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1.
Yonsei Med J ; 61(9): 741-749, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32882758

RESUMO

PURPOSE: Non-vitamin K antagonist oral anticoagulants (NOACs) are widely used in patients with atrial fibrillation (AF) because of their effectiveness in preventing stroke and their better safety, compared with warfarin. However, there are concerns for an increased risk of bleeding associated with concomitant use of non-steroidal anti-inflammatory drugs (NSAIDs) or selective serotonin reuptake inhibitors (SSRIs) with NOACs. In this study, we aimed to evaluate the risk of bleeding events in individuals taking concomitant NSAIDs or SSRIs with NOACs after being diagnosed with AF. MATERIALS AND METHODS: A nested case-control analysis to assess the safety of NSAIDs and SSRIs among NOAC users with AF was performed using data from Korean National Health Insurance Service from January 2012 to December 2017. Among patients who were newly prescribed NOACs, 1233 cases hospitalized for bleeding events were selected, and 24660 controls were determined. RESULTS: The risk of bleeding events was higher in patients receiving concomitant NSAIDs [adjusted odds ratio (aOR) 1.41; 95% confidence interval (CI) 1.24-1.61] or SSRIs (aOR 1.92; 95% CI 1.52-2.42) with NOACs, compared to no use of either drug, respectively. The risk of upper gastrointestinal bleeding was higher in patients receiving concomitant NSAIDs or SSRIs without proton pump inhibitors (PPIs) (NSAIDs: aOR 2.47; 95% CI 1.26-4.83, SSRI: aOR 10.8; 95% CI 2.41-2.48) compared to no use. CONCLUSION: When NSAIDs or SSRIs are required for NOAC users with AF, physicians need to monitor bleeding events and consider the use of PPIs, especially for combined use of both drugs or when initiating NOACs treatment.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Anticoagulantes/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Hemorragia Gastrointestinal/prevenção & controle , Hemorragia/prevenção & controle , Inibidores de Captação de Serotonina/uso terapêutico , Acidente Vascular Cerebral/prevenção & controle , Varfarina/uso terapêutico , Administração Oral , Idoso , Anti-Inflamatórios não Esteroides/efeitos adversos , Fibrilação Atrial/complicações , Estudos de Casos e Controles , Feminino , Hemorragia Gastrointestinal/complicações , Hemorragia/epidemiologia , Humanos , Pessoa de Meia-Idade , Inibidores de Captação de Serotonina/efeitos adversos , Acidente Vascular Cerebral/etiologia
2.
Medicine (Baltimore) ; 99(34): e21866, 2020 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-32846840

RESUMO

INTRODUCTION: Premature ejaculation (PE) affects 8% to 30% of adult men worldwide. Recently, the incidence of PE is on the rise. A series of prior studies suggested that the incidence of PE is related to various biological factors as low testosterone, low serum vitamin D, diabetes, lower urinary tract symptoms, and other psychological factors. At present, the major treatments include selective serotonin reuptake inhibitors antidepressants (dapoxetine, paroxetine), topical anesthetics, phosphodiesterase-5 inhibitor, circumcision, and selective dorsal neurotomy (SDN). The previous study found that SDN is effective for PE. METHODS AND ANALYSIS: The electronic databases of MEDLINE, PubMed, Web of Science, EMBASE, Cochrane Library, Clinicaltrials. org, China National Knowledge Infrastructure Database (CNKI), Wan fang Database, China Biology Medicine Database (CBM), VIP Science Technology Periodical Database, Chinese Clinical Trial Registry will be retrieved. All the randomized controlled trials of selective dorsal penile neurotomy for patients with PE will be included. The outcome includes intravaginal ejaculation latency time and Chinese Index of Sexual Function for Premature Ejaculation-5. We will conduct this study strictly according to the Cochrane Handbook for Systematic Reviews of Interventions. RESULTS: The present study is a protocol for systematic review and meta-analysis without results, and data analysis will be carried out after the protocol. We will share our findings on June 30th of 2021. CONCLUSION: SDN can effectively prolong IELT, but its efficacy has not been assessed scientifically and systematically. To address this limitation, this study will inspect the efficacy and safety of the SDN treatment in patients with PE. ETHICS AND DISSEMINATION: Formal ethical approval is not required in this protocol. We will collect and analyze data based on published studies, and since there are no patients involved in this study, individual privacy will not be under concerns. The results of this review will be disseminated to peer-reviewed journals or submit to related conferences. PROTOCOL REGISTRATION NUMBER: INPLASY202070084.


Assuntos
Pênis/inervação , Ejaculação Precoce/terapia , Nervo Pudendo/cirurgia , Adulto , Anestésicos Locais/uso terapêutico , Benzilaminas/uso terapêutico , Circuncisão Masculina/métodos , Ejaculação/fisiologia , Humanos , Incidência , Masculino , Naftalenos/uso terapêutico , Paroxetina/uso terapêutico , Pênis/fisiopatologia , Inibidores da Fosfodiesterase 5/uso terapêutico , Ejaculação Precoce/epidemiologia , Ejaculação Precoce/fisiopatologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Inibidores de Captação de Serotonina/uso terapêutico
4.
Lancet Neurol ; 19(8): 661-669, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32702335

RESUMO

BACKGROUND: Studies have suggested that fluoxetine could improve neurological recovery after stroke. The Efficacy oF Fluoxetine-a randomisEd Controlled Trial in Stroke (EFFECTS) trial aimed to assess whether administration of oral fluoxetine for 6 months after acute stroke improves functional outcome. METHODS: EFFECTS was an investigator-led, multicentre, randomised, placebo-controlled, double-blind, parallel group trial that enrolled patients aged 18 years or older between 2 and 15 days after stroke onset in 35 stroke and rehabilitation centres in Sweden. Eligible patients had a clinical diagnosis of ischaemic or intracerebral haemorrhage, brain imaging that was consistent with intracerebral haemorrhage or ischaemic stroke, and had at least one persisting focal neurological deficit. A web-based randomisation system that incorporated a minimisation algorithm was used to randomly assign (1:1) participants to receive oral fluoxetine 20 mg once daily or matching placebo capsules for 6 months. Patients, care providers, investigators, and outcomes assessors were masked to the allocation. The primary outcome was functional status, measured with the modified Rankin Scale (mRS) at 6 months, analysed in all patients with available mRS data at the 6-month follow-up; we did an ordinal analysis adjusted for the minimisation variables used in the randomisation. This trial is registered with EudraCT, 2011-006130-16; ISRCTN, 13020412; and ClinicalTrials.gov, NCT02683213. FINDINGS: Between Oct 20, 2014, and June 28, 2019, 1500 patients were enrolled, of whom 750 were randomly assigned to fluoxetine and 750 were randomly assigned to placebo. At 6 months, mRS data were available for 737 (98%) patients in the fluoxetine group and 742 (99%) patients in the placebo group. There was no effect of fluoxetine on the primary outcome-distribution across mRS score categories-compared with placebo (adjusted common odds ratio 0·94 [95% CI 0·78 to 1·13]; p=0·42). The proportion of patients with a new diagnosis of depression was lower with fluoxetine than with placebo (54 [7%] patients vs 81 [11%] patients; difference -3·60% [-6·49 to -0·71]; p=0·015), but fluoxetine was associated with more bone fractures (28 [4%] vs 11 [2%]; difference 2·27% [0·66 to 3·87]; p=0·0058) and hyponatraemia (11 [1%] vs one [<1%]; difference 1·33% [0·43 to 2·23]; p=0·0038) at 6 months. INTERPRETATION: Functional outcome after acute stroke did not improve with oral fluoxetine 20 mg once daily for 6 months. Fluoxetine reduced the occurrence of depression but increased the risk of bone fractures and hyponatraemia. Our results do not support the use of fluoxetine after acute stroke. FUNDING: The Swedish Research Council, the Swedish Heart-Lung Foundation, the Swedish Brain Foundation, the Swedish Society of Medicine, King Gustav V and Queen Victoria's Foundation of Freemasons, and the Swedish Stroke Association (STROKE-Riksförbundet).


Assuntos
Fluoxetina/uso terapêutico , Inibidores de Captação de Serotonina/uso terapêutico , Acidente Vascular Cerebral/tratamento farmacológico , Adulto , Idoso , Método Duplo-Cego , Esquema de Medicação , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Recuperação de Função Fisiológica , Resultado do Tratamento
5.
Lancet Neurol ; 19(8): 651-660, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32702334

RESUMO

BACKGROUND: Trials of fluoxetine for recovery after stroke report conflicting results. The Assessment oF FluoxetINe In sTroke recoverY (AFFINITY) trial aimed to show if daily oral fluoxetine for 6 months after stroke improves functional outcome in an ethnically diverse population. METHODS: AFFINITY was a randomised, parallel-group, double-blind, placebo-controlled trial done in 43 hospital stroke units in Australia (n=29), New Zealand (four), and Vietnam (ten). Eligible patients were adults (aged ≥18 years) with a clinical diagnosis of acute stroke in the previous 2-15 days, brain imaging consistent with ischaemic or haemorrhagic stroke, and a persisting neurological deficit that produced a modified Rankin Scale (mRS) score of 1 or more. Patients were randomly assigned 1:1 via a web-based system using a minimisation algorithm to once daily, oral fluoxetine 20 mg capsules or matching placebo for 6 months. Patients, carers, investigators, and outcome assessors were masked to the treatment allocation. The primary outcome was functional status, measured by the mRS, at 6 months. The primary analysis was an ordinal logistic regression of the mRS at 6 months, adjusted for minimisation variables. Primary and safety analyses were done according to the patient's treatment allocation. The trial is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12611000774921. FINDINGS: Between Jan 11, 2013, and June 30, 2019, 1280 patients were recruited in Australia (n=532), New Zealand (n=42), and Vietnam (n=706), of whom 642 were randomly assigned to fluoxetine and 638 were randomly assigned to placebo. Mean duration of trial treatment was 167 days (SD 48·1). At 6 months, mRS data were available in 624 (97%) patients in the fluoxetine group and 632 (99%) in the placebo group. The distribution of mRS categories was similar in the fluoxetine and placebo groups (adjusted common odds ratio 0·94, 95% CI 0·76-1·15; p=0·53). Compared with patients in the placebo group, patients in the fluoxetine group had more falls (20 [3%] vs seven [1%]; p=0·018), bone fractures (19 [3%] vs six [1%]; p=0·014), and epileptic seizures (ten [2%] vs two [<1%]; p=0·038) at 6 months. INTERPRETATION: Oral fluoxetine 20 mg daily for 6 months after acute stroke did not improve functional outcome and increased the risk of falls, bone fractures, and epileptic seizures. These results do not support the use of fluoxetine to improve functional outcome after stroke. FUNDING: National Health and Medical Research Council of Australia.


Assuntos
Fluoxetina/uso terapêutico , Inibidores de Captação de Serotonina/uso terapêutico , Acidente Vascular Cerebral/tratamento farmacológico , Adulto , Idoso , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Recuperação de Função Fisiológica , Resultado do Tratamento
6.
PLoS Med ; 17(7): e1003215, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32697803

RESUMO

BACKGROUND: The use of antidepressants in children and adolescents remains controversial. We examined trends over time and variation in antidepressant prescribing in children and young people in England and whether the drugs prescribed reflected UK licensing and guidelines. METHODS AND FINDINGS: QResearch is a primary care database containing anonymised healthcare records of over 32 million patients from more than 1,500 general practices across the UK. All eligible children and young people aged 5-17 years in 1998-2017 from QResearch were included. Incidence and prevalence rates of antidepressant prescriptions in each year were calculated overall, for 4 antidepressant classes (selective serotonin reuptake inhibitors [SSRIs], tricyclic and related antidepressants [TCAs], serotonin and norepinephrine reuptake inhibitors [SNRIs], and other antidepressants), and for individual drugs. Adjusted trends over time and differences by social deprivation, region, and ethnicity were examined using Poisson regression, taking clustering within general practitioner (GP) practices into account using multilevel modelling. Of the 4.3 million children and young people in the cohort, 49,434 (1.1%) were prescribed antidepressants for the first time during 20 million years of follow-up. Males made up 52.0% of the cohorts, but only 34.1% of those who were first prescribed an antidepressant in the study period. The largest proportion of the cohort was from London (24.4%), and whilst ethnicity information was missing for 39.5% of the cohort, of those with known ethnicity, 75.3% were White. Overall, SSRIs (62.6%) were the most commonly prescribed first antidepressant, followed by TCAs (35.7%). Incident antidepressant prescribing decreased in 5- to 11-year-olds from a peak of 0.9 in females and 1.6 in males in 1999 to less than 0.2 per 1,000 for both sexes in 2017, but incidence rates more than doubled in 12- to 17-year-olds between 2005 and 2017 to 9.7 (females) and 4.2 (males) per 1,000 person-years. The lowest prescription incidence rates were in London, and the highest were in the South East of England (excluding London) for all sex and age groups. Those living in more deprived areas were more likely to be prescribed antidepressants after adjusting for region. The strongest trend was seen in 12- to 17-year-old females (adjusted incidence rate ratio [aIRR] 1.12, 95% confidence interval [95% CI] 1.11-1.13, p < 0.001, per deprivation quintile increase). Prescribing rates were highest in White and lowest in Black adolescents (aIRR 0.32, 95% CI 0.29-0.36, p < 0.001 [females]; aIRR 0.32, 95% CI 0.27-0.38, p < 0.001 [males]). The 5 most commonly prescribed antidepressants were either licensed in the UK for use in children and young people (CYP) or included in national guidelines. Limitations of the study are that, because we did not have access to secondary care prescribing information, we may be underestimating the prevalence and misidentifying the first antidepressant prescription. We could not assess whether antidepressants were dispensed or taken. CONCLUSIONS: Our analysis provides evidence of a continuing rise of antidepressant prescribing in adolescents aged 12-17 years since 2005, driven by SSRI prescriptions, but a decrease in children aged 5-11 years. The variation in prescribing by deprivation, region, and ethnicity could represent inequities. Future research should examine whether prescribing trends and variation are due to true differences in need and risk factors, access to diagnosis or treatment, prescribing behaviour, or young people's help-seeking behaviour.


Assuntos
Antidepressivos/uso terapêutico , Prescrições de Medicamentos/estatística & dados numéricos , Atenção Primária à Saúde/estatística & dados numéricos , Adolescente , Antidepressivos/farmacologia , Criança , Pré-Escolar , Estudos de Coortes , Transtorno Depressivo/tratamento farmacológico , Transtorno Depressivo/epidemiologia , Inglaterra/epidemiologia , Feminino , Humanos , Incidência , Masculino , Prevalência , Inibidores de Captação de Serotonina/uso terapêutico
9.
Medicine (Baltimore) ; 99(21): e20170, 2020 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-32481286

RESUMO

BACKGROUND: Numerous studies have reported that transcranial magnetic stimulation (TMS) and fluoxetine is used in the treatment of postpartum depression (PPD). Currently, no study has systematically investigated the efficacy and safety of TMS and fluoxetine for the treatment of patients with PPD. Thus, this study will assess the efficacy and safety of TMS and fluoxetine for treating PPD. METHODS: Relevant studies involving TMS and fluoxetine for the treatment of patients with PPD will be comprehensively searched from the electronic databases from inception to the February 1, 2020: Cochrane Library, EMBASE, MEDILINE, CINAHL, AMED, WANGFANG, VIP, and CNKI databases. No language and publication time restrictions will be applied. RevMan 5.3 software will be utilized for data pooling, data analysis, and risk of bias evaluation. If necessary, we will also assess reporting bias using funnel plot and Egger test. RESULTS: This study will comprehensively summarize the existing evidence to assess the efficacy and safety of TMS and fluoxetine for treating PPD. CONCLUSION: The findings of this study may help to establish a better approach to treat PPD using TMS and fluoxetine. DISSEMINATION AND ETHICS: This study will be disseminated through a peer-reviewed journal. This study does not need ethical approval as no primary patient data will be used. SYSTEMATIC REVIEW REGISTRATION: INPLASY202040017.


Assuntos
Depressão Pós-Parto/terapia , Fluoxetina/uso terapêutico , Inibidores de Captação de Serotonina/uso terapêutico , Estimulação Magnética Transcraniana/métodos , Adulto , Terapia Combinada/métodos , Depressão Pós-Parto/epidemiologia , Feminino , Fluoxetina/administração & dosagem , Humanos , Inibidores de Captação de Serotonina/administração & dosagem , Resultado do Tratamento
10.
Expert Opin Pharmacother ; 21(14): 1699-1711, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32543949

RESUMO

Introduction: A substantial number of patients with PD experience relapse after the discontinuation of effective pharmacotherapy, leading to detrimental effects on the individuals and considerable societal costs. This suggests the need to optimize pharmacotherapy to minimize relapse risk. Area covered: The present systematic review examines randomized, double-blind, placebo-controlled relapse prevention studies published over the last 20 years involving recommended medications. The authors aim to provide an overview of this topic and evaluate whether recent advances were achieved. Only seven studies were included, providing limited results. One-year maintenance pharmacotherapy with constant doses had protective effects against relapse in patients who had previously exhibited satisfactory responses to the same medication at the same doses. The duration of maintenance treatment did not influence relapse risk. No data were available concerning the use of lower doses or the predictors of relapse. Expert opinion: Relapse prevention in PD has received limited attention. Recent progress and conclusive indications are lacking. Rethinking pharmacological research in PD may be productive. Collecting a wide range of clinical and individual features/biomarkers in large-scale, multicenter long-term naturalistic studies, and implementing recent technological innovations (e.g., electronic medical records/'big data' platforms, wearable devices, and machine learning techniques) may help identify reliable predictive models.


Assuntos
Antidepressivos/uso terapêutico , Transtorno de Pânico/tratamento farmacológico , Prevenção Secundária/métodos , Inibidores de Captação de Serotonina/uso terapêutico , Antidepressivos/administração & dosagem , Esquema de Medicação , Humanos , Transtorno de Pânico/prevenção & controle , Ensaios Clínicos Controlados Aleatórios como Assunto , Inibidores de Captação de Serotonina/administração & dosagem , Resultado do Tratamento
11.
Pediatrics ; 146(1)2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32499386

RESUMO

BACKGROUND: Benzodiazepines are commonly prescribed to treat anxiety disorders and have been associated with falls and fractures in older adults. It is unknown whether benzodiazepines increase fracture risk in youth. We examined whether youth with anxiety disorders initiating benzodiazepine treatment have an increased risk of fractures compared with youth initiating selective serotonin reuptake inhibitors (SSRIs). METHODS: We used claims from commercially insured children (6-17 years) and young adults (18-24) with a recent anxiety disorder diagnosis, initiating benzodiazepines or SSRIs (2008-2016). Youth were followed until fracture, treatment discontinuation or switching, disenrollment, 3 months, or December 31, 2016. The primary end point was diagnostic codes for upper and lower limb fractures. Incident fracture rates, incident rate ratios (IRRs), and incident rate differences (IRDs) were estimated with propensity score inverse probability of treatment weighting. RESULTS: The cohort included 120 715 children and 179 768 young adults. In children, crude fracture rates during treatment were 33.1 per 1000 person-years (PYs) for benzodiazepine initiators and 25.1 per 1000 PYs for SSRI initiators. Adjusted IRR and IRD were 1.53 (95% confidence interval [CI]: 0.94-2.50) and 13.4 per 1000 PYs. Risk was heightened in children initiating long-acting benzodiazepines versus SSRIs (adjusted IRR = 2.30 [95% CI: 1.08-4.91]). Fracture rates were lower in young adults, with minimal differences between treatments (adjusted IRR = 0.85 [95% CI: 0.57-1.27]; adjusted IRD = -1.3 per 1000 PYs). CONCLUSIONS: An increased rate of fractures in children, but not young adults, with anxiety disorders initiating benzodiazepine treatment compared to SSRI treatment suggests a need for increased caution in the weeks after benzodiazepine initiation in children.


Assuntos
Transtornos de Ansiedade/tratamento farmacológico , Benzodiazepinas/efeitos adversos , Fraturas Ósseas/induzido quimicamente , Fraturas Ósseas/epidemiologia , Inibidores de Captação de Serotonina/efeitos adversos , Adolescente , Benzodiazepinas/uso terapêutico , Criança , Estudos de Coortes , Feminino , Humanos , Masculino , Medição de Risco , Inibidores de Captação de Serotonina/uso terapêutico , Adulto Jovem
12.
PLoS One ; 15(4): e0232245, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32353011

RESUMO

BACKGROUND: Post-traumatic stress disorder (PTSD) is a severe and disabling condition that may lead to functional impairment and reduced productivity. Psychological interventions have been shown to be effective in its management. The objective of this study was to assess the cost-effectiveness of a range of interventions for adults with PTSD. METHODS: A decision-analytic model was constructed to compare costs and quality-adjusted life-years (QALYs) of 10 interventions and no treatment for adults with PTSD, from the perspective of the National Health Service and personal social services in England. Effectiveness data were derived from a systematic review and network meta-analysis. Other model input parameters were based on published sources, supplemented by expert opinion. RESULTS: Eye movement desensitisation and reprocessing (EMDR) appeared to be the most cost-effective intervention for adults with PTSD (with a probability of 0.34 amongst the 11 evaluated options at a cost-effectiveness threshold of £20,000/QALY), followed by combined somatic/cognitive therapies, self-help with support, psychoeducation, selective serotonin reuptake inhibitors (SSRIs), trauma-focused cognitive behavioural therapy (TF-CBT), self-help without support, non-TF-CBT and combined TF-CBT/SSRIs. Counselling appeared to be less cost-effective than no treatment. TF-CBT had the largest evidence base. CONCLUSIONS: A number of interventions appear to be cost-effective for the management of PTSD in adults. EMDR appears to be the most cost-effective amongst them. TF-CBT has the largest evidence base. There remains a need for well-conducted studies that examine the long-term clinical and cost-effectiveness of a range of treatments for adults with PTSD.


Assuntos
Transtornos de Estresse Pós-Traumáticos/tratamento farmacológico , Transtornos de Estresse Pós-Traumáticos/psicologia , Adulto , Terapia Cognitivo-Comportamental/métodos , Análise Custo-Benefício , Inglaterra , Dessensibilização e Reprocessamento através dos Movimentos Oculares/métodos , Feminino , Humanos , Masculino , Psicoterapia/métodos , Anos de Vida Ajustados por Qualidade de Vida , Inibidores de Captação de Serotonina/uso terapêutico , Medicina Estatal
13.
Medicine (Baltimore) ; 99(20): e20264, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32443369

RESUMO

The goal of the study was to examine the association between statin use and the development of acute diverticulitis requiring hospital admission.Acute diverticulitis is a common and costly gastrointestinal disorder. Although the incidence is increasing its pathophysiology and modifiable risk factors are incompletely understood. Statins affect the inflammatory response and represent a potential risk reducing agent.A retrospective, population-based, case-control study was carried out on a cohort of adults, resident in Canterbury, New Zealand. All identified cases were admitted to hospital and had computed tomography confirmed diverticulitis. The positive control group comprised patients on non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs), and the negative control group were patients on selective serotonin reuptake inhibitors (SSRIs). Medicine exposure was obtained from the Pharmaceutical Management Agency of New Zealand. Subgroup analysis was done by age and for complicated and recurrent diverticulitis.During the study period, there were 381,792 adults resident in Canterbury. The annual incidence of diverticulitis requiring hospital presentation was 18.6 per 100,000 per year. Complicated disease was seen in 37.4% (158) of patients, and 14.7% (62) had recurrent disease. Statins were not found to affect the risk of developing acute diverticulitis, nor the risk of complicated or recurrent diverticulitis. Subgroup analysis suggested statin use was associated with a decreased risk of acute diverticulitis in the elderly (age >64 years). NSAIDs were associated with a decreased risk of acute diverticulitis (risk ratio = 0.65, confidence interval: 0.26-0.46, P < .01), as were SSRIs (risk ratio = 0.37, confidence interval: 0.26-0.54, P < .01).This population-based study does not support the hypothesis that statins have a preventative effect on the development of diverticulitis, including complicated disease. We also found a decreased risk of diverticulitis associated with NSAID and SSRI use.


Assuntos
Diverticulite/epidemiologia , Hospitalização/estatística & dados numéricos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Adulto , Fatores Etários , Idoso , Anti-Inflamatórios não Esteroides/uso terapêutico , Estudos de Casos e Controles , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Fatores de Risco , Inibidores de Captação de Serotonina/uso terapêutico , Índice de Gravidade de Doença , Adulto Jovem
14.
Medicine (Baltimore) ; 99(14): e19573, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32243377

RESUMO

OBJECTIVE: The present study aimed to estimate the comprehensive efficacy and tolerability of paroxetine in adult patients with social anxiety disorder (SAD). METHODS: We conducted a comprehensive literature review of the PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, and ClinicalTrials databases for eligible randomized controlled trials (RCTs). The efficacy outcome was the mean change of different kinds of scale scores as well as response and remission rates. The secondary outcome was tolerability, defined as the discontinuation rate and the incidence of adverse events (AEs). RESULTS: Our meta-analysis included 13 RCTs. Mean changes in the Liebowitz Social Anxiety Scale (LSAS) total score, fear and avoidance subscale of LSAS scores were all significantly greater in patients with SAD that received paroxetine compared to those received placebo (total: MD = 13.46, 95%CI 10.59-16.32, P < .00001; fear: MD = 6.76, 95%CI 4.89-8.62, P < .00001; avoidance: MD = 6.54, 95%CI 4.63-8.45, P < .00001). Response and remission rates were both significantly greater in patients with SAD that received paroxetine compared to those received placebo (response: OR = 3.02, 95%CI 2.30-3.97, P < .00001; remission: OR = 3.14, 95%CI 2.25-4.39, P < .00001). There was no significant difference in discontinuation rate due to any reason between two groups (OR = 1.06, 95%CI 0.81-1.39, P = .65). Discontinuation rate due to AEs was higher in paroxetine than placebo group (OR = 3.41, 95%CI 2.45-4.72, P < .00001) whereas the rate due to lack of efficacy was higher in placebo as compared with paroxetine group (OR = 0.14, 95%CI 0.09-0.22, P < .00001). The incidence of any AE was significantly increased in patients that received paroxetine (OR = 1.83, 95%CI 1.43-2.35, P < .00001). CONCLUSION: Paroxetine was an effective and well-tolerated treatment option for adult patients with SAD.


Assuntos
Paroxetina/uso terapêutico , Fobia Social/tratamento farmacológico , Inibidores de Captação de Serotonina/uso terapêutico , Adulto , Feminino , Humanos , Masculino , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
15.
Cochrane Database Syst Rev ; 4: CD000031, 2020 04 22.
Artigo em Inglês | MEDLINE | ID: mdl-32319681

RESUMO

BACKGROUND: Whilst the pharmacological profiles and mechanisms of antidepressants are varied, there are common reasons why they might help people to stop smoking tobacco. Firstly, nicotine withdrawal may produce depressive symptoms and antidepressants may relieve these. Additionally, some antidepressants may have a specific effect on neural pathways or receptors that underlie nicotine addiction. OBJECTIVES: To assess the evidence for the efficacy, safety and tolerability of medications with antidepressant properties in assisting long-term tobacco smoking cessation in people who smoke cigarettes. SEARCH METHODS: We searched the Cochrane Tobacco Addiction Specialized Register, which includes reports of trials indexed in the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and PsycINFO, clinicaltrials.gov, the ICTRP, and other reviews and meeting abstracts, in May 2019. SELECTION CRITERIA: We included randomized controlled trials (RCTs) that recruited smokers, and compared antidepressant medications with placebo or no treatment, an alternative pharmacotherapy, or the same medication used in a different way. We excluded trials with less than six months follow-up from efficacy analyses. We included trials with any follow-up length in safety analyses. DATA COLLECTION AND ANALYSIS: We extracted data and assessed risk of bias using standard Cochrane methods. We also used GRADE to assess the certainty of the evidence. The primary outcome measure was smoking cessation after at least six months follow-up, expressed as a risk ratio (RR) and 95% confidence intervals (CIs). We used the most rigorous definition of abstinence available in each trial, and biochemically validated rates if available. Where appropriate, we performed meta-analysis using a fixed-effect model. Similarly, we presented incidence of safety and tolerance outcomes, including adverse events (AEs), serious adverse events (SAEs), psychiatric AEs, seizures, overdoses, suicide attempts, death by suicide, all-cause mortality, and trial dropout due to drug, as RRs (95% CIs). MAIN RESULTS: We included 115 studies (33 new to this update) in this review; most recruited adult participants from the community or from smoking cessation clinics. We judged 28 of the studies to be at high risk of bias; however, restricting analyses only to studies at low or unclear risk did not change clinical interpretation of the results. There was high-certainty evidence that bupropion increased long-term smoking cessation rates (RR 1.64, 95% CI 1.52 to 1.77; I2 = 15%; 45 studies, 17,866 participants). There was insufficient evidence to establish whether participants taking bupropion were more likely to report SAEs compared to those taking placebo. Results were imprecise and CIs encompassed no difference (RR 1.16, 95% CI 0.90 to 1.48; I2 = 0%; 21 studies, 10,625 participants; moderate-certainty evidence, downgraded one level due to imprecision). We found high-certainty evidence that use of bupropion resulted in more trial dropouts due to adverse events of the drug than placebo (RR 1.37, 95% CI 1.21 to 1.56; I2 = 19%; 25 studies, 12,340 participants). Participants randomized to bupropion were also more likely to report psychiatric AEs compared with those randomized to placebo (RR 1.25, 95% CI 1.15 to 1.37; I2 = 15%; 6 studies, 4439 participants). We also looked at the safety and efficacy of bupropion when combined with other non-antidepressant smoking cessation therapies. There was insufficient evidence to establish whether combination bupropion and nicotine replacement therapy (NRT) resulted in superior quit rates to NRT alone (RR 1.19, 95% CI 0.94 to 1.51; I2 = 52%; 12 studies, 3487 participants), or whether combination bupropion and varenicline resulted in superior quit rates to varenicline alone (RR 1.21, 95% CI 0.95 to 1.55; I2 = 15%; 3 studies, 1057 participants). We judged the certainty of evidence to be low and moderate, respectively; in both cases due to imprecision, and also due to inconsistency in the former. Safety data were sparse for these comparisons, making it difficult to draw clear conclusions. A meta-analysis of six studies provided evidence that bupropion resulted in inferior smoking cessation rates to varenicline (RR 0.71, 95% CI 0.64 to 0.79; I2 = 0%; 6 studies, 6286 participants), whilst there was no evidence of a difference in efficacy between bupropion and NRT (RR 0.99, 95% CI 0.91 to 1.09; I2 = 18%; 10 studies, 8230 participants). We also found some evidence that nortriptyline aided smoking cessation when compared with placebo (RR 2.03, 95% CI 1.48 to 2.78; I2 = 16%; 6 studies, 975 participants), whilst there was insufficient evidence to determine whether bupropion or nortriptyline were more effective when compared with one another (RR 1.30 (favouring bupropion), 95% CI 0.93 to 1.82; I2 = 0%; 3 studies, 417 participants). There was no evidence that any of the other antidepressants tested (including St John's Wort, selective serotonin reuptake inhibitors (SSRIs), monoamine oxidase inhibitors (MAOIs)) had a beneficial effect on smoking cessation. Findings were sparse and inconsistent as to whether antidepressants, primarily bupropion and nortriptyline, had a particular benefit for people with current or previous depression. AUTHORS' CONCLUSIONS: There is high-certainty evidence that bupropion can aid long-term smoking cessation. However, bupropion also increases the number of adverse events, including psychiatric AEs, and there is high-certainty evidence that people taking bupropion are more likely to discontinue treatment compared with placebo. However, there is no clear evidence to suggest whether people taking bupropion experience more or fewer SAEs than those taking placebo (moderate certainty). Nortriptyline also appears to have a beneficial effect on smoking quit rates relative to placebo. Evidence suggests that bupropion may be as successful as NRT and nortriptyline in helping people to quit smoking, but that it is less effective than varenicline. There is insufficient evidence to determine whether the other antidepressants tested, such as SSRIs, aid smoking cessation, and when looking at safety and tolerance outcomes, in most cases, paucity of data made it difficult to draw conclusions. Due to the high-certainty evidence, further studies investigating the efficacy of bupropion versus placebo are unlikely to change our interpretation of the effect, providing no clear justification for pursuing bupropion for smoking cessation over front-line smoking cessation aids already available. However, it is important that where studies of antidepressants for smoking cessation are carried out they measure and report safety and tolerability clearly.


Assuntos
Ansiolíticos/uso terapêutico , Antidepressivos/uso terapêutico , Abandono do Hábito de Fumar/métodos , Fumar/tratamento farmacológico , Ansiolíticos/efeitos adversos , Antidepressivos/efeitos adversos , Bupropiona/efeitos adversos , Bupropiona/uso terapêutico , Humanos , Nortriptilina/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Inibidores de Captação de Serotonina/uso terapêutico , Fumar/psicologia , Abandono do Hábito de Fumar/psicologia , Dispositivos para o Abandono do Uso de Tabaco , Vareniclina/efeitos adversos , Vareniclina/uso terapêutico
16.
PLoS One ; 15(4): e0231700, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32315333

RESUMO

Depression affects over 300 million individuals worldwide and is responsible for most of the 800,000 annual suicides. Clinical practice guidelines (CPGs) for treatment of depression, founded on scientific evidence, are essential to improve patient care. However, economic and sociocultural factors may influence CPG elaboration, potentially leading to divergences in their recommendations. Consequently, we analyzed pharmacological recommendations for the treatment of depression from the most relevant CPGs. We included four CPGs with scores ≥ 80% for Domain 3 (rigor of development) on the Appraisal of Guidelines for Research and Evaluation and two other commonly used CPGs. The recommendations, their strengths, and the level of evidence were extracted from each CPG by two independent researchers and grouped as follows: (1) general recommendations for the pharmacological treatment for depression (suicide risk, acute treatment, continuation and maintenance phases, and treatment discontinuation); (2) treatment of non-responsive or partially responsive patients; and (3) treatment for subtypes of depression (chronic, psychotic, catatonic, melancholic, seasonal, somatic, mixed, and atypical). Only 50% of CPGs included recommendations for the risk of suicide associated with pharmacotherapy. All CPGs included serotonin selective reuptake inhibitors (SSRIs) as first-line treatment; however, one CPG also included agomelatine, milnacipran, and mianserin as first-line alternatives. Recommendations for depression subtypes (catatonic, atypical, melancholic) were included in three CPGs. The strength of recommendation and level of evidence clearly differed among CPGs, especially regarding treatment augmentation strategies. We conclude that, although CPGs converged in some recommendations (e.g., SSRIs as first-line treatment), they diverged in cardinal topics including the absence of recommendations regarding the risk of suicide associated with pharmacotherapy. Consequently, the recommendations listed in a specific CPG should be followed with caution.


Assuntos
Antidepressivos/uso terapêutico , Antipsicóticos/uso terapêutico , Depressão/tratamento farmacológico , Inibidores de Captação de Serotonina/uso terapêutico , Antidepressivos/efeitos adversos , Antipsicóticos/efeitos adversos , Depressão/epidemiologia , Guias como Assunto , Humanos , Farmacologia Clínica , Inibidores de Captação de Serotonina/efeitos adversos , Suicídio/prevenção & controle
17.
Lancet Psychiatry ; 7(4): 337-343, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32199509

RESUMO

BACKGROUND: Better understanding of the heterogeneity of treatment responses could help to improve care for adolescents with depression. We analysed data from a clinical trial to assess whether specific symptom clusters responded differently to various treatments. METHODS: For this secondary analysis, we used data from the Treatment for Adolescents with Depression Study (TADS), in which 439 US adolescents aged 12-17 with a DSM-IV diagnosis of major depressive disorder and a minimum score of 45 on the Children's Depression Rating Scale-Revised (CDRS-R) were randomly assigned (1:1:1:1) to treatment with fluoxetine, cognitive behavioural therapy (CBT), fluoxetine plus CBT, or pill placebo. Our analysis focuses on the acute phase of the trial (ie, the first 12 weeks). Groups of co-occurring symptoms were established by clustering scores for each CDRS-R item at baseline with Ward's method, with Euclidean distances for hierarchical agglomerative clustering. We then used a linear mixed-effects model to investigate the relationship between symptom clusters and treatment efficacy, with the sum of symptom scores within each cluster as the dependent measure. As fixed effects, we entered cluster, time, and treatment assignment, with all two-way and three-way interactions, into the model. The random effect providing better fit was established to be a by-subject random slope for cluster based on improvement in the Schwarz-Bayesian information criterion. OUTCOMES: We identified two symptom clusters: cluster 1 comprised depressed mood, difficulty having fun, irritability, social withdrawal, sleep disturbance, impaired schoolwork, excessive fatigue, and low self-esteem, and cluster 2 comprised increased appetite, physical complaints, excessive weeping, decreased appetite, excessive guilt, morbid ideation, and suicidal ideation. For cluster 1 symptoms, CDRS-R scores were reduced by 5·8 points (95% CI 2·8-8·9) in adolescents treated with fluoxetine plus CBT, and by 4·1 points (1·1-7·1) in those treated with fluoxetine, compared with those given placebo. For cluster 2 symptoms, no significant differences in improvements in CDRS-R scores were detected between the active treatment and placebo groups. INTERPRETATION: Response to fluoxetine and CBT among adolescents with depression is heterogeneous. Clinicians should consider clinical profile when selecting therapeutic modality. The contrast in response patterns between symptom clusters could provide opportunities to improve treatment efficacy by gearing the development of new therapies towards the resolution of specific symptoms. FUNDING: Conselho Nacional de Desenvolvimento Científico e Tecnológico.


Assuntos
Terapia Cognitivo-Comportamental/métodos , Transtorno Depressivo Maior/terapia , Fluoxetina/uso terapêutico , Inibidores de Captação de Serotonina/uso terapêutico , Adolescente , Teorema de Bayes , Criança , Terapia Combinada , Manual Diagnóstico e Estatístico de Transtornos Mentais , Feminino , Humanos , Masculino , Escalas de Graduação Psiquiátrica , Resultado do Tratamento , Estados Unidos
18.
BJOG ; 127(11): 1366-1373, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32162458

RESUMO

OBJECTIVE: Evaluate whether selective serotonin reuptake inhibitor (SSRI) use during pregnancy, as well as prior or current untreated psychiatric illness is associated with postpartum haemorrhage (PPH). DESIGN: National register-based cohort study based on data from the Swedish Pregnancy Register. SETTING: Sweden, nationwide coverage. POPULATION: A total of 31 159 pregnant women with singleton deliveries after gestational week 22+0 between January 2013 and July 2017. METHODS: Pregnant women with self-reported SSRI use at any time point during pregnancy were compared with non-SSRI-treated women with prior or current psychiatric illness, as well as wiith healthy women with no psychiatric illness or reporting SSRI use. MAIN OUTCOME MEASURES: Postpartum haemorrhage defined as blood loss >1000 ml during the first 2 hours postpartum reported by the delivering midwife or obstetrician. RESULTS: Postpartum haemorrhage prevalence was 7.0% among healthy women, 7.6% among women with prior or current psychiatric illness and 9.1% among women treated with SSRI. The unadjusted odds for PPH among women with prior or current psychiatric illness and women on SSRI treatment were increased by 9 and 34%, respectively, compared with healthy unmedicated women without a history of psychiatric illness (odds ratio [OR] 1.09, 95% CI 1.04-1.14 and OR 1.34, 95% CI 1.24-1.44, respectively). The estimates remained unchanged after adjustment for several confounders (such as maternal age, body mass index [BMI], parity, prior caesarean section, smoking, occupation and country of birth) and potential covariates (such as delivery mode, polyhydramnion, preterm delivery, labour dystocia and infant birthweight >4000 g). CONCLUSIONS: Higher risk for PPH was observed both among women treated with SSRI during pregnancy and among women with prior or current psychiatric illness. TWEETABLE ABSTRACT: SSRI use at any point during pregnancy and prior or current history of psychiatric illness was associated with an increased likelihood for PPH.


Assuntos
Transtornos Mentais/tratamento farmacológico , Hemorragia Pós-Parto/epidemiologia , Complicações na Gravidez/tratamento farmacológico , Inibidores de Captação de Serotonina/efeitos adversos , Inibidores de Captação de Serotonina/uso terapêutico , Adulto , Fatores de Confusão Epidemiológicos , Feminino , Humanos , Gravidez , Prevalência , Sistema de Registros , Estudos Retrospectivos , Fatores de Risco , Suécia/epidemiologia
19.
Psychopharmacology (Berl) ; 237(6): 1681-1689, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32125484

RESUMO

RATIONALE: A variety of neural systems are involved in drug addiction, and some of these systems are shared across different addictive drugs. We have found several different types of drug treatments that successfully reduce nicotine self-administration. OBJECTIVES: The current set of studies is the first in a series to determine if drug treatments that have been found to significantly reduce nicotine self-administration would reduce opiate self-administration. METHODS: Amitifadine, a triple reuptake inhibitor of dopamine, norepinephrine, and serotonin, was assessed in female Sprague-Dawley rats to determine whether it significantly reduces remifentanil self-administration with either acute or chronic treatment. RESULTS: Acutely, amitifadine doses of 5, 10, and 20 mg/kg each significantly reduced remifentanil self-administration. In a chronic study, repeated treatment with 10 mg/kg of amitifadine continued to reduce remifentanil self-administration, even after the cessation of treatment. However, amitifadine was not found to attenuate the rise in remifentanil self-administration with continued access. This study and our earlier one showed that the 10 mg/kg amitifadine dose did not significantly affect food motivated responding. Amitifadine did not attenuate remifentanil-induced antinociception as measured on the hot plate test but extended and maintained antinociceptive effects. CONCLUSIONS: These studies show the promise of amitifadine as a treatment for countering opiate self-administration for adjunctive use with opioids for analgesia. Further studies are needed to determine the possible efficacy of amitifadine for combating opiate addiction or preventing it in humans during adjunctive use with opioids for chronic pain.


Assuntos
Analgésicos Opioides/administração & dosagem , Compostos Aza/uso terapêutico , Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Inibidores da Captação de Dopamina/uso terapêutico , Norepinefrina/antagonistas & inibidores , Remifentanil/administração & dosagem , Inibidores de Captação de Serotonina/uso terapêutico , Animais , Compostos Aza/farmacologia , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Dopamina/metabolismo , Inibidores da Captação de Dopamina/farmacologia , Relação Dose-Resposta a Droga , Feminino , Humanos , Motivação/efeitos dos fármacos , Motivação/fisiologia , Nicotina/administração & dosagem , Norepinefrina/metabolismo , Dor/tratamento farmacológico , Dor/metabolismo , Ratos , Ratos Sprague-Dawley , Autoadministração , Serotonina/metabolismo , Inibidores de Captação de Serotonina/farmacologia , Estereoisomerismo
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