RESUMEN
Aim: Hypidone hydrochloride (YL-0919) was a novel combined selective serotonin reuptake inhibitor and 5-hydroxytryptamine receptor agonist for treatment of major depressive disorder. Quantitation of YL-0919 in plasma samples was critical for evaluation of its pharmacokinetics in clinical studies. Methodology & results: An ultra HPLC-MS/MS method has been developed and validated. Plasma samples were extracted by SPE method and then chromatographed on an Acquity BEH C18 column. Detection was performed on an API-5500 tandem mass spectrometer using positive ESI. Conclusion: A sensitive and robust method was developed and validated for quantitative analysis of YL-0919 in human plasma samples for the first time. And this novel method was successfully applied to investigate pharmacokinetic profiles of YL-0919 in Chinese healthy subjects.
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Cromatografía Líquida de Alta Presión , Piperidinas/sangre , Piridonas/sangre , Espectrometría de Masas en Tándem , Cromatografía Líquida de Alta Presión/normas , Semivida , Humanos , Límite de Detección , Piperidinas/aislamiento & purificación , Piperidinas/normas , Piridonas/aislamiento & purificación , Piridonas/normas , Control de Calidad , Reproducibilidad de los Resultados , Inhibidores Selectivos de la Recaptación de Serotonina/sangre , Inhibidores Selectivos de la Recaptación de Serotonina/aislamiento & purificación , Inhibidores Selectivos de la Recaptación de Serotonina/normas , Extracción en Fase Sólida , Espectrometría de Masas en Tándem/normasRESUMEN
INTRODUCTION: Soldiers have a higher risk for developing psychiatric disorders that require treatment; often with antidepressants. However, antidepressants as well as the psychiatric disorder, may influence military readiness in several ways. In the general population, early discontinuation of antidepressant treatment is often seen. It is yet unknown whether this occurs to a similar extent in soldiers. The objective of this study was to evaluate discontinuation of antidepressant use by Dutch soldiers in the first 12 months after start and determinants thereof. MATERIALS AND METHODS: Data were obtained from the military pharmacy. All Dutch soldiers who started using an antidepressant between 2000 and 2014 were included. Kaplan-Meier curves were constructed to estimate the discontinuation rate over time and the influence of each determinant on discontinuation rate was estimated using Cox regression. RESULTS: About 25.9% of de 2479 starters had discontinued their antidepressant use after 1 month; after 3 and 6 months this number increased to 52.7% and 70.3%, respectively. Early discontinuation was higher in soldiers who received their first prescription from a neurologist or rehabilitation specialist (HR 1.85, 95% CI 1.55-2.21, HR 2.66 95% CI 1.97-3.58) compared to soldiers with a first prescription from a general practitioner. In addition, early discontinuation was lower in soldiers who were prescribed serotonin reuptake inhibitors and other antidepressants (HR 0.57, 95% CI 0.51-0.60, HR 0.63, 95% CI 0.55-0.73) and in soldiers between 40 and 50 years of age (HR 0.79, 95% CI 0.70-0.89). CONCLUSION: More than half of the soldiers discontinued their prescribed antidepressant within 3 months and after 6 months, only 30% were still on antidepressants.
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Antidepresivos/uso terapéutico , Cumplimiento de la Medicación/estadística & datos numéricos , Personal Militar/psicología , Adulto , Antidepresivos/normas , Depresión/tratamiento farmacológico , Depresión/epidemiología , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Cumplimiento de la Medicación/psicología , Persona de Mediana Edad , Personal Militar/estadística & datos numéricos , Países Bajos/epidemiología , Inhibidores Selectivos de la Recaptación de Serotonina/normas , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéuticoRESUMEN
A capillary electrophoresis method was developed and validated for the determination of the purity of dapoxetine with regard to the related substances (3S)-3-amino-3-phenylpropan-1-ol, (3S)-3-(dimethylamino)-3-phenylpropan-1-ol, 1-naphthol and the enantiomer (R)-dapoxetine. The separation was based on a dual selector system, which was optimized by a fractional factorial resolution V + design followed by a central composite face centered design with star distance 1 and Monte Carlo simulations for defining the design space. The optimized background electrolyte consisted of a 50 mM sodium phosphate buffer, pH 6.3, containing 45 mg/mL sulfated γ-cyclodextrin and 40.2 mg/mL 2,6-dimethyl-ß-cyclodextrin. Separations were carried out in a 23.5/32 cm, 50 µm fused-silica capillary employing a separation voltage of 9 kV at 15 °C. Following robustness testing using a Plackett-Burman design the method was validated according to the International Council on Harmonization guideline Q2(R1) in the range of 0.05-1.0% relative to the dapoxetine concentration. The method was applied to the analysis of drug substance and a commercial tablet. Data regarding the enantiomeric purity of dapoxetine obtained by the capillary electrophoresis assay were comparable to the data obtained by an enantioselective HPLC method.
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Bencilaminas/análisis , Contaminación de Medicamentos , Electroforesis Capilar/métodos , Naftalenos/análisis , Naftoles/análisis , Inhibidores Selectivos de la Recaptación de Serotonina/análisis , Bencilaminas/normas , Simulación por Computador , Método de Montecarlo , Naftalenos/normas , Control de Calidad , Reproducibilidad de los Resultados , Inhibidores Selectivos de la Recaptación de Serotonina/normas , Estereoisomerismo , ComprimidosAsunto(s)
Colectomía/métodos , Nefrectomía/métodos , Atención Perioperativa/educación , Anciano , Anciano de 80 o más Años , Anticoagulantes/normas , Anticoagulantes/uso terapéutico , Artroplastia de Reemplazo de Cadera/métodos , Artroplastia de Reemplazo de Cadera/normas , Artroplastia de Reemplazo de Rodilla/métodos , Artroplastia de Reemplazo de Rodilla/normas , Aspirina/administración & dosificación , Aspirina/uso terapéutico , Factores Biológicos/normas , Factores Biológicos/uso terapéutico , Extracción de Catarata/métodos , Extracción de Catarata/normas , Colectomía/normas , Puente de Arteria Coronaria/métodos , Puente de Arteria Coronaria/normas , Femenino , Hernia Inguinal/cirugía , Humanos , Insulina/normas , Insulina/uso terapéutico , Masculino , Mastectomía Segmentaria/métodos , Medicina , Persona de Mediana Edad , Nefrectomía/normas , Atención Perioperativa/normas , Guías de Práctica Clínica como Asunto , Factores de Riesgo , Inhibidores Selectivos de la Recaptación de Serotonina/normas , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéutico , Accidente Cerebrovascular/prevención & control , Urinálisis/estadística & datos numéricosAsunto(s)
Antidepresivos Tricíclicos/normas , Trastorno Depresivo/tratamiento farmacológico , Inhibidores Selectivos de la Recaptación de Serotonina/normas , Antidepresivos Tricíclicos/efectos adversos , Antidepresivos Tricíclicos/uso terapéutico , Trastorno Depresivo Mayor/tratamiento farmacológico , Humanos , Inhibidores Selectivos de la Recaptación de Serotonina/efectos adversos , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéuticoRESUMEN
BACKGROUND: Unlike civilian post-traumatic stress disorder (PTSD), the efficacy of sertraline for the treatment of combat-related PTSD has not yet been proven. The present study aimed to evaluate the clinical efficacy of sertraline against combat-related PTSD in a randomized, double-blind, placebo-controlled trial. METHOD: Seventy Iranian veterans of the Iran-Iraq war who met the DSM-IV criteria for diagnosis of PTSD were randomized to receive either flexibly dosed sertraline (50-200 mg/day) (n=35, completers=32) or placebo (n=35, completers=30) for 10 weeks. Efficacy was evaluated by the Impact of Event Scale--Revised (IES-R) and the Clinical Global Impression scale--Severity (CGI-S) and Improvement (CGI-I) ratings. Responder criteria were defined as a ≥30% reduction in the IES-R total score plus a CGI-I rating of 'much' or 'very much' improved. RESULTS: On both intention-to-treat (ITT) and per protocol (completer) methods of analysis, the mean reductions in the IES-R total and subscale (re-experiencing/intrusion, avoidance/numbing and hyperarousal) scores (p<0.001) and also in the CGI-S score (p<0.01) were significantly greater in the sertraline group than in the placebo group. For the CGI-I, the mean endpoint score was significantly lower in the sertraline group than in the placebo group (p≤0.001). The number of responders in the sertraline group was significantly higher than in the placebo group (44% v. 3%, p≤0.001). Sertraline was well tolerated, with a 6% discontinuation rate as a result of adverse reactions. CONCLUSIONS: The results of this study suggest that sertraline can be an effective, safe and tolerable treatment for combat-related PTSD in Iranian veterans.
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Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéutico , Sertralina/uso terapéutico , Trastornos por Estrés Postraumático/tratamiento farmacológico , Veteranos/psicología , Adulto , Método Doble Ciego , Humanos , Análisis de Intención de Tratar , Irán , Masculino , Persona de Mediana Edad , Placebos , Escalas de Valoración Psiquiátrica , Inhibidores Selectivos de la Recaptación de Serotonina/efectos adversos , Inhibidores Selectivos de la Recaptación de Serotonina/normas , Sertralina/efectos adversos , Sertralina/normas , Trastornos por Estrés Postraumático/diagnóstico , Trastornos por Estrés Postraumático/etiología , Resultado del Tratamiento , GuerraRESUMEN
BACKGROUND: Selective serotonin reuptake inhibitors take several weeks to achieve their full antidepressant effects. Post-synaptic 5-HT2A receptor activation is thought to be involved in this delayed therapeutic effect. Pipamperone acts as a highly selective 5-HT2A/D4 antagonist when administered in low doses. The purpose of this study was to compare citalopram 40 mg once daily plus pipamperone 5 mg twice daily (PipCit) versus citalopram plus placebo twice daily for magnitude and onset of therapeutic effect. METHOD: An 8-week, randomized, double-blind study in patients with major depressive disorder was carried out. RESULTS: The study population comprised 165 patients (citalopram and placebo, n=82; PipCit, n=83) with a mean baseline Montgomery-Asberg Depression Rating Scale (MADRS) score of 32.6 (s.d.=5.5). In the first 4 weeks, more citalopram and placebo than PipCit patients discontinued treatment (18% v. 4%, respectively, p=0.003). PipCit patients had significantly greater improvement in MADRS score at week 1 [observed cases (OC), p=0.021; last observation carried forward (LOCF), p=0.007] and week 4 (LOCF, p=0.025) but not at week 8 compared with citalopram and placebo patients. Significant differences in MADRS scores favoured PipCit in reduced sleep, reduced appetite, concentration difficulties and pessimistic thoughts. Mean Clinical Global Impression-Improvement scores were significantly improved after 1 week of PipCit compared with citalopram and placebo (OC and LOCF, p=0.002). CONCLUSIONS: Although the MADRS score from baseline to 8 weeks did not differ between groups, PipCit provided superior antidepressant effects and fewer discontinuations compared with citalopram and placebo during the first 4 weeks of treatment, especially in the first week.
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Butirofenonas/uso terapéutico , Citalopram/uso terapéutico , Trastorno Depresivo Mayor/tratamiento farmacológico , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéutico , Antagonistas de la Serotonina/uso terapéutico , Adolescente , Adulto , Anciano , Butirofenonas/administración & dosificación , Butirofenonas/efectos adversos , Butirofenonas/normas , Citalopram/administración & dosificación , Citalopram/efectos adversos , Citalopram/normas , Trastorno Depresivo Mayor/diagnóstico , Método Doble Ciego , Quimioterapia Combinada , Femenino , Humanos , Masculino , Persona de Mediana Edad , Placebos , Escalas de Valoración Psiquiátrica , Escocia , Antagonistas de la Serotonina/administración & dosificación , Antagonistas de la Serotonina/efectos adversos , Antagonistas de la Serotonina/normas , Inhibidores Selectivos de la Recaptación de Serotonina/administración & dosificación , Inhibidores Selectivos de la Recaptación de Serotonina/efectos adversos , Inhibidores Selectivos de la Recaptación de Serotonina/normas , Resultado del Tratamiento , Adulto JovenRESUMEN
INTRODUCTION: Preliminary studies have suggested that balneotherapy (BT) is an effective and well-tolerated treatment for generalized anxiety disorder (GAD) and psychotropic medication withdrawal syndrome. We carried out a study in 4 spa resorts to assess the efficacy of BT in GAD. METHOD: We compared BT to paroxetine in terms of efficacy and safety in a randomized multicentre study lasting 8 weeks. Patients meeting the diagnostic criteria of GAD (DSM-IV) were recruited. Assessments were conducted using the Hamilton Rating Scale for Anxiety (HAM-A) and other scales, by a specifically trained and independent physician. The primary outcome measure was the change in the total HAM-A score between baseline and week 8. RESULTS: A total of 237 outpatients were enrolled in four centres; 117 were assigned randomly to BT and 120 to paroxetine. The mean change in HAM-A scores showed an improvement in both groups with a significant advantage of BT compared to paroxetine (-12.0 vs -8.7; p<0.001). Remission and sustained response rates were also significantly higher in the BT group (respectively 19% vs 7% and 51% vs 28%). CONCLUSION: BT is an interesting way of treating GAD. Due to its safety profile it could also be tested in resistant forms of generalized anxiety and in patients who do not tolerate or are reluctant to use pharmacotherapies.
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Trastornos de Ansiedad/terapia , Balneología , Paroxetina/uso terapéutico , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéutico , Adulto , Anciano , Balneología/métodos , Balneología/normas , Femenino , Francia , Humanos , Masculino , Persona de Mediana Edad , Paroxetina/efectos adversos , Paroxetina/normas , Escalas de Valoración Psiquiátrica , Inhibidores Selectivos de la Recaptación de Serotonina/efectos adversos , Inhibidores Selectivos de la Recaptación de Serotonina/normas , Resultado del TratamientoAsunto(s)
Ciclohexanoles/normas , Ciclohexanoles/uso terapéutico , Trastorno Depresivo/tratamiento farmacológico , Aprobación de Drogas/legislación & jurisprudencia , Inhibidores Selectivos de la Recaptación de Serotonina/normas , Tiofenos/normas , Tiofenos/uso terapéutico , Vino/normas , Trastornos de Ansiedad/tratamiento farmacológico , Comparación Transcultural , Clorhidrato de Duloxetina , Europa (Continente) , Humanos , Efecto Placebo , Guías de Práctica Clínica como Asunto , Ensayos Clínicos Controlados Aleatorios como Asunto/estadística & datos numéricos , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéutico , Resultado del Tratamiento , Estados Unidos , United States Food and Drug Administration/legislación & jurisprudencia , Clorhidrato de VenlafaxinaRESUMEN
KEY POINTS: (1) A large number of treatment options have shown generally moderate efficacy in the treatment of diabetic painful neuropathy.(2) Tricyclic antidepressants are the mainstay of therapy, with anticonvulsants, opioids and serotonin-noradrenaline reuptake inhibitors also having a place.(3) Head-to-head trials of current treatments are needed. Meanwhile, selection of therapeutic agents should be individualised.
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Analgésicos/normas , Ensayos Clínicos como Asunto/estadística & datos numéricos , Neuropatías Diabéticas/tratamiento farmacológico , Analgésicos/farmacología , Analgésicos Opioides/farmacología , Analgésicos Opioides/normas , Anticonvulsivantes/farmacología , Anticonvulsivantes/normas , Antidepresivos Tricíclicos/farmacología , Antidepresivos Tricíclicos/normas , Neuropatías Diabéticas/fisiopatología , Humanos , Inhibidores Selectivos de la Recaptación de Serotonina/farmacología , Inhibidores Selectivos de la Recaptación de Serotonina/normas , Resultado del TratamientoRESUMEN
Platelets, the smallest corpuscular component of human blood, are central to various crucial biologic pathways in the human body. Diminished platelet function is thought to contribute to the increased risk of ischemic heart disease in patients with major depressive disorder, and to the increased morbidity and diminished survival of depressed patients after an index myocardial infarction. We reviewed both recent studies that evaluated platelet function in various patient groups and recent information regarding the potential beneficial effects of selective serotonin reuptake inhibitors on platelet reactivity.
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Trastornos de las Plaquetas Sanguíneas/psicología , Trastorno Depresivo/complicaciones , Isquemia Miocárdica/psicología , Trastornos de las Plaquetas Sanguíneas/tratamiento farmacológico , Trastornos de las Plaquetas Sanguíneas/etiología , Humanos , Infarto del Miocardio/etiología , Infarto del Miocardio/psicología , Isquemia Miocárdica/etiología , Inhibidores Selectivos de la Recaptación de Serotonina/normas , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéutico , Estrés Psicológico/complicacionesRESUMEN
Although the number of prescriptions for psychotropic drugs has decreased in recent years, prescriptions for antidepressants are still increasing (Fritze 2002). Hypericum perforatum (St John's wort) is the main psychotherapeutic herbal medicinal product used for treatment of mild-to-moderate depression. The lipophilic constituent hyperforin (2-5% of the extract) demonstrated, similarly to chemical antidepressants, a significant effect on the synaptosomal uptake inhibition of several neurotransmitters in in-vitro assays. In Germany, St John's wort products are distributed via two different markets: products that are pharmacy restricted are only allowed to be distributed in pharmacies; traditionally used products, which do not claim to have a curative character, are allowed to be sold in supermarkets. Depending on the market wherein a St John's wort product is offered, it needs to fulfill the legal requirements regarding pharmaceutical quality, safety and efficacy. Our goal was to compare the quality of St John's wort products distributed in pharmacies with that of those available from supermarkets. Therefore, the quantity of the pharmaceutical active ingredients (the phloroglucinol derivate hyperforin, the flavonoids rutin, hyperoside, isoquercitrin, quercitrin and the biflavonoid biapigenin) was determined by high-performance liquid chromatography (HPLC). The naphthodianthrones hypericines and pseudohypericines were quantified by differential pulse polarography (DPP). The efficacy of the products was investigated by measuring their activity to inhibit serotonin (5-HT) uptake in-vitro using a radio ligand uptake assay. It could be demonstrated that the products were different not only in the concentration of pharmaceutically relevant ingredients but also in showing individual IC50 values (concentration producing half-maximal inhibition) in the serotonin reuptake assay (IC50 values between 3.07 and 17.9 microg extract mL(-1)). The results of our study confirm the assumption that the potency of St John's wort products in inhibiting the uptake of serotonin depends on the amount of hyperforin in their dosage forms. St John's wort products having greater hyperforin content and potency on synaptosomal serotonin uptake inhibition are restricted to be sold only in pharmacies.
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Hypericum/química , Inhibidores Selectivos de la Recaptación de Serotonina/química , Inhibidores Selectivos de la Recaptación de Serotonina/farmacología , Sinaptosomas/metabolismo , Animales , Cromatografía Líquida de Alta Presión , Control de Medicamentos y Narcóticos , Lóbulo Frontal/ultraestructura , Alemania , Técnicas In Vitro , Ratones , Extractos Vegetales/química , Extractos Vegetales/farmacología , Extractos Vegetales/normas , Polarografía , Inhibidores Selectivos de la Recaptación de Serotonina/normasAsunto(s)
Antidepresivos de Segunda Generación/antagonistas & inhibidores , Antidepresivos de Segunda Generación/uso terapéutico , Interpretación Estadística de Datos , Industria Farmacéutica , Paroxetina/antagonistas & inhibidores , Paroxetina/uso terapéutico , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéutico , Adolescente , Antidepresivos de Segunda Generación/normas , Niño , Protección a la Infancia , Ensayos Clínicos como Asunto , Depresión/tratamiento farmacológico , Industria Farmacéutica/normas , Humanos , América del Norte , Paroxetina/normas , Inhibidores Selectivos de la Recaptación de Serotonina/normas , Recursos HumanosRESUMEN
Los inhibidores selectivos de la recaptación de serotonina (ISRS) constituyen un grupo de fármacos que ha experimentado un gran auge, tanto a nivel de utilización clínica como de investigación científica. Por este motivo, hemos realizado un estudio bibliométrico sobre el uso clínico de estos fármacos a través de las publicaciones científicas de circulación internacional. La base de datos empleada fue EMBASE: Psychiatry CD-ROM. En total, se recogieron 3622 documentos publicados entre 1980 y 2000, que contenían en el título los descriptores fluvoxamine, fluoxetine, paroxetine, sertraline o citalopram. Nuestros resultados constatan un importante incremento de la producción científica sobre ISRS a lo largo de estas dos décadas. Fluoxetina es el ISRS que aporta mayor número de documentos (1.745), seguido de paroxetina (659). Los documentos se adscribieron a 4 grupos: Farmacología experimental (8,38 por ciento), Tolerancia y seguridad (34,94 por ciento), Eficacia clínica (49,11 por ciento) y Sin especificar (7,56 por ciento). Las categorías diagnósticas DSM-IV más estudiadas correspondieron a depresión (834), trastorno obsesivo-compulsivo (TOC) (171) y trastorno de pánico (75). Entre las patologías psiquiátricas no aprobadas, destaca la esquizofrenia (49) y el alcoholismo (42), y entre las no psiquiátricas, el síndrome premenstrual (30), las demencias (20) y la obesidad (18). Paroxetina ha dedicado, proporcionalmente, más trabajos a la depresión, a la fobia social y al trastorno de ansiedad generalizada, fluvoxamina al TOC, citalopram al trastorno de pánico, fluoxetina a la bulimia nerviosa y sertralina al síndrome premenstrual y al trastorno por estrés posttraumático. Los antidepresivos de control más utilizados en los estudios clínicos comparativos de los ISRS fueron amitriptilina (51), imipramina (42) y clomipramina (32). (AU)
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Inhibidores Selectivos de la Recaptación de Serotonina/administración & dosificación , Inhibidores Selectivos de la Recaptación de Serotonina/análisis , Sistemas de Información , Sistemas de Información/clasificación , Fluoxetina/administración & dosificación , Psicofarmacología/clasificación , Psicofarmacología/estadística & datos numéricos , Psicofarmacología/métodos , Inhibidores Selectivos de la Recaptación de Serotonina/metabolismo , Inhibidores Selectivos de la Recaptación de Serotonina/normas , Esquizofrenia/tratamiento farmacológico , Alcoholismo/tratamiento farmacológico , Síndrome Premenstrual/tratamiento farmacológico , Síndrome Premenstrual/psicología , Trastornos de Ansiedad/tratamiento farmacológico , Trastornos de Ansiedad/psicología , Amitriptilina/administración & dosificación , Imipramina/administración & dosificación , Clomipramina/administración & dosificaciónRESUMEN
We tested whether 14 wk of dexfenfluramine (30 mg) or fluoxetine (40 mg) treatment would prevent weight gain after subjects quit smoking. Normal-weight women (n = 144) were randomly assigned to drug or placebo on a double-blind basis for 2 wk before quitting smoking and 12 wk thereafter. The fluoxetine group had more dropouts (28/49, 57.1%) than the dexfenfluramine group (17/47, 36.2%), with an intermediate number of dropouts from the placebo group (21/48, 43.8%). All groups gained weight during treatment, but their amount and pattern of weight gain differed. In the first month after quitting smoking, the placebo group gained more weight than either the dexfenfluramine or fluoxetine group (P < 0.05). By 2 mo postcessation, dexfenfluramine still suppressed weight gain in comparison with placebo (P < 0.05); weight gain with fluoxetine was not differentiable from either dexfenfluramine or placebo. By 3 mo postcessation, the dexfenfluramine group had gained 1.0 +/- 0.7 kg, significantly less than either the placebo (3.5 +/- 0.7 kg) or fluoxetine (2.7 +/- 0.5 kg) groups. Three months after drug discontinuation, formerly medicated, but not placebo patients, showed additional weight gain, eliminating differences between groups. Results indicate that weight gain, an adverse accompaniment of smoking cessation, can be minimized to some degree by serotoninergic drugs, although only for the duration of drug treatment.