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1.
J Biomol Struct Dyn ; 42(4): 1765-1777, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37097971

RESUMO

Depressive disorders are among most common psychiatric diseases and second most common form of psychiatric illness globally. Commonly available chemical drugs used for treatment of nervous system disorders exert undesirable effects. Therefore, there is a growing need towards exploring novel antidepressants of herbal origin. Earlier, the antidepressant effect of methanolic extract of garlic has been shown. In this study, the ethanolic extract of garlic was prepared and chemically analysed using Gas Chromatography - Mass Spectrometry (GC-MS) screening. A total of 35 compounds were found to be present, which might act as antidepressant. Using computational analyses, these compounds were screened as potential inhibitors (selective serotonin reuptake inhibitor (SSRI)) against serotonin transporter (SERT)/leucine receptor (LEUT). In silico docking studies and other physicochemical, bioactivity and ADMET studies resulted in the selection of compound 1 ((2-Cyclohexyl-1-methylpropyl) cyclohexane) as potential SSRI (binding energy -8.1 kcal/mol) compared to known reference SSRI fluoxetine (binding energy -8.0 kcal/mol). Analysis of conformational stability, residue flexibility, compactness, binding interactions, solvent accessible surface area (SASA), dynamic correlation, and binding free energy predicted from molecular mechanics (MD) with generalised Born and surface area solvation (MM/GBSA) studies revealed formation of a more stable SSRI like complex with compound 1 having strong inhibitory interaction compared to known SSRI fluoxetine/reference complex. Thus, compound 1 may act as an active SSRI leading to discovery of potential antidepressant drug.Communicated by Ramaswamy H. Sarma.


Assuntos
Fluoxetina , Alho , Fluoxetina/farmacologia , Simulação de Dinâmica Molecular , Antidepressivos/farmacologia , Inibidores Seletivos de Recaptação de Serotonina/farmacologia , Cicloexanos , Simulação de Acoplamento Molecular
2.
Physiol Rep ; 11(23): e15881, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38031314

RESUMO

At the end of gestation, fetal skeleton rapidly accumulates calcium, and bone development continues in offspring postnatally. To accommodate, maternal skeletal physiology is modulated in a serotonin-dependent manner. Selective serotonin reuptake inhibitors (SSRIs) are generally considered safe for treatment of major depressive disorder, postpartum depression, and other psychiatric illnesses during the peripartum period, but because serotonin affects bone remodeling, SSRIs are associated with decreased bone mass across all ages and sexes, and the impact of SSRIs during fetal and postnatal development has not been fully investigated. In the present study, our aim was to examine developmental fluoxetine exposure on offspring skeleton and to assess varying degrees of impact depending on dose and window of exposure in short-term and long-term contexts. We established that a low dose of lactational fluoxetine exposure caused a greater degree of insult to offspring bone than either a low dose during fetal and postpartum development or a high dose during lactation only in mice. We further discovered lasting impacts of developmental fluoxetine exposure, especially during lactation only, on adult bone and body composition. Herein, we provide evidence fluoxetine exposure during early development may have detrimental effects on the skeleton of offspring at weaning and into adulthood.


Assuntos
Transtorno Depressivo Maior , Efeitos Tardios da Exposição Pré-Natal , Feminino , Camundongos , Animais , Humanos , Fluoxetina/toxicidade , Inibidores Seletivos de Recaptação de Serotonina/toxicidade , Transtorno Depressivo Maior/tratamento farmacológico , Serotonina , Osso e Ossos , Efeitos Tardios da Exposição Pré-Natal/tratamento farmacológico
3.
Cell Chem Biol ; 30(12): 1557-1570.e6, 2023 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-37992715

RESUMO

Depression pathology remains elusive. The monoamine hypothesis has placed much focus on serotonin, but due to the variable clinical efficacy of monoamine reuptake inhibitors, the community is looking for alternative therapies such as ketamine (neurogenesis theory of antidepressant action). There is evidence that different classes of antidepressants may affect serotonin levels; a notion we test here. We measure hippocampal serotonin in mice with voltammetry and study the effects of acute challenges of escitalopram, fluoxetine, reboxetine, and ketamine. We find that pseudo-equivalent doses of these drugs similarly raise ambient serotonin levels, despite their differing pharmacodynamics because of differences in Uptake 1 and 2, rapid SERT trafficking, and modulation of serotonin by histamine. These antidepressants have different pharmacodynamics but have strikingly similar effects on extracellular serotonin. Our findings suggest that serotonin is a common thread that links clinically effective antidepressants, synergizing different theories of depression (synaptic plasticity, neurogenesis, and the monoamine hypothesis).


Assuntos
Ketamina , Serotonina , Camundongos , Animais , Inibidores Seletivos de Recaptação de Serotonina/farmacologia , Ketamina/farmacologia , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Fluoxetina/farmacologia
4.
Medicina (Kaunas) ; 59(9)2023 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-37763782

RESUMO

Background and Objectives: Almost by default, people with major depression disorder (MDD) also report sexual health issues. This holds even more true when sexual dysfunctions are SSRI-induced. Herbal compounds may have the power to counterbalance such sexual dysfunctions, though research is still scarce. Therefore, we assessed females with diagnosed MDD treated with a standard SSRI (sertraline) and reporting SSRI-induced sexual dysfunctions, and we asked whether compared to placebo, Aphrodite (a blend of ginger, saffron, cinnamon, thistle, and Tribulus terrestris) may favorably impact on sexual dysfunctions, and on symptoms of depression, anxiety, and sleep disturbances. Materials and Methods: A total of 41 females (mean age: 35.05 years) with diagnosed MDD, treated with sertraline (a standard SSRI) at therapeutic dosages, and reporting SSRI-induced sexual dysfunction, were randomly assigned either to Aphrodite or to the placebo condition. At baseline and four and eight weeks later (study end), participants completed a series of self-rating questionnaires covering symptoms of sexual dysfunction, depression, anxiety, and sleep complaints. Results: Symptoms of sexual dysfunction, depression, and anxiety decreased over time, but more so in the Aphrodite condition, compared to the placebo condition (significant p-values and large effect sizes). Over time, sleep disturbances decreased irrespective of the study condition. Conclusions: The pattern of results suggests that compared to placebo, Aphrodite appeared to improve symptoms of sexual dysfunction, depression, and anxiety among females with diagnosed MDD and SSRI-induced sexual dysfunction. Further and similar studies should investigate the underlying psychophysiological mechanisms.


Assuntos
Transtorno Depressivo Maior , Disfunções Sexuais Fisiológicas , Humanos , Feminino , Adulto , Transtorno Depressivo Maior/complicações , Transtorno Depressivo Maior/tratamento farmacológico , Sertralina/uso terapêutico , Inibidores Seletivos de Recaptação de Serotonina/efeitos adversos , Depressão , Disfunções Sexuais Fisiológicas/induzido quimicamente , Disfunções Sexuais Fisiológicas/tratamento farmacológico , Método Duplo-Cego
5.
Am Fam Physician ; 107(4): 406-414, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-37054418

RESUMO

This article summarizes the top 20 research studies of 2022 identified as POEMs (patient-oriented evidence that matters), excluding COVID-19. Statins for primary prevention of cardiovascular disease produce only a small absolute reduction in a person's likelihood of dying (0.6%), having a myocardial infarction (0.7%), or having a stroke (0.3%) over three to six years. Supplemental vitamin D does not reduce the risk of a fragility fracture, even in people with low baseline vitamin D levels or a previous fracture. Selective serotonin reuptake inhibitors are preferred medical therapy for panic disorder, and patients who discontinue antidepressants are more likely to relapse (number needed to harm = 6) compared with those who continue. Combination therapy using a selective serotonin reuptake inhibitor, serotonin-norepinephrine reuptake inhibitor, or tricyclic antidepressant with mirtazapine or trazodone is more effective than monotherapy for first-line treatment of acute severe depression and when monotherapy fails. Using hypnotic agents for insomnia in adults comes with a significant trade-off between effectiveness and tolerability. In patients with moderate to severe asthma, using a combination of albuterol and glucocorticoid inhalers as rescue therapy reduces exacerbations and need for systemic steroids. Observational research shows an increased risk of gastric cancer in patients taking proton pump inhibitors (number needed to harm = 1,191 over 10 years). The American College of Gastroenterology updated its guideline for gastroesophageal reflux disease, and a new guideline provides sound advice for the evaluation and management of irritable bowel syndrome. Adults older than 60 years with prediabetes are more likely to become normoglycemic than to develop diabetes mellitus or die. Treatment of prediabetes via intensive lifestyle intervention or metformin has no impact on long-term cardiovascular outcomes. Persons with painful diabetic peripheral neuropathy have similar degrees of improvement with monotherapy using amitriptyline, duloxetine, or pregabalin and greater improvement with combination therapy. When communicating with patients about disease risk, most patients prefer numbers over words because people overestimate word-based probabilities. In terms of drug therapy, the duration of an initial varenicline prescription should be 12 weeks. Many drugs can interact with cannabidiol. No important difference was found among ibuprofen, ketorolac, and diclofenac for treatment of acute nonradicular low back pain in adults.


Assuntos
COVID-19 , Médicos de Atenção Primária , Estado Pré-Diabético , Adulto , Humanos , Estado Pré-Diabético/tratamento farmacológico , Antidepressivos/uso terapêutico , Antidepressivos/efeitos adversos , Inibidores Seletivos de Recaptação de Serotonina
6.
CNS Neurosci Ther ; 29(9): 2608-2620, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37002793

RESUMO

AIMS: Electroacupuncture (EA) shows advantages in both clinical practice and depression animal models. Dopaminergic-related dysfunction in the prefrontal cortex (PFC) may be a hidden antidepressant mechanism of EA, where dopamine transporter (DAT) plays an essential role. This study aimed to investigate the synaptic transmission and DAT-related changes of EA in depression. METHODS: Male Sprague-Dawley rats were subjected to 3-week chronic unpredictable mild stress (CUMS). The successfully modeled rats were then randomly and equally assigned to CUMS, selective serotonin reuptake inhibitor (SSRI), and EA or SSRI + EA groups, followed by a 2-week treatment respectively. After monitoring body weight and behavioral tests of all rats, the ventromedial PFC (vmPFC) tissue was collected for electrophysiology and the expression detection of DAT, phosphorylated DAT (p-DAT), cyclic adenosine monophosphate (cAMP), protein kinase A (PKA), and trace amine-associated receptor 1 (TAAR1). RESULTS: Depressive-like behaviors induced by CUMS were alleviated by EA, SSRI, and SSRI + EA treatments through behavioral tests. Compared with CUMS group, EA improved synaptic transmission in vmPFC by upregulating spontaneous excitatory postsynaptic currents amplitude. Molecularly, EA reversed the increased total DAT and p-DAT expression as well as the decreased ratio of p-DAT/total DAT along with the activation of TAAR1, cAMP, and PKA in vmPFC. CONCLUSION: We speculated that the antidepressant effect of EA was associated with enhanced synaptic transmission in vmPFC, and the upregulated phosphorylation of DAT relevant to TAAR1, cAMP, and PKA may be the potential mechanism.


Assuntos
Depressão , Eletroacupuntura , Ratos , Masculino , Animais , Ratos Sprague-Dawley , Depressão/tratamento farmacológico , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Hipocampo/metabolismo , Antidepressivos , Transmissão Sináptica , Inibidores Seletivos de Recaptação de Serotonina/farmacologia , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , Córtex Pré-Frontal/metabolismo , Modelos Animais de Doenças
7.
Am J Psychiatry ; 180(5): 357-366, 2023 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-36945823

RESUMO

OBJECTIVE: Social anxiety disorder is common and impairing. The efficacy of pharmacotherapy is moderate, highlighting the need for alternative therapies. This study compared the efficacy of gaze-contingent music reward therapy (GC-MRT), an eye-tracking-based attention bias modification treatment, with a selective serotonin reuptake inhibitor (SSRI) treatment or a waiting list control condition in reducing social anxiety disorder symptoms. Superior clinical effects of similar magnitude were expected for the active treatments relative to the control condition. METHODS: Participants were 105 treatment-seeking adults with social anxiety disorder, randomly allocated to 12 weeks of GC-MRT, SSRI, or waiting list control. Mean changes in clinician-rated and self-reported social anxiety symptoms from baseline to mid- and posttreatment assessments were compared between groups using generalized estimating equations. Changes in attentional dwell time on threat were also examined. RESULTS: Analysis indicated a significant differential reduction in symptoms between groups. Patients in the GC-MRT and SSRI groups had lower social anxiety scores at the mid- and posttreatment assessments compared with patients in the waiting list group. The efficacy of the active treatments did not differ. Only patients in the GC-MRT group showed reduction in dwell time on threat from baseline to posttreatment assessment. CONCLUSIONS: Eye-tracking-based attention bias modification is an acceptable and effective treatment option for social anxiety disorder.


Assuntos
Terapia Cognitivo-Comportamental , Fobia Social , Adulto , Humanos , Fobia Social/tratamento farmacológico , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , Listas de Espera , Transtornos de Ansiedade/tratamento farmacológico , Transtornos de Ansiedade/diagnóstico , Ansiedade
8.
Psychiatr Q ; 94(2): 113-125, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36913163

RESUMO

Antidepressant medications are widely used by patients with depression or a depressive disorder. In spite of a generally favorable safety profile of selective serotonin reuptake inhibitors or serotonin - norepinephrine reuptake inhibitors (SSRI/SNRI), several cases of a possible connection between SSRI/SNRI and hyponatremia have been reported. To describe the clinical characteristics of patients with hyponatremia after SSRI/SNRI exposure, and to examine the association between SSRI/SNRI exposure and the presence of hyponatremia in a Chinese population. A retrospective single-center case series study. We performed a retrospective evaluation of inpatients with SSRI/SNRI-induced hyponatremia from a single institution in China between 2018 and 2020. Clinical data were obtained through review of medical records. Patients who met the initial inclusion criteria but did not develop hyponatremia acted as controls. The study was approved by the Clinical Research Ethics Board of Beijing Hospital (Beijing, P.R. China). We identified 26 patients with SSRI/SNRI-induced hyponatremia. The incidence rate of hyponatremia was 1.34% (26/1937) in the study population. The mean age at diagnosis was 72.58 (±12.84) years, with a male: female ratio of 1:1.42. The duration between SSRI/SNRI exposure and the onset of hyponatremia was 7.65 (±4.88) days. The minimum serum sodium level was 2328.23 (±107.25) mg/dL in the study group. Seventeen patients (65.38%) received sodium supplements. Four patients (15.38%) switched to another antidepressant. Fifteen patients (57.69%) recovered by the time of discharge. There were significant differences in serum potassium, serum magnesium and serum creatinine level between the two groups (p < 0.05). The rate of use of sertraline was significantly higher in the study group compared with the control group (p < 0.05). This pattern was not found in other SSRI/SNRI (p > 0.05). The results of our study show that SSRI/SNRI exposure, in addition to hyponatremia, may also affect the level of serum potassium, serum magnesium and serum creatinine. A history of hyponatremia and exposure to SSRI/SNRI may be potential risk factors for the development of hyponatremia. Future prospective studies are needed to validate these findings.


Assuntos
Hiponatremia , Inibidores da Recaptação de Serotonina e Norepinefrina , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Inibidores Seletivos de Recaptação de Serotonina/efeitos adversos , Serotonina , Inibidores da Recaptação de Serotonina e Norepinefrina/efeitos adversos , Estudos Retrospectivos , Hiponatremia/induzido quimicamente , Hiponatremia/epidemiologia , Hiponatremia/tratamento farmacológico , Norepinefrina/efeitos adversos , Creatinina/efeitos adversos , Magnésio/efeitos adversos , Antidepressivos/efeitos adversos , Sódio/efeitos adversos
9.
ACS Chem Neurosci ; 14(6): 1181-1192, 2023 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-36853167

RESUMO

The present study investigated the antidepressant-like potential of a functionalized 3-selanyl benzo[b]furan (SeBZF) in male Swiss mice. To evaluate possible antidepressant-like actions, the compounds SeBZF1-5 (50 mg/kg, intragastric, i.g., route) were acutely screened in the tail suspension tests (TSTs). The compound 3-((4-methoxyphenyl)selanyl)-2-phenylbenzofuran (SeBZF3) was then selected. Dose-response and time-response curves revealed that SeBFZ3 exerts antidepressant-like effects in the TST (5-50 mg/kg) and forced swimming test (FST; 50 mg/kg). Additional tests demonstrated that pretreatment with receptor antagonists WAY100635 (5-HT1A; 0.1 mg/kg, subcutaneous route), ketanserin (5-HT2A/C; 1 mg/kg, intraperitoneal, i.p.), or ondansetron (5-HT3; 1 mg/kg, i.p.) blocked the SeBZF3 antidepressant-like effects (50 mg/kg) in the TST. In addition, the coadministration of subeffective doses of SeBZF3 (1 mg/kg, i.g.) and fluoxetine (a selective serotonin reuptake inhibitor; 5 mg/kg, i.p.) produced synergistic action. A high dose of SeBZF3 (300 mg/kg) did not produce oral acute toxicity. The present results provide evidence for the antidepressant-like action of SeBZF3 and its relative safety, as well as predict the possible interactions with the serotonergic system, aiding in the development of novel options to alleviate psychiatric disabilities.


Assuntos
Antidepressivos , Serotonina , Masculino , Camundongos , Animais , Serotonina/fisiologia , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Fluoxetina/farmacologia , Inibidores Seletivos de Recaptação de Serotonina/farmacologia , Natação/psicologia , Elevação dos Membros Posteriores/métodos , Elevação dos Membros Posteriores/psicologia , Depressão/tratamento farmacológico
10.
J Obstet Gynaecol Res ; 49(5): 1375-1382, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36822597

RESUMO

AIM: To investigate the current status and problems in the diagnosis and treatment of premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD) from the perspective of obstetricians and gynecologists (OB/GYNs) in Japan, the Japanese Society of Obstetrics and Gynecology (JSOG) conducted a national-wide survey. METHODS: An email survey was sent to all JSOG members (16 732) and a web-based survey was conducted using a Google form between September and November 2021. The current status and problems in PMS/PMDD diagnosis and treatment were surveyed in this cross-sectional study. RESULTS: In total, 1312 respondents (7.8% of all JSOG members) completed the questionnaire. In terms of diagnoses and treatment, OB/GYN was preferred over psychiatrist for PMS (91.4% vs. 45%); however, no differences were noted for PMDD (76.1% vs. 73.7%). A total of 1267 (96.6%) respondents engaged in routine PMS/PMDD treatment. Regarding the general diagnosis procedure, 84.4% respondents answered "only a vague medical interview," 8.4% kept a two-cycle symptom diary, and 10.3% used a screening questionnaire. The most commonly used medication was oral contraceptive pills (OCPs) (98.1%), followed by the Kampo, traditional Japanese herbal medicines, Kamishoyosan (73.6%). Concerning first-line drugs for treatment, OCPs were the most common (76.8%), followed by Kampo medicine (19.5%); selective serotonin reuptake inhibitors (SSRIs) were less frequently used (2.6%). Regarding first-line drugs among OCPs, 65.1% respondents reported drospirenone-ethinylestradriol use. CONCLUSIONS: This study indicates that only a few OB/GYNs practicing PMS/PMDD in Japan use a prospective diary, which is an essential diagnostic criterion for PMS/PMDD. Regarding treatment, SSRIs were used less frequently.


Assuntos
Transtorno Disfórico Pré-Menstrual , Síndrome Pré-Menstrual , Feminino , Humanos , Transtorno Disfórico Pré-Menstrual/diagnóstico , Ginecologista , Obstetra , Inibidores Seletivos de Recaptação de Serotonina , Japão , Estudos Prospectivos , Estudos Transversais , Síndrome Pré-Menstrual/tratamento farmacológico , Anticoncepcionais Orais
11.
Altern Ther Health Med ; 29(3): 282-288, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36634315

RESUMO

Objective: This overview of systematic reviews (SRs) and meta-analyses aims to critically appraise the methodology and reporting quality of relevant SRs and meta-analyses with the aim of identifying whether or not the use of valproate can prevent the switch to mania associated with antidepressant treatment in Chinese patients with depressive episodes. Methods: Electronic databases China National Knowledge Infrastructure (CNKI), Chinese Scientific Journal Database (VIP database) and Wanfang Database were searched for related SRs and meta-analyses from inception to the search date within Chinese restrictions. A total of 2 reviewers independently selected SRs and meta-analyses and collected related data, and a third reviewer was introduced if any disagreement occurred during the assessment. The Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) and the US Agency for Healthcare Research and Quality (AHRQ) were employed to evaluate quality of the reporting and methodology. Results: The switch rate in the sodium valproate group by 99% and was significantly lower than in the antidepressant-only group (0% vs 5.7%; OR = 0.18; 95% CI, 0.04-0.84; Z = 2.18; P = .03). The magnesium valproate group was similar to the sodium valproate group in switch rate; the switch rate in the antidepressant group was (2.2% vs 16.92%; OR = 0.11; 95% CI, 0.03-0.39; Z = 3.47; P = .0005). The switch rate in the salt valproate combined with a selective serotonin reuptake inhibitor (SSRI) group was lower than in the SSRI group (0.51% vs 8.4%; OR = 0.15; 95% CI, 0.04-0.51; Z = 3.01; P = .003). The switch rate in the valproate combined with serotonin noradrenaline reuptake inhibitor (SNRI) group was similar to the valproate combined with SNRI group (2.3% vs 17.5%; OR = 0.12; 95% CI, 0.03-0.53; Z = 2.79; P = .05). Conclusion: Salt valproate can reduce the switch rate related to antidepressant treatment in patients with depression.


Assuntos
Antidepressivos , Inibidores Seletivos de Recaptação de Serotonina , Inibidores da Recaptação de Serotonina e Norepinefrina , Ácido Valproico , Humanos , Antidepressivos/uso terapêutico , População do Leste Asiático , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , Inibidores da Recaptação de Serotonina e Norepinefrina/uso terapêutico , Ácido Valproico/uso terapêutico , Substituição de Medicamentos
12.
Ann Pharmacother ; 57(7): 847-854, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36384314

RESUMO

OBJECTIVE: To evaluate clinical data using oral n-acetylcysteine (NAC) in obsessive-compulsive and related disorders (OCDRD) treatment. DATA SOURCES: PubMed, Ovid MEDLINE (1946-July 2022), and the Cochrane Library database were searched using the terms NAC, children, adolescent, obsessive-compulsive disorder (OCD), trichotillomania (TTM), excoriation, hoarding disorder, and body dysmorphic disorder. Bibliographies were reviewed for relevant trials and case studies. STUDY SELECTION AND DATA EXTRACTION: English language, clinical trials, or case studies analyzing NAC use in patients aged 3 to 21 years old with OCDRD as determined by the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition. DATA SYNTHESIS: Three randomized double-blind placebo-controlled trials of NAC in children and adolescents studied 121 patients with OCDRD. Trials assessed symptom severity from baseline to 10 to 12 weeks of NAC therapy. Two OCD trials identified statistically significant improvements, with only 1 trial demonstrating a clear clinically relevant difference from placebo. One trial in TTM found no difference between the NAC and placebo. Adverse effects were mild and included nausea, blurred vision, fatigue, tremor, and sweats. N-acetylcysteine titrated to 2400 or 2700 mg/day in divided doses was the most studied regimen. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Many OCDRD patients fail to completely respond to first-line treatment with cognitive behavioral therapy (CBT) and/or selective serotonin reuptake inhibitors (SSRIs) leaving practitioners with few additional treatment options. Preliminary efficacy and safety data are presented in this review. CONCLUSIONS: Limited evidence suggests children and adolescents with OCD refractory to SSRIs or CBT may benefit from NAC augmentation.


Assuntos
Terapia Cognitivo-Comportamental , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Transtorno Obsessivo-Compulsivo , Humanos , Adolescente , Criança , Pré-Escolar , Adulto Jovem , Adulto , Acetilcisteína/uso terapêutico , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , Transtorno Obsessivo-Compulsivo/tratamento farmacológico , Transtorno Obsessivo-Compulsivo/diagnóstico , Transtorno Obsessivo-Compulsivo/psicologia , Resultado do Tratamento , Ensaios Clínicos Controlados Aleatórios como Assunto
13.
Adv Clin Exp Med ; 32(2): 151-161, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36226689

RESUMO

BACKGROUND: Depression is the most common mental disorder, affecting about 3.8% of the population worldwide. Clinical symptoms of depression include sadness, anxiety and frequent mood swings, among others. Selective serotonin reuptake inhibitors (SSRIs), psychotherapy and behavioral therapy are commonly used for the treatment of this condition. Since SSRIs are associated with various side effects, extract of St. John's wort (SJW) has been suggested as an effective alternative. However, there are conflicting studies regarding its efficacy. Many studies have reported positive outcomes with low adverse effects, while others did not find it to be a suitable alternative. OBJECTIVES: To analyze the available studies using SJW for depression therapy and to thoroughly evaluate its effectiveness compared to SSRIs and placebo. MATERIAL AND METHODS: Relevant articles for our meta-analysis were found using Medline (via PubMed), Cinahl (via EBSCO), Scopus, and Web of Sciences databases. Studies were included as per the predefined Population, Intervention, Comparison, Outcomes and Study (PICOS) criteria. A demographic summary of the patients treated with either SJW, placebo or SSRIs was collected and Hamilton Depression Rating Scale (HAMD) scores were extracted. Risks of bias analysis, diagnostic odds ratio (OR), risk ratio (RR), and sensitivity calculation were evaluated using Revman software, and the publication bias was assessed using MedCalc software. RESULTS: Fourteen clinical trials with a total of 2270 depression patients were included in accordance with the inclusion criteria. All analyzed papers were published between 2000 and 2022. For patients treated with either SSRIs or SJW, a pooled OR of 2.44 with a 95% confidence interval (95% CI) of 1.33-4.45 was obtained. The data were heterogeneous, with a tau2 value of 0.54, χ2 value of 31.05, degrees of freedom (df) value of 7, I2 value of 77%, and an overall Z-value of 2.90 with p = 0.004. CONCLUSION: Our research supports the use of SJW as it reduced the number of depressive patients and their HAMD scores while having fewer risks and side effects than conventional medications.


Assuntos
Transtorno Depressivo , Hypericum , Humanos , Adulto , Inibidores Seletivos de Recaptação de Serotonina/efeitos adversos , Fitoterapia , Transtorno Depressivo/tratamento farmacológico , Depressão/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Extratos Vegetais/efeitos adversos
14.
Andrology ; 11(1): 112-124, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36193003

RESUMO

BACKGROUND: Premature ejaculation (PE) is still a tough problem in drug treatment. Many clinical trials have proven that traditional Chinese medicine (TCM) has a significant effect in the treatment of PE. This article aims to provide the latest evidence for the efficacy and safety of TCM combined with selective serotonin reuptake inhibitors (SSRIs) in the treatment of PE. METHODS: We looked for randomized controlled trials (RCTs) from China National Knowledge Infrastructure, Wanfang, VIP Database, MEDLINE, PubMed, Web of Science, EMBASE, and Cochrane Library until June 30, 2022. STATA 15.1 software was used to analyze all data for this article. The quality of the included articles was evaluated using the Cochrane Reviewer's Handbook 5.3. RESULTS: Finally, we selected 16 high-quality RCTs in our meta-analysis, which containing 889 patients. Meta-analysis suggested that, compared with SSRIs alone, combination of TCM with SSRIs increased significantly intravaginal ejaculation latencv time and the scores of ejaculation control ability, sexual life satisfaction, PE-related distress, and communication difficulties between partners related to PE. Also, there was no significant difference in adverse effects between the two groups. In addition, the results of publication bias test showed that no significant bias occurred. CONCLUSION: The combined use of TCM and SSRIs has significant effect in the treatment of PE compared with SSRIs monotherapy and was generally well tolerated. Due to the small sample size, multicenter and large sample RCT is still needed in the future to further confirm the effectiveness and safety of TCM combined with SSRIs in the treatment of PE.


Assuntos
Medicina Tradicional Chinesa , Ejaculação Precoce , Humanos , Masculino , Ejaculação , Estudos Multicêntricos como Assunto , Ejaculação Precoce/tratamento farmacológico , Inibidores Seletivos de Recaptação de Serotonina/efeitos adversos
15.
Pharmacotherapy ; 43(7): 691-704, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36524442

RESUMO

Pharmacogenetic testing for psychiatry is growing at a rapid pace, with multiple sites utilizing results to help clinical decision-making. Genotype-guided dosing and drug selection have been implemented at several sites, including Vanderbilt University Medical Center, where clinical decision support (CDS) based on pharmacogenetic results went live for selective serotonin reuptake inhibitors in 2020 for both adult and pediatric patients. Effective and appropriate implementation of CYP2D6- and CYP2C19-guided CDS for the pediatric population requires consideration of the evidence for the pharmacogenetic associations, medication indications, and appropriate alternative therapies to be used when a pharmacogenetic contraindication is identified. In this article, we review these pediatric pharmacogenetic considerations for selective serotonin reuptake inhibitor CDS. We include a case study, the current literature supporting clinical recommendations, considerations when designing pediatric CDS, future implications, and examples of sertraline, (es)citalopram, paroxetine, and fluvoxamine alerts.


Assuntos
Sistemas de Apoio a Decisões Clínicas , Inibidores Seletivos de Recaptação de Serotonina , Adulto , Humanos , Criança , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , Farmacogenética/métodos , Fluvoxamina/farmacologia , Citalopram
16.
BMC Psychiatry ; 22(1): 677, 2022 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-36324116

RESUMO

BACKGROUND: The sociodemographic characteristics and clinical features of the Late-life depression (LLD) patients in psychiatric hospitals have not been thoroughly studied in China. This study aimed to explore the psychiatric outpatient attendance of LLD patients at a psychiatric hospital in China, with a subgroup analysis, such as with or without anxiety, gender differences. METHODS: This retrospective study examined outpatients with LLD from January 2013 to August 2019 using data in the Observational Medical Outcomes Partnership Common Data Model (OMOP-CDM) in Beijing Anding Hospital. Age, sex, number of visits, use of drugs and comorbid conditions were extracted from medical records. RESULTS: In a sample of 47,334 unipolar depression patients, 31,854 (67.30%) were women, and 15,480 (32.70%) were men. The main comorbidities of LDD are generalized anxiety disorder (GAD) (83.62%) and insomnia (74.52%).Among patients with unipolar depression, of which benzodiazepines accounted for the largest proportion (77.77%), Selective serotonin reuptake inhibitors (SSRIs) accounted for 59.00%, a noradrenergic and specific serotonergic antidepressant (NaSSAs) accounted for 36.20%. The average cost of each visit was approximately 646.27 yuan, and the cost of each visit was primarily attributed to Western medicine (22.97%) and Chinese herbal medicine (19.38%). For the cost of outpatient visits, depression comorbid anxiety group had a higher average cost than the non-anxiety group (p < 0.05). There are gender differences in outpatient costs, men spend more than women, for western medicine, men spend more than women, for Chinese herbal medicine, women spend more than men (all p < 0.05). The utilization rate of SSRIs and benzodiazepines in female patients is significantly higher than that in male patients (p < 0.05). CONCLUSION: LLD patients are more commonly women than men and more commonly used SSRIs and NaSSAs. Elderly patients with depression often have comorbid generalized anxiety. LLD patients spend most of their visits on medicines, and while the examination costs are lower.


Assuntos
Depressão , Medicamentos de Ervas Chinesas , Humanos , Feminino , Masculino , Idoso , Depressão/tratamento farmacológico , Depressão/epidemiologia , Estudos Retrospectivos , Big Data , Saúde Mental , Antidepressivos/uso terapêutico , Inibidores Seletivos de Recaptação de Serotonina , Benzodiazepinas , Hospitais
17.
Pharmacol Res ; 184: 106421, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36096427

RESUMO

Depression and anxiety are the most prevalent neuropsychiatric disorders that have emerged as global health concerns. Anxiolytic and antidepressant drugs, such as benzodiazepines, selective serotonin reuptake inhibitors, monoamine oxidase inhibitors, and tricyclics, are the first line used in treating anxiety and depression. Although these drugs lack efficacy and have a delayed response time and numerous side effects, their widespread abuse and market continue to grow. Over time, traditional practices using natural and phytochemicals as alternative therapies to chemical drugs have emerged to treat many pathological conditions, including anxiety and depression. Recent preclinical studies have demonstrated that the phenolic compound, rosmarinic acid, is effective against several neuropsychiatric disorders, including anxiety and depression. In addition, rosmarinic acid showed various pharmacological effects, such as cardioprotective, hepatoprotective, lung protective, antioxidant, anti-inflammatory, and neuroprotective effects. However, the potentialities of the use of rosmarinic acid in the treatment of nervous system-related disorders, such as anxiety and depression, are less or not yet reviewed. Therefore, the purpose of this review was to present several preclinical and clinical studies, when available, from different databases investigating the effects of rosmarinic acid on anxiety and depression. These studies showed that rosmarinic acid produces advantageous effects on anxiety and depression through its powerful antioxidant and anti-inflammatory properties. This review will examine and discuss the possibility that the anxiolytic and anti-depressive effects of rosmarinic acid could be associated with its potent antioxidant and anti-inflammatory activities.


Assuntos
Ansiolíticos , Fármacos Neuroprotetores , Ansiolíticos/farmacologia , Ansiolíticos/uso terapêutico , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Benzodiazepinas , Cinamatos , Depsídeos , Inibidores da Monoaminoxidase , Inibidores Seletivos de Recaptação de Serotonina/farmacologia , Ácido Rosmarínico
18.
Int Urol Nephrol ; 54(11): 2813-2818, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35947279

RESUMO

PURPOSE: Premature ejaculation (PE) is a common sexual dysfunction that significantly affects the quality of life of the patient and their partner. We aimed to compare the efficacy and safety of the combination therapy with biofeedback-guided pelvic floor exercise therapy (BFT) and dapoxetine 30 mg. METHODS: Sixty-five patients diagnosed with lifelong PE were included in the study. Patients were divided into three groups as BFT, dapoxetine 30 mg and a combination of BFT and dapoxetine 30 mg. The patients were compared with the intravaginal ejaculatory latency time (IELT) pre-treatment and post-treatment 1st and 3rd months. RESULTS: The mean IELTs of the patients in Group 1 were 40 s in pre-treatment, 115 s at the end of the 4th week and 140 s at the end of the 12th week. The IELT values of the patients in Group 2 were 40 s in pre-treatment, 145 s in the 4th week and 170 s in the 12th week. The IELT values were calculated in Group 3 as 42.5 s in pre-treatment, 185 s in the 4th week and 205 s in the 12th week When the IELT was statistically compared between the groups at 1st and 3rd months, the duration in the combination group was found to increase significantly (p < 0.001). CONCLUSION: Combination therapy with BFT and dapoxetine 30 mg in lifelong PE treatment is a good alternative with a low side effect profile and acceptable continuous efficiency.


Assuntos
Ejaculação Precoce , Benzilaminas , Biorretroalimentação Psicológica , Ejaculação , Humanos , Masculino , Naftalenos , Ejaculação Precoce/tratamento farmacológico , Estudos Prospectivos , Qualidade de Vida , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , Resultado do Tratamento
19.
J Affect Disord ; 317: 228-235, 2022 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-36029878

RESUMO

BACKGROUND: Persistent low grade depression symptoms are common and impairing in major depressive disorder (MDD) yet rarely reported in treatment follow-up studies (Judd et al., 1998a; Kennedy et al., 2004), suggesting that extant sustained remission rates may not reflect this important clinical feature. Furthermore, no long-term MDD treatment follow-up study has reported on quality of life ratings across functioning levels and years throughout the follow-up period, thus the severity, breadth, and persistence of functional impairment remain unclear. Accordingly, the current study evaluated the course of MDD with consideration of low grade depressive symptomatology and holistic features (e.g., quality of life). METHODS: We report long-term (9-14 years) follow-up data from individuals with MDD (N = 37) who underwent either Cognitive Therapy (CBT) or a course of selective serotonin reuptake inhibitor (SSRI) treatment. Patients provided retrospective reports of depression symptoms and quality of life in the years following treatment. RESULTS: Chronic depression symptoms (most often mild in severity) and decreased quality of life in multiple domains are frequent and suggest poorer sustained remission rates than previously observed in the literature. LIMITATIONS: Study limitations include small sample size recruited via convenience sampling methods. CONCLUSIONS: Findings support a conceptualization of depression recovery that entails persistent symptoms and vulnerabilities. Clinical recommendations are provided for discussing these features of depression recovery with patients.


Assuntos
Transtorno Depressivo Maior , Inibidores Seletivos de Recaptação de Serotonina , Depressão/terapia , Transtorno Depressivo Maior/diagnóstico , Transtorno Depressivo Maior/tratamento farmacológico , Seguimentos , Humanos , Qualidade de Vida , Estudos Retrospectivos , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico
20.
CNS Neurosci Ther ; 28(9): 1461-1463, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35687531

RESUMO

Lifelong premature ejaculation patients had altered structural and functional parameters of the hypothalamus compared with healthy controls. The patients showed increased hypothalamus-related functional connectivity in several regions one hour after dapoxetine administration. The changing trends of the brain functional connectivity after dapoxetine administration possibly provided important information about the selective serotonin reuptake inhibitor effects on the functional neural system.


Assuntos
Ejaculação Precoce , Encéfalo , Cabeça , Humanos , Hipotálamo , Masculino , Ejaculação Precoce/tratamento farmacológico , Inibidores Seletivos de Recaptação de Serotonina/farmacologia
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