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1.
Int J Mol Sci ; 22(15)2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34360852

RESUMO

Fluoxetine is an antidepressant commonly prescribed not only to adults but also to children for the treatment of depression, obsessive-compulsive disorder, and neurodevelopmental disorders. The adverse effects of the long-term treatment reported in some patients, especially in younger individuals, call for a detailed investigation of molecular alterations induced by fluoxetine treatment. Two-year fluoxetine administration to juvenile macaques revealed effects on impulsivity, sleep, social interaction, and peripheral metabolites. Here, we built upon this work by assessing residual effects of fluoxetine administration on the expression of genes and abundance of lipids and polar metabolites in the prelimbic cortex of 10 treated and 11 control macaques representing two monoamine oxidase A (MAOA) genotypes. Analysis of 8871 mRNA transcripts, 3608 lipids, and 1829 polar metabolites revealed substantial alterations of the brain lipid content, including significant abundance changes of 106 lipid features, accompanied by subtle changes in gene expression. Lipid alterations in the drug-treated animals were most evident for polyunsaturated fatty acids (PUFAs). A decrease in PUFAs levels was observed in all quantified lipid classes excluding sphingolipids, which do not usually contain PUFAs, suggesting systemic changes in fatty acid metabolism. Furthermore, the residual effect of the drug on lipid abundances was more pronounced in macaques carrying the MAOA-L genotype, mirroring reported behavioral effects of the treatment. We speculate that a decrease in PUFAs may be associated with adverse effects in depressive patients and could potentially account for the variation in individual response to fluoxetine in young people.


Assuntos
Antidepressivos/efeitos adversos , Comportamento Animal/efeitos dos fármacos , Fluoxetina/efeitos adversos , Metabolismo dos Lipídeos/efeitos dos fármacos , Transtornos Mentais/tratamento farmacológico , Animais , Ácidos Graxos Insaturados/metabolismo , Macaca mulatta , Masculino
2.
J Clin Psychiatry ; 82(3)2021 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-34106530

RESUMO

Stroke is the leading neurologic cause of burden operationalized in terms of disability-adjusted life-years. After stroke, motor deficits, cognitive deficits, and depression cause loss of independence, disability, decreased functioning, and reduced quality of life; these persist into the long term. There are theoretical grounds to consider that, through neuroplasticity and other mechanisms, such impairments can be prevented or attenuated by the early introduction of a selective serotonin reuptake inhibitor such as fluoxetine. However, a recent meta-analysis of 13 randomized controlled trials (RCTs; pooled N = 4,145) found that fluoxetine neither improved independence nor reduced disability; whereas fluoxetine did reduce the risk of poststroke depression, it did not improve other outcomes, such as motor and cognitive outcomes, but, rather, was associated with many adverse outcomes. Two very large RCTs were subsequently published. The findings of these RCTs, in combination with the findings of the meta-analysis, suggest that, if fluoxetine is started within 2 weeks of ischemic or hemorrhagic stroke and is administered in a dose of 20 mg/d for 3-6 months, there is a 3%-4% reduced risk of new onset depression; however, there is no improvement in the likelihood of achieving independence or of reduction of disability. The risk of several adverse outcomes is increased; these include falls (by 2%), bone fractures (by 1%-2%), seizures (by 1%), and hyponatremia (by 1%). Fluoxetine is also associated with the theoretical risk of adverse drug interactions in stroke patients. In summary, there does not appear to be a role for the routine use of fluoxetine in poststroke pharmacologic care.


Assuntos
Depressão/prevenção & controle , Fluoxetina/farmacologia , Avaliação de Resultados em Cuidados de Saúde , Inibidores de Captação de Serotonina/farmacologia , Acidente Vascular Cerebral/tratamento farmacológico , Depressão/etiologia , Fluoxetina/administração & dosagem , Fluoxetina/efeitos adversos , Humanos , Inibidores de Captação de Serotonina/administração & dosagem , Inibidores de Captação de Serotonina/efeitos adversos , Acidente Vascular Cerebral/complicações
3.
BMC Psychiatry ; 21(1): 260, 2021 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-34011310

RESUMO

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


Assuntos
Transtorno Depressivo Maior , Fluoxetina , Cicloexanóis , Transtorno Depressivo Maior/tratamento farmacológico , Método Duplo-Cego , Feminino , Fluoxetina/efeitos adversos , Humanos , Pós-Menopausa , Inibidores de Captação de Serotonina/uso terapêutico , Método Simples-Cego , Resultado do Tratamento , Cloridrato de Venlafaxina/efeitos adversos
5.
Cochrane Database Syst Rev ; 3: CD008591, 2021 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-33661528

RESUMO

BACKGROUND: Seasonal affective disorder (SAD) is a seasonal pattern of recurrent depressive episodes that is often treated with second-generation antidepressants (SGAs), light therapy, or psychotherapy. OBJECTIVES: To assess the efficacy and safety of second-generation antidepressants (SGAs) for the treatment of seasonal affective disorder (SAD) in adults in comparison with placebo, light therapy, other SGAs, or psychotherapy. SEARCH METHODS: This is an update of an earlier review first published in 2011. We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2020, Issue 1) in the Cochrane Library (all years), Ovid MEDLINE, Embase, and PsycINFO (2011 to January 2020), together with the Cochrane Common Mental Disorders Controlled Trials Register (CCMDCTR) (all available years), for reports of randomised controlled trials (RCTs). We hand searched the reference lists of all included studies and other systematic reviews. We searched ClinicalTrials.gov for unpublished/ongoing trials. We ran a separate update search for reports of adverse events in the Ovid databases.  SELECTION CRITERIA: For efficacy we included RCTs of SGAs compared with other SGAs, placebo, light therapy, or psychotherapy in adult participants with SAD. For adverse events we also included non-randomised studies. DATA COLLECTION AND ANALYSIS: Two review authors independently screened abstracts and full-text publications against the inclusion criteria. Data extraction and 'Risk of bias' assessment were conducted individually. We pooled data for meta-analysis where the participant groups were similar, and the studies assessed the same treatments with the same comparator and had similar definitions of outcome measures over a similar duration of treatment. MAIN RESULTS: In this update we identified no new RCT on the effectiveness of SGAs in SAD patients. We included 2 additional single-arm observational studies that reported on adverse events of SGAs.  For efficacy we included three RCTs of between five and eight weeks' duration with a total of 204 participants. For adverse events we included two RCTs and five observational (non-randomised) studies of five to eight weeks' duration with a total of 249 participants. All participants met the DSM (Diagnostic and Statistical Manual of Mental Disorders) criteria for SAD. The average age ranged from 34 to 42 years, and the majority of participants were female (66% to 100%). Results from one trial with 68 participants showed that fluoxetine (20/36) was numerically superior to placebo (11/32) in achieving clinical response; however, the confidence interval (CI) included both a potential benefit as well as no benefit of fluoxetine (risk ratio (RR) 1.62, 95% CI 0.92 to 2.83, very low-certainty evidence). The number of adverse events was similar in both groups (very low-certainty evidence). Two trials involving a total of 136 participants compared fluoxetine versus light therapy. Meta-analysis showed fluoxetine and light therapy to be approximately equal in treating seasonal depression: RR of response 0.98 (95% CI 0.77 to 1.24, low-certainty evidence), RR of remission 0.81 (95% CI 0.39 to 1.71, very low-certainty evidence). The number of adverse events was similar in both groups (low-certainty evidence). We did not identify any eligible study comparing SGA with another SGA or with psychotherapy. Two RCTs and five non-randomised studies reported adverse event data on a total of 249 participants who received bupropion, fluoxetine, escitalopram, duloxetine, nefazodone, reboxetine, light therapy, or placebo. We were only able to obtain crude rates of adverse events, therefore caution is advised regarding interpretation of this information. Between 0% and 100% of participants who received an SGA suffered an adverse event, and between 0% and 25% of participants withdrew from the study due to adverse events. AUTHORS' CONCLUSIONS: Evidence for the effectiveness of SGAs is limited to one small trial of fluoxetine compared with placebo showing a non-significant effect in favour of fluoxetine, and two small trials comparing fluoxetine against light therapy suggesting equivalence between the two interventions. The lack of available evidence precluded us from drawing any overall conclusions on the use of SGAs for SAD. Further, larger RCTs are required to expand and strengthen the evidence base on this topic, and should also include comparisons with psychotherapy and other SGAs. Data on adverse events were sparse, and a comparative analysis was not possible. The data we obtained on adverse events is therefore not robust, and our confidence in the data is limited. Overall, up to 25% of participants treated with SGAs for SAD withdrew from the study early due to adverse events.


Assuntos
Antidepressivos de Segunda Geração/uso terapêutico , Transtorno Afetivo Sazonal/tratamento farmacológico , Adulto , Antidepressivos de Segunda Geração/efeitos adversos , Viés , Citalopram/efeitos adversos , Citalopram/uso terapêutico , Cloridrato de Duloxetina/efeitos adversos , Cloridrato de Duloxetina/uso terapêutico , Feminino , Fluoxetina/efeitos adversos , Fluoxetina/uso terapêutico , Humanos , Masculino , Morfolinas/efeitos adversos , Morfolinas/uso terapêutico , Estudos Observacionais como Assunto , Fototerapia , Placebos/uso terapêutico , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Reboxetina/uso terapêutico , Transtorno Afetivo Sazonal/terapia , Tiofenos/efeitos adversos , Tiofenos/uso terapêutico , Resultado do Tratamento
6.
Proc Biol Sci ; 288(1944): 20202294, 2021 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-33563120

RESUMO

Environmental contamination by pharmaceuticals is global, substantially altering crucial behaviours in animals and impacting on their reproduction and survival. A key question is whether the consequences of these pollutants extend beyond mean behavioural changes, restraining differences in behaviour between individuals. In a controlled, two-year, multigenerational experiment with independent mesocosm populations, we exposed guppies (Poecilia reticulata) to environmentally realistic levels of the ubiquitous pollutant fluoxetine (Prozac). Fish (unexposed: n = 59, low fluoxetine: n = 57, high fluoxetine: n = 58) were repeatedly assayed on four separate occasions for activity and risk-taking behaviour. Fluoxetine homogenized individuals' activity, with individual variation in populations exposed to even low concentrations falling to less than half that in unexposed populations. To understand the proximate mechanism underlying these changes, we tested the relative contribution of variation within and between individuals to the overall decline in individual variation. We found strong evidence that fluoxetine erodes variation in activity between but not within individuals, revealing the hidden consequences of a ubiquitous contaminant on phenotypic variation in fish-likely to impair adaptive potential to environmental change.


Assuntos
Poecilia , Poluentes Químicos da Água , Animais , Comportamento Animal , Poluição Ambiental , Fluoxetina/efeitos adversos , Individualidade , Poluentes Químicos da Água/toxicidade
7.
Psychopharmacology (Berl) ; 238(3): 755-764, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33242109

RESUMO

RATIONALE: Sexual side effects of chronic treatment with selective serotonin reuptake inhibitors (SSRIs) in humans include anorgasmia and loss of sexual desire and/or arousal which interferes with treatment compliance. There are few options at present to reduce these effects. Because orgasm and desire are mediated in part by activation of sympathetic arousal, we asked whether the sympathomimetic effects of acute caffeine treatment could reverse these effects. OBJECTIVE: The present study examined whether acute treatment with caffeine (CAF; 10 or 20 mg/kg, ip) versus vehicle could ameliorate the disruption of appetitive and consummatory measures of copulatory behavior produced by chronic fluoxetine (10 mg/kg, sc) in adult, sexually active female or male rats. METHODS: Sexually experienced female or male rats received daily injections of FLU over a 24-day period and were tested for sexual behaviors five times at 4-day intervals during this period in bilevel pacing chambers. Females had been ovariectomized and given hormone replacement with estradiol benzoate and progesterone prior to each test. Males were left gonadally intact. Four days after the final FLU test, rats were randomly assigned to one of the three doses of CAF and received ip injections of CAF or the saline vehicle 60 min before testing. RESULTS: Chronic FLU reduced solicitations and lordosis over time in females and reduced the number of ejaculations in males. Both doses of CAF restored solicitations and lordosis in females and ejaculations in males. On their own, both doses of CAF increased females' pacing behavior and the number of mounts and intromissions in the males. CONCLUSIONS: Stimulation of sympathetic outflow by CAF may constitute a readily accessible on-demand treatment for the sexual side-effects of SSRIs.


Assuntos
Cafeína/farmacologia , Fluoxetina/efeitos adversos , Libido/efeitos dos fármacos , Inibidores de Captação de Serotonina/efeitos adversos , Comportamento Sexual Animal/efeitos dos fármacos , Animais , Copulação/efeitos dos fármacos , Ejaculação/efeitos dos fármacos , Estradiol/análogos & derivados , Estradiol/farmacologia , Feminino , Masculino , Progesterona/farmacologia , Ratos , Ratos Long-Evans
8.
Int J Psychiatry Med ; 56(1): 3-13, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32216496

RESUMO

OBJECTIVE: The antidepressant medication fluoxetine at 90 mg dosed weekly is as effective and safe as standard formulation fluoxetine 20 mg dosed daily in patients with major depressive disorder. Weekly fluoxetine has not been well studied in hemodialysis patients, and doses beyond 90 mg/week have not been described in this population. This case series, derived from a larger study on depression in hemodialysis patients, describes the use of weekly fluoxetine at dosages beyond 90 mg/week. METHOD: Hemodialysis patients with depressive symptom severity scored ≥10 on the 9-item Patient Health Questionnaire and major depressive disorder confirmed with Mini International Neuropsychiatric Interview were initially prescribed daily fluoxetine for two weeks and then transitioned to weekly fluoxetine. Dosage titration was made at the discretion of the prescribing clinician. Fluoxetine was continued for a total of 12 weeks. RESULTS: Four women, aged 24 to 65 years, on hemodialysis for 1 to 18 years, were started on weekly fluoxetine that was increased over several weeks up to 180 mg. Side effects included restlessness, dry mouth, sedation, and lightheadedness. Two patients ultimately had their weekly fluoxetine decreased back to 90 mg. However, all four continued weekly fluoxetine as part of poststudy aftercare and no longer met diagnostic criteria for major depressive disorder, current episode. CONCLUSIONS: Weekly fluoxetine at doses of 180 mg may be a reasonable treatment consideration for hemodialysis patients who have partial or insufficient antidepressant response. Side effects may limit tolerance of the 180 mg dose in some individuals. Future research should investigate longer term health outcomes of weekly fluoxetine in this population.


Assuntos
Transtorno Depressivo Maior , Fluoxetina , Antidepressivos/uso terapêutico , Transtorno Depressivo Maior/tratamento farmacológico , Feminino , Fluoxetina/efeitos adversos , Humanos , Escalas de Graduação Psiquiátrica , Diálise Renal , Inibidores de Captação de Serotonina/uso terapêutico , Resultado do Tratamento
9.
Fertil Steril ; 114(6): 1278-1287, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33066974

RESUMO

OBJECTIVE: To prospectively investigate the association of selective serotonin reuptake inhibitor (SSRI) exposure through critical windows of pregnancy establishment with fecundability and pregnancy loss. DESIGN: Prospective cohort study using longitudinal urine measurements of common SSRIs while women are actively trying to conceive. SETTING: Four clinical sites. PATIENT(S): A total of 1,228 women without uncontrolled depression/anxiety, attempting natural conception while participating in a randomized trial of preconception-initiated low-dose aspirin. INTERVENTIONS(S): Not applicable. MAIN OUTCOME MEASURE(S): Urinary SSRIs (fluoxetine, sertraline, escitalopram/citalopram) were measured while trying to conceive and, for women who became pregnant, at weeks 0, 4, and 8 of pregnancy. Fecundability odds ratios and incidence of pregnancy loss and live birth were estimated. RESULT(S): A total of 172 women (14%) were exposed to SSRIs while trying to conceive. SSRI exposure was associated with 24% reduced fecundability, and accordingly, a nonsignificant 9% lower live birth incidence, with significantly lower live birth in fluoxetine-exposed women. SSRI exposure was not associated with subsequent pregnancy loss, whether exposure was before conception or at 0, 4, or 8 weeks of gestation, although estimates varied by specific SSRI drug. CONCLUSION(S): Women using SSRIs may have more difficulty becoming pregnant, and although SSRI exposure overall was not associated with pregnancy loss, fluoxetine deserves caution and future study. CLINICAL TRIAL REGISTRATION NUMBER: NCT00467363.


Assuntos
Aborto Espontâneo/induzido quimicamente , Fertilidade/efeitos dos fármacos , Inibidores de Captação de Serotonina/efeitos adversos , Inibidores de Captação de Serotonina/urina , Aborto Espontâneo/diagnóstico , Aborto Espontâneo/urina , Adulto , Citalopram/urina , Feminino , Fluoxetina/efeitos adversos , Fluoxetina/urina , Humanos , Nascido Vivo , Gravidez , Primeiro Trimestre da Gravidez/urina , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , Fatores de Risco , Sertralina/efeitos adversos , Sertralina/urina , Fatores de Tempo , Estados Unidos , Adulto Jovem
10.
Psychopharmacology (Berl) ; 237(9): 2589-2600, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32676774

RESUMO

RATIONALE: Many depressed women continue antidepressant treatment during pregnancy. Selective serotonin reuptake inhibitor (SSRI) treatment during pregnancy increases the risk for abnormal social development of the child, including increased aggressive or defiant behavior, with unknown effects on sexual behavior. OBJECTIVES: Our aim was to investigate the effects of perinatal SSRI treatment and maternal depression, both separately and combined, on aggressive and sexual behavior in male rat offspring. METHODS: Heterozygous serotonin transporter (SERT± ) knockout dams exposed to early life stress (ELSD) were used as an animal model of maternal depression. Early life stress consisted of separating litters from their mother for 6 h a day on postnatal day (PND)2-15, resulting in a depressive-like phenotype in adulthood. Depressive-like dams were treated with fluoxetine (FLX, 10 mg/kg) or vehicle throughout pregnancy and lactation (gestational day 1 until PND 21). Male offspring were tested for aggressive and sexual behavior in adulthood. As lifelong reductions in SERT expression are known to alter behavioral outcome, offspring with normal (SERT+/+) and reduced (SERT± ) SERT expression were assessed. RESULTS: Perinatal FLX treatment reduced offensive behavior and the number of animals attacking and increased the latency to attack, especially in SERT+/+ offspring. Perinatal FLX treatment reduced the mounting frequency in SERT+/+ offspring. ELSD increased offensive behavior, without affecting sexual behavior in SERT± offspring. CONCLUSIONS: Overall, our research demonstrates that perinatal FLX treatment and ELSD have opposite effects on aggressive behavior, with little impact on sexual behavior of male offspring.


Assuntos
Agressão/efeitos dos fármacos , Agressão/psicologia , Fluoxetina/farmacologia , Efeitos Tardios da Exposição Pré-Natal/psicologia , Comportamento Sexual Animal/efeitos dos fármacos , Estresse Psicológico/psicologia , Animais , Antidepressivos/efeitos adversos , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Feminino , Fluoxetina/efeitos adversos , Fluoxetina/uso terapêutico , Masculino , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Ratos , Ratos Wistar , Inibidores de Captação de Serotonina/efeitos adversos , Inibidores de Captação de Serotonina/farmacologia , Comportamento Sexual Animal/fisiologia , Estresse Psicológico/tratamento farmacológico
11.
Pharm Res ; 37(7): 131, 2020 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-32557079

RESUMO

BACKGROUND AND OBJECTIVE: Fluoxetine, antidepressant widely-used during pregnancy, is a selective inhibitor for P-glycoprotein (P-gp). Fexofenadine, an in vivo P-gp probe, is an antihistamine drug for seasonal allergic rhinitis and chronic urticaria treatment during pregnancy and it is available as a racemic mixture. This study evaluated the chiral discrimination of P-gp investigating the effect of fluoxetine on maternal-fetal pharmacokinetics of fexofenadine. METHODS: Healthy parturient women received either a single oral dose of 60 mg racemic fexofenadine (Control group; n = 8) or a single oral dose of 40 mg racemic fluoxetine 3 h before a single oral dose of 60 mg racemic fexofenadine (Interaction group; n = 8). Maternal blood and urine samples were collected up to 48 h after fexofenadine administration. At delivery, maternal-placental-fetal blood samples were collected. RESULTS: The maternal pharmacokinetics of fexofenadine was enantioselective (AUC0-∞R-(+)/S-(-) ~ 1.5) in both control and interaction groups. Fluoxetine increased AUC0-∞ (267.7 vs 376.1 ng.h/mL) and decreased oral total clearance (105.1 vs 74.4 L/h) only of S-(-)-fexofenadine, whereas the renal clearance were reduced for both enantiomers, suggesting that the intestinal P-gp-mediated transport of S-(-)-fexofenadine is influenced by fluoxetine to a greater extent that the R-(+)-fexofenadine. However, the transplacental transfer of fexofenadine is low (~16%), non-enantioselective and non-influenced by fluoxetine. CONCLUSIONS: A single oral dose of 40 mg fluoxetine inhibited the intestinal P-gp mediated transport of S-(-)-fexofenadine to a greater extent than R-(+)-fexofenadine in parturient women. However, the placental P-gp did not discriminate fexofenadine enantiomers and was not inhibited by fluoxetine.


Assuntos
Antidepressivos de Segunda Geração/administração & dosagem , Fluoxetina/administração & dosagem , Antagonistas não Sedativos dos Receptores H1 da Histamina/farmacocinética , Absorção Intestinal/efeitos dos fármacos , Mucosa Intestinal/efeitos dos fármacos , Parto , Terfenadina/análogos & derivados , Subfamília B de Transportador de Cassetes de Ligação de ATP/antagonistas & inibidores , Subfamília B de Transportador de Cassetes de Ligação de ATP/metabolismo , Adulto , Antidepressivos de Segunda Geração/efeitos adversos , Estudos de Casos e Controles , Interações Medicamentosas , Feminino , Sangue Fetal/metabolismo , Fluoxetina/efeitos adversos , Antagonistas não Sedativos dos Receptores H1 da Histamina/administração & dosagem , Antagonistas não Sedativos dos Receptores H1 da Histamina/sangue , Humanos , Mucosa Intestinal/metabolismo , Troca Materno-Fetal , Circulação Placentária , Gravidez , Terfenadina/administração & dosagem , Terfenadina/sangue , Terfenadina/farmacocinética , Adulto Jovem
12.
Actas Esp Psiquiatr ; 48(2): 47-53, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32463910

RESUMO

INTRODUCTION: currently the treatment of mental illness by antidepressants is very frequent. Selective serotonin reuptake 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
Depressão/tratamento farmacológico , Fluoxetina/uso terapêutico , Reflexo Pupilar/efeitos dos fármacos , Inibidores de Captação de Serotonina/uso terapêutico , Acomodação Ocular , Adulto , Feminino , Fluoxetina/efeitos adversos , Humanos , Masculino , Inibidores de Captação de Serotonina/efeitos adversos , Espanha
14.
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
17.
Brain Res ; 1727: 146282, 2020 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-31170382

RESUMO

Perinatal antidepressant drug exposure increases risk for autism spectrum disorder, yet the molecular and neurobehavioral effects of maternal antidepressant drug use on offspring remain poorly understood. In this study, we administered the selective serotonin reuptake inhibitor (SSRI) fluoxetine non-invasively to female mice throughout gestation and early lactation, and then examined social interaction behaviors in offspring. In addition, we measured whole brain gene expression levels of monoamine oxidase A (MAOA), the primary metabolizing enzyme for serotonin. We found deficits in sociability and social novelty-seeking behavior in the juvenile offspring of SSRI-treated mice, and these behaviors persisted into young adulthood. Furthermore, we found decreased MAOA expression in the brains of offspring of SSRI-treated mice. Our findings suggest that exposure to antidepressants during the prenatal and early postnatal period may negatively affect social development. Moreover, reduced MAOA expression may play a role in the mechanistic pathway linking SSRI exposure and behavioral deficits symptomatic of autism.


Assuntos
Antidepressivos/efeitos adversos , Encéfalo/enzimologia , Comportamento Exploratório/efeitos dos fármacos , Fluoxetina/efeitos adversos , Expressão Gênica/efeitos dos fármacos , Exposição Materna , Monoaminoxidase/genética , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Inibidores de Captação de Serotonina/efeitos adversos , Animais , Transtorno do Espectro Autista/induzido quimicamente , Comportamento Animal/efeitos dos fármacos , Feminino , Camundongos , Gravidez , Comportamento Social
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