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1.
J Clin Psychopharmacol ; 34(1): 57-65, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24346751

RESUMEN

OBJECTIVE: This post hoc analysis assessed the predictive value of improvement in depressive scores at early time points for treatment outcomes at week 8 in patients with major depressive disorder treated with desvenlafaxine 50 mg/d or placebo. METHODS: Pooled data from 6 double-blind, fixed-dose studies in adult patients with major depressive disorder. Patients were randomly assigned to desvenlafaxine or placebo. Primary end point was change in 17-item Hamilton Rating Scale for Depression (HAM-D17) scores from baseline to week 8 (or last observation carried forward). Optimal thresholds of improvement (percent change from baseline HAM-D17) at weeks 2 and 3 for predicting 4 levels of treatment success (≥ 45%, ≥ 50%, and ≥ 65% decrease from baseline HAM-D17, HAM-D17 ≤ 7) at week 8 (last observation carried forward) were determined using receiver operating characteristic analysis. Odds ratios of the predictability of improvement thresholds were computed from a logistic regression model adjusting for significant baseline predictors. RESULTS: Desvenlafaxine 50 mg/d (n = 1207) had significantly greater rates of treatment success for each level of treatment success at 8 weeks compared with placebo (n = 1067). Optimal early improvement thresholds for weeks 2 (20%-30%) and 3 (28%-41%) were highly predictive of all 4 levels of treatment success after adjusting for significant baseline predictors (odds ratios, 0.951-0.960; all P < 0.0001). Negative predictive value of early improvement increased, and positive predictive value decreased, for increasingly stringent definitions of treatment success at week 8. CONCLUSIONS: Clinical observations of patients' early response to desvenlafaxine 50 mg/d may have clinical value in predicting treatment success and guiding patient management.


Asunto(s)
Inhibidores de Captación Adrenérgica/administración & dosificación , Antidepresivos/administración & dosificación , Ciclohexanoles/administración & dosificación , Trastorno Depresivo Mayor/tratamiento farmacológico , Inhibidores Selectivos de la Recaptación de Serotonina/administración & dosificación , Adolescente , Inhibidores de Captación Adrenérgica/efectos adversos , Adulto , Anciano , Anciano de 80 o más Años , Antidepresivos/efectos adversos , Ciclohexanoles/efectos adversos , Trastorno Depresivo Mayor/diagnóstico , Trastorno Depresivo Mayor/psicología , Succinato de Desvenlafaxina , Método Doble Ciego , Esquema de Medicación , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Escalas de Valoración Psiquiátrica , Ensayos Clínicos Controlados Aleatorios como Asunto , Inducción de Remisión , Inhibidores Selectivos de la Recaptación de Serotonina/efectos adversos , Factores de Tiempo , Resultado del Tratamiento , Adulto Joven
2.
CNS Spectr ; 19(6): 519-27, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-24571916

RESUMEN

BACKGROUND: The predictive value of early functional improvement for treatment success at week 8 was assessed in a pooled analysis in patients with major depressive disorder (MDD). METHODS: Data were pooled from 7 double-blind studies in adult patients with MDD randomly assigned to desvenlafaxine 50 mg/d or placebo. Four levels of treatment success were determined at week 8 for patients with baseline Sheehan Disability Scale (SDS) score > 12 (N = 2156): functional response (SDS ≤12 and ≥50% improvement in SDS), functional/depression response (SDS ≤12 and ≥50% improvement in both SDS and 17-item Hamilton Rating Scale for Depression [HAM-D17] score), functional remission (SDS < 7), and functional/depression remission (SDS < 7 and HAM-D17 ≤7). Week 2 improvement in SDS was evaluated as a predictor of later functional response/remission using receiver operating characteristic analysis. Odds ratios (ORs) of the predictability of improvement thresholds were computed from a logistic regression model. RESULTS: The proportion of patients achieving each level of treatment success was significantly greater for patients treated with desvenlafaxine (40%, 32%, 23%, 15%, respectively) vs placebo (31%, 22%, 17%, 10%; all P ≤ 0.002). Early change in SDS was a highly significant predictor of functional response/remission (ORs, 0.958-0.970; all P < 0.0001). Discussion Patients' early functional response to desvenlafaxine 50 mg/d is predictive of treatment success.


Asunto(s)
Antidepresivos/uso terapéutico , Ciclohexanoles/uso terapéutico , Trastorno Depresivo Mayor/tratamiento farmacológico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Succinato de Desvenlafaxina , Evaluación de la Discapacidad , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Multicéntricos como Asunto , Valor Predictivo de las Pruebas , Escalas de Valoración Psiquiátrica , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del Tratamiento , Adulto Joven
3.
Hum Psychopharmacol ; 29(5): 492-501, 2014 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-25196042

RESUMEN

BACKGROUND: Desvenlafaxine (administered as desvenlafaxine succinate) for anxious depression was assessed in a post hoc analysis. METHODS: Data were pooled from patients randomly assigned to desvenlafaxine 50 mg/day or placebo in seven double-blind, fixed-dose studies in adults with major depressive disorder. Patients with "anxious depression" had baseline 17-item Hamilton Rating Scale for Depression, anxiety-somatization factor (HAM-D17 A/S) scores ≥7. Primary end point was change in HAM-D17 scores from baseline at week 8 (last observation carried forward), evaluated using analysis of covariance with treatment, study, and baseline value as covariates. RESULTS: A total of 1873/2706 (69%) patients were identified as "anxious depressed". Desvenlafaxine significantly improved HAM-D17 total scores versus placebo in anxious (adjusted mean [95% CI] -1.72 [-2.35, -1.09]; p < 0.001) and nonanxious (-1.48 [-2.40, -0.57]; p = 0.002) populations, with no significant treatment-by-anxiety interaction. Response and remission rates (HAM-D17 ) were significantly higher with desvenlafaxine compared with placebo in both populations. Treatment-emergent adverse events were reported by 78% and 69% (desvenlafaxine versus placebo, respectively) of anxious depressed patients and by 77% and 68% of nonanxious patients. CONCLUSION: Desvenlafaxine 50 mg/day significantly improved depressive symptoms compared with placebo in major depressive disorder patients with clinically relevant anxiety symptoms. Improvement in the HAM-D17 total score was similar for anxious/nonanxious groups.


Asunto(s)
Ansiolíticos/uso terapéutico , Antidepresivos/uso terapéutico , Ansiedad/tratamiento farmacológico , Ciclohexanoles/uso terapéutico , Trastorno Depresivo Mayor/tratamiento farmacológico , Ansiolíticos/efectos adversos , Antidepresivos/efectos adversos , Ciclohexanoles/efectos adversos , Trastorno Depresivo Mayor/psicología , Succinato de Desvenlafaxina , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto
4.
Clin Ther ; 46(2): 96-103, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-38195348

RESUMEN

PURPOSE: Methicillin-resistant Staphylococcus aureus infections are increasing in prevalence in patients with cystic fibrosis (CF) and are associated with worsening lung function and increased mortality. Lefamulin is a pleuromutilin antimicrobial approved to treat community-acquired bacterial pneumonia based on potent in vitro activity and clinical efficacy. This Phase I, open-label, randomized crossover study assessed the safety and pharmacokinetic profile of oral and intravenous (IV) lefamulin in adults with CF. METHODS: The study comprised 2 dosing periods in which adults with CF (N = 13) received a single dose of lefamulin via a 150-mg IV infusion or 600-mg immediate-release orally administered tablet, separated by a 4- to 7-day washout period. Pharmacokinetic and safety parameters were assessed after lefamulin treatment. FINDINGS: Single doses of lefamulin administered via oral tablet or IV infusion resulted in comparable drug exposure, and sputum analysis suggested rapid penetration of lefamulin into the lung. Comparison of the present results with those obtained from prior single-dose studies of healthy volunteers indicate no meaningful difference in the pharmacokinetic properties of lefamulin in patients with CF. Treatment-emergent adverse events were consistent with previous reports, and the majority were mild in severity. IMPLICATIONS: These results show similar lefamulin pharmacokinetic and safety profiles between patients with CF and healthy volunteers receiving the same oral and IV doses, suggesting no need for lefamulin dose adjustment in patients with CF and indicating the potential of lefamulin as therapy for lung infections in patients with CF. CLINICALTRIALS: gov identifier: NCT05225805.


Asunto(s)
Fibrosis Quística , Diterpenos , Staphylococcus aureus Resistente a Meticilina , Neumonía , Compuestos Policíclicos , Tioglicolatos , Adulto , Humanos , Antibacterianos , Fibrosis Quística/tratamiento farmacológico , Fibrosis Quística/inducido químicamente , Estudios Cruzados , Neumonía/tratamiento farmacológico , Comprimidos/farmacocinética
5.
J Clin Psychopharmacol ; 31(5): 569-76, 2011 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-21869698

RESUMEN

OBJECTIVE: This is the first study to assess the efficacy of desvenlafaxine (administered as desvenlafaxine succinate) for improving depressive symptoms and functioning exclusively in employed patients with major depressive disorder (MDD). METHODS: Gainfully employed (≥20 h/wk) male and female outpatients with MDD were randomly assigned (2:1 ratio) to 12 weeks of double-blind treatment with desvenlafaxine 50 mg/d or placebo. Analysis of covariance was used to compare differences in week 12 adjusted mean changes from baseline on the 17-item Hamilton Depression Rating Scale (HAM-D17) (primary outcome) and Sheehan Disability Scale (SDS) (key secondary outcome) in the intent-to-treat (ITT) population. A predefined, modified ITT population (ie, those in the ITT population with baseline HAM-D17 ≥20) was also analyzed. Tolerability was assessed by recording adverse events and change on the Arizona Sexual Experience Scale. RESULTS: Baseline HAM-D17 scores for desvenlafaxine (n = 285) and placebo (n = 142) were 22.0 and 21.8, whereas baseline SDS scores were 19.8 and 20.4. Adjusted mean differences between desvenlafaxine and placebo were 2.1 (95% confidence interval [CI], 0.78-3.46; P = 0.002) on the HAM-D17 and 1.3 (95% CI, -0.09 to 2.76; P = 0.067) on the SDS. For the modified ITT sample, desvenlafaxine (n = 208) and placebo (n = 102), baseline HAM-D17 scores were 23.8 and 23.9; the SDS baseline scores were 20.1 and 20.8. Mean differences were 2.6 (95% CI, 0.93-4.22; P = 0.002) on the HAM-D17 and 2.1 (95% CI, 0.36-3.76; P = 0.017) on the SDS. Adverse events and Arizona Sexual Experience Scale scores were comparable between groups. CONCLUSIONS: Desvenlafaxine 50 mg/d was efficacious for treating MDD in gainfully employed adults. Between-group differences on the SDS narrowly missed statistical significance in the ITT population alone, but the totality of data suggests functional improvements with active treatment.


Asunto(s)
Antidepresivos/uso terapéutico , Ciclohexanoles/uso terapéutico , Trastorno Depresivo Mayor/tratamiento farmacológico , Empleo , Adulto , Análisis de Varianza , Antidepresivos/efectos adversos , Ciclohexanoles/efectos adversos , Trastorno Depresivo Mayor/fisiopatología , Succinato de Desvenlafaxina , Método Doble Ciego , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Pacientes Ambulatorios , Estudios Prospectivos , Escalas de Valoración Psiquiátrica , Resultado del Tratamiento
6.
J Clin Psychopharmacol ; 30(3): 294-9, 2010 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-20473066

RESUMEN

This pooled analysis evaluated the efficacy of desvenlafaxine (administered as desvenlafaxine succinate) for the treatment of major depressive disorder (MDD) in patients grouped by age and sex. Nine clinical trials were pooled. Outpatients 18 years or older with MDD received desvenlafaxine 50, 100, 200, or 400 mg/d (men = 709; women = 1096) or placebo (men = 399; women = 709) for 8 weeks. Data were analyzed by sex and by age groups of 40 years and younger, 41 to 54 years, 55 to 64 years, and 65 years and older. The primary outcome was change from baseline in the 17-item Hamilton Rating Scale for Depression (HAM-D17) total score at the final evaluation. Secondary measures included response (> or =50% reduction in HAM-D17) and remission (HAM-D17 < or =7). No significant sex-treatment, age-treatment, or sex-age-treatment interactions were observed. Differences in the HAM-D17 change from baseline for desvenlafaxine versus placebo were -1.72 for women (P < 0.001) and -2.11 for men (P < 0.001); these changes were significant among women of the 18-to-40 (P = 0.01), 41-to-54 (P = 0.002), and 65-years-and-older subgroups (P = 0.02), and significant among men for the 18-to-40 (P = 0.03) and 41-to-54 subgroups (P = 0.002). The response rates for desvenlafaxine and placebo were 53% and 42% (P < 0.001), respectively, among women, and 53% and 41% (P < 0.001), respectively, among men; the remission rates were 31% and 21% (P < 0.001) and 34% and 26% (P = 0.007), respectively. The response rates were similar across age subgroups, with significant differences from placebo observed in the 18-to-40 (P < or = 0.05), 41-to-54 (P < or = 0.005), and 65-and-older subgroups (P = 0.02). The remission rates were significant versus placebo in the 41-to-54 (P = 0.006), 55-to-64 (P = 0.01), and 65-and-older (P = 0.02) subgroups among women but not in any age subgroup among men. Desvenlafaxine generally improved depressive symptoms across age and sex subgroups.


Asunto(s)
Atención Ambulatoria/normas , Ciclohexanoles/uso terapéutico , Trastorno Depresivo Mayor/tratamiento farmacológico , Trastorno Depresivo Mayor/psicología , Estudios Multicéntricos como Asunto/normas , Ensayos Clínicos Controlados Aleatorios como Asunto/normas , Adolescente , Adulto , Factores de Edad , Anciano , Atención Ambulatoria/estadística & datos numéricos , Trastorno Depresivo Mayor/epidemiología , Succinato de Desvenlafaxina , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Multicéntricos como Asunto/estadística & datos numéricos , Ensayos Clínicos Controlados Aleatorios como Asunto/estadística & datos numéricos , Factores Sexuales , Estadística como Asunto/normas , Resultado del Tratamiento , Adulto Joven
7.
Am J Obstet Gynecol ; 202(3): 221-31, 2010 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-20207238

RESUMEN

Exacerbation of common medical and mental health disorders at specific phases of the menstrual cycle is a prevalent phenomenon. Although the precise cause is unclear, studies implicate complex interactions between the immune and neuroendocrine systems. The menstrual cycle also is a trigger for the onset of depressive disorders, including premenstrual dysphoric disorder, a disorder specific to the luteal phase of the menstrual cycle, and depression associated with the transition to menopause. This article discusses common mental health problems exacerbated by the menstrual cycle, with a particular focus on premenstrual dysphoric disorder and perimenopausal depression. Throughout the reproductive lifespan, routine screening and assessment for the presence of common psychiatric disorders are critical for accurate diagnosis and provision of effective treatment. Management options include referral or consultation with a primary care provider or psychiatrist; treatment options for premenstrual dysphoric disorder and perimenopausal depression include pharmacotherapy with antidepressant agents and/or psychotherapy. Hormones may be helpful.


Asunto(s)
Ciclo Menstrual/fisiología , Trastornos Mentales/fisiopatología , Femenino , Humanos , Tamizaje Masivo , Trastornos Mentales/diagnóstico , Trastornos Mentales/tratamiento farmacológico , Trastornos Mentales/psicología , Perimenopausia/fisiología , Perimenopausia/psicología , Síndrome Premenstrual/fisiopatología , Síndrome Premenstrual/psicología , Derivación y Consulta , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéutico
8.
J Clin Psychopharmacol ; 29(4): 383-6, 2009 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-19593180

RESUMEN

INTRODUCTION: One of the major enzymes of the cytochrome P450 drug-metabolizing system, CYP2D6, shows a high degree of genetic polymorphism and variability in activity. Based on the degree of CYP2D6 activity, individuals can be broadly classified as poor metabolizers (PMs) or extensive metabolizers (EMs); the metabolism of CYP2D6 substrates differs among PMs and EMs. The metabolism of various drugs that are substrates of CYP2D6 has been used as a marker for metabolic phenotype, calculating the plasma or urinary metabolic ratio of the parent compound to its metabolite. The current analysis evaluates the use of the O-desmethylvenlafaxine-venlafaxine ratio (ODV/VEN) after administration of VEN, a CYP2D6 substrate, for determining CYP2D6 metabolic phenotype in healthy adults receiving VEN. METHODS: The analysis included data from 2 studies in which healthy adults were classified as either EMs or PMs using established methods (1 genotypic and 1 phenotypic) and were then administered VEN at daily dosages ranging from 75 to 150 mg. Blood plasma samples were taken at various time points, and the ODV/VEN ratio was calculated. RESULTS: Blood samples from 28 participants in the 2 studies were available for analysis. The ODV/VEN ratio distinguished the EM and PM phenotypes; ratios were 1 or greater for EMs and less than 1 for PMs at 4 hours after dose administration. CONCLUSIONS: The ratio of ODV/VEN is an effective means of phenotyping individuals according to their CYP2D6 metabolizer status.


Asunto(s)
Inhibidores de Captación Adrenérgica/farmacocinética , Ciclohexanoles/farmacocinética , Citocromo P-450 CYP2D6/metabolismo , Inhibidores Selectivos de la Recaptación de Serotonina/farmacocinética , Administración Oral , Adolescente , Inhibidores de Captación Adrenérgica/administración & dosificación , Inhibidores de Captación Adrenérgica/sangre , Adulto , Biotransformación , Ensayos Clínicos como Asunto , Ciclohexanoles/administración & dosificación , Ciclohexanoles/sangre , Citocromo P-450 CYP2D6/genética , Succinato de Desvenlafaxina , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Fenotipo , Valor Predictivo de las Pruebas , Inhibidores Selectivos de la Recaptación de Serotonina/administración & dosificación , Inhibidores Selectivos de la Recaptación de Serotonina/sangre , Especificidad por Sustrato , Clorhidrato de Venlafaxina , Adulto Joven
9.
J Psychopharmacol ; 30(6): 559-67, 2016 06.
Artículo en Inglés | MEDLINE | ID: mdl-27009044

RESUMEN

The objective of this substudy was to examine the effect of desvenlafaxine 50 mg/day compared with placebo on cognitive function in employed outpatients with major depressive disorder. A total of 11/55 (20%) study sites in a 12-week, randomized, double-blind, placebo-controlled trial administered cognitive assessments in memory, attention, and executive functioning domains using the cognitive drug research system. Changes from baseline were subjected to analysis of covariance with baseline levels as covariates, using last observation carried forward data. A significant improvement with desvenlafaxine 50 mg/day (n=52) compared with placebo (n=29) was observed on the quality of working memory composite measure (0.081 units (0.005, 0.156); P=0.0365) at last observation carried forward. Improvement from baseline on the speed of working memory composite was significant for desvenlafaxine (-226.6 msec (-316.7, -136.4); P<0.0001) and for placebo (-133.3 msec (-257.2, -9.4); P=0.0354); however, the treatment effect was not significant. No significant differences between groups were observed on composite measures for attention. Treatment of depression with desvenlafaxine 50 mg/day may improve aspects of cognitive functioning, including working memory.Clinical Trial Registry No.: Clinicaltrials.gov identifier: NCT00824291.


Asunto(s)
Antidepresivos/uso terapéutico , Cognición/efectos de los fármacos , Trastorno Depresivo Mayor/tratamiento farmacológico , Succinato de Desvenlafaxina/uso terapéutico , Adulto , Trastorno Depresivo Mayor/psicología , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pacientes Ambulatorios
10.
Artículo en Inglés | MEDLINE | ID: mdl-26644956

RESUMEN

OBJECTIVE: To assess the effect of baseline body mass index (BMI) on efficacy and weight change in adults with major depressive disorder (MDD) treated with desvenlafaxine or placebo in a pooled, post hoc analysis. METHOD: Adults with MDD were randomly assigned to placebo or desvenlafaxine (50 mg or 100 mg) in 8 short-term, double-blind studies and 1 longer-term randomized withdrawal study (the studies were published between 2007 and 2013). Change from baseline in 17-item Hamilton Depression Rating Scale (HDRS-17) total score at week 8 was analyzed in normal (BMI ≤ 25 kg/m(2)), overweight (25 kg/m(2) < BMI ≤ 30 kg/m(2)), and obese (BMI > 30 kg/m(2)) subgroups using analysis of covariance (ANCOVA). Weight change was analyzed in BMI subgroups using ANCOVA and a mixed-effects model for repeated measures. RESULTS: Desvenlafaxine 50 mg/d or 100 mg/d improved HDRS-17 scores significantly from baseline to week 8 (last observation carried forward) versus placebo in all BMI subgroups (normal: n = 1,122; overweight: n = 960; obese: n = 1,302; all P ≤ .0027); improvement was greatest in normal BMI patients. There was a statistically significant decrease in weight (< 1 kg) with short-term desvenlafaxine 50 mg/d and 100 mg/d versus placebo in all BMI subgroups (all P < .0001). In the randomized withdrawal study (n = 548), no statistically significant difference in weight was observed for desvenlafaxine versus placebo in any BMI subgroup. Baseline BMI predicted weight change in short-term and longer-term desvenlafaxine treatment. CONCLUSIONS: Desvenlafaxine significantly improved symptoms of depression versus placebo regardless of baseline BMI. In all BMI subgroups, desvenlafaxine was associated with statistically significant weight loss (< 1 kg) versus placebo over 8 weeks, but no significant differences longer term. TRIAL REGISTRATION: ClinicalTrials.gov identifiers: NCT00072774, NCT00277823, NCT00300378, NCT00384033, NCT00798707, NCT00863798, NCT01121484, NCT00824291, NCT00887224.

11.
Artículo en Inglés | MEDLINE | ID: mdl-26137355

RESUMEN

OBJECTIVE: To evaluate relapse rates and predictors of relapse in 2 randomized, placebo-controlled trials of desvenlafaxine for major depressive disorder (MDD). METHOD: Study 1: week 8 responders to open-label desvenlafaxine 50 mg/d entered a 12-week open-label stability phase. Patients with a continuing, stable response at week 20 were randomly assigned to 6-month, double-blind treatment (desvenlafaxine 50 mg/d or placebo). Study 1 was conducted between June 2009 and March 2011 at 87 sites worldwide. Study 2: week 12 responders to open-label desvenlafaxine 200 or 400 mg/d were randomly assigned to 6-month, double-blind treatment (desvenlafaxine 200 mg/d, 400 mg/d, or placebo). Study 2 was conducted between June 2003 and August 2005 at 49 sites in Europe, the United States, and Taiwan. Relapse was assessed separately by study with log-rank test using protocol definitions of relapse and with 17-item Hamilton Depression Rating Scale (HDRS-17) score ≥ 16 at any time during the double-blind phase. Kaplan-Meier estimates evaluated time to relapse, censoring data at months 1, 2, and 3 and overall; treatments were compared using hazard ratios. Cox proportional hazards models assessed relapse predictors. RESULTS: Overall relapse rates for all definitions were significantly lower for desvenlafaxine versus placebo for both studies (all P ≤ .002). In study 1, rates were significantly lower for desvenlafaxine versus placebo at month 2 (P = .016) and month 3 (P = .007) using the protocol definition. In study 2, relapse rates were significantly lower for desvenlafaxine versus placebo at months 1, 2, and 3 for both definitions (P < .0001-.002). Hazard ratios were similar at months 1, 2, and 3 and overall for both studies (0.382-0.639). CONCLUSIONS: Desvenlafaxine 50 to 400 mg/d effectively prevented relapse at 6 months. Desvenlafaxine significantly prevented relapse early (month 1) versus placebo only in study 2. TRIAL REGISTRATION: ClinicalTrials.gov identifiers:NCT00887224 and NCT00075257.

12.
Artículo en Inglés | MEDLINE | ID: mdl-26137358

RESUMEN

OBJECTIVE: The purpose of this post hoc analysis was to evaluate the incidence and timing of taper/posttherapy-emergent adverse events (TPAEs) following discontinuation of long-term treatment with desvenlafaxine (administered as desvenlafaxine succinate). METHOD: This was a phase 4, randomized, double-blind, placebo-controlled study conducted at 38 research centers within the United States between March 2010 and February 2011. Adult outpatients with major depressive disorder (MDD; DSM-IV-TR criteria) who completed 24 weeks of open-label treatment with desvenlafaxine 50 mg/d were randomly assigned to 1 of 3 groups for the double-blind taper phase: desvenlafaxine 50 mg/d for 4 weeks (no discontinuation), desvenlafaxine 25 mg/d for 1 week followed by placebo for 3 weeks (taper), or placebo for 4 weeks (abrupt discontinuation). The primary endpoint, Discontinuation-Emergent Signs and Symptoms Scale (DESS) score over the first 2 weeks of the taper phase, was described previously. Secondary assessments included incidence and timing of TPAEs (any adverse event that started or increased in severity during the double-blind phase) and the percentage of patients who could not continue the taper phase due to discontinuation symptoms. The Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR16) assessed MDD status. RESULTS: A total of 480 patients enrolled in the open-label phase; the full analysis set included 357 patients (taper, n = 139; abrupt discontinuation, n = 146; no discontinuation, n = 72). TPAEs occurred in all groups through week 4. The incidence of any TPAE was lower for taper versus abrupt discontinuation at week 1 (P < .001), similar at week 2, and lower for taper versus abrupt discontinuation at weeks 3 and 4 (P ≤ .034). The most common TPAEs (incidence ≥ 3%) in the taper group were nausea and headache (3% each) at week 1 and dizziness (5%) and headache (4%) at week 2. The most common TPAEs in the abrupt discontinuation group were dizziness (8%), headache (8%), nausea (4%), irritability (3%), and diarrhea (3%) at week 1 and headache (3%) at weeks 2 and 3. The most common TPAE in the no discontinuation group was nausea (6%) at week 2. CONCLUSION: The overall incidence of any TPAE was lower in the taper versus abrupt discontinuation groups. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01056289.

13.
J Womens Health (Larchmt) ; 24(4): 281-90, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25860107

RESUMEN

BACKGROUND: Few studies in the literature have examined the efficacy of antidepressant drugs in perimenopausal and postmenopausal women. The objective of the current study was to assess the efficacy of desvenlafaxine (administered as desvenlafaxine succinate) separately in perimenopausal and postmenopausal women with major depressive disorder (MDD). METHODS: Data were pooled from two double-blind, placebo-controlled clinical trials enrolling perimenopausal and postmenopausal women (40-70 years old) diagnosed with MDD. Patients were randomly assigned to receive desvenlafaxine 100 to 200 mg/day or placebo (8 weeks) or desvenlafaxine 50 mg/day or placebo (10 weeks). The primary efficacy end point for each trial was change from baseline in Hamilton Rating Scale for Depression (HAM-D17) total score at week 8. Secondary end points included change from baseline in Sheehan Disability Scale (SDS) and Menopause Rating Scale (MRS) scores. Changes from baseline in continuous variables were analyzed using analysis of covariance with treatment, region, and baseline in the model. All treatment comparisons were carried out separately in perimenopausal or postmenopausal women, in individual studies, and in the pooled population, adjusting for menopausal status and study. RESULTS: A total of 798 patients were included in the full analysis set (perimenopausal, n=252; postmenopausal, n=546). Desvenlafaxine significantly reduced HAM-D17 total scores versus placebo at week 8 in both perimenopausal (-10.3 vs. -6.5; p<0.001) and postmenopausal women (-10.1 vs. -7.6; p<0.001). Significant improvements in SDS and MRS total scores were also observed for desvenlafaxine versus placebo in perimenopausal (p ≤ 0.024) and postmenopausal women (p ≤ 0.009). A significant treatment by menopausal status interaction was observed for SDS only (p=0.036). CONCLUSIONS: Desvenlafaxine demonstrated antidepressant efficacy in both perimenopausal and postmenopausal subgroups of women with MDD. DISCLAIMER: In September 2011, Pfizer received a Complete Response Letter from the United States Food and Drug Administration on its application for approval to market desvenlafaxine for the treatment of moderate to severe vasomotor symptoms associated with menopause. The Complete Response Letter states that the data included in the application are not sufficient to establish an acceptable risk/benefit profile for the treatment of vasomotor symptoms in the general population of postmenopausal women, and therefore desvenlafaxine is not approved for the treatment of vasomotor symptoms in the United States at this time. This decision does not impact desvenlafaxine's approval for the treatment of MDD in adults.


Asunto(s)
Antidepresivos/efectos adversos , Antidepresivos/uso terapéutico , Ciclohexanoles/efectos adversos , Ciclohexanoles/uso terapéutico , Trastorno Depresivo Mayor/tratamiento farmacológico , Menopausia/psicología , Posmenopausia/psicología , Administración Oral , Adulto , Anciano , Trastorno Depresivo Mayor/psicología , Succinato de Desvenlafaxina , Manual Diagnóstico y Estadístico de los Trastornos Mentales , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Femenino , Humanos , Menopausia/efectos de los fármacos , Persona de Mediana Edad , Posmenopausia/efectos de los fármacos , Escalas de Valoración Psiquiátrica , Resultado del Tratamiento
14.
Curr Med Res Opin ; 31(4): 809-20, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25758058

RESUMEN

OBJECTIVE: To evaluate the effect of the serotonin-norepinephrine re-uptake inhibitor desvenlafaxine on blood pressure and incidence of new onset hypertension in pooled short-term studies and in two longer-term, randomized withdrawal studies. RESEARCH DESIGN AND METHODS: Data from patients randomly assigned to desvenlafaxine 10 mg to 400 mg/day or placebo in 11 short-term (8-12 weeks), fixed-dose, double-blind, placebo-controlled studies of major depressive disorder (MDD) were pooled for analysis; two desvenlafaxine randomized withdrawal studies (36 and 46 weeks) were analyzed separately. CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov , NCT00072774, NCT00073762, NCT00277823, NCT00300378, NCT00384033, NCT00798707, NCT00863798, NCT01121484, NCT00824291, NCT01432457, NCT00075257, NCT00887224. MAIN OUTCOME MEASURES: Outcomes included change from baseline in supine systolic blood pressure (SSBP) and supine diastolic blood pressure (SDBP), assessed using a mixed model repeated measures (MMRM) analysis, and incidence of hypertension (defined as three consecutive second SDBP measures ≥90 mm Hg AND increase of ≥10 mm Hg from baseline and/or SSBP ≥140 mm Hg AND increase of ≥10 mm Hg), analyzed using Cochran Mantel Hanzael tests. Potential predictors of change in SSBP and SDBP at LOCF were examined by including predictor variables in a regression model. RESULTS: In the pooled, short-term studies, mean changes from baseline over time in SSBP and SDBP were statistically significant compared with placebo for the desvenlafaxine doses of 10 mg/day or greater for SSBP (p ≤ 0.0004; MMRM) and 25 mg/day or greater for SDBP (p ≤ 0.0449; MMRM). The proportion of patients with new onset hypertension differed significantly from placebo for the 50, 200, and 400 mg/day doses (1.9%, 2.4%, 4.8%, respectively, vs 0.8%; all p ≤ 0.0244). Predictors of change in BP included baseline SDBP, baseline SSBP, dose, body mass index, gender, age, race, and history of hypertension. LIMITATIONS: Data were pooled from studies which differed somewhat in study design and patient demographics. None of the studies were originally designed to examine treatment effects on BP. Study entry criteria limit generalization of these results to medically stable patients with a primary diagnosis of MDD. CONCLUSIONS: Short-term desvenlafaxine treatment was associated with small but statistically significant increases in SSBP and SDBP.


Asunto(s)
Antidepresivos/uso terapéutico , Presión Sanguínea/efectos de los fármacos , Ciclohexanoles/uso terapéutico , Trastorno Depresivo Mayor/tratamiento farmacológico , Adulto , Antidepresivos/efectos adversos , Ciclohexanoles/efectos adversos , Succinato de Desvenlafaxina , Método Doble Ciego , Femenino , Humanos , Hipertensión/inducido químicamente , Hipertensión/epidemiología , Masculino , Persona de Mediana Edad , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del Tratamiento
15.
AAOHN J ; 50(8): 365-72, 2002 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-12227211

RESUMEN

This prospective, pre- and post-evaluation of a worksite cardiovascular health management program consisted of employee education, measurement of cardiovascular risk factors, and onsite individual counseling for all employees, along with follow up screening for high risk participants. Of 1,099 employees (16.4% of those eligible) who participated in the initial screening, 596 (54.2%) were classified as high risk. A total of 167 (28.0%) high risk participants completed the 6 month follow up screening. Most high risk participants in the 6 month follow up screening reported they had increased their exercise (64.7%), improved their diet (71.3%), and visited a physician (61.7%). A minority of the participants (16.8%) began new cardiovascular medications, and 2.4% were diagnosed with diabetes. In addition, there were statistically significant decreases in the percentages of participants with elevated systolic blood pressure, diastolic blood pressure, low density lipoprotein cholesterol, and total cholesterol to high density lipoprotein ratio. Almost all (99.7%) of the 909 participants (82.7% of all participants) who completed the satisfaction survey were satisfied or very satisfied with the overall program. Screening in the workplace can identify individuals at high risk for cardiovascular disease. In this study, more than half of the participants were classified as high risk. Most high risk individuals who attended the 6 month follow up screening had improved their cardiovascular health, but attrition remains a challenge for worksite programs.


Asunto(s)
Enfermedades Cardiovasculares/terapia , Servicios de Salud del Trabajador/organización & administración , Salud Laboral , Lugar de Trabajo , Adulto , Anciano , Enfermedades Cardiovasculares/clasificación , Enfermedades Cardiovasculares/diagnóstico , Técnicas de Apoyo para la Decisión , Femenino , Humanos , Masculino , Tamizaje Masivo/organización & administración , Persona de Mediana Edad , Ohio , Pennsylvania , Proyectos Piloto , Evaluación de Programas y Proyectos de Salud , Estudios Prospectivos , Medición de Riesgo , Factores de Riesgo
16.
Prof Case Manag ; 19(2): 63-74, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24496128

RESUMEN

PURPOSE: The purpose of this study was to identify potential discordance between physician and patient rated measures of depression used by primary care physicians and psychiatrists. PRIMARY PRACTICE SETTING: This study collected data from primary care physicians and psychiatrists in the United States between October and December 2009. METHODOLOGY AND SAMPLE: A real-world, cross-sectional study was conducted using the Neuroses Disease-Specific Programme (Adelphi Real World, Macclesfield, United Kingdom). Treatment practice data were collected by 180 physicians (100 primary care and 80 psychiatrists) who were asked to provide information for the next 15 outpatients presenting prospectively with symptoms of anxiety and/or depression (n = 2,704 patients). The primary outcome measures were the Clinical Global Impressions-and Patient Global Impressions-Improvement scales, completed by both physicians and their matched patients, respectively. Cohen's kappa coefficient (κ) was calculated to assess the level of agreement between the Clinical Global Impressions-and Patient Global Impressions-Improvement scale responses. RESULTS: Physician- and patient-rated overall improvement in illness was 82% and 89%, respectively. Results of the kappa analysis demonstrated fair agreement between patients and physicians regarding overall improvement in illness (44% agreement; κ= 0.23). Physician ratings of patient improvement progressively decreased with increased severity of illness. IMPLICATIONS FOR CASE MANAGEMENT PRACTICE: These real-world data suggest that the degree of reduction in symptoms of anxiety and/or depression may be estimated differently by physicians when compared with their patients. Understanding the potential for disparities between physician- and patient-rated measures in reviewing patient care, particularly in patients with more severe depressive symptoms, can help ensure that treatment plans are aligned with patient needs.


Asunto(s)
Ansiedad/terapia , Actitud del Personal de Salud , Trastorno Depresivo/terapia , Manejo de la Enfermedad , Pacientes/psicología , Adulto , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Resultado del Tratamiento
17.
Menopause ; 21(8): 799-806, 2014 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-24448103

RESUMEN

OBJECTIVE: This post hoc analysis assessed the efficacy of desvenlafaxine 50 mg/day for treating major depressive disorder in perimenopausal versus postmenopausal women enrolled in a 10-week, double-blind, placebo-controlled study. METHODS: Perimenopausal and postmenopausal women (40-70 y) diagnosed with major depressive disorder were randomly assigned to receive desvenlafaxine 50 mg/day or placebo. Changes from baseline in the primary efficacy variable (17-item Hamilton Rating Scale for Depression [HAM-D17] score, week 8) and in other secondary efficacy variables (Sheehan Disability Scale and Menopause Rating Scale) were analyzed using analysis of covariance with treatment, region, and baseline in the model. Clinical Global Impressions-Improvement Scale was analyzed with the Cochran-Mantel-Haenszel test. Response and remission rates were evaluated using logistic regression with treatment, region, and baseline HAM-D17 in the model. RESULTS: Of 426 women (desvenlafaxine, n = 216; placebo, n = 210) included in this analysis, 135 (32%) were perimenopausal and 291 (68%) were postmenopausal at baseline. In both subgroups, improvement from baseline in HAM-D17 scores was significantly greater for desvenlafaxine 50 mg/day than for placebo. Menopause status and time since menopause did not significantly affect HAM-D17 total score. The drug-placebo difference in Sheehan Disability Scale scores was significant in perimenopausal women (-9.3 vs. -5.1, P < 0.001) but not in postmenopausal women (-8.8 vs. -8.1). Menopause Rating Scale and Clinical Global Impressions-Improvement Scale scores were significantly improved with desvenlafaxine in postmenopausal women. CONCLUSIONS: Desvenlafaxine 50 mg/day is effective in treating depression in both perimenopausal and postmenopausal women. Placebo response on measures of functional impairment is lower in perimenopausal women than in postmenopausal women, resulting in a greater apparent treatment benefit with desvenlafaxine among perimenopausal women.


Asunto(s)
Antidepresivos/uso terapéutico , Ciclohexanoles/uso terapéutico , Trastorno Depresivo Mayor/tratamiento farmacológico , Menopausia , Administración Oral , Adulto , Trastorno Depresivo Mayor/psicología , Succinato de Desvenlafaxina , Método Doble Ciego , Femenino , Humanos , Persona de Mediana Edad , Escalas de Valoración Psiquiátrica , Resultado del Tratamiento
18.
Artículo en Inglés | MEDLINE | ID: mdl-24096053

RESUMEN

BACKGROUND: Relationships between brain-derived neurotrophic factor (BDNF), interleukin (IL)-6, and salivary cortisol and both depression severity and treatment response were assessed in patients enrolled in a double-blind, placebo-controlled trial of desvenlafaxine 50mg/d for MDD. METHODS: Outpatients with MDD were randomly assigned to 12weeks of double-blind treatment with desvenlafaxine 50mg/d or placebo (2:1). Baseline severity was assessed using the 17-item Hamilton Rating Scale for Depression (HAM-D17); treatment response at week 12 was based on HAM-D17 total score and response and remission status. Saliva (cortisol) and blood (BDNF, IL-6) samples for biomarker assay were collected at baseline and week 12. Spearman correlations were calculated between the biomarkers at baseline, and between biomarkers and HAM-D17 total score at baseline. Logistic regression analyses were used to assess whether baseline biomarker levels predicted treatment response at week 12, with and without adjustment for baseline HAM-D17 score, treatment, and geographic region. Similarly, an analysis of covariance was used to assess whether baseline disease severity predicted biomarker change at week 12. RESULTS: A total of 427 patients who received ≥1 dose of study drug and had baseline and ≥1 on-therapy primary efficacy evaluations were included in the analysis. At baseline, there was a statistically significant although weak correlation between levels of IL-6 and BDNF (Spearman correlation coefficient [rs]=0.120; P=0.014), but no significant correlation between baseline biomarker levels and baseline HAM-D17 total score (absolute value of all rs, ≤0.061). Desvenlafaxine 50mg/d treatment significantly reduced HAM-D17 total score from baseline at week 12 compared with placebo (P=0.006), but the three potential biomarkers did not predict treatment effects. No significant correlations were observed between the change from baseline in any biomarker level and change in HAM-D17 total score at week 12, either overall, or in desvenlafaxine or placebo groups (absolute value of all rs, 0.003-0.196). Baseline levels of BDNF, IL-6, and salivary cortisol did not significantly predict response to treatment at week 12. Although median increase in BDNF was not significantly different between desvenlafaxine (13.7%) and placebo (5.7%) groups, the increase was significantly greater (33.4% vs 4.3%; P=0.003) in patients with more severe depression at baseline (HAM-D17>22) vs those with less severe depression (HAM-D17≤22). No similar findings were observed for IL-6 or salivary cortisol. DISCUSSION: Weak or no relationships were observed at baseline between the potential biomarkers or between biomarkers and disease severity. While baseline biomarker level did not predict treatment response, improvement in BDNF was significantly greater among patients who were more severely depressed at baseline.


Asunto(s)
Antidepresivos/uso terapéutico , Factor Neurotrófico Derivado del Encéfalo/sangre , Ciclohexanoles/uso terapéutico , Depresión/tratamiento farmacológico , Hidrocortisona/metabolismo , Interleucina-6/sangre , Adulto , Anciano , Depresión/metabolismo , Succinato de Desvenlafaxina , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pacientes Ambulatorios , Escalas de Valoración Psiquiátrica , Saliva/metabolismo , Índice de Severidad de la Enfermedad , Estadística como Asunto , Adulto Joven
19.
J Affect Disord ; 166: 307-14, 2014 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-25012446

RESUMEN

BACKGROUND: Diminished quality of life (QOL) is associated with major depressive disorder (MDD). METHODS: QOL was assessed in a post-hoc analysis of a double-blind, placebo-controlled trial. Employed adult outpatients with MDD were randomly assigned to 12 weeks of treatment with desvenlafaxine 50mg/d or placebo. Changes from baseline in the Short Form of the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) item scores at week 12 were analyzed using analysis of covariance with treatment, region, and baseline in the model. Correlations between change from baseline in the 17-item Hamilton Rating Scale for Depression (HAM-D17) total score and Q-LES-Q scores were computed. RESULTS: The intent-to-treat population included 427 patients. There were statistically significant improvements from baseline for desvenlafaxine vs placebo in 10 of 16 Q-LES-Q item scores (P values ≤0.0441). The percentage of patients with severe QOL impairment (≥2 SD below community norm) at week 12 was significantly lower for desvenlafaxine (46%) vs placebo (62%; P=0.0024; baseline: 95% and 94%, respectively). Change in Q-LES-Q total score was highly correlated with change in HAM-D17 score at week 12, LOCF (P<0.0001), and improvement in HAM-D17 total score at week 2 predicted change in Q-LES-Q total score at week 12 for the desvenlafaxine group (F=24.89; P<0.0001) but not placebo. LIMITATIONS: This analysis excluded patients who were unemployed, had severe comorbidities, and those taking multiple, concomitant medications. CONCLUSION: Improvement in QOL and depressive symptoms was significantly greater for employed depressed patients treated with desvenlafaxine vs placebo.


Asunto(s)
Antidepresivos/uso terapéutico , Ciclohexanoles/uso terapéutico , Trastorno Depresivo Mayor/tratamiento farmacológico , Adulto , Anciano , Depresión , Succinato de Desvenlafaxina , Método Doble Ciego , Empleo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Placebos , Calidad de Vida , Encuestas y Cuestionarios , Adulto Joven
20.
Int Clin Psychopharmacol ; 28(6): 312-21, 2013 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-23881185

RESUMEN

This study assessed the efficacy of desvenlafaxine 50 mg/day compared with placebo for treating moderate or severe major depressive disorder (MDD). Data were pooled from six double-blind, placebo-controlled, desvenlafaxine 50 mg/day fixed-dose studies in adults with MDD. The primary endpoint was improvement in 17-item Hamilton Rating Scale for Depression (HAM-D17) scores from baseline at week 8. HAM-D17 changes were evaluated in patients with moderate (18

Asunto(s)
Antidepresivos/uso terapéutico , Ciclohexanoles/uso terapéutico , Trastorno Depresivo Mayor/tratamiento farmacológico , Trastorno Depresivo Mayor/psicología , Índice de Severidad de la Enfermedad , Adolescente , Adulto , Anciano , Trastorno Depresivo Mayor/epidemiología , Succinato de Desvenlafaxina , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Efecto Placebo , Adulto Joven
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