Generalized anxiety disorder (GAD) is associated with painful physical symptoms (PPS). These post hoc analyses of previous trial data assessed PPS and their response to duloxetine treatment in GAD patients. Studies 1 and 2 (n = 840) were 9- to 10-week efficacy trials; study 3 (n = 887) was a relapse prevention trial comprising a 26-week open-label treatment phase and a 26-week double-blind, placebo-controlled treatment continuation phase. Mean baseline visual analog scale scores (VAS, 0–100; n = 1727) ranged from 26 to 37 for overall pain, headache, back pain, shoulder pain, interference with daily activities, and time in pain while awake. In studies 1 and 2, improvement on all VAS scores was greater in duloxetine-treated than in placebo-treated patients (p ≤ 0.01). In study 3, pain symptoms worsened in responders switched to placebo compared with those maintained on duloxetine (p ≤ 0.02). In conclusion, duloxetine was efficacious in the short- and long-term treatment of PPS, which are common in GAD patients.

The objective was to examine duloxetine 60–120mg/day treatment for relapse prevention in adults with generalized anxiety disorder (GAD). Adult patients (N=887; mean age=43.3 years; 61.0% female) with DSM-IV-TR-defined GAD diagnosis were treated with duloxetine for 26 weeks. Patients who completed open-label phase and were treatment responders (≥50% reduction in Hamilton Anxiety Rating Scale total score to ≤11 and “much”/“very much improved” ratings for the last 2 visits of open-label phase) were randomly assigned to receive duloxetine or placebo for a 26-week double-blind continuation phase. Relapse was defined as ≥2-point increase in illness severity ratings or by discontinuation due to lack of efficacy. During the double-blind phase, placebo-treated patients (N=201) relapsed more frequently (41.8%) than duloxetine-treated patients (13.7%, N=204, P≤0.001) and worsened on each outcome measure (P≤0.001, all comparisons). Duloxetine 60–120 mg/day treatment was efficacious and reduced risk of relapse in patients with GAD.

Depression and post-traumatic stress disorder are common psychiatric comorbidities related to stress. These conditions are frequently treated with antidepressants such as selective serotonin reuptake inhibitors (SSRI’s). However, there are individual differences in susceptibility to stress-induced psychopathologies and response to antidepressants. Therefore, there is a need to identify biologic factors that predict vulnerability to stress and response to treatment. Furthermore, few studies have examined the neural correlates of antidepressant treatment response in a stress-susceptible animal model. This dissertation had three specific aims: 1) to characterize behavioral predictors of stress vulnerability by studying three dimensions of temperament (reward dependence, novelty-specific activity and harm avoidance) before stress exposure using a stress-susceptible rat strain, 2) to identify the neural network effects of response and non-response to SSRI treatment using a stress-susceptible animal model, and 3) to determine the neurophysiologic correlates of helplessness susceptibility. This was examined via measurement of regional brain metabolic capacity and functional connectivity within relevant neural circuits, and measurements of corticosterone and heart rate. These effects were studied in rats that underwent inescapable shock exposure followed by escape testing. Holtzman rats showed greater predisposition to helpless behavior following inescapable shock compared to Sprague Dawley and Long-Evans strains. Also, increased activity in a novel environment and low heart rate appeared to be markers of helplessness susceptibility in Holtzman rats. Limbic-cortical network effects were identified that distinguished between responders and non-responders to antidepressant treatment in the Holtzman strain. Finally, hypermetabolism of the lateral habenula and a less interactive prefrontal-limbic cortex were identified in subjects with higher susceptibility towards helplessness within the Holtzman strain. Similar findings have been reported with other depression animal models and human neuroimaging studies. These findings support that the helpless dimension of mood disorders can be accurately modeled with the Holtzman rat strain and confirm that the lateral habenula and prefrontal cortex are key regions mediating the helpless phenotype and response to SSRI treatment. / text

O uso de fármacos durante a lactação é uma prática comum; porém, os tratamentos farmacológicos impõem grandes dúvidas tanto aos profissionais quanto às nutrizes sobre a segurança do uso destes durante este período. A amamentação é uma forma de vínculo entre mãe e bebê e está associada a diversos benefícios nutricionais, imunológicos, cognitivos, psicoafetivos, econômicos e sociais. A depressão é um problema clínico importante durante o período pós-parto, e a vulnerabilidade para o início ou recorrência de sintomas depressivos aumenta a possibilidade de uso de psicofármacos enquanto ocorre a lactação. Os antidepressivos inibidores seletivos da recaptação da serotonina são comumente prescritos para o tratamento destes quadros depressivos, entre eles fluoxetina, sertralina, citalopram e paroxetina, sendo que a maioria destes é excretada no leite materno e há grande variabilidade na quantidade de analitos que pode ser recebida pelo lactente. Bupropiona é um fármaco antidepressivo utilizado para o tratamento do tabagismo e quadros depressivos e tem sua excreção ao leite materno relatada em literatura. Métodos bioanalíticos para determinação da excreção de fármacos antidepressivos foram desenvolvidos e validados por cromatografia líquida acoplada a espectrômetro de massas e cromatografia líquida com detecção ultravioleta. Estes métodos demonstraram serem seletivos, lineares, precisos e exatos, com limites de quantificação de 5 ng/mL (fluoxetina, citalopram e bupropiona) e 20 ng/mL (sertralina e paroxetina) para método por LC-MS e de 200 ng/mL para todos os analitos no método por CLAE-UV. As amostras de leite materno foram coletadas em Banco de Leite de mães que declararam utilizar fluoxetina ou sertralina ou paroxetina e analisados. Os dados de concentração encontrados para os fármacos referidos estão dentro da faixa encontrada em literatura confirmando sua excreção no leite materno. Paroxetina apresentou valores abaixo do limite de quantificação. Das concentrações encontradas no leite materno, foram estimadas as doses absolutas e relativas no lactante, sendo que os resultados demonstraram baixos valores em relação a estas estimativas, podendo os fármacos analisados ser considerados seguros para manutenção do uso durante a lactação. Foi também detectada nas análises por LC-MS a presença de norfluoxetina, metabólito da fluoxetina, confirmando sua excreção nesta matriz. / The use of medications during lactation is a common practice; however pharmacological treatments impose serious doubts to both, professionals and nursing mothers, about the safety of drugs use during this period. Breastfeeding is a natural form of bonding between mother and baby and it is associated with many nutritional, immunological, cognitive, psychoemotional, social and economic benefits. Depression is a major clinical problem during the postpartum period and the vulnerability to onset or recurrence of depressive symptoms increases the possibility of psychotropic drug use during lactation. Selective inhibitors of serotonin reuptake are commonly prescribed for the treatment of depressive disorders, including fluoxetine, sertraline, citalopram and paroxetine. Most of these drugs are excreted in breast milk and there is great variability in the amount of analytes that can be received by the infant. Bupropion is an antidepressant used for tabagism treatment and for depression symptoms; it is also described in literature its excretion into breast milk. Bioanalytical methods for determining the excretion of antidepressants were developed and validated by liquid chromatography coupled to mass spectrometry and liquid chromatography with ultraviolet detection. These methods proved to be selective, linear, precise and accurate with quantification limits of 5 ng/mL (fluoxetine, citalopram e bupropion) and 20 ng/mL (sertraline e paroxetine) for LC-MS method and 200 ng/mL for all analytes in the CLAE-UV method. Human milk samples were collected in milk banks from mothers to which the antidepressants fluoxetine or sertraline or paroxetine were administered, and the concentrations in this matrix were verified. Found concentrations were within the range described in the literature confirming their excretion in the breast milk. Paroxetine presented values less than limit of quantification. From the found concentrations, the absolute and relative doses in nursing were estimated. The results showed low values for these estimates and so the analyzed drugs can be considered safe to continue use during lactation. The presence of norfluoxetine, a metabolite of fluoxetine, was also detected by LC-MS, confirming its excretion in this matrix.

O uso de fármacos durante a lactação é uma prática comum; porém, os tratamentos farmacológicos impõem grandes dúvidas tanto aos profissionais quanto às nutrizes sobre a segurança do uso destes durante este período. A amamentação é uma forma de vínculo entre mãe e bebê e está associada a diversos benefícios nutricionais, imunológicos, cognitivos, psicoafetivos, econômicos e sociais. A depressão é um problema clínico importante durante o período pós-parto, e a vulnerabilidade para o início ou recorrência de sintomas depressivos aumenta a possibilidade de uso de psicofármacos enquanto ocorre a lactação. Os antidepressivos inibidores seletivos da recaptação da serotonina são comumente prescritos para o tratamento destes quadros depressivos, entre eles fluoxetina, sertralina, citalopram e paroxetina, sendo que a maioria destes é excretada no leite materno e há grande variabilidade na quantidade de analitos que pode ser recebida pelo lactente. Bupropiona é um fármaco antidepressivo utilizado para o tratamento do tabagismo e quadros depressivos e tem sua excreção ao leite materno relatada em literatura. Métodos bioanalíticos para determinação da excreção de fármacos antidepressivos foram desenvolvidos e validados por cromatografia líquida acoplada a espectrômetro de massas e cromatografia líquida com detecção ultravioleta. Estes métodos demonstraram serem seletivos, lineares, precisos e exatos, com limites de quantificação de 5 ng/mL (fluoxetina, citalopram e bupropiona) e 20 ng/mL (sertralina e paroxetina) para método por LC-MS e de 200 ng/mL para todos os analitos no método por CLAE-UV. As amostras de leite materno foram coletadas em Banco de Leite de mães que declararam utilizar fluoxetina ou sertralina ou paroxetina e analisados. Os dados de concentração encontrados para os fármacos referidos estão dentro da faixa encontrada em literatura confirmando sua excreção no leite materno. Paroxetina apresentou valores abaixo do limite de quantificação. Das concentrações encontradas no leite materno, foram estimadas as doses absolutas e relativas no lactante, sendo que os resultados demonstraram baixos valores em relação a estas estimativas, podendo os fármacos analisados ser considerados seguros para manutenção do uso durante a lactação. Foi também detectada nas análises por LC-MS a presença de norfluoxetina, metabólito da fluoxetina, confirmando sua excreção nesta matriz. / The use of medications during lactation is a common practice; however pharmacological treatments impose serious doubts to both, professionals and nursing mothers, about the safety of drugs use during this period. Breastfeeding is a natural form of bonding between mother and baby and it is associated with many nutritional, immunological, cognitive, psychoemotional, social and economic benefits. Depression is a major clinical problem during the postpartum period and the vulnerability to onset or recurrence of depressive symptoms increases the possibility of psychotropic drug use during lactation. Selective inhibitors of serotonin reuptake are commonly prescribed for the treatment of depressive disorders, including fluoxetine, sertraline, citalopram and paroxetine. Most of these drugs are excreted in breast milk and there is great variability in the amount of analytes that can be received by the infant. Bupropion is an antidepressant used for tabagism treatment and for depression symptoms; it is also described in literature its excretion into breast milk. Bioanalytical methods for determining the excretion of antidepressants were developed and validated by liquid chromatography coupled to mass spectrometry and liquid chromatography with ultraviolet detection. These methods proved to be selective, linear, precise and accurate with quantification limits of 5 ng/mL (fluoxetine, citalopram e bupropion) and 20 ng/mL (sertraline e paroxetine) for LC-MS method and 200 ng/mL for all analytes in the CLAE-UV method. Human milk samples were collected in milk banks from mothers to which the antidepressants fluoxetine or sertraline or paroxetine were administered, and the concentrations in this matrix were verified. Found concentrations were within the range described in the literature confirming their excretion in the breast milk. Paroxetine presented values less than limit of quantification. From the found concentrations, the absolute and relative doses in nursing were estimated. The results showed low values for these estimates and so the analyzed drugs can be considered safe to continue use during lactation. The presence of norfluoxetine, a metabolite of fluoxetine, was also detected by LC-MS, confirming its excretion in this matrix.

Parkinson`s Disease is the second most common motor disorder and is also considered a progressive multisystemic disease associated to several nom motor symptoms (NMS), such as depression, with a prevalence of about 50% among PD patients. Selective serotonin reuptake inhibitors (SSIR) are the main treatment for this NMS, although researches with acutely induced parkinsonism has related fluoxetine to increased motor impairment. The aim of the present research is to evaluate the effect of the fluoxetine hydrochloride on a model of parkinsonism induced by low doses of reserpine. Sixty-four male 7-9-month-old Wistar rats were used, and were obtained from vivarium of the Department of Physiology – Federal University of Sergipe. Animals were divided into four groups: fluoxetine vehicle + reserpine vehicle (CTR); fluoxetine 10 mg/kg + reserpine vehicle (F); fluoxetine 10 mg/kg + reserpine 0,1 mg/kg (F + R); and fluoxetine vehicle + reserpine 0,1 mg/kg (R). During the treatment, the animals were submitted to open field test, catalepsy test and tremoulous jaw movement evaluation. It was shown that animals treated with fluoxetine and reserpine spent more time at the catalepsy test, decreased distance travelled, lower number of rearing at the open field test, increased tremulous jaw movements and increased weight loss. The treatment only with fluoxetine caused immunohistochemistry changes, such as decrease of TH expression in the dorsal striatum and increased staining of the dorsal raphe nucleus, with no correlation with MS for this group. The F + R group showed different immunohistochemistry results for both acute and continued administrations. / A Doença de Parkinson (DP) é a segunda desordem motora mais comum e também é considerada uma doença progressiva multissistêmica ligada a vários sintomas não motores (SNM), como a depressão, que acomete cerca de 50% dos pacientes. Os inibidores seletivos da recaptação de serotonina (ISRS) são considerados os principais medicamentos para o tratamento desse SNM, embora pesquisas que utilizaram indução aguda de parkinsonismo tenham relacionado a fluoxetina ao agravamento dos sintomas motores. Diante disso, este estudo objetivou avaliar o efeito da administração de cloridrato de fluoxetina em um modelo de parkinsonismo induzido por baixas doses de reserpina. Foram utilizados 64 ratos Wistar, machos, com idade de 7 a 9 meses, provenientes do Biotério Setorial do Departamento de Fisiologia da Universidade Federal de Sergipe. Os animais foram divididos aleatoriamente em quatro grupos: veículo fluoxetina + veículo reserpina (CTR); fluoxetina 10 mg/kg + veículo reserpina (F); fluoxetina 10 mg/kg + reserpina 0,1 mg/kg (F + R); e veículo fluoxetina + reserpina 0,1 mg/kg (R). Durante o tratamento, os animais foram submetidos aos testes de campo aberto, catalepsia e avaliação dos movimentos orofaciais. Foi observado aumento da latência na barra, diminuição da distância total percorrida em campo aberto, diminuição do número de rearing, aumento dos movimentos involuntários de mandíbula e maior alteração de peso corporal dos animais do grupo F + R. O tratamento apenas com fluoxetina provocou alterações imunohistoquímicas, como a diminuição da expressão de TH no estriado dorsal e aumento da marcação para 5-HT no núcleo dorsal da rafe, sem correlação com nenhum sintoma motor para esse grupo. O grupo F + R apresentou resultados de imunorreatividade distintos para as administrações breve e continuada. / São Cristóvão, SE

Generalized anxiety disorder (GAD) is associated with painful physical symptoms (PPS). These post hoc analyses of previous trial data assessed PPS and their response to duloxetine treatment in GAD patients. Studies 1 and 2 (n = 840) were 9- to 10-week efficacy trials; study 3 (n = 887) was a relapse prevention trial comprising a 26-week open-label treatment phase and a 26-week double-blind, placebo-controlled treatment continuation phase. Mean baseline visual analog scale scores (VAS, 0–100; n = 1727) ranged from 26 to 37 for overall pain, headache, back pain, shoulder pain, interference with daily activities, and time in pain while awake. In studies 1 and 2, improvement on all VAS scores was greater in duloxetine-treated than in placebo-treated patients (p ≤ 0.01). In study 3, pain symptoms worsened in responders switched to placebo compared with those maintained on duloxetine (p ≤ 0.02). In conclusion, duloxetine was efficacious in the short- and long-term treatment of PPS, which are common in GAD patients.

Background and purpose . This pilot study examined SSRI's in association with partial body weight treadmill training (PBWTT) to improve locomotion post stroke. Serotonin is thought to play a role in recovery of motor function such as locomotion on a treadmill eliciting the central pattern generators (CPG's) identified from animal models. There would be benefits in knowing if serotonin combined with PBWTT influenced motor recovery. The purpose of the study was to determine if patients undergoing treatment with an SSRI would improve in locomotor function to a greater degree than patients not receiving an SSRI. Subjects and methods . Non clinically depressed post stroke patients (N = 4) and clinically depressed post stroke patients on SSRI's (N = 4) were assigned to two groups of convenience. Initial baseline performance was established at two evaluation points using functional gait tests, balance tests, and electomyographical analysis during performance of locomotion over an eight week period (Pre 1 & Pre 2). Intervention of PBWTT was introduced for eight weeks and subjects were evaluated again (Post 1). Subjects returned four weeks later for a follow up evaluation (Post 2). The intervention included training three days a week for eight weeks utilizing PBWTT. Data was analyzed using non parametric statistics. Results . All subjects improved in gait velocity, distance covered and assistance needs as it relates to the PBWTT. Functional gait, balance and gait characteristic improved in both groups with significant differences noted in the “timed up and go test” and Tinetti Assessment in the group undergoing treatment with SSRI's. Weight bearing squat scores improved in both groups with a greater significance at 0 and 30 degrees of knee flexion in the subjects under the influence of SSRI's. The limits of stability scores (LOS) and sensory organization test (SOT) improved in both groups without significant differences. Electromyographical data supported visual observations for improvement of gait deviations and improved on-off timing during the gait cycle in both groups. Conclusion . This study would indicate comparing SSRI therapy and specific functional movement learning for further study.

Previous findings in healthy humans suggest that selective serotonin reuptake inhibitors (SSRIs) modulate emotional processing via earlier changes in attention. However, many previous studies have provided inconsistent findings. One possible reason for such inconsistencies is that these studies did not control for the influence of either sex or sex hormone fluctuations. To address this inconsistency, we administered 20 mg escitalopram or placebo for seven consecutive days in a randomized, double-blind, placebocontrolled design to sixty healthy female participants with a minimum of 3 months oral contraceptive (OC) intake. Participants performed a modified version of an emotional flanker task before drug administration, after a single dose, after 1 week of SSRI intake, and after a 1-month wash-out period. Supported by Bayesian analyses, our results do not suggest a modulatory effect of escitalopram on behavioral measures of early attentional-emotional interaction in female individuals with regular OC use. While the specific conditions of our task may be a contributing factor, it is also possible that a practice effect in a healthy sample may mask the effects of escitalopram on the attentional-emotional interplay. Consequently, 1 week of escitalopram administration may not modulate attention toward negative emotional distractors outside the focus of attention in healthy female participants taking OCs. While further research in naturally cycling females and patient samples is needed, our results represent a valuable contribution toward the preclinical investigation of antidepressant treatment.

Pediatric anxiety disorders characterized as Generalized, Separation, and Social Anxiety Disorders, are chronic debilitating conditions that leave children feeling tense and isolated, both physically and emotionally. Selective serotonin reuptake inhibitors (SSRIs) are a classification of antidepressants that can be prescribed to children diagnosed with these disorders. SSRIs have been shown to be effective in treating anxiety disorders in children. The purpose of this literature review was to examine and determine if there are more risks or benefits associated with SSRIs, as well as evaluate teaching and education regarding anxiety disorder medication compliance in both children and parents. A secondary purpose of this research was to provide recommendations in nursing practice to allow children to feel more involved in their medical regimen. The following databases were used for the search: CINAHL, Academic Search Premier, and Web of Science. Key terms used in the search include but are not limited to: child* and anxiety, not autism, and selective serotonin reuptake inhibitors, OR SSRI*, OR adolsecen*, not med*, pediatric*, OR side effects. The results suggest that the benefits of SSRI therapy in children with anxiety disorder, when taken on a regularly scheduled basis, outweigh the risks, however more research aimed at compliance with SSRI therapy in children and parents is necessary. Further research analyzing children with anxiety disorders is needed to assess SSRI usage based specifically on their developmental age, and the inclusion of appropriate teaching and explanation related to their diagnoses to identifying stressors that can include behavioral therapy as well.