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The Journal of Clinical Psychiatry Sep 2008To conduct a comprehensive, systematic review and meta-analysis of the efficacy and tolerability of mirtazapine over other antidepressants in the acute-phase treatment... (Comparative Study)
Comparative Study Meta-Analysis Review
OBJECTIVE
To conduct a comprehensive, systematic review and meta-analysis of the efficacy and tolerability of mirtazapine over other antidepressants in the acute-phase treatment of major depression.
DATA SOURCES
Studies were initially identified through electronic searches of the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register up to June 2006. The following search terms were used: depress*, dysthymi*, adjustment disorder*, mood disorder*, affective disorder, affective symptoms, and mirtazapine. No language restriction was imposed. The reference lists of the included studies, previous relevant systematic reviews, and trial registers were also hand searched. Pharmaceutical companies and experts in the field were contacted for more studies.
STUDY SELECTION
Twenty-five randomized controlled trials were included.
DATA EXTRACTION
Two independent assessors examined the quality of the trials and extracted data on an intention-to-treat basis.
DATA SYNTHESIS
The primary outcome measure was the relative risk (RR) of response (99% CIs) at the conclusion of acute-phase treatment. In relation to the early phase of treatment (at 2 weeks), there were no statistically significant differences between mirtazapine and the tricyclics in terms of the response (RR = 0.90, 99% CI = 0.69 to 1.18, p = .30 [8 trials contributed to this outcome]) or remission (RR = 0.87, 99% CI = 0.52 to 1.47, p = .50 [8 trials]) outcomes, but mirtazapine was superior to the selective serotonin reuptake inhibitors (SSRIs) in terms of both the response (RR = 1.36, 99% CI = 1.13 to 1.64, p < .0001 [12 trials]) and remission (RR = 1.68, 99% CI = 1.20 to 2.36, p < .0001 [12 trials]). In the subgroup analyses, mirtazapine significantly produced more response than paroxetine (RR = 2.02, 99% CI = 1.09 to 3.75, p = .003 [3 trials]) and venlafaxine (RR = 1.77, 99% CI = 1.08 to 2.89, p = .003 [2 trials]). At the end of acute-phase treatment (6-12 weeks, all trials), no significant differences were observed in the efficacy outcomes. No significant differences were observed between mirtazapine and the other antidepressants in terms of either the total number of dropouts due to any reason (21 trials) or the total number of dropouts due to the development of side effect (23 trials) during the trials.
CONCLUSIONS
Although mirtazapine is likely to have a faster onset of action than SSRIs, no significant differences were observed at the end of 6 to 12 weeks' treatment. Clinicians should focus on other practically relevant considerations to tailor treatment to best fit the needs of individual patients.
Topics: Antidepressive Agents, Tricyclic; Depressive Disorder, Major; Humans; Mianserin; Mirtazapine; Randomized Controlled Trials as Topic; Selective Serotonin Reuptake Inhibitors; Treatment Outcome
PubMed: 19193341
DOI: 10.4088/jcp.v69n0908 -
BMJ Clinical Evidence Feb 2010Post-traumatic stress disorder (PTSD) may affect 10% of women and 5% of men at some stage, and symptoms may persist for several years. Risk factors include major trauma,... (Review)
Review
INTRODUCTION
Post-traumatic stress disorder (PTSD) may affect 10% of women and 5% of men at some stage, and symptoms may persist for several years. Risk factors include major trauma, lack of social support, peritraumatic dissociation, and previous psychiatric history or personality factors.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of interventions to prevent PTSD? What are the effects of interventions to treat PTSD? We searched: Medline, Embase, The Cochrane Library, and other important databases up to March 2009 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 46 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: affect management; antiepileptic drugs; antihypertensive drugs; benzodiazepines; brofaromine; CBT; drama therapy; eye movement desensitisation and reprocessing; fluoxetine; group therapy; hydrocortisone; hypnotherapy; inpatient treatment programmes; Internet-based psychotherapy; mirtazapine; multiple-session CBT; multiple-session collaborative trauma support; multiple-session education; nefazodone; olanzapine; paroxetine; phenelzine; psychodynamic psychotherapy; risperidone; SSRIs (versus other antidepressants); sertraline; single-session group debriefing; single-session individual debriefing; supportive psychotherapy; supportive counselling; temazepam; tricyclic antidepressants; and venlafaxine.
Topics: Antidepressive Agents; Fluoxetine; Humans; Psychotherapy, Psychodynamic; Sertraline; Stress Disorders, Post-Traumatic
PubMed: 21718580
DOI: No ID Found -
CNS Drugs Jan 2010Mirtazapine has a unique mechanism of antidepressant action, and thus is thought to have a different profile of adverse events from that of other antidepressants. (Comparative Study)
Comparative Study Meta-Analysis Review
Safety reporting and adverse-event profile of mirtazapine described in randomized controlled trials in comparison with other classes of antidepressants in the acute-phase treatment of adults with depression: systematic review and meta-analysis.
BACKGROUND
Mirtazapine has a unique mechanism of antidepressant action, and thus is thought to have a different profile of adverse events from that of other antidepressants.
OBJECTIVE
To present a methodologically rigorous systematic review of the adverse event profile of mirtazapine and point to possible problems with safety reporting in randomized controlled trials (RCTs) of the acute-phase treatment of major depression in adults with mirtazapine in comparison with other types of antidepressant.
METHODS
The Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register was electronically searched using the following search terms: 'depress*', 'dysthymi*', 'adjustment disorder*', 'mood disorder*', 'affective disorder', 'affective symptoms' and 'mirtazapine'. Pharmaceutical companies and experts in this field were contacted, and the reference lists of the relevant RCTs were checked, for additional data. No language restriction was imposed. Two authors independently assessed the quality of trials for inclusion in the review. Disagreements were resolved by consensus. Two authors independently extracted data on adverse events. Disagreements were resolved by consensus. The adequacy of safety reporting was assessed by one author. Regarding the adequacy of safety reporting, the qualitative and quantitative parameters of safety reporting were determined. Regression analyses were conducted to assess characteristics of trials influencing safety reporting. The primary and secondary outcomes in the systematic review of the adverse events associated with mirtazapine were defined as the proportion of patients having each of 43 adverse events listed in the modified version of the WHO Adverse Reaction Terminology, and the proportion of patients experiencing at least one adverse event, respectively. Meta-analyses were conducted for these outcomes.
RESULTS
Twenty-five RCTs involving 4842 patients were identified as meeting our inclusion criteria. With regard to safety reporting, only two trials and no trials were rated as 'adequate' in terms of the reporting of clinical adverse events and laboratory-determined toxicity, respectively. The proportion of text in the results sections of the study reports devoted to safety reporting was a mean of 22%. No associations were observed between the adequacy of safety reporting and any characteristics of the trials; however, sample size over 100 participants in total and over 50 subjects in a study arm, double blindness and sponsorship by the company marketing mirtazapine were significantly associated with a greater number of reported adverse events in mirtazapine recipients. In terms of individual adverse events, mirtazapine was significantly less likely to cause hypertension or tachycardia (risk ratio [RR] 0.51) and tremor (RR 0.43) than tricyclic antidepressants (TCAs). In comparison with selective serotonin uptake inhibitors (SSRIs), mirtazapine was significantly more likely to cause weight gain or increased appetite (RR 3.68), increased salivation (RR 3.66), somnolence (RR 1.62) and fatigue (RR 1.45), but less likely to cause flatulence (RR 0.26), sweating (RR 0.28), sexual dysfunction (RR 0.34), tremor (RR 0.37), nausea or vomiting (RR 0.40), sleep disturbance (RR 0.55) and diarrhoea (RR 0.61). In comparison with the serotonin-noradrenaline (norepinephrine) reuptake inhibitor (SNRI) venlafaxine, mirtazapine was significantly more likely to cause fatigue (RR 2.02), but less likely to cause sleep disturbance (RR 0.03), sweating (RR 0.03) and constipation (RR 0.25). Relative to trazodone, mirtazapine was significantly more likely to cause weight gain or increased appetite (RR 4.00). Approximately 70% of patients treated with mirtazapine experienced at least one adverse event, with no significant difference in comparison with other antidepressants.
CONCLUSIONS
The study confirmed the paucity of adequate safety reporting in trials comparing mirtazapine with other types of antidepressant in the acute-phase treatment of depression in adults. Based on the available evidence, mirtazapine appears to have a unique adverse-event profile. Using these findings, clinicians can inform their patients, not only of the simple frequency of adverse events with mirtazapine, but also of the relative difference in the frequency of adverse events in comparison with that of other antidepressants, to aid pragmatic clinical decisions.
Topics: Adult; Adverse Drug Reaction Reporting Systems; Antidepressive Agents, Tricyclic; Depressive Disorder, Major; Humans; Mianserin; Mirtazapine; Randomized Controlled Trials as Topic; Regression Analysis
PubMed: 20030418
DOI: 10.2165/11319480-000000000-00000 -
Journal of Psychiatric Practice Jan 2023Antidepressant-induced pancreatitis is a rare, albeit serious, adverse effect, with a frequency of occurrence that is not equally distributed among antidepressant drugs....
OBJECTIVE
Antidepressant-induced pancreatitis is a rare, albeit serious, adverse effect, with a frequency of occurrence that is not equally distributed among antidepressant drugs. The goal of this study was to investigate the association and causal relationship between mirtazapine treatment of patients with depression and pancreatitis.
METHODS
The study was designed as a systematic review of the literature, accompanied by the description of a new case of mirtazapine-associated acute pancreatitis.
RESULTS
Nine cases of mirtazapine-associated pancreatitis have been reported, involving 7 female patients and 2 male patients with a mean age of 46.4 years (range: 26 to 83 y of age). All of the patients were hospitalized, with an average length of stay of 16.2 days (range: 3 to 34 d). In 6 cases, "de-challenge" followed by improvement was reported. The patients for whom the outcome was reported (7 of 9) recovered completely.
CONCLUSION
Although a rare adverse effect, mirtazapine-induced pancreatitis should be considered when patients taking mirtazapine report abdominal discomfort.
Topics: Humans; Male; Female; Middle Aged; Mirtazapine; Acute Disease; Depression; Pancreatitis; Antidepressive Agents; Mianserin; Antidepressive Agents, Tricyclic
PubMed: 36649554
DOI: 10.1097/PRA.0000000000000687 -
Case Reports in Obstetrics and... 2022Hyperemesis gravidarum (HG) is a rare condition (1.1%) characterized by excessive vomiting, malnutrition, dehydration, and laboratorial alterations. Herein, we describe...
Hyperemesis gravidarum (HG) is a rare condition (1.1%) characterized by excessive vomiting, malnutrition, dehydration, and laboratorial alterations. Herein, we describe the even rarer and serious presentation of refractoriness to the usual treatment of antiemetics and parenteral nutrition, with improvement only after the use of olanzapine and mirtazapine. Two subsequent pregnancies of the same woman with HG are described, which were associated with severe weight loss, anemia, hyponatremia, hypokalemia, and mild dysfunction of liver enzymes. In the third pregnancy, the usual treatment for HG was not successful, requiring enteral nutrition and the introduction of olanzapine. In the fourth pregnancy, the patient refused to use enteral nutrition for refractory HG. Hence, the patient was started on mirtazapine at an initial dose of 15 mg/day, which was gradually increased to 30 mg/day. The patient responded well to the new regimen, as demonstrated by the decrease in symptoms, the gain of 10 kg in the pregnancy, and delivering a healthy newborn. A systematic review of literature showed 11 articles and 30 cases that successfully used mirtazapine in HG. Good clinical outcomes were seen with 4 days of the treatment and at an initial dose of 15 mg/day. However, most of these reports were from psychiatric profiles, with a predominance of depression and anxiety symptoms, and a poor description of the obstetric conditions and the disease progression itself. Pulmonary hypertension was described in one case and neonatal hyperexcitability in another. The case described in this paper reinforces the idea that mirtazapine and olanzapine can be considered in refractory HG, with good results. In the world literature, this is the second case of HG that has been successfully treated with olanzapine and the first in Latin America treated with mirtazapine.
PubMed: 36105926
DOI: 10.1155/2022/7324627 -
Ageing Research Reviews Mar 2022Psychotic symptoms of dementia are highly prevalent and lead to poor medical outcomes and substantial dysfunction. To date, which drug to use remains controversial... (Meta-Analysis)
Meta-Analysis Review
Psychotic symptoms of dementia are highly prevalent and lead to poor medical outcomes and substantial dysfunction. To date, which drug to use remains controversial without a summary of all direct or indirect comparisons of pharmacotherapy. Therefore, we conducted a systematic review with pairwise and network meta-analysis to examine efficacy and tolerability outcomes of pharmacological treatments in dementia patients. MEDLINE, Cochrane Library, EMBASE, and PubMed were searched systematically up to August 31, 2020. We included trials of cholinesterase inhibitors (ChEIs), memantine, antipsychotics, antidepressants, and mood stabilizers, with final approval from the U.S. Food and Drug Administration. We ranked the comparative effects of all drugs against placebo with surface under the cumulative ranking (SUCRA) probabilities. This analysis is based on 34 trials, which included 10,415 patients randomly assigned to 15 commonly used drug regimens. Donepezil (standardized mean difference [SMD] -0.30, 95% credible interval [CrI] -0.50 to -0.12; SUCRA, 0.85), memantine (SMD -0.20, 95%CrI -0.34 to -0.07; SUCRA, 0.68) and aripiprazole (SMD -0.17, 95% CrI -0.32 to -0.02; SUCRA, 0.62) showed greater benefit than placebo, and with relatively good tolerability in network meta-analyses. Risperidone was also found to be more efficacious than placebo (SMD -0.16, 95% CrI -0.28 to -0.05; SUCRA, 0.60), but with poor tolerability (odds ratios [OR] 1.50, 95% CrI 1.06-2.26). Donepezil, memantine, haloperidol, aripiprazole and risperidone were more efficacious than quetiapine (SMDs ranged from -0.36 to -0.22). Besides, donepezil, memantine and mirtazapine were more efficacious than sertraline (SMDs ranged from -0.47 to -0.36). Most of the results were rated as "low" to "very low". Several effective treatment choices for psychotic symptoms are available across drug classes. Donepezil, memantine and aripiprazole are probably the appropriate options to consider when a pharmacological treatment is indicated. Given the limitations of the meta-analytic approach and the low methodological quality of the majority of studies, our results should be cautiously interpreted.
Topics: Aripiprazole; Dementia; Donepezil; Humans; Memantine; Network Meta-Analysis; Risperidone; United States
PubMed: 35051646
DOI: 10.1016/j.arr.2022.101568 -
European Neuropsychopharmacology : the... Apr 2024Sleep medications often carry residual effects potentially affecting driving safety, warranting network meta-analysis (NMA).... (Meta-Analysis)
Meta-Analysis
Residual effects of medications for sleep disorders on driving performance: A systematic review and network meta-analysis of randomized controlled trials: NMA driving and hypnotics.
Sleep medications often carry residual effects potentially affecting driving safety, warranting network meta-analysis (NMA). PubMed/EMBASE/TRID/Clinicaltrials.gov/WHO-ICTRP/WebOfScience were inquired for randomized controlled trials of hypnotic driving studies in persons with insomnia and healthy subjects up to 05/28/2023, considering the vehicle's standard deviation of lateral position - SDLP (Standardized Mean Difference/SMD) and driving impairment rates on the first morning (co-primary outcomes) and endpoint. Risk-of-bias, global/local inconsistencies were measured, and CINeMA was used to assess the confidence in the evidence. Of 4,805 identified records, 26 cross-over RCTs were included in the systematic review, of which 22 entered the NMA, focusing on healthy subjects only. After a single administration, most molecules paralleled the placebo, outperforming zopiclone regarding SDLP. In contrast, ramelteon 8 mg, daridorexant 100 mg, zolpidem 10 mg bedtime, zolpidem middle-of-the-night 10 mg and 20 mg, mirtazapine 15-30 mg, and triazolam 0.5 mg performed significantly worse than placebo. Lemborexant 2.5-5 mg, suvorexant 15-20 mg, and zolpidem 3.5 mg middle-of-the-night associated with lower impairment than zopiclone. Repeated administration (maximum follow-up time of ten days) caused fewer residual effects than acute ones, except for flurazepam. Heterogeneity and inconsistency were negligible. Confidence in the evidence was low/very low. Sensitivity analyses confirmed the main analyses. Most FDA-approved hypnotics overlapped placebo at in-label doses, outperforming zopiclone. Repeated administration for 15 days or less reduced residual effects, warranting further research on the matter.
Topics: Humans; Hypnotics and Sedatives; Zolpidem; Network Meta-Analysis; Automobile Driving; Psychomotor Performance; Randomized Controlled Trials as Topic; Sleep Initiation and Maintenance Disorders; Piperazines; Azabicyclo Compounds
PubMed: 38401406
DOI: 10.1016/j.euroneuro.2024.01.011 -
Advances in Clinical and Experimental... Oct 2023Psychosis is a very common feature of Alzheimer's disease (AD) that can emerge as the neurodegenerative disease progresses. The 5-hydroxytryptamine (5-HT2A) receptors... (Meta-Analysis)
Meta-Analysis
Efficacy and safety of negative allosteric modulators of 5-hydroxytryptamine 2A receptors in the treatment of Alzheimer's disease psychosis: A systematic review and meta-analysis.
BACKGROUND
Psychosis is a very common feature of Alzheimer's disease (AD) that can emerge as the neurodegenerative disease progresses. The 5-hydroxytryptamine (5-HT2A) receptors are located postsynaptically to serotonergic neurons in the frontal cortex and mediate both excitatory and inhibitory neurotransmissions. However, the effectiveness and tolerance of negative modulators of 5-HT2A receptors in Alzheimer's disease psychosis (ADP) are uncertain.
OBJECTIVES
To detect the negative modulators of the 5-HT2A receptor as a cure for ADP.
MATERIAL AND METHODS
The primary outcome indicator was the total Neuropsychiatric Inventory (NPI) score. Other prognostic indicators included Mini-Mental State Examination (MMSE), the Katz Index of Independence in Activities of Daily Living (KATZ), the discontinuation rate, and adverse events.
RESULTS
Compared to placebo, 5-HT2A inverse agonists significantly reduced the NPI total score, the KATZ and the MMSE score. The pooled odds ratio (OR) was 1.64 (95% confidence interval (95% CI): 1.01-2.65) and the heterogeneity variance was estimated at Tau2 = 0.52 with an I2 value of 90%, a χ2 value of 111.31, p = 0.04, and z-value of 2.01. The risk difference (RD) between the 5-HT2A receptor negative modulators and placebo groups was 0.12 (95% CI: 0.00-0.24) and the heterogeneity was estimated at Tau2 = 0.03, χ2 value of 127.23, degrees of freedom (df) value of 9, I2 value of 93%, z-value of 1.92, and p-value of 0.01 (<0.05).
CONCLUSION
Our results suggest that negative modulators of 5-HT2A receptors are beneficial and well-tolerated in the treatment of ADP.
Topics: Humans; Alzheimer Disease; Serotonin; Neurodegenerative Diseases; Activities of Daily Living; Drug Inverse Agonism; Receptor, Serotonin, 5-HT2A; Psychotic Disorders
PubMed: 37166012
DOI: 10.17219/acem/161159 -
Alpha Psychiatry Sep 2021The aim of the article is to review systematically current researches investigating the relationship between intrauterine exposure to antidepressants and neonatal... (Review)
Review
The aim of the article is to review systematically current researches investigating the relationship between intrauterine exposure to antidepressants and neonatal hypoglycemia. This paper included studies published in electronic databases from January 2005 to July 2020. The searched keywords were as follows: antidepressants, pregnancy, selective serotonin reuptake inhibitors (SSRIs), citalopram, fluoxetine, paroxetine, escitalopram, sertraline, fluvoxamine, selective serotonin-norepinephrine reuptake inhibitors (SNRIs), venlafaxine, tricyclic antidepressants (TCAs), neonatal outcomes, neonatal hypoglycemia, imipramine, clomipramine, amitriptyline, bupropion, trazodone, and mirtazapine. This review examined 10 relevant studies. The odds ratio/risk ratio reported in the studies were 1.33-1.73 for any antidepressant, 1.30-1.35 for SSRI, 1.42-2.11 for SNRI, and 2.07 for TCAs. The risk of neonatal hypoglycemia in infants exposed to maternal TCAs appears to be slightly higher compared to infants exposed to maternal SSRIs. Data from current studies consistently show that exposure to maternal antidepressants during pregnancy may be related to increased risk of neonatal hypoglycemia in infants.
PubMed: 36447450
DOI: 10.1530/alphapsychiatry.2021.21143 -
European Neuropsychopharmacology : the... Aug 2015Drug-induced changes in serum prolactin (sPrl) levels constitute a relevant issue due to the potentially severe consequences on physical health of psychiatric patients... (Review)
Review
Drug-induced changes in serum prolactin (sPrl) levels constitute a relevant issue due to the potentially severe consequences on physical health of psychiatric patients such as sexual dysfunctions, osteoporosis and Prl-sensitive tumors. Several drugs have been associated to sPrl changes. Only antipsychotics have been extensively studied as sPrl-elevating agents in schizophrenia, but the extent to which bipolar disorder (BD) treatments affect sPrl levels is much less known. The objective of this systematic review is to summarize the evidence of the effects of drugs used in BD on Prl. This review followed the PRISMA statement. The MEDLINE/PubMed/Index Medicus, EMBASE, and Cochrane Library databases were systematically searched for articles in English appearing from any time to May 30, 2014. Twenty-six studies were included. These suggest that treatments for BD are less likely to be associated with Prl elevations, with valproate, quetiapine, lurasidone, mirtazapine, and bupropion reported not to change PRL levels significantly and lithium and aripiprazole to lower them in some studies. Taking into account the effects of the different classes of drugs on Prl may improve the care of BD patients requiring long-term pharmacotherapy. Based on the results of this review, lithium and valproate appear to be safer due to their low potential to elevate sPrL; among antipsychotics, quetiapine, lurasidone and aripiprazole appear to be similarly safe.
Topics: Antipsychotic Agents; Bipolar Disorder; Humans; Hyperprolactinemia; Randomized Controlled Trials as Topic
PubMed: 25937241
DOI: 10.1016/j.euroneuro.2015.04.007