schizophrenia.
SEARCH METHODS
The Information Specialist of Cochrane Schizophrenia searched the Cochrane Schizophrenia Group's Study-Based Register of Trials (including registries of clinical trials) up to May 2018.
SELECTION CRITERIA
All randomised-controlled trials (RCTs) with useable data focusing on mirtazapine adjunct for people with schizophrenia.
DATA COLLECTION AND ANALYSIS
We extracted data independently. For binary outcomes, we calculated risk ratio (RR) and its 95% confidence interval (CI), on an intention-to-treat (ITT) basis. For continuous data, we estimated the mean difference (MD) between groups and its 95% CI. We employed a fixed-effect model for analyses. For included studies we assessed risk of bias and created 'Summary of findings' table using GRADE.
MAIN RESULTS
We included nine RCTs with a total of 310 participants. All studies compared mirtazapine adjunct with placebo adjunct and were of short-term duration. We considered five studies to have a high risk of bias for either incomplete outcome data, selective reporting, or other bias.Our main outcomes of interest were clinically important change in mental state (negative and positive symptoms), leaving the study early for any reason, clinically important change in global state, clinically important change in quality of life, number of days in hospital and incidence of serious adverse events.One trial defined a reduction in the Scale for the Assessment of Negative Symptoms (SANS) overall score from baseline of at least 20% as no important response for negative symptoms. There was no evidence of a clear difference between the two treatments with similar numbers of participants from each group showing no important response to treatment (RR 0.81, 95% CI 0.57 to 1.14, 1 RCT, n = 20, very low-quality evidence).Clinically important change in positive symptoms was not reported, however, clinically important change in overall mental state was reported by two trials and data for this outcome showed a favourable effect for mirtazapine (RR 0.69, 95% CI 0.51 to 0.92; I = 75%, 2 RCTs, n = 77, very low-quality evidence). There was no evidence of a clear difference for numbers of participants leaving the study early (RR 1.03, 95% CI 0.64 to 1.66, 9 RCTs, n = 310, moderate-quality evidence), and no evidence of a clear difference in global state Clinical Global Impressions Scale (CGI) severity scores (MD -0.10, 95% CI -0.68 to 0.48, 1 RCT, n = 39, very low-quality evidence). A favourable effect for mirtazapine adjunct was found for the outcome clinically important change in akathisia (RR 0.33, 95% CI 0.20 to 0.52, 2 RCTs, n = 86, low-quality evidence; I = 61%I). No data were reported for quality life or number of days in hospital.In addition to the main outcomes of interest, there was evidence relating to adverse events that the mirtazapine adjunct groups were associated with an increased risk of weight gain (RR 3.19, 95% CI 1.17 to 8.65, 4 RCTs, n = 127) and sedation/drowsiness (RR 1.64, 95% CI 1.01 to 2.68, 7 RCTs, n = 223).
AUTHORS' CONCLUSIONS
The available evidence is primarily of very low quality and indicates that mirtazapine adjunct is not clearly associated with an effect for negative symptoms, but there is some indication of a positive effect on overall mental state and akathisia. No effect was found for global state or leaving the study early and data were not available for quality of life or service use. Due to limitations of the quality and applicability of the evidence it is not possible to make any firm conclusions, the role of mirtazapine adjunct in routine clinical practice remains unclear. This underscores the need for new high-quality evidence to further evaluate mirtazapine adjunct for schizophrenia.
Topics: Antidepressive Agents, Tricyclic; Antipsychotic Agents; Chemotherapy, Adjuvant; Humans; Mianserin; Mirtazapine; Patient Dropouts; Quality of Life; Randomized Controlled Trials as Topic; Schizophrenia; Schizophrenic Psychology; Weight Gain
PubMed: 29802811
DOI: 10.1002/14651858.CD011943.pub2