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BACKGROUND AND OBJECTIVE: Orodispersible tablets (ODT) rapidly dissolve in the oral cavity and can improve patient's convenience. This pharmacokinetic study assessed the bioequivalence of a novel 20 mg ODT formulation of bilastine compared with bilastine 20 mg tablets in healthy volunteers under fasting conditions. METHODS: A phase I, single-center, open-label, two-period, two-sequence crossover randomized clinical trial was conducted. The study comprised two periods, in which participants were administered a single oral dose of bilastine 20 mg in the form of ODT as the test product, or conventional tablets as the reference product, and a washout of 7 days between each period. Blood samples were collected for up to 72 h. Bioequivalence was established if the 90% confidence intervals of the Cmax and AUC0-t were within the acceptance range (80-125%). Safety was evaluated at the follow-up visit (days 4-7 after the second dose) and throughout the study. RESULTS: A total of 42 healthy volunteers were randomized, and 41 completed the study. Pharmacokinetic parameters were comparable for both formulations after a single dose of 20 mg. Bilastine ODT and conventional tablets were bioequivalent as the 90% confidence intervals of the test over reference ratios were within the predefined range (80-125%). Both formulations were well tolerated and showed a similar safety profile. CONCLUSIONS: Bilastine ODT was bioequivalent to the reference treatment formulated as conventional tablets when administered as a single oral dose of 20 mg under fasting conditions. Both formulations showed a similar tolerability and safety profile, with no serious adverse events or significant analytical alterations reported. TRIAL REGISTRATION: 2019-004071-39. Date of authorization: 10 December 2019.
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BACKGROUND: Crohn's-related rectovaginal fistulas (RVF) greatly impact quality of life and are notoriously difficult to treat. The aim of this study was to assess the burden of recurrent episodes of care for RVF and its economic impact. METHODS: A retrospective observational cohort study of administrative US claims databases was conducted. Eligible patients were female adults, with a diagnosis code for Crohn's disease with or without a diagnosis/procedural code for RVF. For the RVF cohort, rates of recurrence of RVF episodes of care were estimated using Kaplan-Meier analyses. Healthcare resource utilization (HCRU) and direct healthcare costs were compared between the RVF cohort and RVF-free cohort. RESULTS: Mean ages in the RVF cohort (n = 963) and RVF-free cohort (n = 56,564) were 47.2 and 50.8 years, with a mean follow-up period of 58.7 and 49.8 months, respectively. For the RVF cohort, the probability of having a second RVF episode of care within 2 years of the first one was estimated to be 35.9% and of having a third episode within 2 years of the second was 47.8%. During the first 2 years, the RVF cohort had 67% more inpatient admissions than the RVF-free cohort with each RVF episode of care being associated with 16% more admissions. The estimated incremental cost associated with having RVF was US$17,561, with an incremental cost of US$11,607 for each additional RVF episode of care. CONCLUSIONS: This real-world study highlights the significant impact of RVF in patients with Crohn's disease with regard to repeat interventions and associated HCRU and direct healthcare costs, suggesting novel therapeutics are needed in this patient population.
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BACKGROUND: Darvadstrocel is an expanded allogeneic adipose-derived mesenchymal stem cell therapy for the treatment of complex perianal fistulas in patients with Crohn's disease. Safety and efficacy outcomes from the clinical trial known as "Adipose derived mesenchymal stem cells for induction of remission in perianal fistulizing Crohn's disease," or ADMIRE-CD (NCT01541579), from up to 52 weeks posttreatment were previously reported. Here, the outcomes from an extended 104-week follow-up are reported. OBJECTIVE: The goal of this study was to assess the long-term safety and efficacy of darvadstrocel at 2 years post-treatment in patients with Crohn's disease and complex perianal fistulas. DESIGN: This was a phase 3 double-blind randomized controlled study (ADMIRE-CD) in patients with perianal fistulizing Crohn's disease. SETTINGS: This study extension was conducted in multiple hospitals across 7 European countries and Israel. PATIENTS: Forty patients entered the extended follow-up period: 25 patients in the darvadstrocel treatment group and 15 in the control group. INTERVENTIONS: Darvadstrocel or saline solution (control group) was administered once, locally, after fistula tract curettage and internal opening closure (with previous seton placement). All patients were permitted to continue ongoing medical treatments for fistulas. MAIN OUTCOME MEASURES: Treatment-emergent serious adverse events were recorded through week 104. Clinical remission, defined as closure of all treated external openings that were draining at baseline despite gentle finger compression, was assessed at week 104. RESULTS: Of 40 patients, 37 completed the extended follow-up. Through week 104, 7 treatment-emergent serious adverse events were reported, of which 4 occurred between weeks 52 and 104. At week 104, clinical remission was reported in 14/25 (56%) patients in the darvadstrocel group and 6/15 (40%) patients in the control group. LIMITATIONS: Limitations include the small number of patients who entered the extended follow-up period, and no imaging examinations were performed at the 104-week time point. CONCLUSIONS: Darvadstrocel was well tolerated and clinical remission after treatment with darvadstrocel may be sustained for up to 104 weeks in patients with perianal fistulizing Crohn's disease. See Video Abstract at http://links.lww.com/DCR/B812.ClinicalTrials.gov No: NCT01541579. ESTUDIO DE SEGUIMIENTO PARA EVALUAR LA SEGURIDAD Y EFICACIA A LARGO PLAZO DE DARVADSTROCEL TRATAMIENTO CON CLULAS MADRE MESENQUIMALES EN PACIENTES CON ENFERMEDAD DE CROHN PERIANAL FISTULIZANTE ENSAYO CONTROLADO ALEATORIZADO DE FASE ADMIRECD: ANTECEDENTES:Darvadstrocel es una terapia con células madre mesenquimales alogénicas expandidas derivadas de tejido adiposo para el tratamiento de fístulas perianales complejas en pacientes con enfermedad de Crohn. Los resultados del ensayo clínico conocido como "Células madre mesenquimales derivadas de tejido adiposo para la inducción de la remisión en la enfermedad de Crohn fistulizante perianal" o ADMIRE-CD (NCT01541579), en cuanto a la seguridad y eficacia hasta 52 semanas después del tratamiento, fueron previamente informados. Seguidamente, se presentan los resultados de un seguimiento extendido de 104 semanas.OBJETIVO:Evaluar la seguridad y eficacia a largo plazo de darvadstrocel a dos años del tratamiento en pacientes con enfermedad de Crohn y fístulas perianales complejas.DISEÑO:Este fue un estudio de fase 3, aleatorizado, a doble ciego, controlado (ADMIRE-CD) en pacientes con enfermedad de Crohn perianal fistulizante.DESARROLLO:Esta extensión del estudio se realizó en varios hospitales de siete países europeos e Israel.PACIENTES:Cuarenta pacientes participaron en la extensión de seguimiento: tratamiento con darvadstrocel (n = 25); grupo control (n = 15).INTERVENCIONES:Se administró Darvadstrocel o solución salina (grupo control) una vez, localmente, tras el legrado del trayecto fístuloso y cierre del orificio interno (con la colocación previa de setón). A todos los pacientes se les permitió continuar con los tratamientos médicos en curso para las fístulas.PRINCIPALES MEDIDAS DE RESULTADO:Los eventos de efectos adversos graves derivados del tratamiento se registraron hasta la semana 104. La remisión clínica, definida como el cierre de todas las aberturas externas tratadas que drenaban al inicio espontáneamente o por compresión suave de los dedos, fue evaluado en la semana 104.RESULTADOS:Del total de 40 pacientes, 37 completaron la extensión de seguimiento. Hasta la semana 104, se reportaron 7 eventos de efectos adversos graves resultantes del tratamiento, de los cuales 4 ocurrieron entre las semanas 52 y 104. En la semana 104, se reportó remisión clínica en 14/25 (56%) pacientes en el grupo de darvadstrocel y 6/15 (40%) pacientes en el grupo de control.LIMITACIONES:Solo una pequeña cantidad de pacientes participaron en el período de seguimiento extendido y no se realizaron exámenes por técnicas de imagen en la visita a 104 semanas.CONCLUSIONES:Darvadstrocel fue bien tolerado y la remisión clínica después del tratamiento con darvadstrocel puede mantenerse hasta 104 semanas en pacientes con enfermedad de Crohn perianal fistulizante. Consulte Video Resumen en http://links.lww.com/DCR/B812. (Traducción-Dr Osvaldo Gauto and Dr Julian Panés.)ClinicalTrials.gov No. NCT01541579.
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Doença de Crohn , Células-Tronco Mesenquimais , Doença de Crohn/complicações , Doença de Crohn/terapia , Europa (Continente) , Seguimentos , Humanos , Estudos Retrospectivos , Transplante de Células-TroncoRESUMO
RATIONALE: Allogeneic cardiac stem cells (AlloCSC-01) have shown protective, immunoregulatory, and regenerative properties with a robust safety profile in large animal models of heart disease. OBJECTIVE: To investigate the safety and feasibility of early administration of AlloCSC-01 in patients with ST-segment-elevation myocardial infarction. METHODS AND RESULTS: CAREMI (Safety and Efficacy of Intracoronary Infusion of Allogeneic Human Cardiac Stem Cells in Patients With STEMI and Left Ventricular Dysfunction) was a phase I/II multicenter, randomized, double-blind, placebo-controlled trial in patients with ST-segment-elevation myocardial infarction, left ventricular ejection fraction ≤45%, and infarct size ≥25% of left ventricular mass by cardiac magnetic resonance, who were randomized (2:1) to receive AlloCSC-01 or placebo through the intracoronary route at days 5 to 7. The primary end point was safety and included all-cause death and major adverse cardiac events at 30 days (all-cause death, reinfarction, hospitalization because of heart failure, sustained ventricular tachycardia, ventricular fibrillation, and stroke). Secondary safety end points included major adverse cardiac events at 6 and 12 months, adverse events, and immunologic surveillance. Secondary exploratory efficacy end points were changes in infarct size (percentage of left ventricular mass) and indices of ventricular remodeling by magnetic resonance at 12 months. Forty-nine patients were included (92% male, 55±11 years), 33 randomized to AlloCSC-01 and 16 to placebo. No deaths or major adverse cardiac events were reported at 12 months. One severe adverse events in each group was considered possibly related to study treatment (allergic dermatitis and rash). AlloCSC-01 elicited low levels of donor-specific antibodies in 2 patients. No immune-related adverse events were found, and no differences between groups were observed in magnetic resonance-based efficacy parameters at 12 months. The estimated treatment effect of AlloCSC-01 on the absolute change from baseline in infarct size was -2.3% (95% confidence interval, -6.5% to 1.9%). CONCLUSIONS: AlloCSC-01 can be safely administered in ST-segment-elevation myocardial infarction patients with left ventricular dysfunction early after revascularization. Low immunogenicity and absence of immune-mediated events will facilitate adequately powered studies to demonstrate their clinical efficacy in this setting. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov . Unique identifier: NCT02439398.
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Mioblastos Cardíacos/transplante , Infarto do Miocárdio/terapia , Transplante de Células-Tronco/métodos , Disfunção Ventricular Esquerda/terapia , Idoso , Feminino , Humanos , Infusões Intra-Arteriais , Masculino , Pessoa de Meia-Idade , Mioblastos Cardíacos/citologia , Infarto do Miocárdio/complicações , Transplante de Células-Tronco/efeitos adversos , Transplante Homólogo , Disfunção Ventricular Esquerda/complicaçõesRESUMO
BACKGROUND: Goals of treating major depressive disorder (MDD) include achieving remission and avoiding relapse. It is possible that patients may have a broader view of remission than what is captured via clinician-rated scales. This patient perspective may, in turn, have an impact on treatment outcomes. METHODS: The association between a broader conceptualization of remission, based on the Remission from Depression Questionnaire (RDQ) score at baseline, and being in symptomatic remission after 6 months was evaluated in subjects (N = 613) with MDD in symptomatic remission at baseline (17-item Hamilton Rating Scale for Depression [HAMD-17] ≤7). Specific aspects of depression were assessed from physician and patient perspectives as secondary endpoints. A backwards selection strategy was used to statistically model remission status and determine association of factors with potential to influence remission. RESULTS: At month 6, after adjustment for baseline HAMD-17 score, there was no association between baseline RDQ score and symptomatic remission status (HAMD-17), relapse, composite remission status, healthcare resource utilization, or quality of life. There was no association between functional impairment scores at baseline (Sheehan Disability Scale and Social and Occupational Functioning Assessment Scale) and symptomatic remission status (HAMD-17) at month 6. CONCLUSIONS: This study indicates that RDQ-constructs are independent from symptomatic remission. Symptom severity at study entry appeared to be the only significant predictor of eventual relapse during the 6-month follow-up period. However, our results also suggest that the current definition of remission that is based on symptom reduction should be further elaborated and that alternative or additional definitions should be considered in determining remission.
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Transtorno Depressivo Maior/terapia , Escalas de Graduação Psiquiátrica/normas , Qualidade de Vida/psicologia , Indução de Remissão , Adulto , Transtorno Depressivo Maior/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Inquéritos e Questionários , Resultado do TratamentoRESUMO
The aim of treatment of depression is remission of symptoms and functioning. Although there is a relationship between remission of symptoms and remission of functioning, it is not known how individual residual symptoms are related to functioning. Here we report a post-hoc analysis of two studies which treated depressed patients with duloxetine in an open fashion for 10-12 weeks. We evaluated the association of individual residual symptoms and functional impairment in patients who remitted or partially remitted after acute treatment. Logistic regression was used to investigate residual symptoms associated with functional impairment at endpoint. Our results suggest that in partial remitters, the only residual symptom associated with a reduction in the risk of having impaired function was the resolution of painful physical symptoms (PPS). In patients who remitted, the presence of residual core mood symptoms (CMS), particularly in patients without any anxiety, predicted impaired functioning. The resolution of PPS in the presence of residual CMS was associated with less risk of impaired functioning. Our results contribute to understand better the role of specific residual symptoms on functional impairment. To achieve normal functioning, intervention on specific residual symptoms is recommended.
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Transtorno Depressivo Maior/diagnóstico , Transtorno Depressivo Maior/psicologia , Dor/diagnóstico , Dor/psicologia , Transtornos do Sono-Vigília/diagnóstico , Transtornos do Sono-Vigília/psicologia , Adulto , Antidepressivos/uso terapêutico , Ansiedade/diagnóstico , Ansiedade/tratamento farmacológico , Ansiedade/psicologia , Depressão/diagnóstico , Depressão/tratamento farmacológico , Depressão/psicologia , Transtorno Depressivo Maior/tratamento farmacológico , Cloridrato de Duloxetina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dor/tratamento farmacológico , Transtornos do Sono-Vigília/tratamento farmacológico , Tiofenos/uso terapêuticoRESUMO
OBJECTIVE: The aim of this study is to investigate the attitudes towards mental illness and psychiatry among fifth year Spanish medical students. METHODS: The study included 171 students from three medical schools located in different areas of Spain: Cádiz; UCA (n = 113), Madrid; San Pablo-CEU (n = 22), and Barcelona; UAB (n = 36). They responded, prior to their undergraduate medical course in psychiatry, to the AMI questionnaire to measure the attitudes towards mental illness and to Balon's adapted questionnaire to investigate their view towards psychiatry. RESULTS: The students (93.4 %) had a positive attitude towards mental illness (AMI). Attitudes towards psychiatry were fairly positive with a few negative views, specifically regarding the role of psychiatrists (items 11 and 13) and the prestige of the specialty (item 16). There were some statistically significant differences between the three medical schools in the perception of psychiatry as a medical discipline. A better attitude towards mental illness was associated with a better view of the overall merits of psychiatry. CONCLUSIONS: Findings suggest that Spanish medical students do not have a negative attitude towards mental illness and they have a good perception of psychiatry, although there are still some misconceptions about this specialty. These student's attitudes could favor an appropriate management of patients suffering from mental illness.
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Atitude do Pessoal de Saúde , Saúde Mental , Psiquiatria , Estudantes de Medicina/psicologia , Adulto , Estudos Transversais , Feminino , Humanos , Masculino , Transtornos Mentais/psicologia , Psiquiatria/estatística & dados numéricos , Faculdades de Medicina , Espanha , Estudantes de Medicina/estatística & dados numéricos , Inquéritos e Questionários , Adulto JovemRESUMO
Evidence from numerous clinical studies has shown that the optimal goal for the treatment of depression is remission. Remission implies that the signs and symptoms of the disease are absent or virtually absent, which is typically associated with a return to the patient s previous daily functioning. Functioning in depression is a broad concept that covers different domains. There are many validated instruments for its assessment, these being reviewed in this article. Furthermore, recovering the pre-morbid level of functioning level is increasingly being identified as a significant target in addition to symptomatic remission. In this sense, functional recovery has been associated with better prognosis of depression and is also a clinical goal expressed by the patient. Several factors, like complete remission of symptoms, with no residual symptoms, maintenance of remission, quality of remission, early remission, have been identified as contributors to functional recovery. In order to facilitate the clinical outcomes, evaluation of and search for symptomatic remission as well as functional recovery need to be integrated into the clinical practice.
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Transtorno Depressivo Maior/terapia , Transtorno Depressivo Maior/diagnóstico , Humanos , Recuperação de Função Fisiológica , Indução de RemissãoRESUMO
BACKGROUND: Systematic screening for depression in high-risk patients is recommended but remains controversial. The aim of this study was to assess the effectiveness of such screening in everyday clinical practice on depression recognition. METHODS: A pragmatic, cluster randomized, controlled study that randomized primary care physicians (PCPs) in Spain either to an intervention or control group. The intervention group (35-PCPs) received training in depression screening and used depression screening routinely for at least 6 months. The control group (34-PCPs) managed depression in their usual manner. Adherence to (1-6; never-very frequently), feasibility (1-4; unfeasible-very feasible), and acceptance (1-5; very poor-very good) of the screening were evaluated. Underrecognition (primary outcome) and undertreatment rates of major depressive disorder (MDD) in the two groups were compared 6 months after randomization in a random sample of 3737 patients assigned to these PCPs using logistic regression adjusting for the clustering effect. RESULTS: No significant differences were found for recognition rates (58.0% vs. 48.1% intervention vs. control; OR [95%CI] 1.40 [0.73-2.68], p = 0.309). The undertreatment rate did not differ significantly either (p = 0.390). The mean adherence to depression screening was 4.4 ± 1.0 ('occasionally'), the mean feasibility was 3.1 ± 0.5 ('moderately feasible'), and the mean acceptance was 4.2 ± 0.6 ('good'). CONCLUSIONS: This research was not able to show effectiveness of the systematic screening for MDD in high-risk patients on depression recognition in primary care. The poor adherence to screening implementation could partially explain the results. These reflect the difficulties of putting into practice the clinical guidelines usually based on interventional research. TRIAL REGISTRATION: Clinicaltrials.gov NCT01662817.
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Transtorno Depressivo Maior/diagnóstico , Programas de Rastreamento/métodos , Atenção Primária à Saúde/métodos , Erros de Diagnóstico/estatística & dados numéricos , Feminino , Fidelidade a Diretrizes/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Fatores de RiscoRESUMO
BACKGROUND: The degrees to which residual symptoms in major depressive disorder (MDD) adversely affect patient functioning is not known. This post-hoc analysis explored the association between different residual symptoms and patient functioning. METHODS: Patients with MDD who responded (≥50% on the 17-item Hamilton Rating Scale for Depression; HAMD-17) after 3 months of treatment (624/930) were included. Residual core mood-symptoms (HAMD-17 core symptom subscale ≥1), residual insomnia-symptoms (HAMD-17 sleep subscale ≥1), residual anxiety-symptoms (HAMD-17-anxiety subscale ≥1), residual somatic-symptoms (HAMD-17 Item 13 ≥1), pain (Visual Analogue Scale ≥30), and functioning were assessed after 3 months treatment. A stepwise logistic regression model with normal functioning (Social and Occupational Functioning Assessment Scale ≥80) as the dependent variable was used. RESULTS: After 3 months, 59.5% of patients (371/624) achieved normal functioning and 66.0% (412/624) were in remission. Residual symptom prevalence was: core mood symptoms 72%; insomnia 63%; anxiety 78%; and somatic symptoms 41%. Pain reported in 18%. Factors associated with normal functioning were absence of core mood symptoms (odds ratio [OR] 8.7; 95% confidence interval [CI], 4.6-16.7), absence of insomnia symptoms (OR 1.8; 95% CI, 1.2-2.7), episode length (4-24 weeks vs. ≥24 weeks [OR 2.0; 95% CI, 1.1-3.6]) and better baseline functioning (OR 1.0; 95% CI, 1.0-1.1). A significant interaction between residual anxiety symptoms and pain was found (p = 0.0080). CONCLUSIONS: Different residual symptoms are associated to different degrees with patient functioning. To achieve normal functioning, specific residual symptoms domains might be targeted for treatment.
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Transtorno Depressivo Maior/psicologia , Atividades Cotidianas/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Indução de Remissão , Resultado do TratamentoRESUMO
BACKGROUND: Concomitant painful physical symptoms in depressive patients frequently impair functioning and failure to treat these symptoms may adversely impact treatment outcomes of depression. Early vs. conventional switch of antidepressants were compared in patients with major depressive disorder (MDD) and moderate to severe pain. METHOD: Pre-specified subgroup analysis of a 16-week, randomized, double-blind clinical study on MDD patients with >30 mm overall pain visual analog scale (VAS). Patients not achieving 30% reduction Hamilton Depression Rating Scale (HAM-D) after 4 weeks escitalopram (10 mg/day) were randomized to duloxetine 60-120 mg/day (early switch) or continued on escitalopram (conventional switch) with non-responders at week 8 switching to duloxetine. Endpoints were time to confirmed response and remission, VAS pain severity, and Sheehan disability scale (SDS). Switch strategies were compared using Kaplan-Meier, logistic regression, and repeated measures analyses. RESULTS: No differences between early and conventional switching were found in time to confirmed response after randomization (3.9 vs. 4.1 weeks, p=0.511) or remission (6.0 vs. 8.0 weeks, p=0.238). Significantly lower VAS mean pain levels at for overall pain, headache, back pain, shoulder pain, interference with daily activities, and time being awake in pain were found for patients in the early switching group. Time to achieving normal functioning (SDS total score <6) was shorter in the early switching group (p=0.042). Safety results were comparable between switch strategies. CONCLUSIONS: In MDD patients with moderate to severe painful physical symptoms not improving after 4 weeks of treatment with escitalopram, an earlier switch to duloxetine may lead to better pain and functional outcomes.
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Antidepressivos/uso terapêutico , Citalopram/uso terapêutico , Transtorno Depressivo Maior/tratamento farmacológico , Substituição de Medicamentos/métodos , Dor/tratamento farmacológico , Tiofenos/uso terapêutico , Atividades Cotidianas/psicologia , Adulto , Idoso , Transtorno Depressivo Maior/fisiopatologia , Método Duplo-Cego , Cloridrato de Duloxetina , Feminino , Humanos , Quimioterapia de Indução , Masculino , Pessoa de Meia-Idade , Dor/fisiopatologia , Medição da Dor , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVE: Antidepressant switch is a commonly used strategy in the absence of an adequate response, but optimum timing is not well established. We compared the efficacy of an early and a conventional antidepressant switch strategy in patients with major depressive disorder. METHODS: Patients with no or minimal improvement (<30% reduction in baseline 17-item Hamilton Depression Rating Scale [HAMD17] score) after 4 weeks on escitalopram 10 mg/d were randomized to either early switch strategy with duloxetine 60 to 120 mg/d for 12 weeks (arm A) or conventional switch strategy (arm B): 4 further weeks on escitalopram 10 to 20 mg/d; then, in case of nonresponse (response, ≥ 50% reduction in HAMD17), switch to duloxetine 60 to 120 mg/d for 8 weeks, or continued escitalopram in responders. Co-primary end points were time to confirmed response and remission (HAMD17, ≤ 7). Strategies were compared using Kaplan-Meier, logistic regression, and repeated-measures analyses. RESULTS: Sixty-seven percent (566 of 840) of patients showed no or minimal improvement and were randomized to arm A (282 patients) or arm B (284 patients). No between-strategy differences in time to confirmed response (25% Kaplan-Meier estimates, 3.9 vs 4.0 weeks, P = 0.213) or remission (6.0 vs 7.9 weeks, P = 0.075) were found. Rates of confirmed responders were similar (64.9% vs 64.1%); however, more patients randomized to early switch achieved confirmed remission (43.3% vs 35.6%; P = 0.048). CONCLUSIONS: Although no differences in the primary end points were found, a higher remission rate was seen with the early switch strategy. Our findings suggest that further investigations to reevaluate the conventional approach to antidepressant switch strategy would be worthwhile.
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Citalopram/administração & dosagem , Transtorno Depressivo Resistente a Tratamento/tratamento farmacológico , Resistência a Medicamentos/efeitos dos fármacos , Tiofenos/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antidepressivos/administração & dosagem , Antidepressivos/uso terapêutico , Método Duplo-Cego , Esquema de Medicação , Cloridrato de Duloxetina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica/estatística & dados numéricosRESUMO
OBJECTIVE: The goal of treating major depressive disorder (MDD) should be not only achieving remission in a particular episode but also avoiding relapses and attaining long-term recovery. The current study was designed to evaluate whether response and remission achieved within the first 6 weeks of antidepressant treatment are associated with a 12-month good outcome (achieving remission by 6 months and remaining in remission until the end of follow-up). METHOD: This prospective, longitudinal, multicenter study included adult outpatients who had a DSM-IV diagnosis of MDD, baseline scores ≥ 15 on the 17-item Hamilton Depression Rating Scale (HDRS(17)), Clinical Global Impressions-Severity of Illness scores ≥ 4, and a minimum remission period of 12 weeks between the index episode and the immediately prior episode (or who were in their first MDD episode). The primary efficacy measure was early response (a 50% decrease from baseline in HDRS(17) score by week 6). The secondary efficacy measure was early remission (HDRS(17) score ≤ 7 by week 6). RESULTS: Among the total of 930 patients included from December 2006 to June 2007, 38.2% showed early response, and 20.5% showed early remission. Of the early responders, 76.1% had a 12-month good outcome as compared to 81.1% of early remitters. Logistic regression showed that factors associated with a good outcome included early response (odds ratio [OR] = 4.14), being employed, and the absence of physical comorbidities. Early remission was also strongly associated with a good outcome (OR = 4.72). CONCLUSIONS: Either response or remission achieved by week 6 is the strongest prognostic factor for the 12-month good outcome of an episode of MDD.
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Antidepressivos/uso terapêutico , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/prevenção & controle , Indução de Remissão/métodos , Prevenção Secundária , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Escalas de Graduação Psiquiátrica , Qualidade de Vida/psicologia , Fatores de TempoRESUMO
OBJECTIVES: To evaluate the incidence rate of relapse, the clinical profiles, and the therapeutic interventions employed for patients with schizophrenia deemed as likely nonadherers to oral antipsychotic drugs. METHODS: A cohort of 597 outpatients whose therapy was modified because of a psychiatrist-perceived risk of nonadherence was followed for 12 months in an observational study. Baseline correlates of subsequent relapse were analyzed with Cox regression. RESULTS: At baseline, patients' mean (SD) age and time since diagnosis were 40.1 (11.1) and 15.2 (10.0) years, respectively; 63.7% were males. The Clinical Global Impression scale-Severity (CGI-S) score was ≥ 4 in 87.3% of the patients. Antipsychotic drugs were modified in 506 patients (84.8%); nonpharmacologic therapies were modified in 190 patients (31.8%). In both cases, the primary reason for the modifications was insufficient efficacy of current therapeutic regimen. The proportion of patients in oral antipsychotic monopharmacy decreased from 83.8% to 57.6%; 15.4% started long-acting (depot) formulations. Over the 12-month observation period, 90 patients (15.1%) relapsed. The hazard rate of relapse was higher in patients with substance use disorder or familial psychiatric antecedents and lower in patients who underwent modifications of nonpharmacological therapies or with negative attitude toward antipsychotic medication at baseline. CONCLUSIONS: Effective interventions to prevent relapse in patients with long-standing schizophrenia involving therapeutic challenges related to nonadherence are feasible. Rationale for the baseline correlates, and cues for clinical prevention of relapse in these patients are provided.
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Antipsicóticos/uso terapêutico , Adesão à Medicação/psicologia , Esquizofrenia/tratamento farmacológico , Esquizofrenia/prevenção & controle , Esquizofrenia/terapia , Psicologia do Esquizofrênico , Administração Oral , Adulto , Antipsicóticos/administração & dosagem , Estudos de Coortes , Preparações de Ação Retardada/uso terapêutico , Feminino , Humanos , Masculino , Escalas de Graduação Psiquiátrica/estatística & dados numéricos , Psicoterapia/métodos , Psicoterapia/estatística & dados numéricos , Fatores de Risco , Prevenção SecundáriaRESUMO
Awareness of the importance of maintaining physical health for patients with severe mental illnesses has recently been on the increase. Although there are several elements contributing to poor physical health among these patients as compared with the general population, risk factors for cardiovascular disease such as smoking, diabetes mellitus, hypertension, dyslipidemia, metabolic syndrome, and obesity are of particular significance due to their relationship with mortality and morbidity. These patients present higher vulnerability to cardiovascular risk factors based on several issues, such as genetic predisposition to certain pathologies, poor eating habits and sedentary lifestyles, high proportions of smokers and drug abusers, less access to regular health care services, and potential adverse events during pharmacological treatment. Nevertheless, there is ample scientific evidence supporting the benefits of lifestyle interventions based on diet and exercise designed to minimize and reduce the negative impact of these risk factors on the physical health of patients with severe mental illnesses.
RESUMO
BACKGROUND: Generalized anxiety disorder (GAD) is the most frequent anxiety disorder in primary care patients. It is known that painful physical symptoms (PPS) are associated with GAD, regardless the presence of comorbid major depressive disorder (MDD). However the specific role of such symptoms in patients' functional impairment is not well understood. The objective of the present study is to assess functional impairment related to the presence of PPS in patients with GAD. METHODS: This is a post hoc analysis of a cross-sectional study. Functioning, in the presence (overall pain score >30; Visual Analog Scale) or absence of PPS, was assessed using the Sheehan Disability Scale (SDS) in three groups of patients; 1) GAD and comorbid MDD (GAD+MDD+), 2) GAD without comorbid MDD (GAD+MDD-), 3) controls (GAD-MDD-). ANCOVA models were used. RESULTS: Of those patients with GAD+MDD+ (n = 559), 436 (78.0%) had PPS, compared with GAD+MDD- (249 of 422, 59%) and controls (95 of 336, 28.3%). Functioning worsened in both GAD groups in presence of PPS (SDS least squares mean total score: 16.1 vs. 9.8, p < 0.0001, GAD+MDD+; 14.3 vs. 8.2, p < 0.0001, GAD+MDD-). The presence of PPS was significantly associated with less productivity. CONCLUSIONS: Functional impairment related to the presence of PPS was relevant. Clinical implications should be considered.
Assuntos
Transtornos de Ansiedade/epidemiologia , Transtornos de Ansiedade/psicologia , Transtorno Depressivo Maior/epidemiologia , Avaliação da Deficiência , Dor/epidemiologia , Comorbidade , Estudos Transversais , Transtorno Depressivo Maior/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dor/psicologiaRESUMO
The main goal in the treatment of major depressive disorder (MDD) is to achieve remission, defined as the resolution of symptoms and the return to normal levels of functionality. However, the clinical assessment of remission is usually merely based on scores of symptomatic rating scales. One of the most widely used scales to measure remission is the HAM-D(17), in which remission is defined as a score ≤ 7. Nevertheless, several studies have shown that this cutoff could be too high when also functioning is considered. This is a post-hoc analysis of a 6-month prospective study, performed over a sample of 292 Spanish patients with MDD, in order to find the optimal cutoff in the HAM-D(17) scale, considering normal levels of functionality, evaluated by the SOFAS; by means of plotting Receiver Operating Characteristics (ROC) curves. Our results show that a score of ≤ 5 maximized both sensitivity and specificity for identifying normal levels of functionality with respect to other scores, and thus agree with previous works, which suggest that a cutoff ≤ 7 might be too high to consider remission in patients with MDD, when normal levels of functioning are taken into account.
Assuntos
Depressão/diagnóstico , Depressão/psicologia , Emprego , Escalas de Graduação Psiquiátrica , Psicometria , Ajustamento Social , Adulto , Idoso , Área Sob a Curva , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Curva ROCRESUMO
This study investigated changes in the urine dihydroxyphenylglycol to norepinephrine ratio in patients with attention-deficit hyperactivity disorder (ADHD) treated with atomoxetine. The possible relationship with clinical response was also explored. Newly ADHD diagnosed, treatment-naïve children or adolescents were double-blindly randomized (2:1) to atomoxetine (n = 28) or placebo (n = 13). The dihydroxyphenylglycol to norepinephrine ratio decreased in both groups, showing significantly greater changes with atomoxetine than with placebo at week 6 (-42% versus -14%; P = .001), when dosed at 1.2 mg/kg/day, than at week 2 (-20% versus -2%; P = .118) with a dose of 0.5 mg/kg/day. Although the significant dihydroxyphenylglycol to norepinephrine ratio decrease with atomoxetine indicated norepinephrine transporter blockade, no association with ADHD clinical response (ADHD Rating Scale-IV-Parent:Investigator) was found. Therefore, dihydroxyphenylglycol to norepinephrine ratio might be a useful pharmacodynamic/pharmacokinetic biomarker, although not sufficiently sensitive to predict clinical efficacy. It remains a possibility that this ratio might have value to facilitate personalized atomoxetine pharmacotherapy in ADHD patients.
Assuntos
Inibidores da Captação Adrenérgica/uso terapêutico , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Transtorno do Deficit de Atenção com Hiperatividade/urina , Metoxi-Hidroxifenilglicol/análogos & derivados , Norepinefrina/urina , Propilaminas/uso terapêutico , Adolescente , Cloridrato de Atomoxetina , Criança , Método Duplo-Cego , Feminino , Humanos , Masculino , Metoxi-Hidroxifenilglicol/urina , Projetos Piloto , Resultado do TratamentoRESUMO
The traditional view of schizophrenia as a disabling and irremediably progressive disease is being reconsidered because of the evidences arising from long-term follow-up studies. On the other hand, recent advances of therapies have yielded significant functional improvements for some patients. Together, these facts are serving to raise treatment prospects, placing the focus on functional recovery. Although the availability of a valid set of consensus remission criteria has been an important step toward the definition of therapeutic objectives and the conceptualization of recovery, remission and recovery still are rare concepts in the setting of routine clinical practice. The present article includes a brief review of these concepts, and presents the results from two observational European studies that provide empirical data about the actual situation of ambulatory patients with schizophrenia in terms of symptomatic remission, and that help in advancing the conceptualization of recovery, contributing to the development of clinical and research definitional criteria. Such results indicate that remission of symptoms constitutes a realistic therapeutic goal in a number of patients, with a considerable temporal stability; on the other hand, recovery definitions should include functional and subjective dimensions. In conclusion, remission is a tenable and clinically valid concept, with a significant contribution to functional improvement. Meanwhile, the recovery construct still requires substantial development.
RESUMO
PURPOSE: To describe (1) the clinical profiles and the patterns of use of long-acting injectable (LAI) antipsychotics in patients with schizophrenia at risk of nonadherence with oral antipsychotics, and in those who started treatment with LAI antipsychotics, (2) health care resource utilization and associated costs. PATIENTS AND METHODS: A total of 597 outpatients with schizophrenia at risk of nonadherence, according to the psychiatrist's clinical judgment, were recruited at 59 centers in a noninterventional prospective observational study of 1-year follow-up when their treatment was modified. In a post hoc analysis, the profiles of patients starting LAI or continuing with oral antipsychotics were described, and descriptive analyses of treatments, health resource utilization, and direct costs were performed in those who started an LAI antipsychotic. RESULTS: Therapy modifications involved the antipsychotic medications in 84.8% of patients, mostly because of insufficient efficacy of prior regimen. Ninety-two (15.4%) patients started an LAI antipsychotic at recruitment. Of these, only 13 (14.1%) were prescribed with first-generation antipsychotics. During 1 year, 16.3% of patients who started and 14.9% of patients who did not start an LAI antipsychotic at recruitment relapsed, contrasting with the 20.9% who had been hospitalized only within the prior 6 months. After 1 year, 74.3% of patients who started an LAI antipsychotic continued concomitant treatment with oral antipsychotics. The mean (median) total direct health care cost per patient per month during the study year among the patients starting any LAI antipsychotic at baseline was 1,407 (897.7). Medication costs (including oral and LAI antipsychotics and concomitant medication) represented almost 44%, whereas nonmedication costs accounted for more than 55% of the mean total direct health care costs. CONCLUSION: LAI antipsychotics were infrequently prescribed in spite of a psychiatrist-perceived risk of nonadherence to oral antipsychotics. Mean medication costs were lower than nonmedication costs.