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1.
Eur Psychiatry ; 67(1): e20, 2024 Feb 26.
Article En | MEDLINE | ID: mdl-38403888

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.


Hyponatremia , Serotonin and Noradrenaline Reuptake Inhibitors , Adult , Humans , Aged , Selective Serotonin Reuptake Inhibitors , Mirtazapine/adverse effects , Hyponatremia/chemically induced , Hyponatremia/epidemiology , Antidepressive Agents/adverse effects
5.
Syst Rev ; 12(1): 57, 2023 03 30.
Article En | MEDLINE | ID: mdl-36991504

BACKGROUND: Major depressive disorder causes a great burden on patients and societies. Venlafaxine and mirtazapine are commonly prescribed as second-line treatment for patients with major depressive disorder worldwide. Previous systematic reviews have concluded that venlafaxine and mirtazapine reduce depressive symptoms, but the effects seem small and may not be important to the average patient. Moreover, previous reviews have not systematically assessed the occurrence of adverse events. Therefore, we aim to investigate the risks of adverse events with venlafaxine or mirtazapine versus 'active placebo', placebo, or no intervention for adults with major depressive disorder in two separate systematic reviews. METHODS: This is a protocol for two systematic reviews with meta-analysis and Trial Sequential Analysis. The assessments of the effects of venlafaxine or mirtazapine will be reported in two separate reviews. The protocol is reported as recommended by Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols, risk of bias will be assessed with the Cochrane risk-of-bias tool version 2, clinical significance will be assessed using our eight-step procedure, and the certainty of the evidence will be assessed with the Grading of Recommendations Assessment, Development and Evaluation approach. We will search for published and unpublished trials in major medical databases and trial registers. Two review authors will independently screen the results from the literature searches, extract data, and assess risk of bias. We will include published or unpublished randomised clinical trial comparing venlafaxine or mirtazapine with 'active placebo', placebo, or no intervention for adults with major depressive disorder. The primary outcomes will be suicides or suicide attempts, serious adverse events, and non-serious adverse events. Exploratory outcomes will include depressive symptoms, quality of life, and individual adverse events. If feasible, we will assess the intervention effects using random-effects and fixed-effect meta-analyses. DISCUSSION: Venlafaxine and mirtazapine are frequently used as second-line treatment of major depressive disorder worldwide. There is a need for a thorough systematic review to provide the necessary background for weighing the benefits against the harms. This review will ultimately inform best practice in the treatment of major depressive disorder. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022315395.


Depressive Disorder, Major , Humans , Adult , Mirtazapine/adverse effects , Depressive Disorder, Major/drug therapy , Venlafaxine Hydrochloride/adverse effects , Quality of Life , Meta-Analysis as Topic , Review Literature as Topic
7.
J Natl Med Assoc ; 114(6): 617-620, 2022 Dec.
Article En | MEDLINE | ID: mdl-36114064

We report the case of an African American patient who developed drug-associated acute pancreatitis without hypertriglyceridemia, after being treated with mirtazapine for major depressive disorder (MDD). Acute pancreatitis is characterized by rapid inflammation and autodigestion of the pancreas, which may become life-threatening. Although heavy alcohol use and gallstones are the most common causes of acute pancreatitis, some medications are also known to cause drug-induced acute pancreatitis. This report describes a 47-year-old African American female with a history of MDD, insomnia, posttraumatic stress disorder (PTSD), and alcohol use disorder, who was prescribed mirtazapine. A literature search implicated mirtazapine as a rare cause of drug-induced acute pancreatitis. Some reports have suggested that mirtazapine-associated acute pancreatitis may be due to hypertriglyceridemia. This case report instead presents with a normal lipid panel, which is consistent with the majority of prior reports, and it is noteworthy for introducing an alternative mechanism. The Naranjo Adverse Drug Reaction (ADR) Probability Scale calculated an ADR of 5, indicating mirtazapine as the probable cause of the patient's drug-associated acute pancreatitis.


Depressive Disorder, Major , Pancreatitis , Female , Humans , Middle Aged , Mirtazapine/adverse effects , Depressive Disorder, Major/drug therapy , Pancreatitis/chemically induced , Pancreatitis/complications , Acute Disease
8.
Cardiovasc Toxicol ; 22(9): 866-877, 2022 09.
Article En | MEDLINE | ID: mdl-35930218

Many drugs carry some risk of QT interval prolongation, which can lead to life-threatening dysrhythmias including Torsades de Pointes (TdP). CredibleMeds.org identifies medications categorized as "Known Risk of TdP" but does not stratify risk in acute supratherapeutic ingestions. We sought to determine the proportion of cases exhibiting QTc prolongation and life-threatening dysrhythmias including ventricular tachycardia (VT)/ventricular fibrillation (VF), TdP, and asystole in patients exposed to these substances. Retrospective chart review of cases reported to our Regional Poison Center from 2014 to 2019 of exposures to one or more of the "Known Risk" substances was performed. Demographics, therapies, clinical effects, and medical outcome for each case were analyzed. There were 1125 exposures, of which 760 had a documented QTc interval. QTc ≥ 500 ms was reported in 138 (18.2%) of the 760 cases. The most common "Known Risk" substances were citalopram, escitalopram and cocaine. Although not in the "Known Risk" category, mirtazapine, amitriptyline, diphenhydramine, and trazodone had a statistically significant association with QTc > 500 ms. Life-threatening dysrhythmias occurred in 13 cases, with VT/VF in 6 of the 760 (0.8%) cases, and one case of TdP. Flecainide (OR 11.1, 95% CI 2.2-55.8) and methadone (OR 7.1, 95% CI 2.1-23.4) were associated with increased risk of all life-threatening dysrhythmias. Exposures to medications on the Credible Meds list of "Known Risk of TdP" QTc prolongation is common, but life-threatening dysrhythmias are rare. Mirtazapine, amitriptyline, diphenhydramine, and trazodone were associated with prolonged QTc. Flecainide and methadone had the highest associated risk of life-threatening dysrhythmias.


Long QT Syndrome , Tachycardia, Ventricular , Torsades de Pointes , Trazodone , Amitriptyline/adverse effects , Arrhythmias, Cardiac , Diphenhydramine/adverse effects , Electrocardiography , Flecainide/adverse effects , Humans , Long QT Syndrome/chemically induced , Long QT Syndrome/diagnosis , Long QT Syndrome/epidemiology , Methadone/adverse effects , Mirtazapine/adverse effects , Poison Control Centers , Retrospective Studies , Risk Factors , Tachycardia, Ventricular/chemically induced , Tachycardia, Ventricular/diagnosis , Tachycardia, Ventricular/epidemiology , Torsades de Pointes/chemically induced , Torsades de Pointes/diagnosis , Torsades de Pointes/epidemiology , Trazodone/adverse effects , Ventricular Fibrillation
9.
Neuropsychopharmacol Rep ; 42(3): 391-394, 2022 09.
Article En | MEDLINE | ID: mdl-35748411

BACKGROUND: Although resistance to thyroid hormone beta (RTHß) is associated with attention-deficit/hyperactivity disorder, there are few reports of other concomitant mood disorders in individuals with RTHß. CASE PRESENTATION: A 67-year-old woman who had been previously diagnosed with RTHß (Refetoff syndrome) came to our department as a depressed patient. She was hospitalized twice for depression and treated with antidepressants both times. Paroxetine (37.5 mg/day) treatment during the first hospitalization did not cause any side effects, but treatment with mirtazapine (15 mg/day) and venlafaxine (150 mg/day) during the second hospitalization caused clonus and disturbance of consciousness, and these adverse effects resulted in a prolonged period of hospitalization. Finally, the patient's symptoms were controlled with quetiapine (75 mg/day). CONCLUSION: Poor tolerability to antidepressants was observed, which may be related to thyroid hormone intolerance. Low doses of quetiapine may contribute to improvements in depression.


Thyroid Hormone Resistance Syndrome , Aged , Antidepressive Agents/adverse effects , Female , Humans , Mirtazapine/adverse effects , Mood Disorders , Mutation , Paroxetine , Quetiapine Fumarate/adverse effects , Thyroid Hormone Receptors beta/genetics , Thyroid Hormone Resistance Syndrome/diagnosis , Thyroid Hormone Resistance Syndrome/drug therapy , Thyroid Hormone Resistance Syndrome/genetics , Thyroid Hormones , Venlafaxine Hydrochloride/adverse effects
10.
BMC Palliat Care ; 21(1): 84, 2022 May 23.
Article En | MEDLINE | ID: mdl-35599320

BACKGROUND: Advanced cancer patients often experience multiple symptoms at a same time. This might lead to polypharmacy and increase adverse events representing major threats to the quality of health care, especially in palliative care situations. Mirtazapine, an antidepressant agent, has been suggested as a potential relevant drug to alleviate multiple cancer-related symptoms at a same time. Therefore, the present study aims to assess the effectiveness of mirtazapine in alleviating multiple symptoms at a same time in advanced cancer patients suffering from a major depressive episode compared to a group receiving escitalopram, another antidepressant agent. METHODS: Multicentre, prospective, randomized, controlled trial in 12 palliative care services in France. The study will be based on a mixed-method methodology using parallel groups, of oral mirtazapine compared with oral escitalopram, with a 56 day follow-up. The primary outcome will be an improvement of the Global health Status (issued from the EORTC-QLQ-C30) on day 56. 418 participants will be clinically followed-up on day 7 and 56 and will have a telephonic assessment on days 14 and 28. A sub-sample of participants will be invited to take part in semi-structured qualitative interviews at baseline and day 56. For the qualitative part, purposeful sampling will be used. DISCUSSION: This study will provide evidence for the pharmaceutics management of poly-symptomatology in advanced cancer patients. This could lead to important changes in the management of those patients by using a single molecule to alleviate multiple symptoms at a same time, potentially improving medication adherence, symptoms' control, and reducing the risk of medications adverse events. TRIAL REGISTRATION: Trial registration: NCT04763135 . Registered 18 March 2021.


Depressive Disorder, Major , Neoplasms , Antidepressive Agents , Depressive Disorder, Major/chemically induced , Escitalopram , Humans , Mirtazapine/adverse effects , Neoplasms/complications , Neoplasms/drug therapy , Prospective Studies , Randomized Controlled Trials as Topic , Treatment Outcome
11.
Rheumatol Int ; 42(9): 1549-1554, 2022 09.
Article En | MEDLINE | ID: mdl-35475940

On the background of a restricted armamentarium of drugs available for the management of fibromyalgia (FM), we aimed to compare the real-world effectiveness of two serotonin-norepinephrine reuptake inhibitors (SNRIs), mirtazapine (MTZ) and duloxetine (DLX) in FM. A medical records review was done to identify patients diagnosed with FM and prescribed a stable dose of either MTZ or DLX for more than 6 months. Their present status was determined by a telephonic interview which included a subjective assessment of improvement (Likert scale), FIQR (Revised Fibromyalgia Impact Questionnaire), adverse drug effects and compliance. One-fifty-eight patients were screened to include 81 patients [mean age 46.7 (± 13.0) years, 64 (79%) females]. Sixty (79%) had primary fibromyalgia and 66 (81.5%) were on DLX (20-40 mg) while 15(18.5%) were on MTZ (7.5 mg). In addition to the drugs, lifestyle modification was followed by 57 (70.3%). A moderate-to-good improvement was seen in 66 (81.5%), while 15 (18.5%) reported poor to no improvement overall. In the DLX group, a majority (59, 89.4%) showed moderate-to-good improvement compared to 7(46.7%) on MTZ [p = 0.001, 9.6(2.6-34)]. However, FIQR was similar for those on DLX (3.6 ± 0.9) and MTZ (3.8 ± 0.7). Adverse effects were reported for 51 (77%) of patients on DLX and all (100%) on MTZ with a poorer compliance with MTZ 5 (33.3%) compared to DLX 47 (71.2%) [p = 0.008, OR 0.1(0.03-0.4)]. On multivariate analysis, DLX use [OR 16.7 (95% CI 2.7-100); p = 0.008] and lifestyle modification [p = 0.002; OR 11.2(1.5-83.3)] were associated with better subjective outcomes. Low-dose MTZ appears to be inferior to DLX in the management of FM in this real-world cohort.


Fibromyalgia , Duloxetine Hydrochloride/adverse effects , Female , Fibromyalgia/drug therapy , Humans , Male , Middle Aged , Mirtazapine/adverse effects , Retrospective Studies , Serotonin
12.
Acta Psychiatr Scand ; 145(6): 557-567, 2022 06.
Article En | MEDLINE | ID: mdl-35320582

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.


Abortion, Spontaneous , Perinatal Death , Abortion, Spontaneous/chemically induced , Abortion, Spontaneous/epidemiology , Child , Cohort Studies , Female , Humans , Infant, Newborn , Mirtazapine/adverse effects , Pregnancy , Stillbirth/epidemiology
13.
Evid Based Ment Health ; 25(4): 169-176, 2022 11.
Article En | MEDLINE | ID: mdl-35246454

BACKGROUND: Studies report an increased risk of self-harm or suicide in people prescribed mirtazapine compared with other antidepressants. OBJECTIVES: To compare the risk of serious self-harm in people prescribed mirtazapine versus other antidepressants as second-line treatments. DESIGN AND SETTING: Cohort study using anonymised English primary care electronic health records, hospital admission data and mortality data with study window 1 January 2005 to 30 November 2018. PARTICIPANTS: 24 516 people diagnosed with depression, aged 18-99 years, initially prescribed a selective serotonin reuptake inhibitor (SSRI) and then prescribed mirtazapine, a different SSRI, amitriptyline or venlafaxine. MAIN OUTCOME MEASURES: Hospitalisation or death due to deliberate self-harm. Age-sex standardised rates were calculated and survival analyses were performed using inverse probability of treatment weighting to account for baseline covariates. RESULTS: Standardised rates of serious self-harm ranged from 3.8/1000 person-years (amitriptyline) to 14.1/1000 person-years (mirtazapine). After weighting, the risk of serious self-harm did not differ significantly between the mirtazapine group and the SSRI or venlafaxine groups (HRs (95% CI) 1.18 (0.84 to 1.65) and 0.85 (0.51 to 1.41) respectively). The risk was significantly higher in the mirtazapine than the amitriptyline group (3.04 (1.36 to 6.79)) but was attenuated after adjusting for dose. CONCLUSIONS: There was no evidence for a difference in risk between mirtazapine and SSRIs or venlafaxine after accounting for baseline characteristics. The higher risk in the mirtazapine versus the amitriptyline group might reflect residual confounding if amitriptyline is avoided in people considered at risk of self-harm. CLINICAL IMPLICATIONS: Addressing baseline risk factors and careful monitoring might improve outcomes for people at risk of serious self-harm.


Depression , Suicide , Humans , Mirtazapine/adverse effects , Cohort Studies , Venlafaxine Hydrochloride/therapeutic use , Depression/drug therapy , Amitriptyline , Electronic Health Records , Antidepressive Agents/therapeutic use , Selective Serotonin Reuptake Inhibitors/therapeutic use , United Kingdom
14.
Paediatr Drugs ; 24(2): 155-161, 2022 Mar.
Article En | MEDLINE | ID: mdl-35188625

OBJECTIVE: The objective of this study was to assess the clinical response and safety of mirtazapine in the pediatric population with a diagnosis of functional nausea and nausea associated with functional dyspepsia postprandial distress syndrome. METHODS: This was a retrospective chart review to evaluate the safety and efficacy of mirtazapine for pediatric nausea and nausea associated with functional dyspepsia postprandial distress syndrome. Clinical response was classified as complete response, partial response, and no response. We also identified the prescribed doses, side effects, and weight changes during mirtazapine therapy. RESULTS: Among the 57 total patients, 67% were females and ages ranged from 7 to 19 years with a mean of 14 ± 3 years. Clinical (complete and partial) response was reported in 82% of patients. Nausea resolved in 82% and insomnia in 77% of the patients. Eighty-four percent gained weight with a mean of 4 ± 7 kg. Sixty-five percent did not report adverse effects. The most common adverse effects were undesired weight gain (16%) and dysphoria (9%). Two patients discontinued the medicine after the first dose because of adverse effects. There was a significant correlation between the initial dose and weight (rs = 0.478; p = 0.0002). The median initial and final doses were 15 mg, respectively. CONCLUSIONS: Mirtazapine is an option for treating children and adolescents with functional nausea and nausea associated with functional dyspepsia post-prandial distress syndrome, especially for a select group of patients with concurrent weight loss, anxiety, and insomnia.


Depressive Disorder, Major , Dyspepsia , Adolescent , Adult , Child , Depressive Disorder, Major/drug therapy , Dyspepsia/diagnosis , Dyspepsia/drug therapy , Female , Humans , Mirtazapine/adverse effects , Nausea/drug therapy , Retrospective Studies , Young Adult
15.
Br J Clin Pharmacol ; 88(7): 3162-3171, 2022 07.
Article En | MEDLINE | ID: mdl-35001414

Conflicting results have been reported regarding the association between antidepressant use and out-of-hospital cardiac arrest (OHCA) risk. We investigated whether the use of antidepressants is associated with OHCA. METHODS: We conducted a nationwide nested case-control study to assess the association of individual antidepressant drugs within drug classes with the hazard of OHCA. Cases were defined as OHCA from presumed cardiac causes. Cox regression with time-dependent exposure and time-dependent covariates was conducted to calculate hazard ratios (HR) and 95% confidence intervals (95% CIs) overall and in subgroups defined by established cardiac disease and cardiovascular risk factors. Also, we studied antidepressants with and without sodium channel blocking or potassium channel blocking properties separately. RESULTS: During the study period from 2001 to 2015 we observed 10 987 OHCA cases, and found increased OHCA rate for high-dose citalopram (>20 mg) and high-dose escitalopram (>10 mg; HR:1.46 [95% CI:1.27-1.69], HR:1.43 [95% CI:1.16-1.75], respectively) among selective serotonin reuptake inhibitors (reference drug sertraline), and for high-dose mirtazapine (>30; HR:1.59 [95% CI:1.18-2.14]) among the serotonin-norepinephrine reuptake inhibitors or noradrenergic and specific serotonergic antidepressants (reference drug duloxetine). Among tricyclic antidepressants (reference drug amitriptyline), no drug was associated with significantly increased OHCA rate. Increased OHCA rate was found for antidepressants with known potassium channel blocking properties (HR:1.14 [95% CI:1.05-1.23]), but for not those with sodium channel blocking properties. Citalopram, although not statistically significant, and mirtazapine were associated with increased OHCA rate in patients without cardiac disease and cardiovascular risk factors. CONCLUSION: Our findings indicate that careful titration of citalopram, escitalopram and mirtazapine dose may have to be considered due to drug safety issues.


Citalopram , Out-of-Hospital Cardiac Arrest , Antidepressive Agents/adverse effects , Case-Control Studies , Citalopram/adverse effects , Humans , Mirtazapine/adverse effects , Norepinephrine , Out-of-Hospital Cardiac Arrest/chemically induced , Out-of-Hospital Cardiac Arrest/epidemiology , Potassium Channels , Selective Serotonin Reuptake Inhibitors/adverse effects
16.
Br J Clin Pharmacol ; 88(1): 214-225, 2022 01.
Article En | MEDLINE | ID: mdl-34155670

AIMS: Hypothyroxinaemia could be easily neglected if attention is paid only to patients with elevated thyroid-stimulating hormone. We aimed to assess the association between mirtazapine use and hypothyroxinaemia in patients affected by major depressive disorder. METHODS: We conducted a retrospective cohort study in the Second Affiliated Hospital of Xinxiang Medical University between January 2016 and December 2018. Patients affected by major depression disorder and admitted to the hospital for treatment during the study period and who had thyroid tests at admission and after treatment were included. Mirtazapine use during hospitalization was the exposure measure and newly developed hypothyroxinaemia was as the primary outcome and structure parameters of thyroid homeostasis were the secondary outcomes of this study. Log-binomial model was used to estimate the association between mirtazapine use and hypothyroxinaemia, after adjusting for potential confounding factors. RESULTS: A total of 220 eligible patients were included in the final analysis. The incidence of hypothyroxinaemia in patients who used mirtazapine was higher (37.5%) than those patients who did not use (19.7%). The relative risk of developing hypothyroxinaemia was 1.70 (95% confidence interval: 1.21-2.43) for mirtazapine use, after adjusting for confounding factors. The degree of reduction in thyroid feedback quantile-based index in mirtazapine group was significantly greater than that in nonmirtazapine group. CONCLUSION: Mirtazapine use was associated with the increased risk of developing hypothyroxinaemia. The underlying mechanism may be involved the changed central set point of thyroid homeostasis, in which pituitary was in a possibly impaired sensitivity to the lower level of thyroid hormones.


Depressive Disorder, Major , Depressive Disorder, Major/drug therapy , Depressive Disorder, Major/epidemiology , Humans , Incidence , Mirtazapine/adverse effects , Retrospective Studies
17.
Behav Brain Res ; 419: 113667, 2022 02 15.
Article En | MEDLINE | ID: mdl-34798169

Mirtazapine (MIRT) is a multi-target antidepressant used in treatment of severe depression with promising efficacy, but also with important side effects, mainly sedation and weight gain. Thus, the present study aimed to test the effects of the neuroprotective antioxidant lipoic acid (ALA) in the reversal of weight and metabolic changes induced by MIRT in corticosterone-induced depression model in mice, as well as proposed mechanisms for their association antidepressant and pro-cognitive effects. To do these male Swiss mice received Tween 80 (control), corticosterone (CORT 20 mg / kg), MIRT (3 mg / kg) and ALA (100 or 200 mg / kg), alone or associated for 21 days. After this, the animals were subjected to behavioral tests for affective and cognitive domains. Daily weight changes, blood cholesterol fractions and corticosterone were measured. Also, hippocampus (HC) protein expression of the serotonin transporter (SERT), synaptophysin, protein kinase B-Akt (total and phosphorylated) and the cytokines IL-4 and IL-6 were investigated. CORT induced a marked depression-like behavior, memory deficits, metabolic changes (total cholesterol and LDL) and increased serum corticosterone. Also, CORT increased SERT expression in the HC. MIRT alone or combined with ALA sustained its antidepressant-like effect, as well as reversed CORT-induced impairment in spatial recognition memory. Additionally, the association MIRT+ALA200 reversed the weight gain induced by the former antidepressant, as well as reduced serum corticosterone levels and SERT expression in the HC. ALA alone induced significant weight loss and reduced total cholesterol and HDL fraction. Our findings provide promising evidence about the ALA potential to prevent metabolic and weight changes associated to MIRT, without impair its antidepressant and pro-cognition actions. Therefore, ALA+MIRT combination could represent a new therapeutic strategy for treating depression with less side effects.


Antidepressive Agents/pharmacology , Antioxidants/pharmacology , Cognitive Dysfunction , Corticosterone/pharmacology , Depression , Mirtazapine/pharmacology , Thioctic Acid/pharmacology , Weight Gain/drug effects , Animals , Antidepressive Agents/adverse effects , Behavior, Animal/drug effects , Behavior, Animal/physiology , Cognitive Dysfunction/chemically induced , Cognitive Dysfunction/drug therapy , Cognitive Dysfunction/metabolism , Corticosterone/blood , Depression/chemically induced , Depression/drug therapy , Depression/metabolism , Disease Models, Animal , Hippocampus/drug effects , Hippocampus/metabolism , Male , Mice , Mirtazapine/adverse effects
18.
Lancet ; 398(10310): 1487-1497, 2021 10 23.
Article En | MEDLINE | ID: mdl-34688369

BACKGROUND: Agitation is common in people with dementia and negatively affects the quality of life of both people with dementia and carers. Non-drug patient-centred care is the first-line treatment, but there is a need for other treatment when this care is not effective. Current evidence is sparse on safer and effective alternatives to antipsychotics. We assessed the efficacy and safety of mirtazapine, an antidepressant prescribed for agitation in dementia. METHODS: This parallel-group, double-blind, placebo-controlled trial-the Study of Mirtazapine for Agitated Behaviours in Dementia trial (SYMBAD)-was done in 26 UK centres. Participants had probable or possible Alzheimer's disease, agitation unresponsive to non-drug treatment, and a Cohen-Mansfield Agitation Inventory (CMAI) score of 45 or more. They were randomly assigned (1:1) to receive either mirtazapine (titrated to 45 mg) or placebo. The primary outcome was reduction in CMAI score at 12 weeks. This trial is registered with ClinicalTrials.gov, NCT03031184, and ISRCTN17411897. FINDINGS: Between Jan 26, 2017, and March 6, 2020, 204 participants were recruited and randomised. Mean CMAI scores at 12 weeks were not significantly different between participants receiving mirtazapine and participants receiving placebo (adjusted mean difference -1·74, 95% CI -7·17 to 3·69; p=0·53). The number of controls with adverse events (65 [64%] of 102 controls) was similar to that in the mirtazapine group (67 [66%] of 102 participants receiving mirtazapine). However, there were more deaths in the mirtazapine group (n=7) by week 16 than in the control group (n=1), with post-hoc analysis suggesting this difference was of marginal statistical significance (p=0·065). INTERPRETATION: This trial found no benefit of mirtazapine compared with placebo, and we observed a potentially higher mortality with use of mirtazapine. The data from this study do not support using mirtazapine as a treatment for agitation in dementia. FUNDING: UK National Institute for Health Research Health Technology Assessment Programme.


Anti-Anxiety Agents , Dementia/complications , Mirtazapine , Psychomotor Agitation/drug therapy , Aged, 80 and over , Anti-Anxiety Agents/adverse effects , Anti-Anxiety Agents/therapeutic use , Brief Psychiatric Rating Scale , Caregivers/psychology , Double-Blind Method , Female , Humans , Male , Mirtazapine/adverse effects , Mirtazapine/therapeutic use , Quality of Life/psychology , United Kingdom
19.
J Psychopharmacol ; 35(8): 901-909, 2021 Aug.
Article En | MEDLINE | ID: mdl-34238048

BACKGROUND: Depression is considered as one of the most common neuropsychiatric symptoms (NPS) in Alzheimer's disease (AD) patients. Prescription of antidepressants is a current clinical practice well-established as the first-line treatment for such patients. Our study was aimed at systematically examining the evidence on the efficacy of antidepressants in the treatment of depression in AD patients. METHODS: We conducted a network meta-analysis of randomized controlled trials retrieved by systematic search of the Cochrane Central Register of Controlled Trials, PubMed, Embase, and CNKI databases. Primary outcomes included mean depression score and safety. Secondary outcomes were cognition. The surface under the cumulative ranking curve was performed to estimate a ranking probability for different treatments. RESULTS: A total of 25 studies including 14 medications met the inclusion criteria. Compared with placebo, only mirtazapine (standard mean deviation [SMD], -1.94; 95% confidence interval [CI], -3.53 to -0.36; p < 0.05) and sertraline (SMD, -1.16; 95% CI, -2.17 to -0.15; p < 0.05) showed a slightly better effect in treating symptoms of depression. Clomipramine increased risk of adverse events than placebo (odds ratio, 3.01; 95% CI, 1.45 to 4.57; p < 0.05). In terms of cognitive function, there was no statistically significant difference between antidepressants and placebo. CONCLUSION: Overall, in the short-term treatment, these data suggest that commonly used antidepressants sertraline and mirtazapine should be considered as an alternative treatment for depression in AD patients. However, more high-quality trials with large samples and longer following-up are proposed.


Alzheimer Disease/drug therapy , Antidepressive Agents/administration & dosage , Depression/drug therapy , Alzheimer Disease/psychology , Antidepressive Agents/adverse effects , Cognition/drug effects , Depression/etiology , Humans , Mirtazapine/administration & dosage , Mirtazapine/adverse effects , Network Meta-Analysis , Randomized Controlled Trials as Topic , Sertraline/administration & dosage , Sertraline/adverse effects
20.
Rev. chil. neuro-psiquiatr ; 59(1): 66-71, mar. 2021. tab
Article Es | LILACS | ID: biblio-1388379

Resumen La mirtazapina es un antidepresivo atípico con características complejas, que incluye actividad agonista/antagonista en una amplia variedad de receptores que produce efectos terapéuticos en la ansiedad, depresión y el sueño. Sin embargo, se han reportado casos de lesión hepática inducida por antidepresivos con ausencia de sintomatología, bajo la forma de variantes hepatocelular, colestásica y mixta. Este es el caso de una paciente que de carácter incidental presenta cambios en la analítica hepática tras el uso de mirtazapina a partir del cual se hace una breve revisión de la evidencia encontrada hasta el momento.


Mirtazapine is an atypical antidepressant with complex characteristics, including agonist/antagonist activity at a wide variety of receptors that produces therapeutic effects on anxiety, depression and sleep disorder. However, cases of antidepressant-induced liver injury with no symptoms have been reported, in the form of hepatocellular, cholestatic, and mixed variants. This is the case of a patient who incidentally presents changes in liver analysis after the use of mirtazapine, from which a brief review of the evidence found so far is made.


Humans , Female , Middle Aged , Chemical and Drug Induced Liver Injury , Mirtazapine/adverse effects , Antidepressive Agents/adverse effects , Anxiety/drug therapy , Depression/drug therapy , Asymptomatic Diseases
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