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1.
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
2.
Life Sci ; 278: 119598, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-33984361

RESUMO

AIMS: To determine if treatment with the selective serotonin reuptake inhibitor (SSRI) sertraline reduces the bladder dysfunction caused by water avoidance stress in mice. MAIN METHODS: Adult female mice were randomly allocated to (1) Unstressed, (2) Stressed or (3) Stress + Sertraline experimental groups. Stressed mice were subjected to water avoidance for 1 h/day for 10 days and received sertraline or vehicle in drinking water, starting 10-days prior to the first stress exposure. Age matched control/unstressed mice were house under normal conditions without stress exposure. Voiding behaviour was assessed throughout the experimental protocol. After the final stress exposure, a blood sample was taken to measure plasma corticosterone levels and bladders were removed, catheterised and intravesical pressure responses recorded during distension and in response to pharmacological agents. KEY FINDINGS: Plasma corticosterone levels in sertraline-treated animals were equivalent to unstressed controls and significantly decreased compared to the stressed group. Voiding frequency was significantly increased in the stressed group, and treatment with sertraline significantly decreased voiding frequency, however, this remained elevated compared to unstressed control animals. Bladders from stressed mice displayed enhanced maximal contractile response to the muscarinic agonist carbachol and greater release of ACh in the serosal fluid, which was reduced to control levels by sertraline treatment. Spontaneous phasic contractions were not altered by stress but were significantly reduced in bladders from sertraline treated animals, relative to controls. SIGNIFICANCE: These results indicate that management of voiding dysfunction caused by psychological stress may be aided by the addition of an SSRI such as sertraline.


Assuntos
Inibidores de Captação de Serotonina/uso terapêutico , Sertralina/uso terapêutico , Estresse Psicológico/tratamento farmacológico , Estresse Psicológico/fisiopatologia , Bexiga Urinária/efeitos dos fármacos , Animais , Feminino , Camundongos , Camundongos Endogâmicos C57BL , Bexiga Urinária/fisiopatologia , Micção/efeitos dos fármacos
3.
Transl Psychiatry ; 11(1): 268, 2021 05 04.
Artigo em Inglês | MEDLINE | ID: covidwho-1216450

RESUMO

Maternal stress has debilitating implications for both mother and child, including increased risk for anxiety. The current COVID-19 pandemic escalates these phenomena, thus, urging the need to further explore and validate feasible therapeutic options. Unlike the protracted nature of clinical studies, animal models could offer swift evidence. Prominent candidates for treatment are selective serotonin reuptake inhibitors (SSRIs) to the mother, that putatively accommodate maternal functioning, and, thereby, also protect the child. However, SSRIs might have deleterious effects. It is important to assess whether SSRIs and other pharmacotherapies can moderate the transference of anxiety by soothing maternal anxiety and to examine the extent of offspring's exposure to the drugs via lactation. To our knowledge, the possibility that antenatal stress exacerbates lactation-driven exposure to SSRIs has not been tested yet. Thirty ICR-outbred female mice were exposed to stress during gestation and subsequently administered with either the SSRI, escitalopram, or the novel herbal candidate, shan-zha, during lactation. Upon weaning, both dams' and pups' anxiety-like behavior and serum escitalopram levels were assessed. The major findings of the current study show that both agents moderated the antenatal stress-induced transgenerational transference of anxiety by ameliorating dams' anxiety. Interestingly though, pups' exposure to escitalopram via lactation was exacerbated by antenatal stress. The latter finding provides a significant insight into the mechanism of lactation-driven exposure to xenobiotics and calls for a further consideration vis-à-vis the administration of other drugs during breastfeeding.


Assuntos
Ansiedade/tratamento farmacológico , Ansiedade/fisiopatologia , Lactação/metabolismo , Efeitos Tardios da Exposição Pré-Natal/prevenção & controle , Inibidores de Captação de Serotonina/administração & dosagem , Inibidores de Captação de Serotonina/uso terapêutico , Estresse Psicológico/fisiopatologia , Animais , COVID-19 , Citalopram/administração & dosagem , Citalopram/farmacologia , Citalopram/uso terapêutico , Crataegus , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas , Feminino , Masculino , Camundongos , Camundongos Endogâmicos ICR , Pandemias , Gravidez , Inibidores de Captação de Serotonina/farmacologia , Xenobióticos/metabolismo
4.
J Clin Neurosci ; 88: 163-172, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: covidwho-1142062

RESUMO

The current 2019 novel coronavirus disease (COVID-19), an emerging infectious disease, is undoubtedly the most challenging pandemic in the 21st century. A total of 92,977,768 confirmed cases of COVID-19 and 1,991,289 deaths were reported globally up to January 14, 2021. COVID-19 also affects people's mental health and quality of life. At present, there is no effective therapeutic strategy for the management of this disease. Therefore, in the absence of a specific vaccine or curative treatment, it is an urgent need to identify safe, effective and globally available drugs for reducing COVID-19 morbidity and fatalities. In this review, we focus on selective serotonin reuptake inhibitors (SSRIs: a class of antidepressant drugs with widespread availability and an optimal tolerability profile) that can potentially be repurposed for COVID-19 and are currently being tested in clinical trials. We also summarize the existing literature on what is known about the link between serotonin (5-HT) and the immune system. From the evidence reviewed here, we propose fluoxetine as an adjuvant therapeutic agent for COVID-19 based on its known immunomodulatory, anti-inflammatory and antiviral properties. Fluoxetine may potentially reduce pro-inflammatory chemokine/cytokines levels (such as CCL-2, IL-6, and TNF-α) in COVID-19 patients. Furthermore, fluoxetine may help to attenuate neurological complications of COVID-19.


Assuntos
COVID-19/tratamento farmacológico , Reposicionamento de Medicamentos , Inibidores de Captação de Serotonina/uso terapêutico , Anti-Inflamatórios/uso terapêutico , COVID-19/complicações , Fluoxetina/uso terapêutico , Humanos , Pandemias
5.
Cochrane Database Syst Rev ; 5: CD006687, 2021 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-33998674

RESUMO

BACKGROUND: Numerous agents have been suggested for the symptomatic treatment of primary Raynaud's phenomenon. Apart from calcium channel blockers, which are considered to be the drugs of choice, evidence of the effects of alternative pharmacological treatments is limited. This is an update of a review first published in 2008. OBJECTIVES: To assess the effects of drugs with vasodilator effects on primary Raynaud's phenomenon as determined by frequency, severity, and duration of vasospastic attacks; quality of life; adverse events; and Raynauds Condition Score. SEARCH METHODS: The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, and CINAHL databases, and the World Health Organization International Clinical Trials Registry Platform and the ClinicalTrials.gov trial register to November 16, 2020. SELECTION CRITERIA: We included randomized controlled trials evaluating effects of oral, intravenous, and topical formulations of any drug with vasodilator effects on subjective symptoms, severity scores, and radiological outcomes in primary Raynaud's phenomenon. Treatment with calcium channel blockers was not assessed in this review, nor were these agents compared. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies for inclusion, assessed studies using the Cochrane "Risk of bias" tool, and extracted study data. Outcomes of interest included frequency, severity, and duration of attacks; quality of life (QoL); adverse events (AEs); and the Raynaud Condition Score (RCS). We assessed the certainty of the evidence using GRADE. MAIN RESULTS: We identified seven new studies for this update. In total, we included 15 studies involving 635 participants. These studies compared different vasodilators to placebo. Individual studies used different methods and measures to report different outcomes. Angiotensin-converting enzyme (ACE) inhibitors Combining data from three studies revealed a possible small increase in the frequency of attacks per week after treatment (captopril or enalapril) compared to placebo (mean difference [MD] 0.79, 95% confidence interval [CI] 0.43 to 1.17; low-certainty evidence). There was no evidence of a difference between groups in severity of attacks (MD -0.17, 95% CI -4.66 to 4.31; 34 participants, 2 studies; low-certainty evidence); duration of attacks (MD 0.54, 95% CI -2.42 to 1.34; 14 participants, 1 study; low-certainty evidence); or AEs (risk ratio [RR] 1.35, 95% CI 0.67 to 2.73; 46 participants, 3 studies; low-certainty evidence). QoL and RCS were not reported. Alpha blockers Two studies used alpha blockers (buflomedil or moxisylyte). We were unable to combine data due to the way results were presented. Buflomedil probably reduced the frequency of attacks compared to placebo (MD -8.82, 95% CI -11.04 to -6.60; 31 participants, 1 study; moderate-certainty evidence) and may improve severity scores (MD -0.41, 95% CI -0.62 to -0.30; moderate-certainty evidence). With moxisylyte, investigators reported fewer attacks (P < 0.02), less severe symptoms (P < 0.01), and shorter duration of attacks, but the clinical relevance of these results is unclear. No evidence of a difference in AEs between buflomedil and placebo groups was noted (RR 1.41, 95% CI 0.27 to 7.28; 31 participants, 1 study; moderate-certainty evidence). More AEs were observed in participants in the moxisylyte group than in the placebo group. Prostaglandin/prostacyclin analogues One study compared beraprost versus placebo. There was no evidence of benefit for frequency (MD 2.00, 95% CI -0.35 to 4.35; 118 participants, low-certainty evidence) or severity (MD -0.06, 95% CI -0.34 to 0.22; 118 participants, low-certainty evidence) of attacks. Overall, more AEs were noted in the beraprost group (RR 1.59, 95% CI 1.05 to 2.42; 125 participants; low-certainty evidence). This study did not report on duration of attacks, QoL, or RCS. Thromboxane synthase inhibitors One study compared a thromboxane synthase inhibitor (dazoxiben) versus placebo. There was no evidence of benefit for frequency of attacks (MD 0.8, 95% CI -1.81 to 3.41; 6 participants; very low-certainty evidence). Adverse events were not reported in subgroup analyses of participants with primary Raynaud's phenomenon, and the study did not report on duration of attacks, severity of symptoms, QoL, or RCS. Selective serotonin reuptake inhibitors One study compared ketanserin with placebo. There may be a slight reduction in the number of attacks per week with ketanserin compared to placebo (MD -14.0, 95% CI -27.72 to -0.28; 41 participants; very low-certainty evidence) and reduced severity score (MD -133.00, 95% CI -162.40 to -103.60; 41 participants; very low-certainty evidence). There was no evidence that ketanserin reduced the duration of attacks (MD -4.00, 95% CI -14.82 to 6.82; 41 participants; very low-certainty evidence), or that AEs were increased in either group (RR 1.54, 95% CI 0.89 to 2.65; 41 participants; very low-certainty evidence). This study did not report on QoL or RCS. Nitrate/nitrate derivatives Four studies compared topical treatments of nitroglycerin or glyceryl trinitrate versus placebo, each reporting on limited outcomes. Meta-analysis demonstrated no evidence of effect on frequency of attacks per week (MD -1.57, 95% CI -4.31 to 1.17; 86 participants, 2 studies; very low-certainty evidence). We were unable to pool any data for the remaining outcomes. Phosphodiesterase inhibitors Three studies compared phosphodiesterase inhibitors (vardenafil, cilostazol or PF-00489791) to an equivalent placebo. Results showed no evidence of a difference in frequency of attacks (standardized MD [SMD] -0.05, 95% CI -6.71 to 6.61; 111 participants, 2 studies; low-certainty evidence), severity of attacks (MD -0.03, 95% CI -1.04 to 0.97; 111 participants, 2 studies; very low-certainty evidence), duration of attacks (MD -1.60, 95% CI -7.51 to 4.31; 73 participants, 1 study; low-certainty evidence), or RCS (SMD -0.8, 95% CI -1.74 to 0.13; 79 participants, 2 studies; low-certainty evidence). Study authors reported that 35% of participants on cilostazol complained of headaches, which were not reported in the placebo group. PF-00489791 caused 34 of 54 participants to experience AEs versus 43 of 102 participants receiving placebo (RR 1.49). Headache was most common, affecting 14 participants (PF-00489791) versus nine participants (placebo). AUTHORS' CONCLUSIONS: The included studies investigated several different vasodilators (topical and oral) for treatment of primary Raynaud's phenomenon. Small sample sizes, limited data, and variability in outcome reporting yielded evidence of very low to moderate certainty. Evidence is insufficient to support the use of vasodilators and suggests that vasodilator use may even worsen disease.


Assuntos
Doença de Raynaud/tratamento farmacológico , Vasodilatadores/administração & dosagem , Administração Oral , Administração Tópica , Antagonistas Adrenérgicos alfa/administração & dosagem , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Viés , Humanos , Inibidores de Fosfodiesterase/administração & dosagem , Placebos/uso terapêutico , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Inibidores de Captação de Serotonina/uso terapêutico , Tromboxano-A Sintase/antagonistas & inibidores
6.
Transl Psychiatry ; 11(1): 268, 2021 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-33947833

RESUMO

Maternal stress has debilitating implications for both mother and child, including increased risk for anxiety. The current COVID-19 pandemic escalates these phenomena, thus, urging the need to further explore and validate feasible therapeutic options. Unlike the protracted nature of clinical studies, animal models could offer swift evidence. Prominent candidates for treatment are selective serotonin reuptake inhibitors (SSRIs) to the mother, that putatively accommodate maternal functioning, and, thereby, also protect the child. However, SSRIs might have deleterious effects. It is important to assess whether SSRIs and other pharmacotherapies can moderate the transference of anxiety by soothing maternal anxiety and to examine the extent of offspring's exposure to the drugs via lactation. To our knowledge, the possibility that antenatal stress exacerbates lactation-driven exposure to SSRIs has not been tested yet. Thirty ICR-outbred female mice were exposed to stress during gestation and subsequently administered with either the SSRI, escitalopram, or the novel herbal candidate, shan-zha, during lactation. Upon weaning, both dams' and pups' anxiety-like behavior and serum escitalopram levels were assessed. The major findings of the current study show that both agents moderated the antenatal stress-induced transgenerational transference of anxiety by ameliorating dams' anxiety. Interestingly though, pups' exposure to escitalopram via lactation was exacerbated by antenatal stress. The latter finding provides a significant insight into the mechanism of lactation-driven exposure to xenobiotics and calls for a further consideration vis-à-vis the administration of other drugs during breastfeeding.


Assuntos
Ansiedade/tratamento farmacológico , Ansiedade/fisiopatologia , Lactação/metabolismo , Efeitos Tardios da Exposição Pré-Natal/prevenção & controle , Inibidores de Captação de Serotonina/administração & dosagem , Inibidores de Captação de Serotonina/uso terapêutico , Estresse Psicológico/fisiopatologia , Animais , COVID-19 , Citalopram/administração & dosagem , Citalopram/farmacologia , Citalopram/uso terapêutico , Crataegus , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas , Feminino , Masculino , Camundongos , Camundongos Endogâmicos ICR , Pandemias , Gravidez , Inibidores de Captação de Serotonina/farmacologia , Xenobióticos/metabolismo
7.
J Clin Neurosci ; 88: 163-172, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33992179

RESUMO

The current 2019 novel coronavirus disease (COVID-19), an emerging infectious disease, is undoubtedly the most challenging pandemic in the 21st century. A total of 92,977,768 confirmed cases of COVID-19 and 1,991,289 deaths were reported globally up to January 14, 2021. COVID-19 also affects people's mental health and quality of life. At present, there is no effective therapeutic strategy for the management of this disease. Therefore, in the absence of a specific vaccine or curative treatment, it is an urgent need to identify safe, effective and globally available drugs for reducing COVID-19 morbidity and fatalities. In this review, we focus on selective serotonin reuptake inhibitors (SSRIs: a class of antidepressant drugs with widespread availability and an optimal tolerability profile) that can potentially be repurposed for COVID-19 and are currently being tested in clinical trials. We also summarize the existing literature on what is known about the link between serotonin (5-HT) and the immune system. From the evidence reviewed here, we propose fluoxetine as an adjuvant therapeutic agent for COVID-19 based on its known immunomodulatory, anti-inflammatory and antiviral properties. Fluoxetine may potentially reduce pro-inflammatory chemokine/cytokines levels (such as CCL-2, IL-6, and TNF-α) in COVID-19 patients. Furthermore, fluoxetine may help to attenuate neurological complications of COVID-19.


Assuntos
COVID-19/tratamento farmacológico , Reposicionamento de Medicamentos , Inibidores de Captação de Serotonina/uso terapêutico , Anti-Inflamatórios/uso terapêutico , COVID-19/complicações , Fluoxetina/uso terapêutico , Humanos , Pandemias
8.
BMC Psychiatry ; 21(1): 260, 2021 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-34011310

RESUMO

BACKGROUND: In the population of postmenopausal patients with major depressive disorder (MDD), the superiority of serotonin-norepinephrine reuptake inhibitors (SNRIs) over selective serotonin reuptake inhibitors (SSRIs) has not yet been definitively proven. Consequently, a direct comparison of the efficacy of SSRIs and SNRIs in the treatment of postmenopausal depression could provide relevant data. The aim of this study was to compare the efficacy and safety of venlafaxine vs. fluoxetine in the treatment of postmenopausal MDD. METHODS: This was an 8-week, multicenter, randomized, single-blind, active-controlled trial conducted at a psychiatric hospital (Beijing Anding Hospital) and a general hospital (Beijing Chaoyang Hospital) between April 2013 and September 2017. The primary outcome measure was improving depressive symptoms (Hamilton Depression Rating Scale (HAMD-24) score). The secondary outcomes included the change of HAMD-24 anxiety/somatization factor score and Clinical Global Impressions-Improvement (CGI-I) response rate. Safety was assessed by treatment-emergent adverse events (TEAEs) and laboratory tests. Efficacy was analyzed by using the full analysis set (FAS) following the modified intention-to-treat (mITT) principle. The primary endpoint measurements were analyzed using a mixed-effect model for repeated measures (MMRM) model with patients as a random-effect factor, treatment group as the independent variable, time as a repeated measure, and baseline covariates, using a first-order ante dependence covariance matrix. RESULTS: A total of 184 women were randomized. The full analysis set (FAS) included 172 patients (venlafaxine, n = 82; fluoxetine, n = 90). Over the 8-week study period, the reduction in HAMD-24 scores was significant (P < 0.001) in both groups, while a significantly greater decline from baseline was observed in the venlafaxine group compared with the fluoxetine group (least-squares mean difference [95% CI]: - 2.22 [- 7.08, - 0.41]), P = 0.001). The baseline-to-week-8 least-squares mean change of the anxiety/somatization factor scores, CGI-I response rate were greater in the venlafaxine group than in the fluoxetine group (all P < 0.05). The most frequent TEAEs (≥5%) in both groups were nausea, somnolence, dizziness, headache, and dry mouth. There was no significant difference in the incidence of adverse events between the two groups. CONCLUSION: Venlafaxine was well tolerated and compared to fluoxetine, it led to a greater improvement in the treatment of postmenopausal MDD. TRIAL REGISTRATION: Clinical Trials. gov #NCT01824433 . The trial was registered on April 4, 2013.


Assuntos
Transtorno Depressivo Maior , Fluoxetina , Cicloexanóis , Transtorno Depressivo Maior/tratamento farmacológico , Método Duplo-Cego , Feminino , Fluoxetina/efeitos adversos , Humanos , Pós-Menopausa , Inibidores de Captação de Serotonina/uso terapêutico , Método Simples-Cego , Resultado do Tratamento , Cloridrato de Venlafaxina/efeitos adversos
10.
J Affect Disord ; 290: 240-244, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-34010748

RESUMO

BACKGROUND: Ketamine can act as antidepressant in patients with major depressive disorder (MDD) who are treatment-resistant. P11 has been implicated in ketamine's mechanism of action and proposed as biomarker for treatment response to other antidepressants. This study explores the effect of ketamine on peripheral p11 and the potential role for p11 as response marker for ketamine treatment. METHODS: Thirty Selective Serotonin Reuptake Inhibitor resistant MDD patients were randomized to either 0.5 mg/kg ketamine or placebo intravenous treatment. Using multicolor Flow Cytometry, peripheral p11 levels were measured before and 1-2 days after treatment. RESULTS: P11 levels were decreased within the ketamine group in both cytotoxic T cell and T helper cells populations, although this did not significantly differ from changes seen in the placebo group. Baseline p11 levels in cytotoxic T cells were significantly correlated with antidepressant response to ketamine treatment. LIMITATIONS: This study was part of a larger study examining the effect of ketamine on the serotonin system in MDD patients, therefore the number of study subjects was limited to that of the primary study. CONCLUSIONS: High baseline p11 levels in cytotoxic T cells were associated with a stronger reduction of depressive symptoms in MDD patients after ketamine treatment. Future studies should confirm if peripheral p11 levels could be used as a predictor of ketamine treatment response.


Assuntos
Transtorno Depressivo Maior , Transtorno Depressivo Resistente a Tratamento , Ketamina , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Depressão , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Resistente a Tratamento/tratamento farmacológico , Humanos , Ketamina/farmacologia , Ketamina/uso terapêutico , Inibidores de Captação de Serotonina/farmacologia , Inibidores de Captação de Serotonina/uso terapêutico
11.
Neurosciences (Riyadh) ; 26(2): 152-157, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33814367

RESUMO

OBJECTIVES: To examine the prescribing patterns of antidepressants among a sample of psychiatrists working in Oman and to compare these practices to the current evidence for prescribing specific antidepressant in particular clinical situations. METHODS: This retrospective cross sectional study. Massachusetts General Hospital Psychopharmacology Questionnaire, a 10-item questionnaire listing factors that might have influenced the choice of antidepressant medication, was sent to 83 psychiatrists working in governmental health sectors in Oman. The study was done from March to July 2019. RESULTS: A total number of 78 psychiatrists responded to the questionnaire. Of these, 44 of the psychiatrists (56.4%) believed that one type of antidepressant is more efficacious than others, while 74 psychiatrists (94.9%) indicated that selective serotonin reuptake inhibitors (SSRIs) were their first-line treatment preference. Mirtazapine was chosen as the most likely antidepressant to cause weight gain by two-thirds of the participants. For the treatment of anxious depression and depression with melancholic feature, SSRIs were the first choice of treatment for 64.1% and 7% of respondents, respectively. For depression with atypical features, 42.3% indicated that a monoamine oxidase inhibitor would be their first option. CONCLUSION: There is a discrepancy between the current antidepressant prescribing practices in Oman and empirical antidepressant-prescribing evidence, and this finding is consistent with previous studies.


Assuntos
Antidepressivos/uso terapêutico , Transtorno Depressivo/tratamento farmacológico , Prescrições de Medicamentos , Padrões de Prática Médica , Inibidores de Captação de Serotonina/uso terapêutico , Estudos Transversais , Feminino , Pesquisas sobre Serviços de Saúde , Humanos , Masculino , Omã , Psiquiatria , Estudos Retrospectivos
12.
Cochrane Database Syst Rev ; 4: CD010682, 2021 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-33860531

RESUMO

BACKGROUND: Depressive disorders are the most common psychiatric comorbidity in people with epilepsy, affecting around one-third, with a significant negative impact on quality of life. There is concern that people may not be receiving appropriate treatment for their depression because of uncertainty regarding which antidepressant or class works best, and the perceived risk of exacerbating seizures. This review aimed to address these issues, and inform clinical practice and future research. This is an updated version of the original Cochrane Review published in Issue 12, 2014. OBJECTIVES: To evaluate the efficacy and safety of antidepressants in treating depressive symptoms and the effect on seizure recurrence, in people with epilepsy and depression. SEARCH METHODS: For this update, we searched CRS Web, MEDLINE, SCOPUS, PsycINFO, and ClinicalTrials.gov (February 2021). We searched the World Health Organization Clinical Trials Registry in October 2019, but were unable to update it because it was inaccessible. There were no language restrictions. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and prospective non-randomised studies of interventions (NRSIs), investigating children or adults with epilepsy, who were treated with an antidepressant and compared to placebo, comparative antidepressant, psychotherapy, or no treatment for depressive symptoms.  DATA COLLECTION AND ANALYSIS: The primary outcomes were changes in depression scores (proportion with a greater than 50% improvement, mean difference, and proportion who achieved complete remission) and change in seizure frequency (mean difference, proportion with a seizure recurrence, or episode of status epilepticus). Secondary outcomes included the number of participants who withdrew from the study and reasons for withdrawal, quality of life, cognitive functioning, and adverse events. Two review authors independently extracted data for each included study. We then cross-checked the data extraction. We assessed risk of bias using the Cochrane tool for RCTs, and the ROBINS-I for NRSIs. We presented binary outcomes as risk ratios (RRs) with 95% confidence intervals (CIs) or 99% CIs for specific adverse events. We presented continuous outcomes as standardised mean differences (SMDs) with 95% CIs, and mean differences (MDs) with 95% CIs.  MAIN RESULTS: We included 10 studies in the review (four RCTs and six NRSIs), with 626 participants with epilepsy and depression, examining the effects of antidepressants. One RCT was a multi-centre study comparing an antidepressant with cognitive behavioural therapy (CBT). The other three RCTs were single-centre studies comparing an antidepressant with an active control, placebo, or no treatment. The NRSIs reported on outcomes mainly in participants with focal epilepsy before and after treatment for depression with a selective serotonin reuptake inhibitor (SSRI); one NRSI compared SSRIs to CBT.  We rated one RCT at low risk of bias, three RCTs at unclear risk of bias, and all six NRSIs at serious risk of bias. We were unable to conduct any meta-analysis of RCT data due to heterogeneity of treatment comparisons. We judged the certainty of evidence to be moderate to very low across comparisons, because single studies contributed limited outcome data, and because of risk of bias, particularly for NRSIs, which did not adjust for confounding variables. More than 50% improvement in depressive symptoms ranged from 43% to 82% in RCTs, and from 24% to 97% in NRSIs, depending on the antidepressant given. Venlafaxine improved depressive symptoms by more than 50% compared to no treatment (mean difference (MD) -7.59 (95% confidence interval (CI) -11.52 to -3.66; 1 study, 64 participants; low-certainty evidence); the results between other comparisons were inconclusive. Two studies comparing SSRIs to CBT reported inconclusive results for the proportion of participants who achieved complete remission of depressive symptoms.  Seizure frequency data did not suggest an increased risk of seizures with antidepressants compared to control treatments or baseline. Two studies measured quality of life; antidepressants did not appear to improve quality of life over control. No studies reported on cognitive functioning. Two RCTs and one NRSI reported comparative data on adverse events; antidepressants did not appear to increase the severity or number of adverse events compared to controls. The NSRIs reported higher rates of withdrawals due to adverse events than lack of efficacy. Reported adverse events for antidepressants included nausea, dizziness, sedation, headache, gastrointestinal disturbance, insomnia, and sexual dysfunction.  AUTHORS' CONCLUSIONS: Existing evidence on the effectiveness of antidepressants in treating depressive symptoms associated with epilepsy is still very limited. Rates of response to antidepressants were highly variable. There is low certainty evidence from one small RCT (64 participants) that venlafaxine may improve depressive symptoms more than no treatment; this evidence is limited to treatment between 8 and 16 weeks, and does not inform longer-term effects. Moderate to low evidence suggests neither an increase nor exacerbation of seizures with SSRIs.  There are no available comparative data to inform the choice of antidepressant drug or classes of drug for efficacy or safety for treating people with epilepsy and depression. RCTs of antidepressants utilising interventions from other treatment classes besides SSRIs, in large samples of patients with epilepsy and depression, are needed to better inform treatment policy. Future studies should assess interventions across a longer treatment duration to account for delayed onset of action, sustainability of treatment responses, and to provide a better understanding of the impact on seizure control.


Assuntos
Antidepressivos/uso terapêutico , Depressão/tratamento farmacológico , Epilepsia/tratamento farmacológico , Adolescente , Adulto , Antidepressivos/efeitos adversos , Viés , Criança , Terapia Cognitivo-Comportamental , Depressão/etiologia , Epilepsia/induzido quimicamente , Epilepsia/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados não Aleatórios como Assunto , Estudos Prospectivos , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Inibidores de Captação de Serotonina/efeitos adversos , Inibidores de Captação de Serotonina/uso terapêutico , Adulto Jovem
13.
Asian J Psychiatr ; 60: 102642, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33930709

RESUMO

OBJECTIVE: The data on the course of obsessive compulsive disorder (OCD) is mostly derived from studying chronic, severely ill patients with varying degree of treatment resistance. We studied the course and outcome of OCD patients who were medication-naïve at initial assessment compared to those who were medicated. MATERIAL AND METHODS: We analyzed the clinical chart data of all patients with a primary diagnosis of OCD attending a speciality OCD clinic in India during a specified period and compared outcome between medication-naïve (n = 75) and medicated (n = 117) patients. RESULTS: The mean time to remission was shorter in the medication-naïve [18.99 months (95 % CI: 14.61-23.37)] compared to medicated [33.91 months (95 % CI: 27.55-40.28)] patients. The survival distribution of the two groups was significantly different as per the log-rank test (χ2 = 5.76, p = 0.02). In the Cox proportional hazards regression, medication-naïve status predicted time to remission. Overall, the rate of remission was the same in both groups (57 %). CONCLUSIONS: Medication-naïve OCD patients seem to remit faster than the previously treated patients. Future prospective naturalistic studies can compare the outcome of medication naïve OCD patients treated with medications and CBT.


Assuntos
Transtorno Obsessivo-Compulsivo , Inibidores de Captação de Serotonina , Humanos , Índia , Transtorno Obsessivo-Compulsivo/tratamento farmacológico , Estudos Prospectivos , Inibidores de Captação de Serotonina/uso terapêutico , Resultado do Tratamento
14.
Biomed Res Int ; 2021: 6699028, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33791379

RESUMO

Introduction: Depression is a major global health problem with a relatively high lifetime prevalence and significant disability. Antidepressants are the most effective medications used for the treatment of depression. Hence, this study is aimed at summarizing the studies on antidepressant use among patients diagnosed with depression. Method: PubMed, Embase, Web of Science, Scopus, and Google Scholar were searched for literature (2000-2019) using keywords such as depression, drug utilization, antidepressants, prescription, serotonin reuptake inhibitor, serotonin and norepinephrine reuptake inhibitor, tricyclic antidepressants, and atypical antidepressants. Results: Antidepressant users were mostly females, married people, housewives, lower-income people, employees, and highly educated people, as they were found to be more prone to develop depression than their counterparts. Selective serotonin reuptake inhibitors (SSRIs), such as sertraline, were most commonly prescribed among depressive patients. Conclusion: Our study suggested that out of five major antidepressant drugs available for the treatment of depression, selective serotonin reuptake inhibitors are preferred over others because of their better side effects and tolerability profile.


Assuntos
Antidepressivos/uso terapêutico , Depressão/tratamento farmacológico , Inibidores de Captação de Serotonina/uso terapêutico , Antidepressivos/efeitos adversos , Depressão/metabolismo , Humanos , Inibidores de Captação de Serotonina/efeitos adversos
15.
J Affect Disord ; 287: 372-379, 2021 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-33836365

RESUMO

OBJECTIVE: Selective serotonin reuptake inhibitors (SSRIs) are suggested as the first-line treatment for patients with major depressive disorder (MDD), but the remission rate is unsatisfactory. We aimed to establish machine learning models and explore variables available at baseline to predict the 8-week outcome among patients taking SSRIs. METHODS: Data from 400 patients were used to build machine learnings. The last observation carried forward approach was used to determine the remitter/non-remitter status of the patients at week 8. Using least absolute shrinkage and selection operator (LASSO) to select features, we built 4 different machine learning algorithms including gradient boosting decision tree, support vector machine (SVM), random forests, and logistic regression with five-fold cross-validation. Then, we adopted Shapley additive explanations (SHAP) values to interpret the model output. RESULTS: The remission rate is 67.8%. We obtained 78 features from the baseline characteristics, including 25 sociodemographic characteristics, 31 clinical features, 15 psychological traits and 7 neurocognitive functions, and 13 of these features were selected to establish SVM. The accuracy of the SVM prediction is 74.49%, reaching an average area under the curve of 0.734±0.043. The sensitivity is 0.899±0.038 with a positive predictive value of 0.776±0.028. The specificity is 0.422±0.091 with a negative predictive value of 0.674±0.086. According to the SHAP values, neurocognitive functions and anxiety and hypochondriasis symptoms were important predictors. CONCLUSION: Our study supports the utilization of machine learning approaches with inexpensive and highly accessible variables to accurately predict the 8-week treatment outcome of SSRIs in patients with MDD.


Assuntos
Transtorno Depressivo Maior , Inibidores de Captação de Serotonina , Transtorno Depressivo Maior/tratamento farmacológico , Humanos , Modelos Logísticos , Aprendizado de Máquina , Valor Preditivo dos Testes , Inibidores de Captação de Serotonina/uso terapêutico
16.
Cochrane Database Syst Rev ; 3: CD012799, 2021 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-33745183

RESUMO

BACKGROUND: Premature ejaculation (PE) is a common problem among men that occurs when ejaculation happens sooner than a man or his partner would like during sex; it may cause unhappiness and relationship problems. Selective serotonin re-uptake inhibitors (SSRIs), which are most commonly used as antidepressants are being used to treat this condition. OBJECTIVES: To assess the effects of SSRIs in the treatment of PE in adult men. SEARCH METHODS: We performed a comprehensive search using multiple databases (the Cochrane Library, MEDLINE, Embase, Scopus, CINAHL), clinical trial registries, conference proceedings, and other sources of grey literature, up to 1 May 2020. We applied no restrictions on publication language or status. SELECTION CRITERIA: We included only randomized controlled clinical trials (parallel group and cross-over trials) in which men with PE  were administered SSRIs or placebo. We also considered 'no treatment' to be an eligible comparator but did not find any relevant studies. DATA COLLECTION AND ANALYSIS: Two review authors independently classified and abstracted data from the included studies. Primary outcomes were participant-perceived change with treatment, satisfaction with intercourse and study withdrawal due to adverse events. Secondary outcomes included self-perceived control over ejaculation, participant distress about PE, adverse events and intravaginal ejaculatory latency time (IELT). We performed statistical analyses using a random-effects model. We rated the certainty of evidence according to GRADE. MAIN RESULTS: We identified 31 studies in which 8254 participants were randomized to receiving either SSRIs or placebo. Primary outcomes: SSRI treatment probably improves self-perceived PE symptoms (defined as a rating of 'better' or 'much better') compared to placebo (risk ratio (RR) 1.92, 95% confidence interval (CI) 1.66 to 2.23; moderate-certainty evidence). Based on 220 participants per 1000 reporting improvement with placebo, this corresponds to 202 more men per 1000 (95% CI 145 more to 270 more) with improved symptoms with SSRIs.  SSRI treatment probably improves satisfaction with intercourse compared to placebo (defined as a rating of 'good' or 'very good'; RR 1.63, 95% CI 1.42 to 1.87; moderate-certainty evidence). Based on 278 participants per 1000 reporting improved satisfaction with placebo, this corresponds to 175 more (117 more to 242 more) per 1000 men with greater satisfaction with intercourse with SSRIs. SSRI treatment may increase treatment cessations due to adverse events compared to placebo (RR 3.80, 95% CI 2.61 to 5.51; low-certainty evidence). Based 11 study withdrawals per 1000 participants with placebo, this corresponds to 30 more men per 1000 (95% CI 17 more to 49 more) ceasing treatment due to adverse events with SSRIs.  Secondary outcomes: SSRI treatment likely improve participants' self-perceived control over ejaculation (defined as rating of 'good' or 'very good') compared to placebo (RR 2.29, 95% CI 1.72 to 3.05; moderate-certainty evidence). Assuming 132 per 1000 participants perceived at least good control, this corresponds to 170 more (95 more to 270 more) reporting at least good control with SSRIs.  SSRI probably lessens distress (defined as rating of 'a little bit' or 'not at all') about PE (RR 1.54, 95% CI 1.26 to 1.88; moderate-certainty evidence). Based on 353 per 1000 participants reporting low levels of distress, this corresponds to 191 more men (92 more to 311 more) per 1000 reporting low levels of distress with SSRIs.  SSRI treatment probably increases adverse events compared to placebo (RR 1.71, 95% CI 1.48 to 1.99; moderate-certainty evidence). Based on 243 adverse events per 1000 among men receiving placebo, this corresponds to 173 more (117 more to 241 more) men having an adverse event with SSRIs.  SSRI treatment may increase IELT compared to placebo (mean difference (MD) 3.09 minutes longer, 95% CI 1.94 longer to 4.25 longer; low-certainty evidence). AUTHORS' CONCLUSIONS: SSRI treatment for PE appears to substantially improve a number of outcomes of direct patient importance such as symptom improvement, satisfaction with intercourse and perceived control over ejaculation when compared to placebo. Undesirable effects are a small increase in treatment withdrawals due to adverse events as well as substantially increased adverse event rates. Issues affecting the certainty of evidence of outcomes were study limitations and imprecision.


Assuntos
Ejaculação Precoce/tratamento farmacológico , Inibidores de Captação de Serotonina/uso terapêutico , Adolescente , Adulto , Coito/psicologia , Intervalos de Confiança , Ejaculação/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Satisfação do Paciente/estatística & dados numéricos , Placebos/uso terapêutico , Ejaculação Precoce/psicologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Inibidores de Captação de Serotonina/efeitos adversos , Adulto Jovem
17.
Transl Psychiatry ; 11(1): 153, 2021 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-33654056

RESUMO

Selective serotonin reuptake inhibitors (SSRIs) are the first-line treatment for major depressive disorder (MDD), yet their mechanisms of action are not fully understood and their therapeutic benefit varies among individuals. We used a targeted metabolomics approach utilizing a panel of 180 metabolites to gain insights into mechanisms of action and response to citalopram/escitalopram. Plasma samples from 136 participants with MDD enrolled into the Mayo Pharmacogenomics Research Network Antidepressant Medication Pharmacogenomic Study (PGRN-AMPS) were profiled at baseline and after 8 weeks of treatment. After treatment, we saw increased levels of short-chain acylcarnitines and decreased levels of medium-chain and long-chain acylcarnitines, suggesting an SSRI effect on ß-oxidation and mitochondrial function. Amines-including arginine, proline, and methionine sulfoxide-were upregulated while serotonin and sarcosine were downregulated, suggesting an SSRI effect on urea cycle, one-carbon metabolism, and serotonin uptake. Eighteen lipids within the phosphatidylcholine (PC aa and ae) classes were upregulated. Changes in several lipid and amine levels correlated with changes in 17-item Hamilton Rating Scale for Depression scores (HRSD17). Differences in metabolic profiles at baseline and post-treatment were noted between participants who remitted (HRSD17 ≤ 7) and those who gained no meaningful benefits (<30% reduction in HRSD17). Remitters exhibited (a) higher baseline levels of C3, C5, alpha-aminoadipic acid, sarcosine, and serotonin; and (b) higher week-8 levels of PC aa C34:1, PC aa C34:2, PC aa C36:2, and PC aa C36:4. These findings suggest that mitochondrial energetics-including acylcarnitine metabolism, transport, and its link to ß-oxidation-and lipid membrane remodeling may play roles in SSRI treatment response.


Assuntos
Transtorno Depressivo Maior , Aminas/uso terapêutico , Antidepressivos/uso terapêutico , Carnitina/análogos & derivados , Citalopram/uso terapêutico , Depressão , Transtorno Depressivo Maior/tratamento farmacológico , Humanos , Lipídeos , Inibidores de Captação de Serotonina/uso terapêutico
18.
J Affect Disord ; 287: 34-40, 2021 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-33773357

RESUMO

BACKGROUND: Research on predictors of treatment outcome in body dysmorphic disorder, a common and severe disorder, is very limited, and no prior studies have examined moderators of outcome. Because treatment is often but not always efficacious, it is important to identify who is more likely to benefit. We examined predictors and moderators of improvement with therapist-delivered cognitive-behavioral therapy versus supportive psychotherapy in the only study of these treatments for body dysmorphic disorder. This report presents secondary analyses from a study whose primary findings have previously been published (Wilhelm et al., 2019). METHODS: Participants (N=120) with DSM-IV body dysmorphic disorder were randomized to therapist-delivered weekly cognitive-behavioral therapy or supportive therapy for 24 weeks. Using reliable and valid measures, we tested baseline body dysmorphic disorder severity, insight/delusionality, and depression severity as predictors and moderators of overall and treatment modality-specific symptom change. We explored additional variables as predictors and moderators of outcome. RESULTS: Greater treatment credibility (p=0.02) and presence of obsessive-compulsive personality disorder (p=0.03) predicted greater improvement. Serotonin-reuptake inhibitor treatment at baseline (unchanged during the study) (p=0.01) predicted less improvement. No other variables predicted or moderated outcome (all p>0.05). LIMITATIONS: The study was not powered a priori to detect predictor or moderation effects, which limited our ability to detect them unless they were strong. CONCLUSIONS: Because greater treatment credibility predicted better outcomes, fostering credibility during therapy may maximize gains. Improvement was not impeded by more severe body dysmorphic disorder, depressive symptoms, or poorer insight. No variables moderated treatment-specific improvement.


Assuntos
Transtornos Dismórficos Corporais , Terapia Cognitivo-Comportamental , Transtornos Dismórficos Corporais/terapia , Humanos , Psicoterapia , Inibidores de Captação de Serotonina/uso terapêutico , Resultado do Tratamento
19.
Sci Rep ; 11(1): 5890, 2021 03 15.
Artigo em Inglês | MEDLINE | ID: covidwho-1135696

RESUMO

To circumvent time-consuming clinical trials, testing whether existing drugs are effective inhibitors of SARS-CoV-2, has led to the discovery of Remdesivir. We decided to follow this path and screened approved medications "off-label" against SARS-CoV-2. Fluoxetine inhibited SARS-CoV-2 at a concentration of 0.8 µg/ml significantly in these screenings, and the EC50 was determined with 387 ng/ml. Furthermore, Fluoxetine reduced viral infectivity in precision-cut human lung slices showing its activity in relevant human tissue targeted in severe infections. Fluoxetine treatment resulted in a decrease in viral protein expression. Fluoxetine is a racemate consisting of both stereoisomers, while the S-form is the dominant serotonin reuptake inhibitor. We found that both isomers show similar activity on the virus, indicating that the R-form might specifically be used for SARS-CoV-2 treatment. Fluoxetine inhibited neither Rabies virus, human respiratory syncytial virus replication nor the Human Herpesvirus 8 or Herpes simplex virus type 1 gene expression, indicating that it acts virus-specific. Moreover, since it is known that Fluoxetine inhibits cytokine release, we see the role of Fluoxetine in the treatment of SARS-CoV-2 infected patients of risk groups.


Assuntos
Antivirais/farmacologia , COVID-19/virologia , Fluoxetina/farmacologia , Pulmão/efeitos dos fármacos , Pulmão/virologia , SARS-CoV-2/efeitos dos fármacos , Inibidores de Captação de Serotonina/farmacologia , Animais , Antivirais/uso terapêutico , COVID-19/tratamento farmacológico , Linhagem Celular , Células Cultivadas , Fluoxetina/uso terapêutico , Humanos , Pulmão/patologia , Inibidores de Captação de Serotonina/uso terapêutico , Replicação Viral/efeitos dos fármacos
20.
Sci Rep ; 11(1): 5890, 2021 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-33723270

RESUMO

To circumvent time-consuming clinical trials, testing whether existing drugs are effective inhibitors of SARS-CoV-2, has led to the discovery of Remdesivir. We decided to follow this path and screened approved medications "off-label" against SARS-CoV-2. Fluoxetine inhibited SARS-CoV-2 at a concentration of 0.8 µg/ml significantly in these screenings, and the EC50 was determined with 387 ng/ml. Furthermore, Fluoxetine reduced viral infectivity in precision-cut human lung slices showing its activity in relevant human tissue targeted in severe infections. Fluoxetine treatment resulted in a decrease in viral protein expression. Fluoxetine is a racemate consisting of both stereoisomers, while the S-form is the dominant serotonin reuptake inhibitor. We found that both isomers show similar activity on the virus, indicating that the R-form might specifically be used for SARS-CoV-2 treatment. Fluoxetine inhibited neither Rabies virus, human respiratory syncytial virus replication nor the Human Herpesvirus 8 or Herpes simplex virus type 1 gene expression, indicating that it acts virus-specific. Moreover, since it is known that Fluoxetine inhibits cytokine release, we see the role of Fluoxetine in the treatment of SARS-CoV-2 infected patients of risk groups.


Assuntos
Antivirais/farmacologia , COVID-19/virologia , Fluoxetina/farmacologia , Pulmão/efeitos dos fármacos , Pulmão/virologia , SARS-CoV-2/efeitos dos fármacos , Inibidores de Captação de Serotonina/farmacologia , Animais , Antivirais/uso terapêutico , COVID-19/tratamento farmacológico , Linhagem Celular , Células Cultivadas , Fluoxetina/uso terapêutico , Humanos , Pulmão/patologia , Inibidores de Captação de Serotonina/uso terapêutico , Replicação Viral/efeitos dos fármacos
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