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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 -
Cureus Apr 2023Acute pancreatitis is a concerning cause of hospitalization in the United States, with the most common etiologies being secondary to alcohol abuse and gallstones....
Acute pancreatitis is a concerning cause of hospitalization in the United States, with the most common etiologies being secondary to alcohol abuse and gallstones. Rarely, medications can trigger this inflammatory response, whether via direct toxic effects or other metabolic derangements. Mirtazapine is an antidepressant that has been associated with elevations in triglyceride levels on initiation. Relatedly, high triglyceride levels and autoimmune disorders are other causes of pancreatitis exacerbations. Here, we present the case of a female who was started on mirtazapine therapy and found to have elevated triglyceride levels. The course was complicated by acute pancreatitis requiring plasmapheresis, despite medication discontinuation, to which she responded well.
PubMed: 37153315
DOI: 10.7759/cureus.37129 -
Annales de Biologie Clinique Jun 2018We report the case of a 40-year-old patient followed for post-traumatic stress disorder. A re-evaluation of its pharmacological treatment with the introduction of...
We report the case of a 40-year-old patient followed for post-traumatic stress disorder. A re-evaluation of its pharmacological treatment with the introduction of mirtazapine (30 mg/day) was associated with a rhabdomyolysis (CK> 20,000 IU/L at day 3). The diagnosis of mirtazapine induced rhabdomyolysis was made. After withdrawal of this drug combined with a symptomatic treatment (hydratation), the patient recovered well and was discharged without any nephrological sequelae. This article is intended to underline the diagnostic approach to elevated CK activity and the potential role of the "medical biologist" as a consultant for the relevant use of biological examinations. A physiopathological mechanism of this rhabdomyolysis is also proposed.
Topics: Adult; Antipsychotic Agents; Humans; Male; Mianserin; Mirtazapine; Rhabdomyolysis; Stress Disorders, Post-Traumatic
PubMed: 29862972
DOI: 10.1684/abc.2018.1351 -
Research Synthesis Methods Jan 2020Missing data result in less precise and possibly biased effect estimates in single studies. Bias arising from studies with incomplete outcome data is naturally... (Review)
Review
Missing data result in less precise and possibly biased effect estimates in single studies. Bias arising from studies with incomplete outcome data is naturally propagated in a meta-analysis. Conventional analysis using only individuals with available data is adequate when the meta-analyst can be confident that the data are missing at random (MAR) in every study-that is, that the probability of missing data does not depend on unobserved variables, conditional on observed variables. Usually, such confidence is unjustified as participants may drop out due to lack of improvement or adverse effects. The MAR assumption cannot be tested, and a sensitivity analysis to assess how robust results are to reasonable deviations from the MAR assumption is important. Two methods may be used based on plausible alternative assumptions about the missing data. Firstly, the distribution of reasons for missing data may be used to impute the missing values. Secondly, the analyst may specify the magnitude and uncertainty of possible departures from the missing at random assumption, and these may be used to correct bias and reweight the studies. This is achieved by employing a pattern mixture model and describing how the outcome in the missing participants is related to the outcome in the completers. Ideally, this relationship is informed using expert opinion. The methods are illustrated in two examples with binary and continuous outcomes. We provide recommendations on what trial investigators and systematic reviewers should do to minimize the problem of missing outcome data in meta-analysis.
Topics: Bias; Data Collection; Data Interpretation, Statistical; Depression; Haloperidol; Humans; Meta-Analysis as Topic; Mirtazapine; Models, Statistical; Probability; Randomized Controlled Trials as Topic; Reproducibility of Results; Research Design; Schizophrenia; Treatment Outcome; Uncertainty
PubMed: 30991455
DOI: 10.1002/jrsm.1349 -
Cureus Dec 2021Hyponatremia is the most common fluid and electrolyte imbalance in hospitalized patients. Among hyponatremia causes, syndrome of inappropriate antidiuretic hormone... (Review)
Review
Hyponatremia is the most common fluid and electrolyte imbalance in hospitalized patients. Among hyponatremia causes, syndrome of inappropriate antidiuretic hormone secretion is a condition characterized by excessive release of antidiuretic hormone from the pituitary gland or nonpituitary sources. One of the most common drugs associated with hyponatremia is selective serotonin reuptake inhibitors, especially in elderly patients. Therefore, distinct therapeutic alternatives are essential for patients having risk factors for hyponatremia or syndrome of inappropriate antidiuretic hormone secretion development. The present article aims to review the available literature evaluating mirtazapine-induced hyponatremia or syndrome of inappropriate antidiuretic hormone secretion in adult or elderly patients in order to determine the incidence of these adverse effects and analyze the existence of any correlation between the administered dose of mirtazapine and serum sodium levels. A systematic search was conducted, using key terms from the research topic, their synonyms, and Boolean/logic operators. From this evidence pool, inclusion and exclusion criteria were applied. We abstracted population characteristics and clinical endpoints. Relevant data from selected studies was abstracted and subject to statistical analysis. A total sample size of 30,851 patients treated with mirtazapine was included. Mirtazapine-induced hyponatremia incidence was 3.26% (95% CI 3.06-3.45%), with the syndrome of inappropriate antidiuretic hormone secretion (SIADH) the most probable underlying cause. Among case series and case reports evaluated (n=7), hyponatremia and SIADH were more frequent in female patients (71.4%) and the most frequent clinical manifestations included confusion (57%), somnolence (42%), and altered speech (28%). Mean serum sodium levels were (117 mEq/L, ranging from 113-130 mEq/L). The average time lapse between mirtazapine administration and clinical findings was 34 days. The Spearman's rank correlation coefficient between mirtazapine dosage and serum sodium levels was -0.3181 with a p-value >0.05. In conclusion, mirtazapine presents a moderate risk of hyponatremia and should be considered as an alternative therapy in patients requiring antidepressants with risk factors for this preventable adverse effect.
PubMed: 35141079
DOI: 10.7759/cureus.20823 -
The Mental Health Clinician May 2018Anorexia nervosa (AN) is a severe psychiatric disorder that is difficult to treat and is associated with frequent relapses and high mortality rates. Psychiatric... (Review)
Review
INTRODUCTION
Anorexia nervosa (AN) is a severe psychiatric disorder that is difficult to treat and is associated with frequent relapses and high mortality rates. Psychiatric symptomatology (eg, depression, anxiety, obsessive-compulsive disorder/behaviors) are common comorbidities. This review provides current information about safety and efficacy of antidepressant therapy for management of AN in adults.
METHODS
A literature review of randomized controlled trials, open-label studies, and case reports with adults or adults/adolescents was conducted. PubMed and Medline were searched using anorexia management and treatment, antidepressants, selective serotonin reuptake inhibitors (SSRIs), fluoxetine, sertraline, citalopram, and mirtazapine in AN, relapse prevention in AN, and psychotropic medications in AN.
RESULTS
The role and utility of antidepressants in AN were published in double-blind, placebo-controlled studies; open-label trials; and a retrospective study. Antidepressants should not be used as sole therapy for AN although their use for confounding symptomatology makes discerning efficacy difficult as they are given together with other therapies. Neurobiological changes due to starvation and AN itself complicate results interpretation. For safety, tricyclic antidepressants and monoamine oxidase inhibitors are not recommended, and bupropion is contraindicated. Use of SSRIs during acute treatment lacks efficacy. Use of SSRIs-primarily fluoxetine and to some extent citalopram, sertraline, or mirtazapine-may aid in relapse prevention and improvement of psychiatric symptomatology in weight-restored anorexic patients.
DISCUSSION
Health care professionals should use clinical judgment regarding fluoxetine or possibly citalopram, sertraline or mirtazapine as adjunctive treatment to psychotherapy for relapse prevention, improvement of depressive and anxiety symptoms, and/or obsessive-compulsive behaviors unresolved with nutritional rehabilitation and psychotherapy.
PubMed: 29955558
DOI: 10.9740/mhc.2018.05.127 -
The Cochrane Database of Systematic... Mar 2023Major depression and other depressive conditions are common in people with cancer. These conditions are not easily detectable in clinical practice, due to the overlap... (Review)
Review
BACKGROUND
Major depression and other depressive conditions are common in people with cancer. These conditions are not easily detectable in clinical practice, due to the overlap between medical and psychiatric symptoms, as described by diagnostic manuals such as the Diagnostic and Statistical Manual of Mental Disorders (DSM) and International Classification of Diseases (ICD). Moreover, it is particularly challenging to distinguish between pathological and normal reactions to such a severe illness. Depressive symptoms, even in subthreshold manifestations, have a negative impact in terms of quality of life, compliance with anticancer treatment, suicide risk and possibly the mortality rate for the cancer itself. Randomised controlled trials (RCTs) on the efficacy, tolerability and acceptability of antidepressants in this population are few and often report conflicting results.
OBJECTIVES
To evaluate the efficacy, tolerability and acceptability of antidepressants for treating depressive symptoms in adults (aged 18 years or older) with cancer (any site and stage).
SEARCH METHODS
We used standard, extensive Cochrane search methods. The latest search date was November 2022.
SELECTION CRITERIA
We included RCTs comparing antidepressants versus placebo, or antidepressants versus other antidepressants, in adults (aged 18 years or above) with any primary diagnosis of cancer and depression (including major depressive disorder, adjustment disorder, dysthymic disorder or depressive symptoms in the absence of a formal diagnosis).
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods. Our primary outcome was 1. efficacy as a continuous outcome. Our secondary outcomes were 2. efficacy as a dichotomous outcome, 3. Social adjustment, 4. health-related quality of life and 5. dropouts. We used GRADE to assess certainty of evidence for each outcome.
MAIN RESULTS
We identified 14 studies (1364 participants), 10 of which contributed to the meta-analysis for the primary outcome. Six of these compared antidepressants and placebo, three compared two antidepressants, and one three-armed study compared two antidepressants and placebo. In this update, we included four additional studies, three of which contributed data for the primary outcome. For acute-phase treatment response (six to 12 weeks), antidepressants may reduce depressive symptoms when compared with placebo, even though the evidence is very uncertain. This was true when depressive symptoms were measured as a continuous outcome (standardised mean difference (SMD) -0.52, 95% confidence interval (CI) -0.92 to -0.12; 7 studies, 511 participants; very low-certainty evidence) and when measured as a proportion of people who had depression at the end of the study (risk ratio (RR) 0.74, 95% CI 0.57 to 0.96; 5 studies, 662 participants; very low-certainty evidence). No studies reported data on follow-up response (more than 12 weeks). In head-to-head comparisons, we retrieved data for selective serotonin reuptake inhibitors (SSRIs) versus tricyclic antidepressants (TCAs) and for mirtazapine versus TCAs. There was no difference between the various classes of antidepressants (continuous outcome: SSRI versus TCA: SMD -0.08, 95% CI -0.34 to 0.18; 3 studies, 237 participants; very low-certainty evidence; mirtazapine versus TCA: SMD -4.80, 95% CI -9.70 to 0.10; 1 study, 25 participants). There was a potential beneficial effect of antidepressants versus placebo for the secondary efficacy outcomes (continuous outcome, response at one to four weeks; very low-certainty evidence). There were no differences for these outcomes when comparing two different classes of antidepressants, even though the evidence was very uncertain. In terms of dropouts due to any cause, we found no difference between antidepressants compared with placebo (RR 0.85, 95% CI 0.52 to 1.38; 9 studies, 889 participants; very low-certainty evidence), and between SSRIs and TCAs (RR 0.83, 95% CI 0.53 to 1.22; 3 studies, 237 participants). We downgraded the certainty of the evidence because of the heterogeneous quality of the studies, imprecision arising from small sample sizes and wide CIs, and inconsistency due to statistical or clinical heterogeneity.
AUTHORS' CONCLUSIONS
Despite the impact of depression on people with cancer, the available studies were few and of low quality. This review found a potential beneficial effect of antidepressants against placebo in depressed participants with cancer. However, the certainty of evidence is very low and, on the basis of these results, it is difficult to draw clear implications for practice. The use of antidepressants in people with cancer should be considered on an individual basis and, considering the lack of head-to-head data, the choice of which drug to prescribe may be based on the data on antidepressant efficacy in the general population of people with major depression, also taking into account that data on people with other serious medical conditions suggest a positive safety profile for the SSRIs. Furthermore, this update shows that the usage of the newly US Food and Drug Administration-approved antidepressant esketamine in its intravenous formulation might represent a potential treatment for this specific population of people, since it can be used both as an anaesthetic and an antidepressant. However, data are too inconclusive and further studies are needed. We conclude that to better inform clinical practice, there is an urgent need for large, simple, randomised, pragmatic trials comparing commonly used antidepressants versus placebo in people with cancer who have depressive symptoms, with or without a formal diagnosis of a depressive disorder.
Topics: Adult; Humans; Antidepressive Agents; Antidepressive Agents, Tricyclic; Depression; Depressive Disorder, Major; Mirtazapine; Neoplasms; Selective Serotonin Reuptake Inhibitors
PubMed: 36999619
DOI: 10.1002/14651858.CD011006.pub4 -
The Primary Care Companion For CNS... Apr 2019
Topics: Antidepressive Agents; Dyskinesia, Drug-Induced; Female; Humans; Mental Disorders; Middle Aged; Mirtazapine
PubMed: 30985094
DOI: 10.4088/PCC.18l02377 -
What is the evidence for mirtazapine in treating cancer-related symptomatology? A systematic review.Supportive Care in Cancer : Official... Apr 2020Cancer patients often experience multiple distressing symptoms which are challenging to manage. It would therefore be helpful to find a treatment that alleviates more... (Review)
Review
PURPOSE
Cancer patients often experience multiple distressing symptoms which are challenging to manage. It would therefore be helpful to find a treatment that alleviates more than one symptom, to avoid polypharmacy: mirtazapine has been used in several studies for this purpose. The objective of this study was to assess the effectiveness and safety of mirtazapine in alleviating one or more frequently encountered cancer-related symptoms.
METHODS
Systematic review of clinical trials in English or French. Eight databases were searched. Included studies assessed the effectiveness of mirtazapine in alleviating one or more frequently encountered cancer-related symptoms. Comparator and validated assessment tools were required. Studies were independently appraised by two investigators before data synthesis.
RESULTS
The search yielded 1898 references, from which we identified 12 relevant articles evaluating highly heterogeneous outcomes. These were two randomised-controlled (RCTs), three non-randomised controlled, and seven non-randomised non-controlled trials. In total, 392 participants were included and 185 were in RCTs. No study assessed the effectiveness of mirtazapine in alleviating symptoms at the same time, but some considered more than one symptom. Overall, the data was of poor quality, limited by small sample size and bias. However, mirtazapine showed effectiveness in treating depression, anxiety, sleep disorders, emesis and neuropathic pain. Across all studies, mirtazapine is safe to use, with drowsiness and dizziness the most common side-effects.
CONCLUSION
Study design and small sample sizes limit the ability to interpret results. Trials to assess the impact of mirtazapine or other medicines in alleviating multiple symptoms would be valuable.
Topics: Adrenergic alpha-2 Receptor Antagonists; Antidepressive Agents; Clinical Trials as Topic; Depression; Humans; Mirtazapine; Neoplasms; Palliative Care; Randomized Controlled Trials as Topic
PubMed: 31858251
DOI: 10.1007/s00520-019-05229-7 -
European Psychiatry : the Journal of... Feb 2024Hyponatremia (hypoNa) is a potentially serious adverse event of antidepressant treatment. Previous research suggests the risk of drug-induced hyponatremia differs... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Hyponatremia (hypoNa) is a potentially serious adverse event of antidepressant treatment. Previous research suggests the risk of drug-induced hyponatremia differs between antidepressants. This meta-analysis sought to determine the risk of antidepressant-induced hypoNa, stratified by different compounds and classes.
METHODS
A PRISMA-compliant systematic search of Web of Science and PubMed databases was performed from inception until Jan 5, 2023, for original studies reporting incidences or risks of hypoNa in adults using antidepressants. We modelled random-effects meta-analyses to compute overall event rates and odds ratios of any and clinically relevant hypoNa for each compound and class, and ran head-to-head comparisons based on hypoNa event rates. We conducted subgroup analyses for geriatric populations and sodium cut-off value. The study is registered with PROSPERO, CRD42021269801.
RESULTS
We included 39 studies (n = 8,175,111). Exposure to antidepressants was associated with significantly increased odds of hypoNa (k = 7 studies, OR = 3.160 (95%CI 1.911-5.225)). The highest event rates were found for SNRIs (7.44%), SSRIs (5.59%), and TCAs (2.66%); the lowest for mirtazapine (1.02%) and trazodone (0.89%). Compared to SSRIs, SNRIs were significantly more likely (k = 10, OR = 1.292 (1.120 - 1.491), p < 0.001) and mirtazapine significantly less likely (k = 9, OR = 0.607 (0.385 - 0.957), p = 0.032) to be associated with hypoNa.
CONCLUSION
Our meta-analysis demonstrated that, while no antidepressant can be considered completely risk-free, for hypoNa-prone patients mirtazapine should be considered the treatment of choice and SNRIs should be prescribed more cautiously than SSRIs and TCAs.
Topics: Adult; Humans; Aged; Selective Serotonin Reuptake Inhibitors; Mirtazapine; Serotonin and Noradrenaline Reuptake Inhibitors; Hyponatremia; Antidepressive Agents
PubMed: 38403888
DOI: 10.1192/j.eurpsy.2024.11