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1.
J Coll Physicians Surg Pak ; 34(9): 1061-1065, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39262006

RESUMO

OBJECTIVE: To compare oral pregabalin with oral sertraline for treatment of uraemic pruritus. STUDY DESIGN: Randomised controlled trial. Place and Duration of the Study: Department of Nephrology, Pak Emirates Military Hospital Rawalpindi, Pakistan, from October 2023 to January 2024. METHODOLOGY: Patients with end-stage renal disease having pruritus for at least 6 weeks were included. Exclusion criteria comprised other dermatological or systemic diseases associated with pruritus, mental health issues, thrice-a-week haemodialysis schedule, and use of other treatments for uraemic pruritus. They were randomised to receive either pregabalin 75mg daily or sertraline 50mg daily for six weeks using computer-generated sequences. The Urdu version of the 5-D Itch scale was used to document the severity of pruritus at the baseline and at the end of therapy. Side effects to the treatment were also monitored. RESULTS: There were 8 (16.67%) females and 40 (83.33%) males, with a mean age of 52.19 ± 12.19 years. The baseline 5-D Itch scale scores were equal in both groups. Mean improvement in 5-D Itch scale scores was 3.75 ± 1.26 and 2.08 ± 1.18 with pregabalin and sertraline, respectively (p <0.001). Side effects were reported by 2 (8.33%) patients on pregabalin and none using sertraline (p = 0.489). CONCLUSION: Pregabalin was found to be more effective than sertraline in treating uraemic pruritus, though with a statistically insignificant trend towards a higher frequency of side effects. KEY WORDS: Chronic renal failure, Pruritus, Renal dialysis, Selective serotonin reuptake inhibitors, Uraemia.


Assuntos
Falência Renal Crônica , Pregabalina , Prurido , Diálise Renal , Sertralina , Uremia , Humanos , Sertralina/uso terapêutico , Sertralina/administração & dosagem , Pregabalina/uso terapêutico , Feminino , Prurido/tratamento farmacológico , Prurido/etiologia , Masculino , Pessoa de Meia-Idade , Falência Renal Crônica/terapia , Falência Renal Crônica/complicações , Adulto , Uremia/complicações , Uremia/terapia , Paquistão , Resultado do Tratamento , Idoso
2.
Psychoneuroendocrinology ; 169: 107145, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39096755

RESUMO

RATIONALE: Premenstrual dysphoric disorder (PMDD) is characterized by severe affective symptoms during the luteal phase of the menstrual cycle. There is some evidence of altered interactions between the hypothalamic pituitary gonadal (HPG) and hypothalamic pituitary adrenal (HPA) axes in PMDD. There is also evidence that similar affective disorders such as major depression and perinatal depression are associated with dysregulation in immune factors, but this has not been characterized in PMDD. AIMS: The goals of this exploratory study were to identify 1) whether HPA-HPG axis interactions and immune markers differ between PMDD patients and controls across the menstrual cycle; 2) how luteal phase sertraline treatment impacts stress and inflammatory markers. METHODS: Participants were females age 18-50 with regular menstrual cycles, not using psychotropic or hormonal medications, and were assigned to a control group or PMDD group based on prospective daily symptom ratings and clinical interview. Blood was drawn in the follicular and luteal phases, during laboratory sessions involving a mildly stressful task. In a second luteal phase, PMDD participants received open-label sertraline (50 mg/d) from ovulation to menses. Serum cortisol and ACTH were measured via ELISA and operationalized as area under the curve with respect to ground (AUCg), and peak level following laboratory task. Serum TNF-α, IL-6, CXCL-8, and IL-1ß were measured using multiplex kits. Serum allopregnanolone (ALLO) was measured by gas chromatography/mass spectroscopy. To characterize HPA-HPG axis interactions across the menstrual cycle in PMDD participants and controls, multilevel linear models predicted cortisol and ACTH from the interaction of cycle phase (controlling for sertraline treatment), ALLO, and group. To determine the effects of sertraline treatment on inflammatory markers and how groups might differ in cyclical change on each marker, multilevel linear models predicted inflammatory markers from cycle phase (controlling for sertraline treatment) and group. A final set of exploratory models tested whether inflammatory markers predict premenstrual symptom score severity. RESULTS: The sample included n=77 participants (41 controls, 36 PMDD); 28 participants with PMDD completed sertraline treatment. Group x phase x ALLO interactions showed that higher ALLO levels predicted lower cortisol peak in the treated luteal phase (interaction between phase and ALLO, p=0.042), and there was a higher cortisol peak in the treated luteal phase than the untreated luteal phase (p=0.038). CXCL-8 was significantly associated with premenstrual symptom severity after controlling for group and cycle phase (p=0.011). There were no main effects of group, phase, or ALLO on cortisol AUCg, ACTH AUCg, IL-6, CXCL-8, IL-1ß, nor TNF-α (p's>0.05). CONCLUSION: Serum markers of HPA axis and immune function did not vary by menstrual cycle phase nor PMDD status. However, sertraline treatment in the luteal phase was associated with higher ALLO levels predicting lower cortisol peak in response to mild laboratory stress, suggesting that sertraline treatment may normalize HPG-HPA axis interactions among individuals with PMDD. Greater premenstrual symptomatology was associated with higher levels of the inflammatory marker CXCL-8, but further research is needed into the potential role of inflammation in PMDD.


Assuntos
Sistema Hipotálamo-Hipofisário , Inflamação , Fase Luteal , Sistema Hipófise-Suprarrenal , Transtorno Disfórico Pré-Menstrual , Sertralina , Humanos , Feminino , Adulto , Sistema Hipotálamo-Hipofisário/metabolismo , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Sertralina/uso terapêutico , Sistema Hipófise-Suprarrenal/metabolismo , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Transtorno Disfórico Pré-Menstrual/metabolismo , Transtorno Disfórico Pré-Menstrual/tratamento farmacológico , Adulto Jovem , Inflamação/metabolismo , Inflamação/tratamento farmacológico , Pessoa de Meia-Idade , Adolescente , Biomarcadores/sangue , Hidrocortisona/sangue , Hidrocortisona/metabolismo
3.
Eur J Med Res ; 29(1): 438, 2024 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-39210432

RESUMO

OBJECTIVE: To study the effects of selective serotonin reuptake inhibitors (SSRIs) on cognitive functions, mental improvements, and adverse effects in patients with Alzheimer's disease (AD). METHODS: Registered in INPLASY (INPLASY202450004), five drugs (citalopram, s-citalopram, quetiapine, olanzapine, and sertraline) were selected as representatives. A comprehensive search was conducted in PubMed, EMBASE, Web of Science, and the Cochrane Library up to May 15, 2024. Search terms were combined using Boolean operators, specifically 'AND' between different categories (e.g., 'Alzheimer's Disease' AND 'SSRIs') and 'OR' within the same category (e.g., 'citalopram OR s-citalopram OR quetiapine OR olanzapine OR sertraline'), to ensure a thorough retrieval of relevant studies. The selection followed rigorous inclusion and exclusion criteria for meta-analysis. RESULTS: Fourteen articles from 1118 were selected for meta-analysis. The indicators, including Neuropsychiatric Inventory (NPI), Mini-Mental State Examination (MMSE), Brief Psychiatric Rating Scale (BPRS), and Cornell Scale for Depression in Dementia (CSDD), were used to assess the effects of the drugs on AD treatment. According to the results of NPI, CSDD, BPRS, MMSE, and security assessments, the five antidepressants have significant advantages in AD treatment compared with placebo, while the MMSE of the patient treated with the antidepressants did not show notable changes compared with patients treated only with placebo. Statistical analyses were conducted using Review Manager 5.3, employing random-effects models to account for study heterogeneity and sensitivity analyses to test the robustness of our findings. CONCLUSION: This study suggests that SSRI-related antidepressants have great potential values in AD treatment, and further research on the application of SSRI-related antidepressants in AD treatment is necessary.


Assuntos
Doença de Alzheimer , Inibidores Seletivos de Recaptação de Serotonina , Doença de Alzheimer/tratamento farmacológico , Humanos , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , Inibidores Seletivos de Recaptação de Serotonina/efeitos adversos , Antidepressivos/uso terapêutico , Antidepressivos/efeitos adversos , Citalopram/uso terapêutico , Citalopram/efeitos adversos , Sertralina/uso terapêutico , Sertralina/efeitos adversos
4.
Cochrane Database Syst Rev ; 8: CD001396, 2024 08 14.
Artigo em Inglês | MEDLINE | ID: mdl-39140320

RESUMO

BACKGROUND: Premenstrual syndrome (PMS) is a combination of physical, psychological and social symptoms in women of reproductive age, and premenstrual dysphoric disorder (PMDD) is a severe type of the syndrome, previously known as late luteal phase dysphoric disorder (LLPDD). Both syndromes cause symptoms during the two weeks leading up to menstruation (the luteal phase). Selective serotonin reuptake inhibitors (SSRIs) are increasingly used as a treatment for PMS and PMDD, either administered in the luteal phase or continuously. We undertook a systematic review to assess the evidence of the positive effects and the harms of SSRIs in the management of PMS and PMDD. OBJECTIVES: To evaluate the benefits and harms of SSRIs in treating women diagnosed with PMS and PMDD. SEARCH METHODS: We searched the Cochrane Gynaecology and Fertility (CGF) Specialised Register of Controlled Trials, CENTRAL, MEDLINE, Embase and PsycINFO for randomised controlled trials (RCTs) in November 2023. We checked reference lists of relevant studies, searched trial registers and contacted experts in the field for any additional trials. This is an update of a review last published in 2013. SELECTION CRITERIA: We considered studies in which women with a prospective diagnosis of PMS, PMDD or LLPDD were randomised to receive SSRIs or placebo. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. We pooled data using a random-effects model. We calculated standardised mean differences (SMDs) with 95% confidence intervals (CIs) for premenstrual symptom scores, using 'post-treatment' scores for continuous data. We calculated odds ratios (ORs) with 95% CIs for dichotomous outcomes. We stratified analyses by type of administration (luteal phase or continuous). We calculated absolute risks and the number of women who would need to be taking SSRIs in order to cause one additional adverse event (i.e. the number needed to treat for an additional harmful outcome (NNTH)). We rated the overall certainty of the evidence for the main findings using GRADE. MAIN RESULTS: We included 34 RCTs in the review. The studies compared SSRIs (i.e. fluoxetine, paroxetine, sertraline, escitalopram and citalopram) to placebo. SSRIs probably reduce overall self-rated premenstrual symptoms in women with PMS and PMDD (SMD -0.57, 95% CI -0.72 to -0.42; I2 = 51%; 12 studies, 1742 participants; moderate-certainty evidence). SSRI treatment was probably more effective when administered continuously than when administered only in the luteal phase (P = 0.03 for subgroup difference; luteal phase group: SMD -0.39, 95% CI -0.58 to -0.21; 6 studies, 687 participants; moderate-certainty evidence; continuous group: SMD -0.69, 95% CI -0.88 to -0.51; 7 studies, 1055 participants; moderate-certainty evidence). The adverse effects associated with SSRIs were nausea (OR 3.30, 95% CI 2.58 to 4.21; I2 = 0%; 18 studies, 3664 women), insomnia (OR 1.99, 95% CI 1.51 to 2.63; I2 = 0%; 18 studies, 3722 women), sexual dysfunction or decreased libido (OR 2.32, 95% CI 1.57 to 3.42; I2 = 0%; 14 studies, 2781 women), fatigue or sedation (OR 1.52, 95% CI 1.05 to 2.20; I2 = 0%; 10 studies, 1230 women), dizziness or vertigo (OR 1.96, 95% CI 1.36 to 2.83; I2 = 0%; 13 studies, 2633 women), tremor (OR 5.38, 95% CI 2.20 to 13.16; I2 = 0%; 4 studies, 1352 women), somnolence and decreased concentration (OR 3.26, 95% CI 2.01 to 5.30; I2 = 0%; 8 studies, 2050 women), sweating (OR 2.17, 95% CI 1.36 to 3.47; I2 = 0%; 10 studies, 2304 women), dry mouth (OR 2.70, 95% CI 1.75 to 4.17; I2 = 0%; 11 studies, 1753 women), asthenia or decreased energy (OR 3.28, 95% CI 2.16 to 4.98; I2 = 0%; 7 studies, 1704 women), diarrhoea (OR 2.06, 95% CI 1.37 to 3.08; I2 = 0%; 12 studies, 2681 women), and constipation (OR 2.39, 95% CI 1.09 to 5.26; I2 = 0%; 7 studies, 1022 women). There was moderate-certainty evidence for all adverse effects other than somnolence/decreased concentration, which was low-certainty evidence. Overall, the certainty of the evidence was moderate. The main weakness was poor reporting of study methodology. Heterogeneity was low or absent for most outcomes, although there was moderate heterogeneity in the analysis of overall self-rated premenstrual symptoms. Based on the meta-analysis of response rate (the outcome with the most included studies), there was suspected publication bias. In total, 68% of the included studies were funded by pharmaceutical companies. This stresses the importance of interpreting the review findings with caution. AUTHORS' CONCLUSIONS: SSRIs probably reduce premenstrual symptoms in women with PMS and PMDD and are probably more effective when taken continuously compared to luteal phase administration. SSRI treatment probably increases the risk of adverse events, with the most common being nausea, asthenia and somnolence.


Assuntos
Transtorno Disfórico Pré-Menstrual , Síndrome Pré-Menstrual , Ensaios Clínicos Controlados Aleatórios como Assunto , Inibidores Seletivos de Recaptação de Serotonina , Humanos , Feminino , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , Inibidores Seletivos de Recaptação de Serotonina/efeitos adversos , Síndrome Pré-Menstrual/tratamento farmacológico , Transtorno Disfórico Pré-Menstrual/tratamento farmacológico , Adulto , Viés , Fase Luteal/efeitos dos fármacos , Sertralina/uso terapêutico , Sertralina/efeitos adversos
5.
J Psychiatr Res ; 178: 219-224, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39163659

RESUMO

BACKGROUND: Selective Serotonin Reuptake Inhibitors (SSRIs) represent a diverse class of medications widely prescribed for depression and anxiety. Despite their common use, there is an absence of large-scale, real-world evidence capturing the heterogeneity in their effects on individuals. This study addresses this gap by utilizing naturalistic search data to explore the varied impact of six different SSRIs on user behavior. METHODS: The study sample included ∼508 thousand Bing users with searches for one of six SSRIs (citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline) from April-December 2022, comprising 510 million queries. Cox proportional hazard models were employed to examine 30 topics (e.g., shopping, tourism, health) and 195 health symptoms (e.g., anxiety, weight gain, impotence), using each SSRI as a reference. We assessed the relative hazard ratios between drugs and, where feasible, ranked the SSRIs based on their observed effects. We used Cox proportional hazard models in order to account for both the likelihood of users searching for a particular topic or symptom and the associated time to that search. The temporal aspect aided in distinguishing between potential symptoms of the disorder, short-term medication side effects, and later appearing side effects. RESULTS: Differences were found in search behaviors associated with each SSRI. E.g., fluvoxamine was associated with a significantly higher likelihood of searching weight gain compared to all other SSRIs (HRs 1.85-2.93). Searches following citalopram were associated with significantly higher rates of later impotence queries compared to all other SSRIs (HRs 5.11-7.76), except fluvoxamine. Fluvoxamine was associated with a significantly higher rate of health related searches than all other SSRIs (HRs 2.11-2.36). CONCLUSIONS: Our study reveals new insights into the varying SSRI impacts, suggesting distinct symptom profiles. This novel use of large-scale, naturalistic search data contributes to pharmacovigilance efforts, enhancing our understanding of intra-class variation among SSRIs, potentially uncovering previously unidentified drug effects.


Assuntos
Citalopram , Fluvoxamina , Inibidores Seletivos de Recaptação de Serotonina , Humanos , Inibidores Seletivos de Recaptação de Serotonina/efeitos adversos , Inibidores Seletivos de Recaptação de Serotonina/farmacologia , Fluvoxamina/efeitos adversos , Fluvoxamina/farmacologia , Citalopram/efeitos adversos , Masculino , Adulto , Feminino , Antidepressivos/efeitos adversos , Fluoxetina/efeitos adversos , Modelos de Riscos Proporcionais , Paroxetina/efeitos adversos , Escitalopram/farmacologia , Escitalopram/administração & dosagem , Sertralina/efeitos adversos , Depressão/tratamento farmacológico
6.
Molecules ; 29(16)2024 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-39202813

RESUMO

Colorectal cancer (CRC) is the second leading cause of cancer-related death worldwide. It is important to discover new therapeutic regimens for treating CRC. Depression is known to be an important complication of cancer diseases. Repurposing antidepressants into anticancer drugs and exploring the combinational efficacy of antidepressants and chemotherapy are potentially good options for developing CRC treatment regimens. In this study, sertraline, an antidepressant drug, and paclitaxel, an anticancer drug, were chosen to study their antitumor effects in the treatment of colorectal cancer, alone or in combination, and to explore their underlying mechanisms. The data showed that sertraline exerted a dose-dependent cytotoxic effect on MC38 and CT26 colorectal cancer cell lines with IC50 values of 10.53 µM and 7.47 µM, respectively. Furthermore, sertraline synergistically sensitized chemotherapeutic agent paclitaxel efficacy in CRC cells with combination index (CI) values at various concentrations consistently lower than 1. Sertraline remarkably augmented paclitaxel-induced autophagy by increasing autophagosome formation indicated by elevated LC3-II/I ratio and promoting autophagic flux by degrading autophagy cargo receptor SQSTM1/p62, which may explain the synergistically cytotoxic effect of sertraline and paclitaxel combination therapy on CRC cells. This study provides important evidence to support repurposing sertraline as an anticancer agent and suggests a novel combinational regimen for effectively treating CRC as well as in the simultaneous treatment of CRC and depression.


Assuntos
Antidepressivos , Autofagia , Neoplasias Colorretais , Sinergismo Farmacológico , Paclitaxel , Sertralina , Sertralina/farmacologia , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Autofagia/efeitos dos fármacos , Paclitaxel/farmacologia , Humanos , Linhagem Celular Tumoral , Antidepressivos/farmacologia , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Animais
7.
Aquat Toxicol ; 273: 107012, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38954869

RESUMO

This study examined the impact of sertraline, an antidepressant common in treated wastewater, on the host-parasite dynamics between parasitic freshwater mussel (Unio tumidus, Unionidae) larvae (glochidia) and their host fish (Squalius cephalus, Cyprinidae). Employing a full-factorial design, both fish and glochidia were subjected to sertraline at the combinations of 0 µg L-1 (control), 0.2 µg L-1 (environmentally relevant concentration), and 4 µg L-1 (elevated concentration, short-term exposure of the parasite). The results showed that long-term host exposure (involving intensive sertraline accumulation in the fish brain) marginally increased subsequent glochidia attachment success by 2 %, while parasite exposure at the same environmentally relevant concentrations had no detectable effect. There was also no effect of exposure of glochidia to 0.2 µg L-1 of sertraline on their viability and encapsulation success during the initial parasitic stage. However, a significant alteration in attachment behavior, marked by a 3.3 % increase in attachment success and changes in the glochidia spatial distribution on the host body, was noted after 24 h of glochidia exposure to 4 µg L-1 of sertraline. Importantly, this study provides the first evidence of sertraline transfer from exposed glochidia to nonexposed host fish, as indicated by elevated levels of sertraline (12.8 ng g-1) in the brain tissue of nonexposed hosts. These findings highlight the subtle yet significant effects of pharmaceutical pollutants on freshwater ecosystems but also underscore the importance of understanding the unexpected dynamics of such contamination to predict and address future ecological changes.


Assuntos
Antidepressivos , Interações Hospedeiro-Parasita , Sertralina , Poluentes Químicos da Água , Animais , Sertralina/toxicidade , Poluentes Químicos da Água/toxicidade , Interações Hospedeiro-Parasita/efeitos dos fármacos , Cyprinidae , Larva/efeitos dos fármacos , Unionidae/efeitos dos fármacos
8.
Biomed Pharmacother ; 178: 117160, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39029404

RESUMO

BACKGROUND: Infertility caused by drugs that inhibit serotonin reuptake has been attributed to serotonin toxicity. Serotonin has been linked to cause a rise in prolactin and cortisol. This study examined the effects of meperidine, sertraline, tianeptine and combinations on female rat reproductive function. METHODS: Female rats were split into 8 groups (n=7): healthy control (HG), meperidine (MG), sertraline (SG), tianeptine (TG), meperidine+sertraline (MSG), meperidine+tianeptine (MTG), sertraline+tianeptine (STG), meperidine+sertraline+tianeptine (MSTG). Meperidine (20 mg/kg, 2×1) was injected intramuscularly. Sertraline (30 mg/kg, 1×1) and tianeptine (5 mg/kg, 1×1) were given orally. The HG received distilled water as solvent. Treatments continued for 20 days. Then, adult males were added to the rat groups and drug treatment continued for another five days. Blood samples were collected on day 26 for biochemical tests. RESULTS: Total oxidant status (TOS) and total antioxidant status (TAS) were not statistically significant between groups (p>0.05). Meperidine (p<0.001) and sertraline (p<0.001) alone increased prolactin levels in comparison to HG and tianeptine inhibited the increase (p<0.001). While meperidine increased corticosterone levels versus HG (p<0.001), sertraline and tianeptine were close to HG (p>0.05). Number of infertile animals was 6 for meperidine, 3 for sertraline, and none for tianeptine. While the duration of pregnancy in MG (15 days) and SG (15 days) was longer compared to HG (2.86 days), no change was observed in TG (2.5 days). CONCLUSION: Tianeptine and other serotonin re-uptake stimulants may be useful in the treatment of reproductive dysfunction and infertility due to serotonin re-uptake inhibitor treatment.


Assuntos
Meperidina , Reprodução , Sertralina , Tiazepinas , Animais , Feminino , Sertralina/farmacologia , Tiazepinas/farmacologia , Ratos , Meperidina/farmacologia , Masculino , Reprodução/efeitos dos fármacos , Ratos Wistar , Inibidores Seletivos de Recaptação de Serotonina/farmacologia , Antioxidantes/farmacologia , Prolactina/sangue
9.
Acta Psychiatr Scand ; 150(4): 198-208, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38994727

RESUMO

BACKGROUND: The comparative effectiveness of selective serotonin reuptake inhibitors (SSRIs) has been subjected to relatively little research. However, a recent study based on target trial emulation suggested that sertraline may be more effective than escitalopram. AIMS: To investigate whether sertraline, citalopram, and escitalopram differ in their effectiveness-assessed via the risk of psychiatric hospital admission and suicide following treatment initiation. The choice to focus on sertraline, citalopram, and escitalopram was made to limit confounding by indication, as the Danish depression treatment guideline from 2007 specifically listed these three SSRIs as first choice. METHOD: We conducted a target trial emulation based on data from Danish registers. We identified all individuals that initiated treatment for depression with sertraline, citalopram, or escitalopram in the period from January 1, 2007, to March 1, 2019. These individuals were followed until psychiatric hospital admission or suicide (separate analyses), death, 1 year after treatment initiation or end of data. Cox proportional hazards regression adjusted for relevant baseline covariates was performed to emulate randomized treatment allocation, comparing the rate of psychiatric hospital admission and suicide for individuals treated with sertraline (used as reference), citalopram or escitalopram, respectively. For escitalopram, we conducted a sensitivity analysis excluding data from the period during which the drug was sold under patent, as the price of the drug during that time likely entailed a different prescription pattern, increasing the risk of ("patent-related") confounding by indication. RESULTS: We identified 56,865, 118,145, and 31,083 individuals initiating treatment with sertraline, citalopram, and escitalopram, respectively. Using sertraline as reference, the adjusted hazard rate ratio (aHRR) for psychiatric admission was 0.98 (95% CI = 0.91-1.05) for citalopram and 1.21 (95% CI = 1.10-1.32) for escitalopram. Notably, in the sensitivity analysis only including patients initiating treatment after the escitalopram patent had expired, the increased risk of psychiatric hospital admission associated with escitalopram treatment was no longer present (aHRR = 0.98, 95% CI = 0.82-1.18). The results of the analyses of suicide were inconclusive, due to few outcome events. CONCLUSIONS: Sertraline, citalopram, and escitalopram do not seem to have differential effectiveness in the treatment of depression. Taking potential patent-related, time varying, confounding by indication (via severity) into account is critical for pharmacoepidemiological studies, including those employing target trial emulation.


Assuntos
Citalopram , Inibidores Seletivos de Recaptação de Serotonina , Sertralina , Humanos , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , Citalopram/uso terapêutico , Sertralina/uso terapêutico , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Dinamarca , Escitalopram/uso terapêutico , Escitalopram/farmacologia , Patentes como Assunto/estatística & dados numéricos , Sistema de Registros , Suicídio/estatística & dados numéricos , Hospitalização/estatística & dados numéricos , Idoso , Transtorno Depressivo/tratamento farmacológico , Antidepressivos/uso terapêutico
10.
Nervenarzt ; 95(7): 622-629, 2024 Jul.
Artigo em Alemão | MEDLINE | ID: mdl-38916664

RESUMO

In addition to trauma-focussed psychotherapy, pharmacological treatment is often unavoidable, especially in patients with severe posttraumatic stress disorder (PTSD). As long as comorbid disorders do not dictate the pharmacotherapy approach, sertraline and paroxetine, along with other off-label prescribable substances approved in Germany, can be used for the treatment of PTSD. Venlafaxine, in particular, has shown good effectiveness in studies, whereas risperidone has shown lower effectiveness in augmentation. Overall, only a small to medium effect size is to be expected for all substances. Psychopharmacotherapy plays an important role in addressing sleep disorders, which are highly prevalent in PTSD. Treatment of trauma-related nightmares can be attempted with doxazosin or clonidine. In contrast, there are limited empirical data available for sleep disorders associated with PTSD, but the pharmacological treatment of insomnia can provide some guidance.


Assuntos
Transtornos de Estresse Pós-Traumáticos , Transtornos de Estresse Pós-Traumáticos/terapia , Transtornos de Estresse Pós-Traumáticos/tratamento farmacológico , Transtornos de Estresse Pós-Traumáticos/psicologia , Humanos , Resultado do Tratamento , Sertralina/uso terapêutico , Medicina Baseada em Evidências , Transtornos do Sono-Vigília/tratamento farmacológico , Transtornos do Sono-Vigília/terapia , Paroxetina/uso terapêutico , Terapia Combinada , Distúrbios do Início e da Manutenção do Sono/terapia , Distúrbios do Início e da Manutenção do Sono/tratamento farmacológico
11.
Anal Chim Acta ; 1312: 342721, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38834258

RESUMO

This study reports a fast and visual detection method of antidepressant sertraline (SRT) drug by the core-shell AuNPs@CDs as the nanoprobes. The CDs has been eco-friendly synthesized from sweet lemon wastes to directly reduce Au+ to AuNPs without any external photoirradiation process or additional reductants. Optimizing key variables that impact the sensing process has been done using the central composite design (CCD) approach to simulate the assay condition before the analysis. Adding SRT with different concentrations to the nanoprobes under mildly acidic conditions presents an absorbance peak at 560 nm with purple color tonalities that differ from the behavior of alone nanoprobes (530 nm, pink color). The obtained absorption change is linearly proportional to the increase of SRT concentration from 1 µM to 35 µM with a limit of detection (LOD) value of 100 nM. The color changes with a vivid tonality from pink and purple to violet as the colorful fingerprint patterns are readily traceable by the naked eye, allowing the visual assay of SRT. The greenness of the developed approach is well evaluated by some international indexes including the complimentary green analytical procedure (ComplexGAPI) and also, the analytical greenness (AGREE) indexes. The proposed waste-derived nanoprobes based on the eco-friendly procedure not only conduct quantitative and qualitative non-invasive analysis of SRT by the naked eye but also, may widen for other applications in various fields.


Assuntos
Compostos de Cádmio , Ouro , Nanopartículas Metálicas , Sertralina , Sulfetos , Ouro/química , Nanopartículas Metálicas/química , Sertralina/análise , Sertralina/química , Sulfetos/química , Compostos de Cádmio/química , Citrus/química , Colorimetria/métodos , Limite de Detecção , Antidepressivos/análise
12.
Diabetes Obes Metab ; 26(9): 3606-3617, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38888050

RESUMO

AIMS: To investigate the effects of the selective serotonin reuptake inhibitors (SSRIs) sertraline and paroxetine at therapeutically relevant concentrations on beta-cell mass and function. METHODS: Viability was quantified in mouse insulinoma (MIN6) beta cells and mouse islets after 48-h exposure to sertraline (1-10 µM) or paroxetine (0.01-1 µM) using the Trypan blue exclusion test. The effects of therapeutic concentrations of these SSRIs on insulin secretion were determined by static incubation and perifusion experiments, while islet apoptosis was investigated by Caspase-Glo 3/7 assay, TUNEL staining and quantitative PCR analysis. Finally, proliferation of MIN6 and mouse islet beta cells was assessed by bromodeoxyuridine (BrdU) enzyme-linked immunosorbent assay and immunofluorescence. RESULTS: Sertraline (0.1-1 µM) and paroxetine (0.01-0.1 µM) were well tolerated by MIN6 beta cells and islets, whereas 10 µM sertraline and 1 µM paroxetine were cytotoxic. Exposure to 1 µM sertraline and 0.1 µM paroxetine significantly potentiated glucose-stimulated insulin secretion from mouse and human islets. Moreover, they showed protective effects against cytokine- and palmitate-induced apoptosis of islets, they downregulated cytokine-induced Stat1 and Traf1 mRNA expression, and they significantly increased proliferation of mouse beta cells. CONCLUSIONS: Our data demonstrate that sertraline and paroxetine act directly on beta cells to enhance glucose-stimulated insulin secretion and stimulate beta-cell mass expansion by increasing proliferation and decreasing apoptosis. These drugs are therefore likely to be appropriate for treating depression in people with type 2 diabetes.


Assuntos
Apoptose , Proliferação de Células , Secreção de Insulina , Células Secretoras de Insulina , Paroxetina , Inibidores Seletivos de Recaptação de Serotonina , Sertralina , Paroxetina/farmacologia , Sertralina/farmacologia , Animais , Inibidores Seletivos de Recaptação de Serotonina/farmacologia , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , Células Secretoras de Insulina/efeitos dos fármacos , Células Secretoras de Insulina/metabolismo , Camundongos , Secreção de Insulina/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Humanos , Insulina/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Masculino , Ilhotas Pancreáticas/efeitos dos fármacos , Ilhotas Pancreáticas/metabolismo
13.
Comput Biol Med ; 178: 108748, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38925084

RESUMO

The CUSP9 protocol is a polypharmaceutical strategy aiming at addressing the complexity of glioblastoma by targeting multiple pathways. Although the rationale for this 9-drug cocktail is well-supported by theoretical and in vitro data, its effectiveness compared to its 511 possible subsets has not been comprehensively evaluated. Such an analysis could reveal if fewer drugs could achieve similar or better outcomes. We conducted an exhaustive in vitro evaluation of the CUSP9 protocol using COMBImageDL, our specialized framework for testing higher-order drug combinations. This study assessed all 511 subsets of the CUSP9v3 protocol, in combination with temozolomide, on two clonal cultures of glioma-initiating cells derived from patient samples. The drugs were used at fixed, clinically relevant concentrations, and the experiment was performed in quadruplicate with endpoint cell viability and live-cell imaging readouts. Our results showed that several lower-order drug combinations produced effects equivalent to the full CUSP9 cocktail, indicating potential for simplified regimens in personalized therapy. Further validation through in vivo and precision medicine testing is required. Notably, a subset of four drugs (auranofin, disulfiram, itraconazole, sertraline) was particularly effective, reducing cell growth, altering cell morphology, increasing apoptotic-like cells within 4-28 h, and significantly decreasing cell viability after 68 h compared to untreated cells. This study underscores the importance and feasibility of comprehensive in vitro evaluations of complex drug combinations on patient-derived tumor cells, serving as a critical step toward (pre-)clinical development.


Assuntos
Glioblastoma , Temozolomida , Glioblastoma/tratamento farmacológico , Glioblastoma/patologia , Humanos , Temozolomida/farmacologia , Temozolomida/uso terapêutico , Linhagem Celular Tumoral , Dissulfiram/farmacologia , Dissulfiram/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/patologia , Sobrevivência Celular/efeitos dos fármacos , Sertralina/uso terapêutico , Sertralina/farmacologia , Itraconazol/farmacologia , Itraconazol/uso terapêutico , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico
14.
Drugs ; 84(6): 645-659, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38811474

RESUMO

Depression during the first year postpartum (postpartum depression) impacts millions of women and their families worldwide. In this narrative review, we provide a summary of postpartum depression, examining the etiology and consequences, pharmacological and psychological treatments, and potential mechanisms of change and current barriers to care. Psychological treatments are effective and preferred by many perinatal patients over medications, but they often remain inaccessible. Key potential mechanisms underlying their effectiveness include treatment variables (e.g., dosage and therapeutic alliance) and patient behaviors (e.g., activation and avoidance and emotional regulation). Among pharmacological treatments, the selective serotonin reuptake inhibitor (SSRI) sertraline is generally the first-line antidepressant medication recommended to women in the postpartum period due to its minimal passage into breastmilk and the corresponding decades of safety data. Importantly, most antidepressant drugs are considered compatible with breastfeeding. Neurosteroids are emerging as an effective treatment for postpartum depression, although currently this treatment is not widely available. Barriers to widespread access to treatment include those that are systematic (e.g., lack of specialist providers), provider-driven (e.g., lack of flexibility in treatment delivery), and patient-driven (e.g., stigma and lack of time for treatment engagement). We propose virtual care, task-sharing to non-specialist treatment providers, and collaborative care models as potential solutions to enhance the reach and scalability of effective treatments to address the growing burden of postpartum depression worldwide and its negative impact on families and society.


Assuntos
Antidepressivos , Depressão Pós-Parto , Inibidores Seletivos de Recaptação de Serotonina , Humanos , Depressão Pós-Parto/tratamento farmacológico , Depressão Pós-Parto/terapia , Feminino , Antidepressivos/uso terapêutico , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , Sertralina/uso terapêutico , Psicoterapia/métodos , Gravidez
15.
PLoS One ; 19(5): e0300366, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38722970

RESUMO

PURPOSE: Antidepressants are a first-line treatment for depression, yet many patients do not respond. There is a need to understand which patients have greater treatment response but there is little research on patient characteristics that moderate the effectiveness of antidepressants. This study examined potential moderators of response to antidepressant treatment. METHODS: The PANDA trial investigated the clinical effectiveness of sertraline (n = 326) compared with placebo (n = 329) in primary care patients with depressive symptoms. We investigated 11 potential moderators of treatment effect (age, employment, suicidal ideation, marital status, financial difficulty, education, social support, family history of depression, life events, health and past antidepressant use). Using multiple linear regression, we investigated the appropriate interaction term for each of these potential moderators with treatment as allocated. RESULTS: Family history of depression was the only variable with weak evidence of effect modification (p-value for interaction = 0.048), such that those with no family history of depression may have greater benefit from antidepressant treatment. We found no evidence of effect modification (p-value for interactions≥0.29) by any of the other ten variables. CONCLUSION: Evidence for treatment moderators was extremely limited, supporting an approach of continuing discuss antidepressant treatment with all patients presenting with moderate to severe depressive symptoms.


Assuntos
Antidepressivos , Depressão , Atenção Primária à Saúde , Sertralina , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Antidepressivos/uso terapêutico , Depressão/tratamento farmacológico , Análise de Dados Secundários , Sertralina/uso terapêutico , Resultado do Tratamento
16.
Anticancer Agents Med Chem ; 24(14): 1038-1046, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38766835

RESUMO

BACKGROUND: Drug repurposing in oncology promises benefits to many patients through its ability to provide novel, and fast-tracked treatments. Previous studies have demonstrated that depression may influence tumor progression. Anti-proliferative activity of certain antidepressants, mainly selective serotonin reuptake inhibitors (SSRIs), are reported in the literature. OBJECTIVE: This study was conducted to repurpose selective serotonin reuptake inhibitors (SSRIs) for the treatment of breast cancers, and it merits further validation and research. METHODS: Changes in cell morphology were studied using DAPI staining, while the Annexin V/PI method was employed for apoptotic analysis. The expression of specific genes involved in cancer progression was also analyzed via RT-PCR. Caspase-3 activation was measured through fluorometric assay. RESULTS: We have identified that sertraline hydrochloride significantly inhibited the growth of breast cancer cell in vitro. Preliminary mechanistic studies demonstrated that the cytotoxicity of sertraline hydrochloride was possibly through the induction of apoptosis, as inferred from enhanced nuclear fragmentation, flow cytometric data, and caspase-3/7 activation. Gene expression analysis also showed an increased expression of pro-apoptotic Bax, and a slight decrease in oncogene c-myc in the presence of sertraline hydrochloride. CONCLUSION: In conclusion, our study suggest that sertraline hydrochloride, an antidepressant drug, can potentially be used for the treatment of breast cancer.


Assuntos
Antidepressivos , Antineoplásicos , Apoptose , Neoplasias da Mama , Pontos de Checagem do Ciclo Celular , Proliferação de Células , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Sertralina , Sertralina/farmacologia , Sertralina/química , Humanos , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Antidepressivos/farmacologia , Antidepressivos/química , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Neoplasias da Mama/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/química , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Relação Estrutura-Atividade , Estrutura Molecular , Receptor ErbB-2/metabolismo , Receptor ErbB-2/antagonistas & inibidores , Feminino , Células Tumorais Cultivadas
17.
Environ Pollut ; 352: 124149, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38735458

RESUMO

This study investigated the effects of the antidepressant sertraline hydrochloride (Ser-HCI) on rice physiology when combined with arsenic (III) or cadmium. Hydroponic experiments revealed that combined lower concentrations (0.2 and 0.6 mg L-1) of Ser-HCl and As (III) or Cd increased rice biomass and reduced pH and low molecular weight organic acids. The fluorescence intensity was enhanced with Ser-HCl and As-only treatments, with a significant difference (p < 0.05) in the dissolved organic matter index. There was a decrease in endophyte-specific operational taxonomic units, with proteobacteria dominating the rice root endophytes. The addition of Ser-HCl resulted in the Verrucomicrobiota increasing by 6.4 times, which was positively correlated with malic acid and negatively correlated with pH. Functional annotation highlighted alterations in carbohydrate metabolism pathways. This study provides insights into the interactive effects of Ser-HCl on rice when combined with As (III) or Cd, addressing gaps in our understanding of the impact of antidepressants on plant systems.


Assuntos
Arsênio , Cádmio , Endófitos , Oryza , Raízes de Plantas , Rizosfera , Sertralina , Poluentes do Solo , Oryza/microbiologia , Sertralina/farmacologia , Cádmio/toxicidade , Poluentes do Solo/toxicidade , Raízes de Plantas/microbiologia , Raízes de Plantas/efeitos dos fármacos , Endófitos/fisiologia , Arsênio/toxicidade , Microbiologia do Solo
19.
Compr Psychiatry ; 133: 152486, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38703743

RESUMO

OBJECTIVE: To examine the long-term safety and tolerability of off-label high-dose serotonin reuptake inhibitors (OLHD-SRIs) in the treatment of obsessive-compulsive disorder (OCD). METHODS: A retrospective longitudinal study was performed on 105 randomly selected outpatients diagnosed with OCD and were treated with OLHD-SRIs for at least 6 months. Patients received sertraline >200 mg/day, escitalopram >20 mg/day, fluvoxamine >300 mg/day, and fluoxetine >60 mg/day, combined with exposure and response prevention therapy. Patients were divided into three dosing groups: sertraline equivalent dose (SED) ≤ 200 mg/day (n = 26, 24.7%), 201-400 mg/day (n = 51, 48.5%) and 401-650 mg/day (n = 28, 26.6%). Safety and tolerability were assessed with an electrocardiogram, blood biochemistry, complete blood count, and side-effects monitoring. RESULTS: SED ranged from 100 to 650 mg/day and the mean duration of OLHD-SRI treatment was 20.8 months. The most common side-effects reported were sexual dysfunction (n = 36, 34%), weight gain (n = 28, 27%), sedation (n = 27, 26%), hyperhidrosis (n = 20, 19%), and tremor (n = 11, 10%). Abnormal ECG was documented in one patient, and another patient experienced a first-time seizure, whereas elevated liver enzymes were seen in 4.8% of the sample (n = 5). None of the patients had serotonin syndrome or drug-induced liver injury. Side-effects did not differ among the three dosing groups. CONCLUSION: OLHD-SRIs appear to be safe and well tolerated in OCD patients in SED ≤ 650 mg/day doses and the side-effects did not differ between the three dosing groups.


Assuntos
Fluvoxamina , Transtorno Obsessivo-Compulsivo , Uso Off-Label , Inibidores Seletivos de Recaptação de Serotonina , Sertralina , Humanos , Transtorno Obsessivo-Compulsivo/tratamento farmacológico , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , Inibidores Seletivos de Recaptação de Serotonina/administração & dosagem , Inibidores Seletivos de Recaptação de Serotonina/efeitos adversos , Feminino , Adulto , Masculino , Estudos Retrospectivos , Fluvoxamina/uso terapêutico , Fluvoxamina/administração & dosagem , Fluvoxamina/efeitos adversos , Sertralina/uso terapêutico , Sertralina/administração & dosagem , Sertralina/efeitos adversos , Pessoa de Meia-Idade , Estudos Longitudinais , Fluoxetina/uso terapêutico , Fluoxetina/administração & dosagem , Fluoxetina/efeitos adversos , Escitalopram/uso terapêutico , Escitalopram/administração & dosagem , Adulto Jovem , Resultado do Tratamento , Relação Dose-Resposta a Droga
20.
BMC Psychiatry ; 24(1): 365, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38750479

RESUMO

OBJECTIVES: This study aims to evaluate the safety and efficacy of escitalopram and sertraline in post-stroke depression (PSD) patients, to provide more reliable therapeutics for cardiovascular and psychiatric clinical practice. METHODS: We recruited 60 patients (aged 40-89 years old) with an ICD-10 diagnosis of PSD, who were then randomly assigned to two groups and treated with flexible doses of escitalopram (10 to 20 mg/day, n = 30) or sertraline (50 to 200 mg/day, n = 30) for consecutive 8 weeks, respectively. The 24-item Hamilton Depression Rating Scale (HAMD-24), the 14-item Hamilton Anxiety Rating Scale (HAMA-14), the Treatment Emergent Symptom Scale (TESS), the Montreal Cognitive Assessment Scale (MOCA), and the Activity of Daily Living scale (ADL) were used to assess patients before, during, and after treatment for depression, anxiety, adverse effects, cognitive function, and daily living activities. Repeated measures ANOVA, the Mann-Whitney U test, the chi-square test (χ2), or Fisher's exact test was employed to assess baseline demographics, response rate, adverse effects rate, and changes in other clinical variables. RESULTS: Significant reduction in HAMD-24 and HAMA-14 scores was evaluated at baseline, as well as 1, 3, 4, 6, and 8 weeks of drug intervention (p < 0.01). There was a significant group difference in post-treatment HAMD-24 scores (p < 0.05), but no difference was observed in HAMA-14 scores (p > 0.05). Further analysis showed a significant variance in the HAMD-24 scores between the two groups at the end of the first week (p < 0.01). The incidence of adverse effects in both patient groups was mild, but there was a statistically significant difference between the two groups (p < 0.05). The improvement in cognitive function and the recovery of daily living abilities were comparable between both groups (p > 0.05). CONCLUSION: Escitalopram and sertraline showed comparable efficacy for anxiety symptoms, cognitive function, and daily living abilities in PSD patients. In addition, escitalopram was more appropriate for alleviating depressive symptoms. To validate the conclusion, trials with a larger sample size are in demand in the future. The registration number is ChiCTR1800017373.


Assuntos
Atividades Cotidianas , Escitalopram , Sertralina , Acidente Vascular Cerebral , Humanos , Sertralina/uso terapêutico , Sertralina/efeitos adversos , Masculino , Idoso , Feminino , Pessoa de Meia-Idade , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/tratamento farmacológico , Adulto , Idoso de 80 Anos ou mais , Escitalopram/uso terapêutico , Escitalopram/efeitos adversos , Depressão/tratamento farmacológico , Depressão/etiologia , Resultado do Tratamento , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , Inibidores Seletivos de Recaptação de Serotonina/efeitos adversos , Escalas de Graduação Psiquiátrica , Antidepressivos/uso terapêutico , Antidepressivos/efeitos adversos , Citalopram/uso terapêutico , Citalopram/efeitos adversos
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