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1.
JAMA Netw Open ; 3(5): e206027, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32463470

RESUMO

Importance: Apathy is a frequent neuropsychiatric symptom in dementia of Alzheimer type and negatively affects the disease course and patients' and caregivers' quality of life. Effective treatment options are needed. Objective: To examine the efficacy and safety of the dopamine and noradrenaline reuptake inhibitor bupropion in the treatment of apathy in patients with dementia of Alzheimer type. Design, Setting, and Participants: This 12-week, multicenter, double-blind, placebo-controlled, randomized clinical trial was conducted in a psychiatric and neurological outpatient setting between July 2010 and July 2014 in Germany. Patients with mild-to-moderate dementia of Alzheimer type and clinically relevant apathy were included. Patients with additional clinically relevant depressed mood were excluded. Data analyses were performed between August 2018 and August 2019. Interventions: Patients received either bupropion or placebo (150 mg for 4 weeks plus 300 mg for 8 weeks). In case of intolerability of 300 mg, patients continued to receive 150 mg throughout the study. Main Outcomes and Measures: Change on the Apathy Evaluation Scale-Clinician Version (AES-C) (score range, 18-72 points) between baseline and week 12 was the primary outcome parameter. Secondary outcome parameters included measures of neuropsychiatric symptoms, cognition, activities of daily living, and quality of life. Outcome measures were assessed at baseline and at 4, 8, and 12 weeks. Results: A total of 108 patients (mean [SD] age, 74.8 [5.9] years; 67 men [62%]) were included in the intention-to-treat analysis, with 54 randomized to receive bupropion and 54 randomized to receive placebo. The baseline AES-C score was comparable between the bupropion group and the placebo group (mean [SD], 52.2 [8.7] vs 50.4 [8.2]). After controlling for the baseline AES-C score, site, and comedication with donepezil or galantamine, the mean change in the AES-C score between the bupropion and placebo groups was not statistically significant (mean change, 2.22; 95% CI, -0.47 to 4.91; P = .11). Results on secondary outcomes showed statistically significant differences between bupropion and placebo in terms of total neuropsychiatric symptoms (mean change, 5.52; 95% CI, 2.00 to 9.04; P = .003) and health-related quality of life (uncorrected for multiple comparisons; mean change, -1.66; 95% CI, -3.01 to -0.31; P = .02) with greater improvement in the placebo group. No statistically significant changes between groups were found for activities of daily living (mean change, -2.92; 95% CI, -5.89 to 0.06; P = .05) and cognition (mean change, -0.27; 95% CI, -3.26 to 2.73; P = .86). The numbers of adverse events (bupropion group, 39 patients [72.2%]; placebo group, 33 patients [61.1%]) and serious adverse events (bupropion group, 5 patients [9.3%]; placebo group, 2 patients [3.7%]) were comparable between groups. Conclusions and Relevance: Although it is safe, bupropion was not superior to placebo for the treatment of apathy in patients with dementia of Alzheimer type in the absence of clinically relevant depressed mood. Trial Registration: EU Clinical Trials Register Identifier: 2007-005352-17.


Assuntos
Doença de Alzheimer/psicologia , Antidepressivos de Segunda Geração/uso terapêutico , Apatia/efeitos dos fármacos , Bupropiona/uso terapêutico , Idoso , Doença de Alzheimer/tratamento farmacológico , Antidepressivos de Segunda Geração/efeitos adversos , Bupropiona/efeitos adversos , Método Duplo-Cego , Feminino , Humanos , Masculino , Testes de Estado Mental e Demência
2.
Actas esp. psiquiatr ; 48(2): 47-53, mar.-abr. 2020. graf
Artigo em Espanhol | IBECS | ID: ibc-191904

RESUMO

INTRODUCCIÓN: Actualmente el tratamiento de enfermedades mentales mediante antidepresivos es muy frecuente. Los inhibidores selectivos de la recaptación de serotonina son los antidepresivos más prescritos a nivel mundial y han sido asociados con alteraciones en la acomodación o la pupila. El objetivo de este estudio es evaluar los efectos de la fluoxetina sobre el reflejo pupilar y la acomodación en población joven. METODOLOGÍA: El grupo de estudio contó con siete pacientes diagnosticados de depresión y tratados con fluoxetina; como grupo control se incluyeron 22 sujetos. Se evaluaron los reflejos pupilares y el estado acomodativo mediante el pupilómetro Power Refractor II. Se midieron 5 fases de 3 segundos cada una. En la fase 2 se produjo un deslumbramiento con una luz blanca. RESULTADOS: Para el diámetro pupilar se han obtenido valores máximos y mínimos mayores en el grupo de pacientes tratados con fluoxetina que en el control en todas las fases de medida. Para el grupo control se observa una contracción pupilar máxima en la fase de deslumbramiento, sin embargo, en el grupo de estudio se observa en la fase tras el deslumbramiento. En cuanto a la acomodación no se obtuvieron diferencias significativas entre ambos grupos. CONCLUSIONES: En pacientes tratados con fluoxetina existen alteraciones pupilares observándose diámetros pupilares mayores y menor velocidad de contracción pupilar. La falta de resultados concluyentes en cuanto a la acomodación no significa que no existan cambios relacionados con esta, cuya detección requerirá de futuros estudios utilizando diferentes metodologías y con un tamaño muestral mayor


INTRODUCTION: currently the treatment of mental illness by antidepressants is very frequent. Selective serotonin re-uptake inhibitors are the most prescribed antidepressants worldwide and have been associated with alterations in accommodation or pupil. The objective of this study is to evaluate the effects of fluoxetine on the pupillary reflex and the accommodation in young population. METHODOLOGY: The study group included seven patients diagnosed with depression and treated with fluoxetine; 22 subjects were included as a control group. The pupillary reflexes and the accommodative state were evaluated using the Power Refractor II pupilometer. Five phases of 3 seconds each were measured. In phase 2 there was a glare with a white light. RESULTS: For the pupil diameter, maximum and minimum values were obtained in the group of patients treated with fluoxetine than in the control in all the measurement phases. For the control group, a maximum pupillary contraction is observed in the glare phase, however, in the study group it is observed in the phase after glare. As for the accommodation, there are no significant differences between the two groups. CONCLUSIONS: In patients treated with fluoxetine there are pupillary alterations like a bigger pupillary diameters and slower pupillary contraction. The lack of conclusive results in terms of accommodation does not mean that there are no changes related to it, whose detection requires future studies with different methodologies and with a larger sample size


Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto Jovem , Adulto , Fluoxetina/efeitos adversos , Antidepressivos de Segunda Geração/efeitos adversos , Visão Mesópica/efeitos dos fármacos , Depressão/tratamento farmacológico , Distúrbios Pupilares/induzido quimicamente , Fluoxetina/uso terapêutico , Antidepressivos de Segunda Geração/uso terapêutico
4.
J Stroke Cerebrovasc Dis ; 29(5): 104664, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32093988

RESUMO

OBJECTIVE: The purpose of our study is to evaluate the efficacy of paroxetine in poststroke depression (PSD) patients by conducting a meta-analysis. METHODS: We searched Web of Science (science and social science citation index), PubMed, the Cochrane Central Register of Controlled Trials, Embase up to August 2019. Randomized controlled trials that paroxetine compared to other antidepressants or control treatments as monotherapy for patients with PSD. RESULTS: This review identified a total of 4 studies including 212 patients. This meta-analysis presented that paroxetine exhibits beneficial efficacy than routine treatment in PSD patients in terms of the reducing score of Hamilton Depression Scale (HAMD). Control treatment is more effective than paroxetine. No significant advantage was found with paroxetine. CONCLUSIONS: The efficacy of paroxetine maybe not very significant compared to other pharmacological and nonpharmacological interventions. Further high quality and large sample size studies are needed to evaluate the efficacy and safety of paroxetine in treating PSD in future.


Assuntos
Afeto/efeitos dos fármacos , Antidepressivos de Segunda Geração/uso terapêutico , Depressão/tratamento farmacológico , Paroxetina/uso terapêutico , Inibidores de Captação de Serotonina/uso terapêutico , Acidente Vascular Cerebral/complicações , Antidepressivos de Segunda Geração/efeitos adversos , Depressão/diagnóstico , Depressão/etiologia , Depressão/psicologia , Humanos , Paroxetina/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Inibidores de Captação de Serotonina/efeitos adversos , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/psicologia , Fatores de Tempo , Resultado do Tratamento
5.
Pharm Res ; 37(1): 7, 2019 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-31845095

RESUMO

PURPOSE: Antidepressants like the serotonin reuptake inhibitors (SRIs) are often used concomitantly with tamoxifen (e.g. for treatment of depression). This may lead to an additional prolongation of the QTc-interval, with an increased risk of cardiac side effects. Therefore we investigated whether there is a drug-drug interaction between tamoxifen and SRIs resulting in a prolonged QTc-interval. METHODS: Electrocardiograms (ECGs) of 100 patients were collected at steady state tamoxifen treatment, with or without concomitant SRI co-medication. QTc-interval was manually measured and calculated using the Fridericia formula. Primary outcome was difference in QTc-interval between tamoxifen monotherapy and tamoxifen concomitantly with an SRI. RESULTS: The mean QTc-interval was 12.4 ms longer when tamoxifen was given concomitantly with an SRI (95% CI:1.8-23.1 ms; P = 0.023). Prolongation of the QTc-interval was particularly pronounced for paroxetine (17.2 ms; 95%CI:1.4-33.0 ms; P = 0.04), escitalopram (12.5 ms; 95%CI:4.4-20.6 ms; P < 0.01) and citalopram (20.7 ms; 95%CI:0.7-40.7 ms; P = 0.047), where other agents like venlafaxine did not seem to prolong the QTc-interval. None of the patients had a QTc-interval of >500 ms. CONCLUSIONS: Concomitant use of tamoxifen and SRIs resulted in a significantly higher mean QTc-interval, which was especially the case for paroxetine, escitalopram and citalopram. When concomitant administration with an SRI is warranted venlafaxine is preferred.


Assuntos
Antidepressivos de Segunda Geração/farmacologia , Antineoplásicos Hormonais/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/fisiopatologia , Inibidores de Captação de Serotonina/efeitos adversos , Tamoxifeno/efeitos adversos , Idoso , Antidepressivos de Segunda Geração/efeitos adversos , Antineoplásicos Hormonais/farmacologia , Neoplasias da Mama/complicações , Citalopram/farmacologia , Feminino , Humanos , Síndrome do QT Longo/induzido quimicamente , Pessoa de Meia-Idade , Inibidores de Captação de Serotonina/farmacologia , Tamoxifeno/farmacologia
7.
Turk Psikiyatri Derg ; 30(2): 145-148, 2019.
Artigo em Turco | MEDLINE | ID: mdl-31487381

RESUMO

Bupropion is a selective norepinephrine and dopamine reuptakeinhibitor. It is used in the treatment of depression and nicotineaddiction. When compared to the other antidepressants, bupropion hasa relatively lower risk of triggering shift to hypomania or mania in bipolardepression treatment. Here we report two cases of bipolar depressionpatients with manic shift when bupropion was used as an adjunct tomood stabilizer treatment. The first was a 43-year old female patient.Manic symptoms occurred after bupropion was added to lithium andquetiapine treatment for bipolar disorder (BD) depressive episode.Her manic symptoms regressed rapidly after discontinuing bupropiontreatment. The second patient was a 26-year old male on lithium andvalproate therapy with a BD diagnosis. After bupropion was added tohis treatment for depressive symptoms, psychotic mania ensued and hehad to be admitted to the hospital. Significant improvement was notedshortly after bupropion was discontinued and antipsychotic treatmentwas initiated.


Assuntos
Antidepressivos de Segunda Geração/efeitos adversos , Antipsicóticos/administração & dosagem , Transtorno Bipolar/psicologia , Bupropiona/efeitos adversos , Transtorno Depressivo/psicologia , Adulto , Transtorno Bipolar/complicações , Transtorno Bipolar/tratamento farmacológico , Transtorno Depressivo/complicações , Transtorno Depressivo/tratamento farmacológico , Quimioterapia Combinada , Feminino , Humanos , Masculino
8.
Riv Psichiatr ; 54(4): 137-149, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31379379

RESUMO

AIM: To provide a review of the clinically relevant evidence pertaining to the use of trazodone in major depressive disorder. METHODS: Medline and Cochrane Library searches were searched using the keywords 'trazodone' AND 'depression', to identify the most relevant literature pertinent to the pharmacological properties of trazodone and its use in clinical practice. Articles that were selected included basic pharmacology papers, clinical trials, clinical practice guidelines, and reviews. Related references were cross checked. European and United States prescribing information was reviewed as well. An effort was made to give weight to the information that was most relevant for daily clinical practice. RESULTS: Trazodone is an antidepressant with a mechanism of action that remains innovative and with a favorable profile for the treatment of depression. The appropriate antidepressant doses are usually 150-300 mg/day and are often higher than the doses that are used when trazodone is prescribed to augment the antidepressant effect of another medication, for instance when trazodone is prescribed to address insomnia in a patient treated with an SSRI. Trazodone is usually well tolerated and has a low risk of anticholinergic side effects, weight gain and sexual side effects. DISCUSSION: Trazodone is an established medication that is efficacious for the treatment of a broad array of depressive symptoms, including symptoms that are less likely to respond to other antidepressants (e.g. SSRI), such as insomnia. As an antidepressant, trazodone has proven as efficacious as the tricyclic and second-generation antidepressants and is tolerated relatively well. Trazodone may be helpful for patients with major depression and comorbid insomnia, anxiety or psychomotor agitation. CONCLUSIONS: Trazodone is efficacious antidepressants with a relatively low risks of side effects such as weight gain, sexual or anticholinergic effects (such as constipation, urinary retention, dry mouth). In addition to being able to control a wide range of depressive symptoms, trazodone may improve sleep and be particularly helpful for patients whose symptoms of depression include insomnia.


Assuntos
Antidepressivos de Segunda Geração , Transtorno Depressivo Maior/tratamento farmacológico , Trazodona , Antidepressivos de Segunda Geração/efeitos adversos , Antidepressivos de Segunda Geração/metabolismo , Antidepressivos de Segunda Geração/farmacologia , Antidepressivos de Segunda Geração/uso terapêutico , Ansiedade/tratamento farmacológico , Bulimia/tratamento farmacológico , Preparações de Ação Retardada , Interações Medicamentosas , Fibromialgia/tratamento farmacológico , Humanos , Transtornos Neurocognitivos/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Disfunções Sexuais Fisiológicas/tratamento farmacológico , Distúrbios do Início e da Manutenção do Sono/tratamento farmacológico , Transtornos de Estresse Pós-Traumáticos/tratamento farmacológico , Transtornos Relacionados ao Uso de Substâncias/tratamento farmacológico , Trazodona/efeitos adversos , Trazodona/metabolismo , Trazodona/farmacologia , Trazodona/uso terapêutico
10.
Medicina (Kaunas) ; 55(7)2019 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-31261805

RESUMO

Objectives: The aim of this study was to determine the incidence of metabolic syndrome in patients treated with second-generation antipsychotics (SGAs). Methods: In this retrospective study, we reviewed patients' electronic medical records (EMRs) of all patients who received one SGA for at least six months, excluding patients who were taking other medications that are associated with significant effect on metabolic syndrome. Relevant clinical information was collected prior to starting the SGA and after six months of continuous use of the same SGA. Results: A total of 91 patients were included in the study. The majority of patients (72%) were diagnosed with schizophrenia. After six months of taking the SGA, 44% of patients experienced elevated systolic pressure, 54.9% had elevated triglyceride, and 31.9% had impaired glucose levels (p value < 0.05). Prior to initiating SGA therapy, 14.3% of patients had metabolic syndrome, while 37.4% had metabolic syndrome after six months of therapy, and it was more prominent in males compared to female patients (p value < 0.05). Conclusion: This study found a strong correlation between SGA use and the appearance of metabolic alterations, such as weight gain, glucose intolerance, and increased triglyceride levels. These findings highlight the importance of assessing metabolic deregulations to minimize SGA associated metabolic abnormalities.


Assuntos
Antidepressivos de Segunda Geração/uso terapêutico , Síndrome Metabólica/etiologia , Adulto , Antidepressivos de Segunda Geração/efeitos adversos , Glicemia/análise , Registros Eletrônicos de Saúde/estatística & dados numéricos , Feminino , Humanos , Jordânia/epidemiologia , Masculino , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/fisiopatologia , Pessoa de Meia-Idade , Vigilância da População/métodos , Estudos Retrospectivos , Fatores de Risco , Esquizofrenia/tratamento farmacológico , Triglicerídeos/análise , Triglicerídeos/sangue
11.
PLoS One ; 14(7): e0219137, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31323024

RESUMO

OBJECTIVE: Traumatic brain injury (TBI) is common and associated with a marked increased risk of developing epilepsy. Animal studies indicate that treatment with selective serotonin reuptake inhibitors (SSRIs) may increase the risk of epilepsy after TBI. The aim of this study was to investigate whether use of SSRIs modifies the risk of epilepsy after TBI. METHODS: This was a cohort study of 205,715 persons, who suffered a TBI in Denmark from 1996 to 2013. For each person with TBI, we matched 10 reference persons (N = 2,057,150) who were alive on the day of TBI and who had the same age and gender but had no history of TBI. We used a stratified Cox regression to calculate the relative risk of epilepsy after TBI for persons exposed to TBI, SSRI or both after adjustment for income, civil status, medical and neurological comorbidities, severe mental disease, and substance abuse. RESULTS: The risk of epilepsy was 5.61 times higher for persons who used SSRI at time of TBI (adjusted Hazard Ratio (aHR): 5.61 (95% CI: 4.88; 6.45)), 3.23 times higher for persons who had a TBI but did not use SSRI at time of TBI (aHR: 3.23 (95% CI: 3.12;3.35)), and 1.31 times higher for persons who used SSRI but had no TBI (aHR: 1.31 (95% CI: 1.18; 1.45)) compared to persons unexposed to both TBI and SSRI. CONCLUSIONS: This large population based cohort study showed that people using SSRI at the time of a TBI had higher risk of developing epilepsy compared to people not using SSRI at the time of TBI. The results are in line with those of animal studies and calls for further studies to evaluate whether the association is due to SSRIs or to the underlying disease (e.g. depression or anxiety).


Assuntos
Lesões Encefálicas Traumáticas/complicações , Epilepsia/etiologia , Inibidores de Captação de Serotonina/efeitos adversos , Antidepressivos de Segunda Geração/efeitos adversos , Estudos de Coortes , Dinamarca/epidemiologia , Epilepsia/induzido quimicamente , Epilepsia/epidemiologia , Feminino , Humanos , Masculino , Modelos de Riscos Proporcionais , Sistema de Registros , Fatores de Risco
12.
Drug Metab Rev ; 51(3): 293-313, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31124380

RESUMO

Bupropion is an atypical antidepressant of the aminoketone group, structurally related to cathinone, associated with a wide interindividual variability. An extensive pharmacokinetic and pharmacodynamic review of bupropion was performed, also focusing on chemical, pharmacological, toxicological, clinical and forensic aspects of this drug without a limiting period. Bupropion is a chiral, basic, highly lipophilic drug, clinically used as racemate that undergoes extensive stereoselective metabolism. Its major active metabolites, hydroxybupropion, threohydrobupropion, and erythrohydrobupropion reach higher plasma concentrations than bupropion. Bupropion exerts its effects mainly by inhibiting dopamine and norepinephrine reuptake and by blocking several nicotinic receptors. Recent reports highlight recreational use of bupropion via intranasal insufflation and intravenous use. Seizures, insomnia, agitation, headache, dry mouth, and nausea are some of the reported adverse effects. Neurologic effects are major signs of intoxication that should be carefully managed. Finally, the characterization of the polymorphic enzymes involved in the metabolism of bupropion is essential to understand factors that may influence the interindividual and intraindividual variability in bupropion metabolite exposure, including the evaluation of potential drug-drug interactions and pharmacogenetic implications.


Assuntos
Bupropiona/farmacologia , Bupropiona/farmacocinética , Animais , Antidepressivos de Segunda Geração/efeitos adversos , Antidepressivos de Segunda Geração/química , Antidepressivos de Segunda Geração/farmacocinética , Antidepressivos de Segunda Geração/farmacologia , Bupropiona/efeitos adversos , Bupropiona/química , Toxicologia Forense , Humanos
13.
Pharmacogenomics ; 20(5): 343-351, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30983508

RESUMO

Aim: To examine the impact of CYP2C19 genotype on selective serotonin reuptake inhibitor (SSRI) prescribing patterns. Patients & methods: Observational cohort containing 507 unique individuals receiving an SSRI prescription with CYP2C19 genotype already in their electronic medical record. Genotype was distributed as follows: n = 360 (71%) had no loss of function alleles, 136 (26.8%) had one loss of function allele and 11 (2.2%) had two loss of function alleles. Results & conclusion: For poor metabolizers exposed to sertraline, citalopram or escitalopram, providers changed prescribing patterns in response to alerts in the electronic medical record by either changing the drug, changing the dose or monitoring serial EKGs longitudinally. For intermediate metabolizers exposed to sertraline, citalopram or escitalopram, no alert was needed (mean QTc = 440.338 ms [SD = 31.1273] for CYP2C19*1/*1, mean QTc = 440.371 ms [SD = 29.2706] for CYP2C19*1/*2; p = 0.995).


Assuntos
Citocromo P-450 CYP2C19/genética , Síndrome do QT Longo/induzido quimicamente , Síndrome do QT Longo/genética , Inibidores de Captação de Serotonina/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Antidepressivos de Segunda Geração/efeitos adversos , Antidepressivos de Segunda Geração/metabolismo , Antidepressivos de Segunda Geração/uso terapêutico , Estudos de Coortes , Citocromo P-450 CYP2C19/metabolismo , Feminino , Genótipo , Humanos , Síndrome do QT Longo/metabolismo , Masculino , Pessoa de Meia-Idade , Testes Farmacogenômicos , Padrões de Prática Médica , Inibidores de Captação de Serotonina/metabolismo , Inibidores de Captação de Serotonina/uso terapêutico
14.
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
15.
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
16.
Neonatology ; 115(4): 320-327, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30836356

RESUMO

BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) are antidepressants prescribed in 10% of pregnancies in the USA. We have previously shown in preclinical studies that sertraline exposure impacts cardiomyocyte development, leading to reductions in left ventricular size and cardiac function. OBJECTIVES: We hypothesized that in utero SSRI exposure will lead to reduced left ventricular dimensions and cardiac function on echocardiography immediately after birth. METHODS: Twenty term infants with and 21 term infants without in utero exposure to SSRIs underwent echocardiograms to assess cardiac size and function. The exclusion criteria for infants were prematurity, small or large for gestational age, any respiratory or cardiovascular support needed after birth, and any major congenital malformation. RESULTS: Infants exposed to in utero SSRIs had significantly reduced right ventricular dimensions in the diastole (controls 1.0 cm [0.86, 1.20], SSRI 0.89 cm [0.730, 1.05], p = 0.03), and left ventricular lengths in the diastole and systole (diastole: controls 3.4 cm [3.25, 3.65], SSRI 3.25 cm [3.10, 3.45], p = 0.03; systole: controls 2.9 cm [2.65, 3.05], SSRI 2.6 cm [2.50, 2.85], p = 0.01). No differences were observed in cardiac function. Importantly, there were no differences in maternal conditions or infant birth weight, body surface area, or gestational age. CONCLUSIONS: Our findings suggest an association between in utero exposure to SSRIs and ventricular size in infants. Given the increasing use of SSRIs during pregnancy and the importance of early life programming on future cardiovascular health, larger studies need to be completed to determine if in utero SSRI exposure impacts ventricular size.


Assuntos
Antidepressivos de Segunda Geração/efeitos adversos , Ventrículos do Coração/patologia , Exposição Materna/efeitos adversos , Inibidores de Captação de Serotonina/efeitos adversos , Adulto , Antidepressivos de Segunda Geração/uso terapêutico , Depressão/tratamento farmacológico , Ecocardiografia , Feminino , Idade Gestacional , Ventrículos do Coração/diagnóstico por imagem , Humanos , Recém-Nascido , Iowa , Masculino , Tamanho do Órgão/efeitos dos fármacos , Gravidez , Complicações na Gravidez/tratamento farmacológico , Estudos Prospectivos , Inibidores de Captação de Serotonina/uso terapêutico , Nascimento a Termo , Função Ventricular/efeitos dos fármacos
18.
J Pediatr Surg ; 54(11): 2398-2401, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30867098

RESUMO

PURPOSE: Hirschsprung disease (HSCR) is a multifactorial disease. Maternal intake of selective serotonin reuptake inhibitors (SSRI) during early pregnancy has previously been associated with increased risk for HSCR. The aim of this study was to assess the risk for HSCR in newborns after maternal intake of SSRI in a population-based Swedish cohort. METHODS: This was a Swedish nationwide, population-based, case-control cohort study containing all children born in Sweden between 1/12006 and 31/122012. The cases were identified in the Swedish National Patient Register and the controls (five age- and sex-matched controls per case) were randomly selected among children without HSCR in the cohort. Data on maternal SSRI use during pregnancy were collected from the Swedish Prescribed Drug Register. RESULTS: Out of 775,024 born children during the study period, 150 cases of HSCR (112 males) and 750 controls (560 males) were included. Five (3.3%) mothers of newborns with HSCR had used SSRI during pregnancy compared to 16 (2.1%) mothers of the controls (p = 0.372). The mean age was similar in mothers who had used SSRI compared to those who had not (30.9 (SD +/- 5.1) versus 30.6 (SD +/- 5.0), p = 0.81). CONCLUSIONS: There was no increased risk of HSCR owing to maternal intake of SSRI in this cohort. LEVEL OF EVIDENCE: Level I.


Assuntos
Antidepressivos de Segunda Geração/efeitos adversos , Depressão/tratamento farmacológico , Doença de Hirschsprung/epidemiologia , Complicações na Gravidez/tratamento farmacológico , Inibidores de Captação de Serotonina/efeitos adversos , Adulto , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Doença de Hirschsprung/induzido quimicamente , Humanos , Recém-Nascido , Masculino , Parto , Gravidez , Fatores de Risco , Suécia/epidemiologia
19.
Cerebrovasc Dis ; 47(1-2): 72-79, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30844812

RESUMO

INTRODUCTION: Serotonin affects several brain functions including cognition. The serotonin transporter (SERT) regulates brain serotonin levels through reuptake into neurons. The gene encoding this transporter, the SERT gene, has several functional polymorphisms affecting the number of transporters and thereby the serotonin levels. SERT gene expression may be important for cognition and selective serotonin reuptake inhibitors (SSRI) may improve cognition post stroke. We therefore examined the association between SERT genotypes, cognitive function and early treatment with the SSRI citalopram among non-depressed Caucasian stroke patients. PATIENTS AND METHODS: SERT gene polymorphisms in 270 non-depressed first-ever acute ischemic stroke patients randomized to citalopram, n = 130, or placebo, n = 140, were investigated. Patients were genotyped for a length polymorphism (L = long and S = short allele) and a single nucleotide polymorphism (A/G substitution) dividing the L-allele into LA and LG. According to these genotypes, patients were further grouped according to low (S/S, LG/S and LG/LG), medium (S/LA and LG/LA), or high functional gene expression (LALA). Cognition was measured by the Symbol Digit Modalities Test (SDMT) at 1 and 6 months. Mean SDMT scores according to genotype and randomization groups were compared using multiple logistic regression adjusting for age, stroke severity, premorbid functional status, and vascular risk factors including smoking, hypertension, and diabetes. RESULTS: Stratified by genotype groups, there were no statistically significant differences in SDMT scores between randomization groups. Placebo-treated patients with low SERT expression genotypes, however, tended to have lower mean SDMT scores (at 1 month: 30.2, SD 10.8) compared to citalopram-treated patients (33.6, SD 13.7). Within the placebo group, the low genotype expression patients had significantly lower adjusted mean SDMT scores at 1 month compared to the high genotype expression patients (adjusted mean difference of -6 points, CI -12.0 to -0.05). We found similar results at 6 months, although not statistically significant. The genotype expression was not associated with SDMT scores among citalopram-treated patients. CONCLUSION: There was no difference in cognition between citalopram and placebo-treated patients according to the genotype group. Our results indicate, however, that low expression SERT genotype may contribute to reduced cognitive function post stroke as placebo-treated patients with low SERT expression tended to score lower on the SDMT. The significant difference in SDMT scores between low and high expression patients was present only in the placebo-treated group, thereby warranting further exploration of the potential effect of early citalopram treatment on cognitive functioning. Our results are preliminary and need replication in larger-scale studies.


Assuntos
Antidepressivos de Segunda Geração/uso terapêutico , Citalopram/uso terapêutico , Transtornos Cognitivos/tratamento farmacológico , Cognição/efeitos dos fármacos , Polimorfismo de Nucleotídeo Único , Proteínas da Membrana Plasmática de Transporte de Serotonina/genética , Inibidores de Captação de Serotonina/uso terapêutico , Acidente Vascular Cerebral/complicações , Idoso , Antidepressivos de Segunda Geração/efeitos adversos , Citalopram/efeitos adversos , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/genética , Transtornos Cognitivos/psicologia , Dinamarca , Método Duplo-Cego , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Variantes Farmacogenômicos , Fenótipo , Inibidores de Captação de Serotonina/efeitos adversos , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/psicologia , Fatores de Tempo , Resultado do Tratamento
20.
Cochrane Database Syst Rev ; 3: CD011268, 2019 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-30883669

RESUMO

BACKGROUND: Seasonal affective disorder (SAD) is a seasonal pattern of recurrent major depressive episodes that most commonly occurs during autumn or winter and remits in spring. The prevalence of SAD ranges from 1.5% to 9%, depending on latitude. The predictable seasonal aspect of SAD provides a promising opportunity for prevention. This review - one of four reviews on efficacy and safety of interventions to prevent SAD - focuses on second-generation antidepressants (SGAs). OBJECTIVES: To assess the efficacy and safety of SGAs (in comparison with other SGAs, placebo, light therapy, melatonin or agomelatine, psychological therapies or lifestyle interventions) in preventing SAD and improving patient-centred outcomes among adults with a history of SAD. SEARCH METHODS: We searched Ovid MEDLINE (1950- ), Embase (1974- ), PsycINFO (1967- ) and the Cochrane Central Register of Controlled Trials (CENTRAL) to 19 June 2018. An earlier search of these databases was conducted via the Cochrane Common Mental Disorders Controlled Trial Register (CCMD-CTR) (all years to 11 August 2015). Furthermore, we searched the Cumulative Index to Nursing and Allied Health Literature, Web of Science, the Cochrane Library, the Allied and Complementary Medicine Database and international trial registers (to 19 June 2018). We also conducted a grey literature search and handsearched the reference lists of included studies and pertinent review articles. SELECTION CRITERIA: For efficacy, we included randomised controlled trials (RCTs) on adults with a history of winter-type SAD who were free of symptoms at the beginning of the study. For adverse events, we planned to include non-randomised studies. Eligible studies compared a SGA versus another SGA, placebo, light therapy, psychological therapy, melatonin, agomelatine or lifestyle changes. We also intended to compare SGAs in combination with any of the comparator interventions versus placebo or the same comparator intervention as monotherapy. DATA COLLECTION AND ANALYSIS: Two review authors independently screened abstracts and full-text publications, extracted data and assessed risk of bias of included studies. When data were sufficient, we conducted random-effects (Mantel-Haenszel) meta-analyses. We assessed statistical heterogeneity by calculating the Chi2 statistic and the Cochran Q. We used the I2 statistic to estimate the magnitude of heterogeneity. We assessed publication bias by using funnel plots.We rated the strength of the evidence using the system developed by the GRADE Working Group. MAIN RESULTS: We identified 3745 citations after de-duplication of search results and excluded 3619 records during title and abstract reviews. We assessed 126 full-text papers for inclusion in the review, of which four publications (on three RCTs) providing data from 1100 people met eligibility criteria for this review. All three RCTs had methodological limitations due to high attrition rates.Overall, moderate-quality evidence indicates that bupropion XL is an efficacious intervention for prevention of recurrence of depressive episodes in people with a history of SAD (risk ratio (RR) 0.56, 95% confidence interval (CI) 0.44 to 0.72; 3 RCTs, 1100 participants). However, bupropion XL leads to greater risk of headaches (moderate-quality evidence), insomnia and nausea (both low-quality evidence) when compared with placebo. Numbers needed to treat for additional beneficial outcomes (NNTBs) vary by baseline risks. For a population with a yearly recurrence rate of 30%, the NNTB is 8 (95% CI 6 to 12). For populations with yearly recurrence rates of 50% and 60%, NNTBs are 5 (95% CI 4 to 7) and 4 (95% CI 3 to 6), respectively.We could find no studies on other SGAs and no studies comparing SGAs with other interventions of interest, such as light therapy, psychological therapies, melatonin or agomelatine. AUTHORS' CONCLUSIONS: Available evidence indicates that bupropion XL is an effective intervention for prevention of recurrence of SAD. Nevertheless, even in a high-risk population, three out of four people will not benefit from preventive treatment with bupropion XL and will be at risk for harm. Clinicians need to discuss with patients advantages and disadvantages of preventive SGA treatment, and might want to consider offering other potentially efficacious interventions, which might confer a lower risk of adverse events. Given the lack of comparative evidence, the decision for or against initiating preventive treatment of SAD and the treatment selected should be strongly based on patient preferences.Future researchers need to assess the effectiveness and risk of harms of SGAs other than bupropion for prevention of SAD. Investigators also need to compare benefits and harms of pharmacological and non-pharmacological interventions.


Assuntos
Antidepressivos de Segunda Geração/uso terapêutico , Bupropiona/uso terapêutico , Transtorno Afetivo Sazonal/tratamento farmacológico , Adulto , Antidepressivos de Segunda Geração/efeitos adversos , Bupropiona/efeitos adversos , Diarreia/induzido quimicamente , Cefaleia/induzido quimicamente , Humanos , Incidência , Náusea/induzido quimicamente , Números Necessários para Tratar , Ensaios Clínicos Controlados Aleatórios como Assunto , Recidiva , Transtorno Afetivo Sazonal/epidemiologia , Distúrbios do Início e da Manutenção do Sono/induzido quimicamente
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