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1.
J Opioid Manag ; 15(4): 342-344, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31637686

RESUMO

A 49-year-old male with major depressive disorder well-managed with venlafaxine [serotonin and norepinephrine reuptake inhibitor (SNRI)] and no history of manic episodes developed his first manic episode following use of tramadol. Tramadol-induced mania has been described with selective serotonin reuptake inhibitors but not SNRIs. In addition, mania is not listed as a potential clinical side effect-further illustrating this relative rarity. Due to tramadol's SNRI activity, there is definitive risk for mood lability in individuals managed with tramadol and other serotonergic medications as seen in this patient. The authors findings suggest the need for greater risk consideration when prescribing tramadol with other related agents such as venlafaxine.


Assuntos
Transtorno Bipolar , Transtorno Depressivo Maior , Tramadol , Cloridrato de Venlafaxina , Analgésicos Opioides , Transtorno Bipolar/induzido quimicamente , Transtorno Depressivo Maior/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores de Captação de Serotonina/efeitos adversos , Tramadol/efeitos adversos , Tramadol/uso terapêutico , Cloridrato de Venlafaxina/efeitos adversos , Cloridrato de Venlafaxina/uso terapêutico
3.
Ecotoxicology ; 28(6): 612-618, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31154538

RESUMO

Wastewater effluents are teeming with organisms, nutrients and chemical substances which water treatment processes fail to remove. Among these substances, pharmaceuticals such as antidepressants are a frequent occurrence, and have been reported to lead to severe effects in the physiology and behaviour of non-target marine species across taxa. Venlafaxine (VFX) is one of the most consistently prescribed substances for the treatment of human depressive disorders, acting as a serotonin and norepinephrine reuptake inhibitor. In the present study, the potential effects of this antidepressant on the survival and key behaviours (i.e. movement, aggression and foraging) of white seabream (Diplodus sargus) larvae were addressed. Larvae were submitted to an acute exposure of two different VFX treatments (low concentration, 10 µg L-1; and high concentration, 100 µg L-1) for a total of 48 h. Sampling took place after 24 and 48 h of exposure. Overall, results showed a significant effect of a two-day exposure to VFX in larvae of D. sargus. Survival was significantly reduced by exposure to a high concentration, but behavioural effects of antidepressant exposure were subtle: i.e. increased attack frequency and temporary modulation of capture success. Further research efforts should be directed towards evaluating the potential chronic effects of antidepressants in marine species, if we are to anticipate possible pressures on natural populations, and effectively advice policymakers towards the investment in new and more efficient methods of wastewater treatments.


Assuntos
Traços de História de Vida , Dourada/fisiologia , Cloridrato de Venlafaxina/efeitos adversos , Poluentes Químicos da Água/efeitos adversos , Agressão/efeitos dos fármacos , Animais , Relação Dose-Resposta a Droga , Comportamento Alimentar/efeitos dos fármacos , Longevidade/efeitos dos fármacos , Movimento/efeitos dos fármacos , Distribuição Aleatória
4.
J Clin Psychopharmacol ; 39(3): 258-260, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30932946

RESUMO

PURPOSE: The time course of adverse events is an important factor for patient management. Clinicians are better able to prepare patients for specific adverse events, which leads to better treatment adherence. METHODS: Adverse events were followed longitudinally for 6 months during the open-label phase of a relapse prevention trial with 264 patients with generalized anxiety disorder. Adverse events were assessed at each treatment visit using a 21-item checklist. Logistic regression modeling, continuation ratio modeling, and hierarchical linear modeling were used to determine whether adverse events led to early attrition and whether adverse events decreased in enrolled patients over time. FINDINGS: Adverse events were found to have decreased highly significantly during treatment. A highly significant race effect was found in that whites had a significantly higher adverse event rate than did nonwhites. Early attrition rates were predicted by presence of nausea and fatigue, late attrition by dizziness, nervousness, and sexual dysfunction. IMPLICATIONS: Our findings provide information for clinicians on the course of adverse events over treatment, useful to prepare patients for treatment adherence.


Assuntos
Antidepressivos de Segunda Geração/administração & dosagem , Transtornos de Ansiedade/tratamento farmacológico , Cloridrato de Venlafaxina/administração & dosagem , Antidepressivos de Segunda Geração/efeitos adversos , Preparações de Ação Retardada , Feminino , Humanos , Modelos Lineares , Modelos Logísticos , Masculino , Fatores de Tempo , Cloridrato de Venlafaxina/efeitos adversos
5.
Eur Arch Psychiatry Clin Neurosci ; 269(7): 851-857, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30923938

RESUMO

To address the potential correlation between plasma concentrations of venlafaxine (VEN), its active metabolite O-desmethylvenlafaxine (ODVEN) and the active moiety, AM, (ODVEN + VEN) and adverse drug reactions (ADR) in a large naturalistic sample of in- and outpatients. We compared plasma concentrations of VEN, ODVEN and AM and dose-adjusted (C/D) levels as well the ODVEN/VEN ratios between patients complaining ADRs, following the Udvalg for Kliniske Undersogelser side effect rating scales (UKU) (n = 114) and patients without ADRs (control group, n = 688) out of a naturalistic database. We also investigated potential pharmacokinetic correlates of the four UKU categories by comparing patients complaining ADRs with those who did not. Based on previous literature we applied different ODVEN/VEN ratio values as cut-offs to split our sample into two groups at a time and compare frequencies of ADRs between the groups. No differences for demographic and pharmacokinetic variables including plasma and C/D concentrations as well as ODVEN/VEN ratios were observed between study groups. Neither the comparisons between females and males nor between elderly and non-elderly patients revealed significant differences (p > 0.05 in all cases). No differences were also reported exploring the patients complaining ADRs from the 4 UKU categories separately. After applying various ODVEN/VEN cut-offs, groups did not display differences in frequencies of ADRs (p > 0.05 in all cases). Our findings do not demonstrate a direct link between venlafaxine metabolism measures and ADRs. Therefore, additional dimensions are needed to be considered in future trials aiming to disentangle the involved aspects of ADRs in patients receiving venlafaxine.


Assuntos
Antidepressivos de Segunda Geração/efeitos adversos , Antidepressivos de Segunda Geração/sangue , Succinato de Desvenlafaxina/sangue , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Cloridrato de Venlafaxina/efeitos adversos , Cloridrato de Venlafaxina/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Bases de Dados Factuais , Feminino , Alemanha/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos do Humor/tratamento farmacológico , Transtornos do Humor/epidemiologia , Adulto Jovem
6.
J Clin Neurosci ; 63: 27-31, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30837110

RESUMO

Narcolepsy is a life-long neurological disorder characterized by excessive daytime sleepiness (EDS) and cataplexy. At present, Sodium oxybate, modafinil, methylphenidate and other stimulants are recommended first-line therapies for narcolepsy but are difficult to obtain in China. One hundred forty-eight patients with narcolepsy were treated with antidepressants and administered the Epworth Sleepiness Scale (ESS) and the Maintenance of Wakefulness Test (MWT) before and after treatment from August 2012 to August 2017. The subjects were followed for 1-6 years after treatment. Improvement in sleepiness, cataplexy, cataplexy-like episodes, and antidepressant side effects were assessed. There were significant differences in the mean sleep latency (MSL) and sleep onset rapid eye movement periods (SOREMPs) in MWT and ESS scores, cataplexy and cataplexy-like episodes before and after treatment (p < 0.01). Venlafaxine demonstrated significantly greater improvements in MSL in the MWT (p < 0.01). Early awakenings and dry mouth were the most common adverse effects.


Assuntos
Antidepressivos/uso terapêutico , Modafinila/uso terapêutico , Narcolepsia/tratamento farmacológico , Cloridrato de Venlafaxina/uso terapêutico , Adulto , Antidepressivos/administração & dosagem , Antidepressivos/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modafinila/administração & dosagem , Modafinila/efeitos adversos , Estudos Prospectivos , Cloridrato de Venlafaxina/administração & dosagem , Cloridrato de Venlafaxina/efeitos adversos
10.
Pharmacopsychiatry ; 52(1): 38-43, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29466824

RESUMO

INTRODUCTION: Many antidepressants cause QT prolongation but the classification of cardiac risk of these drugs varies markedly in different published lists. This retrospective study analyzed the correlation of QTc time with amitriptyline and venlafaxine serum level in elderly psychiatric inpatients. METHODS: Elderly inpatients aged≥65 years for whom venlafaxine or amitriptyline serum level had been measured were selected retrospectively from a therapeutic drug monitoring database and screened for an electrocardiogram measurement at the time of blood withdrawal. The correlation of amitriptyline or venlafaxine serum levels with QTc time was examined by using Pearson's correlation analysis. RESULTS: Amitriptyline serum levels (n=11) correlated significantly with QTc time (r=0.918, p<0.001, CI 95%). Venlafaxine serum levels (n=27) also correlated significantly with QTc time (r=0.382, p<0.05, CI 95%). DISCUSSION: Amitriptyline and venlafaxine induce QT prolongation depending on drug concentrations in blood. Its extent, however, is very low when drug serum levels are within the therapeutic range. Future pharmacokinetic studies that correlate drug serum level and QT time should classify the cardiac risk of drugs based on the grade of the regression line in relation to the therapeutic range.


Assuntos
Amitriptilina/efeitos adversos , Eletrocardiografia/efeitos dos fármacos , Síndrome do QT Longo/sangue , Cloridrato de Venlafaxina/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Amitriptilina/sangue , Antidepressivos/efeitos adversos , Antidepressivos/sangue , Bases de Dados Factuais , Feminino , Humanos , Pacientes Internados , Masculino , Estudos Retrospectivos , Cloridrato de Venlafaxina/sangue
11.
Pharmacopsychiatry ; 52(5): 222-231, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30485867

RESUMO

BACKGROUND: The association between CYP2D6 metabolizer status and clinical outcomes of venlafaxine was extensively investigated previously, but no widely accepted conclusion has been reached so far. To obtain a more precise estimation of the association, a systematic review by meta-analysis was conducted in the present study. METHODS: The PubMed, EMBASE, Cochrane Library, Chinese National Knowledge Infrastructure, Technology of Chongqing, and Wan Fang Database were searched for eligible studies up to August 2018. RESULTS: Fourteen related studies involving 1035 patients were finally included. Significant associations were found among 3 CYP2D6 phenotypes (NM, IM, and PM) and most pharmacokinetic parameters of venlafaxine. However, CYP2D6 phenotypes were not associated with Hamilton Depression Rating Scale response of venlafaxine. In addition, we also found no significant association between CYP2D6 phenotype and overall rate of adverse events. CONCLUSIONS: CYP2D6 metabolizer status had significant influence on venlafaxine pharmacokinetics, but insufficient evidence demonstrated that CYP2D6 metabolizer status was associated with its therapeutic effects and overall rate of adverse events, which provided further evidence regarding the relationship between CYP2D6 metabolizer status and venlafaxine.


Assuntos
Citocromo P-450 CYP2D6/genética , Depressão/tratamento farmacológico , Cloridrato de Venlafaxina/farmacocinética , Cloridrato de Venlafaxina/uso terapêutico , Antidepressivos de Segunda Geração/uso terapêutico , Humanos , Resultado do Tratamento , Cloridrato de Venlafaxina/efeitos adversos
12.
Placenta ; 72-73: 62-73, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30501883

RESUMO

INTRODUCTION: Between 2 and 10% of pregnant women are treated with selective serotonin-reuptake inhibitors (SSRIs) for depression. The extravillous trophoblasts (evTBs), which migrate and invade maternal tissues, are crucial for embryo implantation and remodeling of maternal spiral arteries. Poor migration/invasion of evTBs can cause serious pregnancy complications, yet the effects of SSRIs on these processes has never been studied. To determine the effects of five SSRIs (fluoxetine, norfluoxetine, citalopram, sertraline and venlafaxine) on migration/invasion, we used JEG-3 and HIPEC cells as evTB models. METHODS: Cells were treated with increasing concentrations (0.03-10 µM) of SSRIs. Cell proliferation was monitored using an impedance-based system and cell cycle by flow cytometry. Migration was determined using a scratch test, and metalloproteinase (MMP) activities, by zymography. Invasion markers were determined by RT-qPCR. RESULTS: Fluoxetine and sertraline (10 µM) significantly decreased cell proliferation by 94% and by 100%, respectively, in JEG-3 cells, and by 58.6% and 100%, respectively, in HIPEC cells. Norfluoxetine increased MMP-9 activity in JEG-3 cells by 2.0% at 0.03 µM and by 43.9% at 3 µM, but decreased MMP-9 activity in HIPEC cells by 63.7% at 3 µM. Sertraline at 0.03 µM increased mRNA level of TIMP-1 in JEG-3 cells by 36% and that of ADAM-10 by 85% and 115% at 0.3 and 3 µM, respectively. In HIPEC cells, venlafaxine at 0.03 and 0.3 µM, increased ADAM-10 mRNA levels by 156% and 167%, respectively. DISCUSSION: This study shows that SSRIs may affect evTBs homeostasis at therapeutic levels and provides guidance for future research.


Assuntos
Inibidores de Captação de Serotonina/efeitos adversos , Trofoblastos/efeitos dos fármacos , Proteína ADAM10/genética , Secretases da Proteína Precursora do Amiloide/genética , Linhagem Celular , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Coriocarcinoma , Feminino , Fluoxetina/efeitos adversos , Fluoxetina/análogos & derivados , Expressão Gênica/efeitos dos fármacos , Humanos , Metaloproteinase 9 da Matriz/efeitos dos fármacos , Metaloproteinase 9 da Matriz/metabolismo , Proteínas de Membrana/genética , Modelos Biológicos , Gravidez , RNA Mensageiro/análise , Inibidores de Captação de Serotonina/uso terapêutico , Sertralina/efeitos adversos , Inibidor Tecidual de Metaloproteinase-1/genética , Trofoblastos/fisiologia , Cloridrato de Venlafaxina/efeitos adversos
13.
Tijdschr Psychiatr ; 60(11): 782-785, 2018.
Artigo em Holandês | MEDLINE | ID: mdl-30484571

RESUMO

Patients wanting to discontinue their antidepressant use may experience antidepressant discontinuation syndrome (ADS). This is characterized by symptoms such as nausea, vomiting, diarrhea, headaches and sweating. Withdrawal symptoms can discourage patients from permanently discontinuing antidepressants. We present the case of a 48-year-old visually impaired woman where, after a first attempt failed, venlafaxine was successfully discontinued after a switch to fluoxetine. Fluoxetine mediated discontinuation is a simple, effective and inexpensive method for patients who suffer from withdrawal symptoms when tapering off antidepressants.


Assuntos
Antidepressivos/uso terapêutico , Transtorno Depressivo Maior/tratamento farmacológico , Fluoxetina/uso terapêutico , Síndrome de Abstinência a Substâncias/prevenção & controle , Cloridrato de Venlafaxina/efeitos adversos , Feminino , Humanos , Pessoa de Meia-Idade , Síndrome de Abstinência a Substâncias/tratamento farmacológico
14.
J Clin Psychopharmacol ; 38(5): 498-501, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30102628

RESUMO

BACKGROUND: Amlodipine (AMLO) and ramipril (RAMI) belong to the most prescribed drugs in patients with hypertension, a condition also encountered in depression. Venlafaxine may worsen hypertension because of noradrenergic properties. Although of special clinical relevance, data on pharmacokinetic interactions between AMLO, RAMI, and venlafaxine (VEN) are lacking. METHODS: Two TDM databases consisting of plasma concentrations of VEN and its active metabolite O-desmethylvenlafaxine (ODVEN) were analyzed. We considered a group of patients comedicated with AMLO, VAMLO (n = 22); a group comedicated with RAMI, VRAMI (n = 20); and a 4:1 control group age matched to the VAMLO group receiving VEN without confounding medications, V0 (n = 88). Plasma concentrations of VEN, ODVEN, and active moiety, AM (VEN + ODVEN); metabolic ratio (ODVEN/VEN); and dose-adjusted plasma concentrations (C/D) were compared using nonparametric tests. RESULTS: Groups did not differ in daily VEN dose, age, or sex. The metabolic ratio (ODVEN/VEN) was lower in the AMLO group (P = 0.029), whereas the RAMI group showed lower values for ODVEN (P = 0.029). All other parameters showed no significant differences. CONCLUSIONS: Significantly lower values for the metabolic ratio in the AMLO group are unlikely to be explained by cytochrome P450 (CYP) 3A4 and weak CYP2D6 inhibition by AMLO. Other factors such as differences in CYP2D6 polymorphisms and metabolizer status may better explain the findings. Ramipril showed modest effects with changes in ODVEN concentrations that did not remain significant after dose-adjusted comparisons.


Assuntos
Anlodipino/farmacocinética , Anti-Hipertensivos/farmacocinética , Hipertensão/tratamento farmacológico , Ramipril/farmacocinética , Inibidores da Recaptação de Serotonina e Norepinefrina/farmacocinética , Cloridrato de Venlafaxina/farmacocinética , Anlodipino/administração & dosagem , Anlodipino/efeitos adversos , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/efeitos adversos , Inibidores do Citocromo P-450 CYP2D6/administração & dosagem , Inibidores do Citocromo P-450 CYP2D6/efeitos adversos , Inibidores do Citocromo P-450 CYP2D6/farmacocinética , Bases de Dados Factuais , Interações de Medicamentos/fisiologia , Prescrições de Medicamentos/normas , Feminino , Humanos , Hipertensão/sangue , Hipertensão/diagnóstico , Masculino , Ramipril/administração & dosagem , Ramipril/efeitos adversos , Inibidores da Recaptação de Serotonina e Norepinefrina/administração & dosagem , Inibidores da Recaptação de Serotonina e Norepinefrina/efeitos adversos , Cloridrato de Venlafaxina/administração & dosagem , Cloridrato de Venlafaxina/efeitos adversos
16.
Am J Case Rep ; 19: 833-835, 2018 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-30008467

RESUMO

BACKGROUND Serotonin syndrome is a life-threatening condition that can lead to neurologic complications and is associated with the use of serotonergic medications. As the use of antidepressant medications has increased, the incidence of perioperative serotonin syndrome has transitioned from a rare diagnosis to one that should be considered as a differential diagnosis for any patient displaying signs of neuroexcitation. CASE REPORT A 70-year-old man (ASA 2) with a history of vestibular migraines (treated with venlafaxine), gastroesophageal reflux disease, and benign prostatic hyperplasia presented to our institution for photoselective vaporization of the prostate. Upon review of prior anesthetic records, his medical chart was found to list a propofol allergy. In discussion with the patient, he stated the reaction was rigidity. The anesthesiologist and patient agreed this was not an allergy. Thus, the patient was induced with propofol and given ketamine and fentanyl boluses throughout the procedure. During emergence, the patient exhibited myoclonic jerks in the upper and lower extremities. He was given intravenous meperidine for postoperative shivering; minutes after administration, the myoclonic jerks and rigidity worsened. The anesthesia team raised concern about serotonin syndrome. Intravenous midazolam improved the patient's myoclonic jerks and rigidity. CONCLUSIONS Patients with a history of rigidity/movement disorders during the perioperative period may have experienced serotonin toxicity. It is possible, as in our case, for this history to have been labelled as an allergy to a perioperative medication. Clinicians should remain vigilant for patients at risk of developing serotonin syndrome, such as those taking outpatient medications that increase neuronal serotonin.


Assuntos
Hipnóticos e Sedativos/administração & dosagem , Midazolam/administração & dosagem , Síndrome da Serotonina/diagnóstico , Inibidores da Recaptação de Serotonina e Norepinefrina/efeitos adversos , Cloridrato de Venlafaxina/efeitos adversos , Idoso , Humanos , Masculino , Prostatectomia , Hiperplasia Prostática/cirurgia , Serotonina/metabolismo , Síndrome da Serotonina/tratamento farmacológico , Síndrome da Serotonina/etiologia
17.
Psychother Psychosom ; 87(4): 195-203, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30016772

RESUMO

BACKGROUND: Serotonin-noradrenaline reuptake inhibitors (SNRI) are widely used in medical practice. Their discontinuation has been associated with a wide range of symptoms. The aim of this paper is to identify the occurrence, frequency, and features of withdrawal symptoms after SNRI discontinuation. METHODS: PRISMA guidelines were followed to conduct a systematic review. Electronic databases included PubMed, the Cochrane Library, Web of Science, and MEDLINE from the inception of each database to June 2017. Titles, abstracts, and topics were searched using a combination of the following terms: "duloxetine" OR "venlafaxine" OR "desvenlafaxine" OR "milnacipran" OR "levomilnacipran" OR "SNRI" OR "second generation antidepressant" OR "serotonin norepinephrine reuptake inhibitor" AND "discontinuation" OR "withdrawal" OR "rebound." Only published trials in the English language were included. RESULTS: Sixty-one reports met the criteria for inclusion. There were 22 double-blind randomized controlled trials, 6 studies where patients were treated in an open fashion and then randomized to a double-blind controlled phase, 8 open trials, 1 prospective naturalistic study, 1 retrospective study, and 23 case reports. Withdrawal symptoms occurred after discontinuation of any type of SNRI. The prevalence of withdrawal symptoms varied across reports and appeared to be higher with venlafaxine. Symptoms typically ensued within a few days from discontinuation and lasted a few weeks, also with gradual tapering. Late onset and/or a longer persistence of disturbances occurred as well. CONCLUSIONS: Clinicians need to add SNRI to the list of drugs potentially inducing withdrawal symptoms upon discontinuation, together with other types of psychotropic drugs. The results of this study challenge the use of SNRI as first-line treatment for mood and anxiety disorders.


Assuntos
Inibidores da Captação Adrenérgica/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Síndrome de Abstinência a Substâncias/diagnóstico , Inibidores da Captação Adrenérgica/uso terapêutico , Succinato de Desvenlafaxina/efeitos adversos , Succinato de Desvenlafaxina/uso terapêutico , Cloridrato de Duloxetina/efeitos adversos , Cloridrato de Duloxetina/uso terapêutico , Humanos , Transtornos do Humor/tratamento farmacológico , Cloridrato de Venlafaxina/efeitos adversos , Cloridrato de Venlafaxina/uso terapêutico
19.
Chemosphere ; 209: 286-297, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29933165

RESUMO

The presence of antidepressants, such as venlafaxine (VFX), in marine ecosystems is increasing, thus, potentially posing ecological and human health risks. The inherent mechanisms of VFX uptake and elimination still require further understanding, particularly accounting for the impact of climate change-related stressors, such as warming and acidification. Hence, the present work aimed to investigate, for the first time, the effects of increased seawater temperature (ΔT°C = +5 °C) and pCO2 levels (ΔpCO2 ∼1000 µatm, equivalent to ΔpH = -0.4 units) on the uptake and elimination of VFX in biological tissues (muscle, liver, brain) and plasma of juvenile meagre (Argyrosomus regius) exposed to VFX through two different exposure pathways (via water, i.e. [VFX ] ∼20 µg L-1, and via feed, i.e. [VFX] ∼160 µg kg-1 dry weight, dw). Overall, results showed that VFX can be uptaken by fish through both water and diet. Fish liver exhibited the highest VFX concentration (126.7 ±â€¯86.5 µg kg-1 and 6786.4 ±â€¯1176.7 µg kg-1 via feed and water exposures, respectively), as well as the highest tissue:plasma concentration ratio, followed in this order by brain and muscle, regardless of exposure route. Both warming and acidification decreased VFX uptake in liver, although VFX uptake in brain was favoured under warming conditions. Conversely, VFX elimination in liver was impaired by both stressors, particularly when acting simultaneously. The distinct patterns of VFX uptake and elimination observed in the different scenarios calls for a better understanding of the effects of exposure route and abiotic conditions on emerging contaminants' toxicokinetics.


Assuntos
Antidepressivos/efeitos adversos , Oceanos e Mares/epidemiologia , Cloridrato de Venlafaxina/efeitos adversos , Animais , Antidepressivos/farmacologia , Peixes , Aquecimento Global , Cloridrato de Venlafaxina/farmacologia
20.
J Clin Psychopharmacol ; 38(4): 349-356, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29901567

RESUMO

BACKGROUND: Antidepressants are one of the most prescribed classes of medications. A number of case reports have linked these drugs to extrapyramidal symptoms (EPSs), but no large epidemiologic study to date has examined this association. We sought to quantify the association of EPSs with different antidepressants by undertaking a large pharmacoepidemiologic study. METHODS: A nested case-control study was conducted using a large health claims database in the United States from June 2006 to December 2015. Subjects with a diagnosis of primary Parkinson disease and those who received prescriptions of levodopa, ropinirole, pramipexole, domperidone, metoclopramide, entacapone, benztropine, selegiline, rasagiline, diphenhydramine, trihexyphenidyl, typical and atypical antipsychotics, and tricyclic antidepressants were excluded. Cases were followed to the first billing code for an extrapyramidal event or last date of enrollment in the cohort. For each case, 10 control subjects were matched by follow-up time, calendar time, and age through density-based sampling. Rate ratios were computed using conditional logistic regression adjusting for other covariates. RESULTS: We identified 3,838 subjects with EPSs compared with 38,380 age-matched control subjects. Rate ratios with respect to EPSs were as follows: duloxetine, 5.68 (95% confidence interval [CI], 4.29-7.53); mirtazapine, 3.78 (95% CI, 1.71-8.32); citalopram, 3.47 (95% CI, 2.68-4.50); escitalopram, 3.23 (95% CI, 2.44-4.26); paroxetine, 3.07 (95% CI, 2.15-4.40); sertraline, 2.57 (95% CI, 2.02-3.28); venlafaxine, 2.37 (95% CI, 1.71-3.29); bupropion, 2.31 (95% CI, 1.67-3.21); and fluoxetine, 2.03 (95% CI, 1.48-2.78). CONCLUSIONS: This observational study demonstrates a harmful association between the incidence of Parkinson disease or associated EPSs and use of the antidepressants duloxetine, mirtazapine, citalopram, escitalopram, paroxetine, sertraline, venlafaxine, bupropion, and fluoxetine.


Assuntos
Antidepressivos/efeitos adversos , Doenças dos Gânglios da Base/induzido quimicamente , Doenças dos Gânglios da Base/epidemiologia , Bupropiona/efeitos adversos , Estudos de Casos e Controles , Citalopram/efeitos adversos , Cloridrato de Duloxetina/efeitos adversos , Feminino , Fluoxetina/efeitos adversos , Humanos , Masculino , Mianserina/efeitos adversos , Mianserina/análogos & derivados , Pessoa de Meia-Idade , Mirtazapina , Paroxetina/efeitos adversos , Farmacoepidemiologia , Sertralina/efeitos adversos , Estados Unidos/epidemiologia , Cloridrato de Venlafaxina/efeitos adversos
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