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1.
J Affect Disord ; 295: 1310-1318, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34706445

RESUMO

BACKGROUND: Patients with depression and comorbid obesity may be more prone to weight modulating and cardiovascular side effects of selected antidepressants (AD). It is important to ascertain whether these AD prescriptions differ by patient weight status. METHODS: Canadian Primary Care Sentinel Surveillance Network (CPCSSN) electronic medical records were used. Participants were adults with depression prescribed an AD in 2000-2016, with weight categories established before the first prescription. Logistic regression and mixed effects models were applied to examine associations between obesity and AD prescribing, adjusted for sex, age, and comorbidities. Machine learning algorithm random forest (RF) was used to evaluate the importance of weight in predicting prescribing patterns. RESULTS: Of 26,571 participants, 72.4% were women, mean age was 38.9 years (standard deviation (SD)=14.2) and mean BMI 27.0 kg/m2 (SD = 6.5); 9.5% had ≥ 1 comorbidity. Patients with obesity, compared to normal weight patients, were more likely to receive bupropion (adjusted odds ratio (aOR) 1.24, 95%CI: 1.09,1.42), fluoxetine (aOR 1.14, 95%CI: 0.97,1.34), and amitriptyline (aOR 1.13, 95%CI: 0.93,1.36), and less likely to receive mirtazapine (aOR 0.55, 95%CI: 0.44,0.68) and escitalopram (aOR 0.88, 95%CI: 0.80, 0.97). RF analysis showed that weight was among the most important predictors of prescribing patterns, equivalent to age and more important than sex. CONCLUSIONS: AD prescribing patterns for patients with obesity appear to be different for selected AD types, including AD known for their weight-modulating and cardiovascular side effects. Longitudinal studies are needed to examine whether these prescribing patterns are associated with significant health outcomes.


Assuntos
Antidepressivos , Citalopram , Adulto , Antidepressivos/efeitos adversos , Canadá , Feminino , Humanos , Mirtazapina , Obesidade/induzido quimicamente , Obesidade/epidemiologia
2.
BMJ Open ; 11(9): e047142, 2021 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-34475156

RESUMO

INTRODUCTION: For over more than a decade, low-dose amitriptyline and mirtazapine are prescribed off-label for insomnia. However, placebo-controlled evidence on these antidepressants for insomnia is still lacking. Therefore, the present trial aims to assess the effectiveness of low-dose amitriptyline (10-20 mg/day) and mirtazapine (7.5-15 mg/day) in patients with insomnia disorder with difficulty maintaining sleep or early-morning awakening problems in general practice. METHODS AND ANALYSIS: The Drug REdiscovery: low-dose Amitriptyline and Mirtazapine for INsomnia disorder in General practice (DREAMING) study is a randomised, double-blind, placebo-controlled trial in about 50 general practices. Adults (18-85 years) with insomnia disorder (Diagnostic and Statistical Manual of Mental Disorders-5) who ask their general practitioner (GP) for sleep medication when non-pharmacological treatment is deemed not effective, are eligible. EXCLUSION CRITERIA: isolated sleep initiation problem, contraindications for or drug-drug interactions with either amitriptyline or mirtazapine. Participants (n=156) will be randomly assigned to three parallel treatment groups of 16-week treatment with either amitriptyline (one or two tablets of 10 mg/day) or mirtazapine (one or two tablets of 7.5 mg/day) or placebo (one or two tablets) alongside usual GP care. All participants start and end with single dose, but dose can be doubled following GP consultation in week 3. Questionnaire assessments will be conducted at baseline, week 6, 12, 20 and 52. The primary study outcome is self-reported insomnia severity at 6 weeks, measured with the Insomnia Severity Index (ISI) in an intention to treat analysis. Secondary outcomes include subjective sleep quality quantified by sleep indices, daytime functioning and symptoms, safety and treatment evaluation and other sleep care consumption. ETHICS AND DISSEMINATION: The Medical Ethics Committee of the VU Medical Centre Amsterdam approved this trial. The results of this trial will be published in peer-reviewed scientific journals and presented at relevant academic conferences and to key stakeholders. TRIAL REGISTRATION NUMBER: NTR7449.


Assuntos
Medicina Geral , Distúrbios do Início e da Manutenção do Sono , Adulto , Amitriptilina , Antidepressivos/uso terapêutico , Método Duplo-Cego , Humanos , Mirtazapina , Ensaios Clínicos Controlados Aleatórios como Assunto , Distúrbios do Início e da Manutenção do Sono/tratamento farmacológico , Resultado do Tratamento
3.
J Affect Disord ; 295: 1474-1481, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34565589

RESUMO

BACKGROUND: Receiving treatment for depression is increasingly common among young adults. Antidepressants (AD) are important in depression treatment and modification of medication is common. We examined switches and discontinuations of ADs among young Finnish adults aged 18-29 years. METHODS: All persons diagnosed with depression in inpatient or specialized outpatient care or having received sickness absence or disability pension due to depression at age of 18-29 years during 2004-17 were included (N = 110761). Among them, we focused on incident AD users (N = 52855, 47.7%) who were identified with a 6 month washout before AD initiation. The follow-up was 2 years. RESULTS: The majority (76.3%) initiated with selective serotonin reuptake inhibitors (SSRIs). The initial AD was switched in 17.4% of cases. Switching was most common when treatment was initiated with tricyclic antidepressants (TCA) or polytherapy, and least common when initiated with SSRIs or serotonin-noradrenaline reuptake inhibitors. Factors associated with switch included initiation with polytherapy, TCA or mirtazapine, and use of benzodiazepines or Z-drugs at baseline. During the first 3 months, 27.6% discontinued AD use, and only 14.1% used AD for 2 years. Factors associated with discontinuation included substance abuse, ADHD, previous suicide attempt and initiation with mirtazapine. SSRIs had the longest time to discontinuation (median 144 days, IQR 64-302). LIMITATIONS: Our data sources lack those treated in primary care only, without receiving a sick leave of ≥2 weeks. In addition, we do not have data on severity of depression, social factors or psychotherapy. CONCLUSIONS: Special emphasis should be paid to persons with increased risk of discontinuation, including those with previous self-harm/suicide attempt or substance abuse.


Assuntos
Antidepressivos , Depressão , Adolescente , Adulto , Antidepressivos/uso terapêutico , Antidepressivos Tricíclicos/uso terapêutico , Humanos , Mirtazapina , Inibidores de Captação de Serotonina/uso terapêutico , Adulto Jovem
4.
Brain Behav ; 11(8): e2311, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34333871

RESUMO

OBJECTIVE: To compare the effectiveness and tolerability of agomelatine with mirtazapine in patients with depressive disorder. To illustrate the prescribing pattern of agomelatine and identify factors that affect the pattern of treatment result and therapeutic outcome of it. METHODS: The clinical data of patients using agomelatine or mirtazapine, 93 patients in each group, were included and reviewed in this retrospective study. Background characteristics, adverse events, therapeutic outcomes (discontinued or continued), reason of discontinuation, and the presence of positive pattern of treatment result were assessed. Positive pattern of treatment result was defined as either recovery or improvement of depressive disorder after therapy. RESULTS: Patients using agomelatine were associated with higher starting dose and higher dose titrated than mirtazapine. More patients started agomelatine due to intolerability, and less due to ineffectiveness of the previous antidepressant. More patients started agomelatine before the use of at least two selective serotonin reuptake inhibitor (SSRI)/serotonin-noradrenaline reuptake inhibitor (SNRI). Patients using agomelatine were associated with less discontinuation due to intolerability, and less experience of adverse events within 90 days of initiation or dose increase, but more discontinuation due to ineffectiveness versus mirtazapine. The use of 50 mg resulted in less discontinuation. The use of at least two SSRI(s)/SNRI(s) before and more concomitant medications are independently associated with more discontinuation due to intolerability. The use of at least two SSRI(s)/SNRI(s) before was also associated with more adverse events. Using agomelatine as an augmentation to other antidepressant(s) and at a higher dose were independently associated with the experience of positive pattern of treatment result. CONCLUSION: Agomelatine was more tolerable than mirtazapine, but could result in more discontinuation due to ineffectiveness. The use of higher dose and as an augmentation to other antidepressant(s) could improve the desired treatment result of agomelatine.


Assuntos
Transtorno Depressivo Maior , Preparações Farmacêuticas , Acetamidas , Transtorno Depressivo Maior/tratamento farmacológico , Humanos , Mirtazapina , Estudos Retrospectivos , Inibidores de Captação de Serotonina
5.
Molecules ; 26(13)2021 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-34201675

RESUMO

The complex pathophysiology of depression, together with the limits of currently available antidepressants, has resulted in the continuous quest for alternative therapeutic strategies. Numerous findings suggest that pharmacological blockade of α2-adrenoceptor might be beneficial for the treatment of depressive symptoms by increasing both norepinephrine and serotonin levels in certain brain areas. Moreover, the antidepressant properties of 5-HT7 receptor antagonists have been widely demonstrated in a large set of animal models. Considering the potential therapeutic advantages in targeting both α2-adrenoceptors and 5-HT7 receptors, we designed a small series of arylsulfonamide derivatives of (dihydrobenzofuranoxy)ethyl piperidines as dually active ligands. Following green chemistry principles, the designed compounds were synthesized entirely using a sustainable mechanochemical approach. The identified compound 8 behaved as a potent α2A/5-HT7 receptor antagonist and displayed moderate-to-high selectivity over α1-adrenoceptor subtypes and selected serotonin and dopaminergic receptors. Finally, compound 8 improved performance of mice in the forced swim test, displaying similar potency to the reference drug mirtazapine.


Assuntos
Antagonistas de Receptores Adrenérgicos alfa 2/química , Antagonistas de Receptores Adrenérgicos alfa 2/farmacologia , Antidepressivos/farmacologia , Depressão/tratamento farmacológico , Atividade Motora/efeitos dos fármacos , Receptores Adrenérgicos alfa 2/metabolismo , Receptores de Serotonina/metabolismo , Antagonistas de Receptores Adrenérgicos alfa 2/síntese química , Antagonistas de Receptores Adrenérgicos alfa 2/uso terapêutico , Animais , Antidepressivos/uso terapêutico , Escala de Avaliação Comportamental , Depressão/fisiopatologia , Células HEK293 , Humanos , Ligantes , Masculino , Camundongos , Mirtazapina/farmacologia , Mirtazapina/uso terapêutico , Norepinefrina/metabolismo , Piperidinas/química , Ratos , Receptores de Serotonina/genética , Serotonina/metabolismo , Natação
6.
Clin Neuropharmacol ; 44(5): 189-190, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34326284

RESUMO

OBJECTIVE: Excoriation disorder is a disabling behavioral disorder characterized by compulsive and repetitive picking of the skin. Excoriation disorder has a lifetime prevalence of 3% to 5% in the general population, and it is most common in females. Its course is chronic, and it is characterized by fluctuating and frequent periods of exacerbation. Excoriation disorder is commonly comorbid with several psychiatric disorders. The treatment of this disorder is challenging and requires a multidisciplinary approach. Current literature has described an improvement in skin picking when patients are treated with fluoxetine or escitalopram; other studies have involved augmentation strategies using antipsychotics, such as olanzapine and aripiprazole; serotonin norepinephrine reuptake inhibitors; and N-acetyl-cysteine. Other pharmacological therapies include lamotrigine and opioid antagonists. Psychotherapies are additional nonpharmacological treatment modalities to consider in this condition. METHODS: We report the case of a 60-year-old Hispanic woman with severe excoriation disorder and several psychiatric comorbidities who responded remarkably to augmentation treatment with mirtazapine. CONCLUSION: Mirtazapine is a noradrenergic and specific serotonergic antidepressant, and its antihistaminergic effect can relieve skin itching and pain.


Assuntos
Antipsicóticos , Transtornos Mentais , Antidepressivos , Antipsicóticos/uso terapêutico , Feminino , Humanos , Transtornos Mentais/tratamento farmacológico , Pessoa de Meia-Idade , Mirtazapina/uso terapêutico , Inibidores de Captação de Serotonina
7.
Sci Total Environ ; 792: 148368, 2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34147801

RESUMO

In the last decade, mirtazapine has become an important antidepressant in clinical use and has also been found at many different environmental sampling sites. Several homologies between the zebrafish Danio rerio and humans, combined with a number of advantages for behavioural and gene expression research using zebrafish embryos, make their use for the analysis of mirtazapine appropriate. The sedative effect of mirtazapine in humans was also found for a specific concentration range in zebrafish embryos (1333.4 µg/L - 2666.9 µg/L). Specifically, 116 hpf old zebrafish embryos showed a reduced swimming distance when exposed to 1334.4 µg/L mirtazapine. Furthermore, changes at the gene regulatory level could be measured (1333.4 µg/L), in particular in the superordinate regulatory systems. For selected transporters of all regulatory systems, an up regulation of the genes by a factor of more than five times could be measured at the highest mirtazapine exposure concentration that was tested. Finally, studies on the protein levels demonstrated an increase in acetylcholinesterase activity for several exposure concentrations (83.3 µg/L and 666.7 µg/L). The physiological changes in zebrafish embryos caused by mirtazapine demonstrate the relevance of these types of studies in aquatic non-target organisms. Such neuroactive substances could pose a potential risk for aquatic organisms below the previously considered concentration threshold for morphological effects.


Assuntos
Poluentes Químicos da Água , Peixe-Zebra , Animais , Antidepressivos/toxicidade , Embrião não Mamífero , Expressão Gênica , Humanos , Mirtazapina , Natação , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/genética
8.
J Appl Physiol (1985) ; 131(1): 414-423, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-34080920

RESUMO

Studies in humans and animal models with spinal cord injury (SCI) have demonstrated that medications targeting serotonin receptors may decrease the susceptibility to central sleep-disordered breathing (SDB). We hypothesized that mirtazapine would decrease the propensity to develop hypocapnic central sleep apnea (CSA) during sleep. We performed a single-blind pilot study on a total of 10 men with SDB (7 with chronic SCI and 3 noninjured) aged 52.0 ± 11.2 yr. Participants were randomly assigned to either mirtazapine (15 mg at bedtime) or a placebo for at least 1 wk, followed by a 7-day washout period before crossing over to the other intervention. Split-night studies included polysomnography and induction of hypocapnic CSA using a noninvasive ventilation (NIV) protocol. The primary outcome was CO2 reserve, defined as the difference between eupneic and end of NIV end-tidal CO2 ([Formula: see text]) preceding induced hypocapneic CSA. Secondary outcomes included controller gain (CG), other ventilatory parameters, and SDB severity. CG was defined as the ratio of change in minute ventilation (V̇e) between control and hypopnea to the change in CO2 during sleep. CO2 reserve was significantly widened on mirtazapine than placebo (-3.8 ± 1.2 vs. -2.0 ± 1.5 mmHg; P = 0.015). CG was significantly decreased on mirtazapine compared with placebo [2.2 ± 0.7 vs. 3.5 ± 1.9 L/(mmHg × min); P = 0.023]. There were no significant differences for other ventilatory parameters assessed or SDB severity between mirtazapine and placebo trials. These findings suggest that the administration of mirtazapine can decrease the susceptibility to central apnea by reducing chemosensitivity and increasing CO2 reserve; however, considering the lack of changes in apnea-hypopnea index (AHI), further research is required to understand the significance of this finding.NEW & NOTEWORTHY To our knowledge, this research study is novel as it is the first study in humans assessing the effect of mirtazapine on CO2 reserve and chemosensitivity in individuals with severe sleep-disordered breathing. This is also the first study to determine the potential therapeutic effects of mirtazapine on sleep parameters in individuals with a spinal cord injury.


Assuntos
Síndromes da Apneia do Sono , Apneia do Sono Tipo Central , Animais , Humanos , Masculino , Mirtazapina , Projetos Piloto , Método Simples-Cego , Apneia do Sono Tipo Central/tratamento farmacológico
9.
Artigo em Russo | MEDLINE | ID: mdl-34037367

RESUMO

The history of the creation and putting into practice of antidepressants and experimental agents - blockers of α2-adrenergic receptors and serotonin 5-HT2-receptors is described. The author analyzes the history of development of mianserin, mirtazapine and other drugs and their position in the classification of antidepressants. On the basis of a generalization of historical facts, the rationality of assigning mianserin, mirtazapine, and possibly other compounds similar in chemical structure and mechanism of action to one neurochemical group and its designation by the term 'stimulators of the release of norepinephrine and (presumably) serotonin' is determined.


Assuntos
Norepinefrina , Serotonina , Antidepressivos , Antidepressivos Tricíclicos , Humanos , Mianserina , Mirtazapina
10.
Expert Rev Clin Pharmacol ; 14(8): 1039-1050, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34030558

RESUMO

OBJECTIVES: This study was conducted to evaluate the potential nephroprotective effects of febuxostat, mirtazapine, and their combination against gentamicin-induced nephrotoxicity. METHODS: Induction of nephrotoxicity was achieved via gentamicin injection (100 mg/kg, I.P., for 7 days). Two different doses of mirtazapine (15-30 mg/kg), febuxostat (5-10 mg/kg), and their combination were administered daily for 14 days prior to gentamicin injection and then concomitantly with gentamicin for additional 7 days. Nephrotoxicity was evaluated histopathologically and biochemically. Renal caspase-3, extracellular signal-regulated protein kinase 1/2 (ERK1/2), nuclear factor-kappa-ß (NF-κß), and monocyte chemoattractant protein (MCP-1) were assayed. RESULTS: Febuxostat and mirtazapine significantly (p < 0.05) alleviated biochemical and histopathological alterations that were induced by gentamicin and, for the first time, significantly decreased the renal levels of ERK1/2 and MCP-1. Conclusion: Febuxostat and mirtazapine were found to have a synergistic impact in reducing gentamicin-induced nephrotoxicity. EXPERT OPINION: The utility of nonpurine xanthine oxidase inhibitor, such as febuxostat and mirtazapine are offering a new potential opportunity for the future nephroprotective effects therapy: Febuxostat and mirtazapine are found to have a synergistic impact in reducing gentamicin-induced nephrotoxicity.


Assuntos
Febuxostat/farmacologia , Gentamicinas/toxicidade , Nefropatias/prevenção & controle , Mirtazapina/farmacologia , Animais , Antibacterianos/administração & dosagem , Antibacterianos/toxicidade , Antidepressivos/administração & dosagem , Antidepressivos/farmacologia , Quimiocina CCL2/metabolismo , Sinergismo Farmacológico , Febuxostat/administração & dosagem , Gentamicinas/administração & dosagem , Supressores da Gota/administração & dosagem , Supressores da Gota/farmacologia , Nefropatias/induzido quimicamente , Masculino , Mirtazapina/administração & dosagem , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , NF-kappa B/metabolismo , Ratos
11.
Cochrane Database Syst Rev ; 5: CD013674, 2021 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-34029378

RESUMO

BACKGROUND: Major depressive disorders have a significant impact on children and adolescents, including on educational and vocational outcomes, interpersonal relationships, and physical and mental health and well-being. There is an association between major depressive disorder and suicidal ideation, suicide attempts, and suicide. Antidepressant medication is used in moderate to severe depression; there is now a range of newer generations of these medications. OBJECTIVES: To investigate, via network meta-analysis (NMA), the comparative effectiveness and safety of different newer generation antidepressants in children and adolescents with a diagnosed major depressive disorder (MDD) in terms of depression, functioning, suicide-related outcomes and other adverse outcomes. The impact of age, treatment duration, baseline severity, and pharmaceutical industry funding was investigated on clinician-rated depression (CDRS-R) and suicide-related outcomes. SEARCH METHODS: We searched the Cochrane Common Mental Disorders Specialised Register, the Cochrane Library (Central Register of Controlled Trials (CENTRAL) and Cochrane Database of Systematic Reviews (CDSR)), together with Ovid Embase, MEDLINE and PsycINFO till March 2020. SELECTION CRITERIA: Randomised trials of six to 18 year olds of either sex and any ethnicity with clinically diagnosed major depressive disorder were included. Trials that compared the effectiveness of newer generation antidepressants with each other or with a placebo were included. Newer generation antidepressants included: selective serotonin reuptake inhibitors; selective norepinephrine reuptake inhibitors (SNRIs); norepinephrine reuptake inhibitors; norepinephrine dopamine reuptake inhibitors; norepinephrine dopamine disinhibitors (NDDIs); and tetracyclic antidepressants (TeCAs). DATA COLLECTION AND ANALYSIS: Two reviewers independently screened titles/abstracts and full texts, extracted data, and assessed risk of bias. We analysed dichotomous data as Odds Ratios (ORs), and continuous data as Mean Difference (MD) for the following outcomes: depression symptom severity (clinician rated), response or remission of depression symptoms, depression symptom severity (self-rated), functioning, suicide related outcomes and overall adverse outcomes. Random-effects network meta-analyses were conducted in a frequentist framework using multivariate meta-analysis. Certainty of evidence was assessed using Confidence in Network Meta-analysis (CINeMA). We used "informative statements" to standardise the interpretation and description of the results. MAIN RESULTS: Twenty-six studies were included. There were no data for the two primary outcomes (depressive disorder established via clinical diagnostic interview and suicide), therefore, the results comprise only secondary outcomes. Most antidepressants may be associated with a "small and unimportant" reduction in depression symptoms on the CDRS-R scale (range 17 to 113) compared with placebo (high certainty evidence: paroxetine: MD -1.43, 95% CI -3.90, 1.04; vilazodone: MD -0.84, 95% CI -3.03, 1.35; desvenlafaxine MD -0.07, 95% CI -3.51, 3.36; moderate certainty evidence: sertraline: MD -3.51, 95% CI -6.99, -0.04; fluoxetine: MD -2.84, 95% CI -4.12, -1.56; escitalopram: MD -2.62, 95% CI -5.29, 0.04; low certainty evidence: duloxetine: MD -2.70, 95% CI -5.03, -0.37; vortioxetine: MD 0.60, 95% CI -2.52, 3.72; very low certainty evidence for comparisons between other antidepressants and placebo). There were "small and unimportant" differences between most antidepressants in reduction of depression symptoms (high- or moderate-certainty evidence). Results were similar across other outcomes of benefit. In most studies risk of self-harm or suicide was an exclusion criterion for the study. Proportions of suicide-related outcomes were low for most included studies and 95% confidence intervals were wide for all comparisons. The evidence is very uncertain about the effects of mirtazapine (OR 0.50, 95% CI 0.03, 8.04), duloxetine (OR 1.15, 95% CI 0.72, 1.82), vilazodone (OR 1.01, 95% CI 0.68, 1.48), desvenlafaxine (OR 0.94, 95% CI 0.59, 1.52), citalopram (OR 1.72, 95% CI 0.76, 3.87) or vortioxetine (OR 1.58, 95% CI 0.29, 8.60) on suicide-related outcomes compared with placebo. There is low certainty evidence that escitalopram may "at least slightly" reduce odds of suicide-related outcomes compared with placebo (OR 0.89, 95% CI 0.43, 1.84). There is low certainty evidence that fluoxetine (OR 1.27, 95% CI 0.87, 1.86), paroxetine (OR 1.81, 95% CI 0.85, 3.86), sertraline (OR 3.03, 95% CI 0.60, 15.22), and venlafaxine (OR 13.84, 95% CI 1.79, 106.90) may "at least slightly" increase odds of suicide-related outcomes compared with placebo. There is moderate certainty evidence that venlafaxine probably results in an "at least slightly" increased odds of suicide-related outcomes compared with desvenlafaxine (OR 0.07, 95% CI 0.01, 0.56) and escitalopram (OR 0.06, 95% CI 0.01, 0.56). There was very low certainty evidence regarding other comparisons between antidepressants. AUTHORS' CONCLUSIONS: Overall, methodological shortcomings of the randomised trials make it difficult to interpret the findings with regard to the efficacy and safety of newer antidepressant medications. Findings suggest that most newer antidepressants may reduce depression symptoms in a small and unimportant way compared with placebo. Furthermore, there are likely to be small and unimportant differences in the reduction of depression symptoms between the majority of antidepressants. However, our findings reflect the average effects of the antidepressants, and given depression is a heterogeneous condition, some individuals may experience a greater response. Guideline developers and others making recommendations might therefore consider whether a recommendation for the use of newer generation antidepressants is warranted for some individuals in some circumstances. Our findings suggest sertraline, escitalopram, duloxetine, as well as fluoxetine (which is currently the only treatment recommended for first-line prescribing) could be considered as a first option. Children and adolescents considered at risk of suicide were frequently excluded from trials, so that we cannot be confident about the effects of these medications for these individuals. If an antidepressant is being considered for an individual, this should be done in consultation with the child/adolescent and their family/caregivers and it remains critical to ensure close monitoring of treatment effects and suicide-related outcomes (combined suicidal ideation and suicide attempt) in those treated with newer generation antidepressants, given findings that some of these medications may be associated with greater odds of these events. Consideration of psychotherapy, particularly cognitive behavioural therapy, as per guideline recommendations, remains important.


Assuntos
Antidepressivos/uso terapêutico , Transtorno Depressivo Maior/tratamento farmacológico , Adolescente , Antidepressivos/efeitos adversos , Viés , Criança , Citalopram/uso terapêutico , Transtorno Depressivo Maior/psicologia , Succinato de Desvenlafaxina/uso terapêutico , Cloridrato de Duloxetina/uso terapêutico , Feminino , Fluoxetina/uso terapêutico , Humanos , Masculino , Mirtazapina/uso terapêutico , Metanálise em Rede , Paroxetina/uso terapêutico , Inibidores de Captação de Serotonina/uso terapêutico , Sertralina/uso terapêutico , Ideação Suicida , Cloridrato de Venlafaxina/uso terapêutico , Cloridrato de Vilazodona/uso terapêutico , Vortioxetina/uso terapêutico
12.
J Psychiatr Res ; 138: 96-102, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33838579

RESUMO

Effective and targeted interventions for improving quality of life (QOL) in addition to achieving 'clinical remission' are imperatives for patients with major depressive disorder (MDD). This study aimed to examine potential predictors and moderators of QOL in depression. Data were obtained from the Algorithm Guided Treatment Strategies for Major Depressive Disorder (AGTs-MDD) study, a multisite, randomized controlled trial composed of 980 depressed patients. Mixed Model Repeated Measures (MMRM) analyses were conducted to identify baseline characteristics associated with QOL overall (predictors) and their interaction effects (moderators). Severe core depressive, anxiety and pain symptoms were found to be independently associated with poor QOL over the 12-week acute phase treatment. Severe depression, severe anxiety or pain symptoms, or severe suicidal ideation predicted a larger improvement of QOL during acute phase treatment, whereas males showed less improvement. None of the putative moderators were identified except for the educational level. Patients with lower educational level showed a larger improvement of QOL in the AGT started with escitalopram (AGT-E) group and AGT started with mirtazapine (AGT-M) group compared to the treatment as usual (TAU) group. These findings may help to instruct informed decision-making for heterogeneous patients with MDD in the view of full recovery.


Assuntos
Transtorno Depressivo Maior , Qualidade de Vida , Citalopram/uso terapêutico , Transtorno Depressivo Maior/tratamento farmacológico , Feminino , Humanos , Masculino , Mirtazapina , Ideação Suicida
13.
Front Immunol ; 12: 622537, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33841403

RESUMO

Introduction: B cells are important regulators of both adaptive and innate immunity. The normal liver contains significant numbers of B cells, and their numbers increase dramatically in immune-mediated liver diseases. Our previous observations suggest a hepatoprotective effect of the antidepressant mirtazapine in human and experimental immune-mediated liver disease. Therefore, we performed a series of experiments to determine the impact of mirtazapine treatment on hepatic B cell homeostasis, as reflected by B cell number, trafficking and phenotype using flow cytometry (FCM) and intravital microscopy (IVM) analysis. Mirtazapine treatment rapidly induced a significant reduction in total hepatic B cell numbers, paralleled by a compositional shift in the predominant hepatic B cell subtype from B2 to B1. This shift in hepatic B cells induced by mirtazapine treatment was associated with a striking increase in total hepatic levels of the chemokine CXCL10, and increased production of CXCL10 by hepatic macrophages and dendritic cells. Furthermore, mirtazapine treatment led to an upregulation of CXCR3, the cognate chemokine receptor for CXCL10, on hepatic B cells that remained in the liver post-mirtazapine. A significant role for CXCR3 in the hepatic retention of B cells post-mirtazapine was confirmed using CXCR3 receptor blockade. In addition, B cells remaining in the liver post-mirtazapine produced lower amounts of the proinflammatory Th1-like cytokines IFNγ, TNFα, and IL-6, and increased amounts of the Th2-like cytokine IL-4, after stimulation in vitro. Conclusion: Mirtazapine treatment rapidly alters hepatic B cell populations, enhancing hepatic retention of CXCR3-expressing innate-like B cells that generate a more anti-inflammatory cytokine profile. Mirtazapine-induced hepatic B cell shifts could potentially represent a novel therapeutic approach to immune-mediated liver diseases characterized by B cell driven pathology.


Assuntos
Antidepressivos/uso terapêutico , Subpopulações de Linfócitos B/imunologia , Linfócitos B/imunologia , Hepatopatias/imunologia , Fígado/imunologia , Mirtazapina/uso terapêutico , Animais , Células Cultivadas , Citocinas/genética , Citocinas/metabolismo , Humanos , Imunidade Inata , Hepatopatias/terapia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Receptores CXCR3/metabolismo , Células Th1/imunologia , Células Th2/imunologia
14.
J Pain Palliat Care Pharmacother ; 35(2): 113-116, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33856954

RESUMO

While mirtazapine is primarily prescribed for major depressive disorder, it is less commonly prescribed for anorexia related to various disease states. Mirtazapine is associated with few adverse events but potential for a discontinuation syndrome does exist. Here we describe a case of a 53-year-old man prescribed mirtazapine 15 mg/day for appetite stimulation who experienced anxiousness, nausea, tremor, loss of appetite, lack of desire for food, and an 8-pound weight loss after abrupt, inadvertent discontinuation. Symptom onset was acute and presented within 48-hours of stopping his medication. Mirtazapine was restarted at the same dose after 14 days of ongoing symptoms and his symptoms subsided immediately. Scant literature exists to highlight the potentially serious adverse events associated with abrupt mirtazapine discontinuation, even at low doses, and this case contributes to advocating for the need of mirtazapine taper when medication cessation is being considered.


Assuntos
Transtorno Depressivo Maior , Apetite , Humanos , Fome , Masculino , Mianserina/efeitos adversos , Pessoa de Meia-Idade , Mirtazapina
15.
J Psychiatr Pract ; 27(2): 137-144, 2021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-33656821

RESUMO

The widespread prevalence of coronavirus disease 2019 (COVID-19) means that inpatient psychiatric units will necessarily manage patients who have COVID-19 that is comorbid with acute psychiatric symptoms. We report a case of recurrence of respiratory symptoms and positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse transcription-polymerase chain reaction (RT-PCR) testing in a patient on an inpatient psychiatric unit occurring 42 days after the initial positive SARS-CoV-2 RT-PCR test, 38 days after initial symptom resolution, and 30 days after the first of 3 negative SARS-CoV-2 RT-PCR tests. Over the course of the admission, the patient was safely initiated on clozapine. Recent literature on COVID-19's potential recurrence and neuropsychiatric effects is reviewed and implications for the management of COVID-19 on inpatient psychiatric units are discussed. In the era of COVID-19 and our still-developing understanding of this illness, psychiatrists' role as advocates and collaborators in our patients' physical health care has become even more critical.


Assuntos
Antidepressivos/uso terapêutico , Antipsicóticos/uso terapêutico , COVID-19/complicações , Transtorno Depressivo Maior/complicações , Transtorno Depressivo Maior/tratamento farmacológico , Transtornos Psicóticos/complicações , Transtornos Psicóticos/tratamento farmacológico , Adulto , Alcoolismo/complicações , Alcoolismo/diagnóstico , COVID-19/diagnóstico , COVID-19/psicologia , Teste de Ácido Nucleico para COVID-19 , Clozapina , Transtorno Depressivo Maior/diagnóstico , Hospitais Psiquiátricos , Humanos , Pacientes Internados/psicologia , Masculino , Mirtazapina/uso terapêutico , Transtornos Psicóticos/diagnóstico , Recidiva , SARS-CoV-2 , Sertralina/uso terapêutico , Tentativa de Suicídio
16.
J Forensic Sci ; 66(3): 1165-1170, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33559900

RESUMO

Mirtazapine is an antidepressant drug, used to treat depression, but also, in some specific conditions, to treat obsessive-compulsive disorder and anxiety. Although mirtazapine is not a hypnotic, it can make the subject feel drowsy. Children under the age of 18 should not take mirtazapine, but for some very special diseases, a physician can prescribe it for a limited period of time. The authors report a case involving 2 children (7- and 9-year-old) who were administered mirtazapine without consent by the mother, who was under daily therapy with this antidepressant. Hair specimens, collected from the children were tested by liquid chromatography coupled to tandem mass spectrometry for mirtazapine and its metabolite, N-desmethylmirtazapine, on 3 × 1 cm segments. The hair test results (3 × 1 cm segments) have demonstrated that both children have been repetitively exposed to mirtazapine for approximately the last 3 months before hair collection, with concentrations in the range 1.32-3.79 and 0.64-2.54 ng/mg for mirtazapine and N-desmethylmirtazapine, respectively. Environmental contamination was ruled out as the measured concentrations are highly variable according to the pattern of drug distribution and the washes were negative. Hair testing for drugs appears as an excellent diagnostic tool for child protection toward drug exposure.


Assuntos
Antidepressivos/análise , Antidepressivos/envenenamento , Cabelo/química , Mirtazapina/análise , Mirtazapina/envenenamento , Criança , Maus-Tratos Infantis/diagnóstico , Cromatografia Líquida , Toxicologia Forense , Humanos , Espectrometria de Massas , Mianserina/análogos & derivados , Mianserina/análise
17.
BMJ Case Rep ; 14(2)2021 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-33542022

RESUMO

Pancreatic cancer is the tumour related to higher rates of depression. Several papers have validated the association between pancreatic cancer and depression. It was noticed that in some cases the psychiatric symptoms precede the somatic ones. We present a case of a progressive and incapacitating diffuse abdominal pain, initially attributed to psychosomatic disorder. This hindered a timely correct diagnosis leading to a poor outcome. A pancreatic adenocarcinoma in an unresectable stage was confirmed by histopathology. The patient underwent chemotherapy.


Assuntos
Antidepressivos/uso terapêutico , Depressão , Tratamento Farmacológico , Mirtazapina/uso terapêutico , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/tratamento farmacológico , Dor Abdominal/etiologia , Depressão/diagnóstico , Depressão/tratamento farmacológico , Depressão/etiologia , Fadiga/etiologia , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Pancreáticas/patologia
18.
Biol Pharm Bull ; 44(2): 238-244, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33518675

RESUMO

Mirtazapine (MTZ) is a noradrenergic and specific serotonergic antidepressant. MTZ is reportedly associated with an increased risk of bleeding. However, the underlying mechanism remains unclear. In this study, we investigated the antiplatelet effect of MTZ in mice via light transmission aggregometry to elucidate the mechanism of MTZ-induced bleeding. The results of the ex vivo study showed that the oral administration of MTZ (20 or 100 mg/kg) significantly suppressed platelet aggregation mediated by the synergic interaction of 5-hydroxytryptamine (5-HT) and adrenaline. Additionally, MTZ significantly suppressed platelet aggregation, mediated by the synergic interaction of ADP and 5-HT or adrenaline. Similar results were obtained in vitro, under the condition of 5-HT- and adrenaline-induced platelet aggregation. Overall, the results suggest that MTZ exerts antiplatelet effect by co-blocking 5-HT2A and α2-adrenergic receptors on platelets and suppresses platelet aggregation mediated by ADP, increased by either 5-HT or adrenaline. Thus, a detailed monitoring of bleeding is recommended for patients taking MTZ.


Assuntos
Antagonistas de Receptores Adrenérgicos alfa 2/efeitos adversos , Mirtazapina/efeitos adversos , Agregação Plaquetária/efeitos dos fármacos , Antagonistas do Receptor 5-HT2 de Serotonina/efeitos adversos , Administração Oral , Antagonistas de Receptores Adrenérgicos alfa 2/administração & dosagem , Animais , Plaquetas/efeitos dos fármacos , Plaquetas/metabolismo , Epinefrina/metabolismo , Masculino , Camundongos , Mirtazapina/administração & dosagem , Modelos Animais , Receptor 5-HT2A de Serotonina/metabolismo , Serotonina/metabolismo , Antagonistas do Receptor 5-HT2 de Serotonina/administração & dosagem , Succinatos/administração & dosagem , Ioimbina/administração & dosagem
19.
J Med Primatol ; 50(2): 128-133, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33528049

RESUMO

BACKGROUND: Hyporexia and weight loss are important indicators of physical and psychological well-being in macaque colonies. An FDA-approved transdermal formulated Mirtazapine (MTZ) shows effectiveness in managing feline hyporexia. This study sought to determine its effectiveness as an appetite stimulant in macaques. METHODS: Fourteen macaques with idiopathic hyporexia, intractable to conventional management were treated with transdermal MTZ (0.5 mg/kg) topically administered to aural pinnae once daily for 14 days. Qualitative food consumption was monitored daily for 6 months. Body weights were collected prior to treatment, every 2 weeks for the first 6 weeks, 10 weeks, and 6 months post-treatment. RESULTS: Transdermal MTZ significantly reduced the frequency of hyporexia during treatment and monthly for 6 months. No significant increase in weight noted until approximately 6 months post-treatment. CONCLUSIONS: Results from this study indicate that a short course of transdermal MTZ is an effective way to increase food consumption in macaques chronically.


Assuntos
Anorexia/tratamento farmacológico , Estimulantes do Apetite/administração & dosagem , Macaca fascicularis , Macaca mulatta , Mirtazapina/administração & dosagem , Doenças dos Macacos/tratamento farmacológico , Administração Cutânea , Animais , Feminino , Masculino
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