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OBJECTIVE: To compare the tolerability and efficacy of different antipsychotic cross-titration schedules, using data from a brexpiprazole study (Equator; NCT01668797). METHODS: Patients with schizophrenia were cross-titrated from other antipsychotics to brexpiprazole monotherapy in a 1-4 week open-label conversion phase, then entered a single-blind brexpiprazole treatment phase. Patients were stratified into four "conversion groups," according to the amount of time spent in the conversion phase. Discontinuation rates, treatment-emergent adverse events (TEAEs), and efficacy (Positive and Negative Syndrome Scale [PANSS]) were compared between conversion groups. RESULTS: Of the 404 patients treated with brexpiprazole, the majority (72.0%) spent 22-33 days in the conversion phase. Discontinuation rates due to lack of efficacy or adverse events were low in all conversion groups. Of the 292 patients who successfully switched and completed 8 weeks of brexpiprazole treatment, most were converted to brexpiprazole over 22-33 days (80.1%), and fewer were converted over 1-7 days (2.4%), 8-14 days (6.5%), or 15-21 days (11.0%). The incidence of TEAEs over 8 weeks was lower among those converted over 22-33 days (44.4%) than in other conversion groups (62.5-84.2%), although low patient numbers with shorter conversion times limit the generalizability of this finding. Each conversion group showed comparable improvement in PANSS total score from baseline. CONCLUSION: The majority of patients were cross-titrated to brexpiprazole over a period of 22-33 days, by investigators' choice. Additional data on shorter conversions may help clinicians to choose a switching paradigm that best meets their patients' needs.
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Antipsicóticos/administração & dosagem , Quinolonas/administração & dosagem , Esquizofrenia/tratamento farmacológico , Tiofenos/administração & dosagem , Adulto , Antipsicóticos/efeitos adversos , Antipsicóticos/uso terapêutico , Esquema de Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Quinolonas/efeitos adversos , Quinolonas/uso terapêutico , Tiofenos/efeitos adversos , Tiofenos/uso terapêuticoRESUMO
BACKGROUND: Evidence suggests that nearly half of patients with major depressive disorder (MDD) do not achieve an adequate response to antidepressant treatments (ADTs), which impacts patients' functioning, quality of life (QoL), and well-being. This patient survey aimed to better understand patient perspectives on the emotional impact of experiencing an inadequate response to ADTs. METHODS: An online survey was conducted in 6 countries with respondents diagnosed with MDD and experiencing an inadequate response to ADTs. The survey was designed to explore how patients felt about their medications and health care provider (HCP). Those indicating they were 'frustrated' with their medications and/or HCP were asked to provide reasons for their frustration and its impact on their relationship with their HCP and decisions about their treatment. RESULTS: Overall, 2096 respondents with MDD and inadequate response to ADT completed the survey. The most frequent emotion reported by patients regarding their medication was frustration (29.8% of respondents) followed by hopeless (27.4%) and apprehensive/anxious/scared (27.4%). Regarding their HCP, patients reported feeling understood (31.6%) and trusting/confident (28.8%) most often; however, 19.2% reported feelings of frustration. Main reasons for frustration with medication were poor symptom control/lack of efficacy (59.3%) and tolerability issues (19.7%), and the main reasons for frustration with their HCP were not feeling heard (22.4%), ineffective treatment (13.5%) and feeling rushed/lack of quality visit (12.5%). The longer the current episode duration and the greater the disruption to daily living, the more likely the respondents experienced feelings of frustration with medication. Feelings of frustration lead to adherence issues, with 33.3 and 27.3% of respondents indicating their frustration with their medication and HCP, respectively, made them want to quit their medication. Approximately one in six patients frustrated with either their medication and/or HCP indicated their frustration had resulted in them not taking their medication regularly. Frustration with their HCP also impacted patient's confidence in HCPs abilities (34.7%), sharing less information with their HCP (28.9%) as well as missing appointments (17.4%) and medications (14.5%). CONCLUSIONS: Feelings of frustration are frequent in patients with inadequate response to ADT and this frustration may impact treatment adherence and the patient-HCP relationship.
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Antidepressivos/uso terapêutico , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/psicologia , Emoções , Internet , Inquéritos e Questionários , Adolescente , Adulto , Idoso , Transtorno Depressivo Maior/diagnóstico , Feminino , Pessoal de Saúde/psicologia , Humanos , Internacionalidade , Masculino , Pessoa de Meia-Idade , Qualidade de Vida/psicologia , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Despite the availability of effective antidepressants, about half of patients with major depressive disorder (MDD) display an inadequate response to their initial treatment. A large patient survey recently reported that 29.8% of MDD patients experiencing an inadequate treatment response felt frustrated about their medication and 19.2% were frustrated with their healthcare provider. This survey and chart audit evaluated healthcare professionals' (HCP) views on the emotional impact of having an inadequate response to antidepressant medication. METHODS: HCPs who frequently treat patients with MDD completed a survey and chart audit of their MDD patients currently experiencing an inadequate response to antidepressant treatment. RESULTS: 287 HCPs completed 1336 chart audits. HCPs reported that 38% of their patients were trusting/accepting of their MDD medications and 41% of their patients trusted/felt confident with their healthcare provision. Conversely, HCPs reported that 11% of their patients were frustrated with their medication and 5% with their healthcare benefits. HCPs cited impact on daily life (53%) and treatment issues (lack of efficacy and side effects; 50%) as the main drivers for their patients' feelings of frustration. When HCPs recognized patients' feelings of frustration, the top concerns of the HCPs were worsening of symptoms (43%) and non-compliance (41%). CONCLUSIONS: This survey and chart audit highlights the emotional burden associated with inadequate responses to MDD treatment in addition to persistent symptoms. Differences between the views of the HCPs and patients are highlighted and suggest that HCPs may underestimate the full impact that having to try numerous medications has on their patients.
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Background: Approximately 50% of patients with major depressive disorder do not respond adequately to their antidepressant treatment, underscoring the need for more effective treatment options. The objective of this study was to investigate the effect of adjunctive brexpiprazole on depressive symptoms in patients with major depressive disorder who were not responding to adjunctive or combination therapy of their current antidepressant treatments with several different classes of agents (NCT02012218). Methods: In this 6-week, open-label, phase 3b study, patients with major depressive disorder who had an inadequate response to ≥1 adjunctive or combination therapy, in addition to history of ≥1 failure to monotherapy antidepressant treatment, were switched to adjunctive brexpiprazole. Efficacy was assessed by change from baseline to week 6 in Montgomery-Åsberg Depression Rating Scale total score. Patient functioning was assessed using the Sheehan Disability Scale and the Cognitive and Physical Functioning Questionnaire. Safety and tolerability were also assessed. Results: A total of 51/61 (83.6%) patients completed 6 weeks of treatment with adjunctive brexpiprazole. Improvements in depressive symptoms were observed (least squares mean change from baseline to week 6 in Montgomery-Åsberg Depression Rating Scale total score, -17.3 [P < .0001]) as well as improvements in general and cognitive functioning (mean changes from baseline to week 6: Sheehan Disability Scale, -3.1 [P < .0001]; Massachusetts General Hospital-Cognitive and Physical Functioning Questionnaire, -9.2 [P < .0001]). The most common adverse event was fatigue (14.8%); akathisia was reported by 8.2% of patients. Conclusions: In patients with major depressive disorder who had switched to open-label adjunctive brexpiprazole following inadequate response to previous adjunctive or combination therapy, improvements were observed in depressive symptoms, general functioning, cognitive function, and energy/alertness.
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Antidepressivos/uso terapêutico , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Resistente a Tratamento/tratamento farmacológico , Quinolonas/uso terapêutico , Tiofenos/uso terapêutico , Antidepressivos/efeitos adversos , Aripiprazol/uso terapêutico , Bupropiona/uso terapêutico , Estimulantes do Sistema Nervoso Central/uso terapêutico , Cognição/efeitos dos fármacos , Quimioterapia Combinada , Feminino , Humanos , Comportamento Impulsivo/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Fumarato de Quetiapina/uso terapêutico , Quinolonas/efeitos adversos , Sono/efeitos dos fármacos , Tiofenos/efeitos adversos , Resultado do TratamentoRESUMO
Background: Brexpiprazole has previously demonstrated efficacy in acute schizophrenia trials. The objective of this trial was to assess the efficacy, safety, and tolerability of maintenance treatment with brexpiprazole in adults with schizophrenia. Methods: Patients with an acute exacerbation of psychotic symptoms were converted to brexpiprazole (1-4mg/d) over 1 to 4 weeks and entered a single-blind stabilization phase. Those patients who met stability criteria for 12 weeks were randomized 1:1 to double-blind maintenance treatment with either brexpiprazole (at their stabilization dose) or placebo for up to 52 weeks. The primary efficacy endpoint was the time from randomization to impending relapse. Safety and tolerability were also assessed. Results: A total of 524 patients were enrolled, 202 of whom were stabilized on brexpiprazole and randomized to brexpiprazole (n=97) or placebo (n=105). Efficacy was demonstrated at a prespecified interim analysis (conducted after 45 events), and so the trial was terminated early. The final analysis showed that time to impending relapse was statistically significantly delayed with brexpiprazole treatment compared with placebo (P<.0001, log-rank test). The hazard ratio for the final analysis was 0.292 (95% confidence interval: 0.156, 0.548); mean dose at last visit, 3.6mg. The proportion of patients meeting the criteria for impending relapse was 13.5% with brexpiprazole and 38.5% with placebo (P<.0001). During the maintenance phase, the incidence of adverse events was comparable to placebo. Conclusions: or patients with schizophrenia already stabilized on brexpiprazole, maintenance treatment with brexpiprazole was efficacious, with a favorable safety profile.
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Antipsicóticos/uso terapêutico , Quinolonas/uso terapêutico , Esquizofrenia/tratamento farmacológico , Tiofenos/uso terapêutico , Adolescente , Adulto , Idoso , Antipsicóticos/efeitos adversos , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Escalas de Graduação Psiquiátrica , Quinolonas/efeitos adversos , Recidiva , Tiofenos/efeitos adversos , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVE: Review efficacy, safety, and tolerability of brexpiprazole in patients with schizophrenia in short- and long-term phase 3 studies. METHODS: Patients experiencing a current exacerbation of schizophrenia received brexpiprazole in two fixed-dose (2 and 4 mg), 6-week, placebo-controlled studies, one flexible-dose (2-4 mg), 6-week, placebo-control and active reference study, and one fixed-dose (1-4 mg), 52-week, placebo-controlled maintenance study. RESULTS: The efficacy of brexpiprazole was demonstrated in the two short-term fixed-dose studies with statistically significant improvements from baseline in Positive and Negative Syndrome Scale (PANSS) total score compared with placebo. In the flexible-dose short-term study, treatment with brexpiprazole resulted in numerically greater improvements in PANSS total score than with placebo that approached statistical significance (p=0.056). A meta-analysis of these short-term studies showed a mean change in PANSS total score of -20.1, reflecting a clinically meaningful reduction in symptoms. In the maintenance study, brexpiprazole had a beneficial effect relative to placebo on time to exacerbation of psychotic symptoms/impending relapse (p<0.0001). For all studies, brexpiprazole demonstrated clinically meaningful treatment effects on the Personal and Social Performance scale. Brexpiprazole had a favourable safety profile, with a relatively low prevalence of activating and sedating side effects. Weight gain in the short-term studies was ~1 kg greater than placebo. No safety concerns were observed with brexpiprazole in laboratory values, electrocardiogram, or vital signs. CONCLUSIONS: Overall, the results indicate brexpiprazole, used either short-term or as part of a long-term maintenance treatment programme, is an efficacious therapy option in adults with schizophrenia and has a favourable safety/tolerability profile.
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Antipsicóticos/uso terapêutico , Quinolonas/uso terapêutico , Esquizofrenia/tratamento farmacológico , Tiofenos/uso terapêutico , Adulto , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoAssuntos
Antidepressivos/farmacologia , Antipsicóticos/farmacologia , Transtorno Depressivo Maior/tratamento farmacológico , Humor Irritável/efeitos dos fármacos , Quinolonas/farmacologia , Tiofenos/farmacologia , Adulto , Antipsicóticos/administração & dosagem , Quimioterapia Combinada , Humanos , Pessoa de Meia-Idade , Quinolonas/administração & dosagem , Tiofenos/administração & dosagemRESUMO
BACKGROUND: Escitalopram has shown efficacy and tolerability in the prevention of relapse in elderly patients with major depressive disorder (MDD). This post-hoc analysis compared time to relapse for young-old patients (n = 197) to that for old-old patients (n = 108). METHOD: Relapse prevention: after 12-weeks open-label treatment, remitters (MADRS ≤12) were randomised to double-blind treatment with escitalopram or placebo and followed over 24-weeks. Patients were outpatients with MDD from 46 European centers aged ≥75 years (old-old) or 65-74 years of age (young-old), treated with escitalopram 10-20 mg/day. Efficacy was assessed using the Montgomery Åsberg Depression Rating Scale (MADRS). RESULTS: After open-label escitalopram treatment, a similar proportion of young-old patients (78%) and old-old patients (72%) achieved remission. In the analysis of time to relapse based on the Cox model (proportional hazards regression), with treatment and age group as covariates, the hazard ratio was 4.4 for placebo versus escitalopram (χ(2)-test, df = 1, χ(2)= 22.5, p < 0.001), whereas the effect of age was not significant, with a hazard ratio of 1.2 for old-old versus young-old (χ(2)-test, df = 1, χ(2) = 0.41, p = 0.520). Escitalopram was well tolerated in both age groups with adverse events reported by 53.1% of young-old patients and 58.3% of old-old patients. There was no significant difference in withdrawal rates due to AEs between age groups (χ(2)-test, χ(2) = 1.669, df = 1, p = 0.196). CONCLUSIONS: Young-old and old-old patients with MDD had comparable rates of remission after open-label escitalopram, and both age groups had much lower rates of relapse on escitalopram than on placebo.
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Citalopram/uso terapêutico , Transtorno Depressivo Maior/tratamento farmacológico , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Citalopram/administração & dosagem , Transtorno Depressivo Maior/prevenção & controle , Método Duplo-Cego , Feminino , Humanos , Masculino , Modelos de Riscos Proporcionais , Prevenção Secundária , Inibidores Seletivos de Recaptação de Serotonina/administração & dosagemRESUMO
OBJECTIVE: Episodes of major depressive disorder (MDD) characterized by high levels of anxiety symptoms are less likely to respond to some forms of antidepressant treatment (ADT). This report examines the effects of adjunctive brexpiprazole on depressive symptoms among patients with MDD and anxiety symptoms. MATERIALS AND METHODS: This was a post hoc analysis of 1,171 patients from the 6-week, randomized, double-blind phases of three studies in adults with MDD and inadequate response to ADTs (NCT01360645, NCT01360632, NCT02196506). Data were pooled for brexpiprazole 2-3 mg/day and for placebo (adjunct to ADT). Montgomery-Åsberg Depression Rating Scale Total score changes were assessed in subgroups of patients with and without anxious distress (based on proxies for the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria) and anxious depression (defined as a Hamilton Depression Rating Scale Anxiety/somatization factor score of ≥7). Safety was assessed by the incidence of treatment-emergent adverse events (TEAEs). RESULTS: Benefits were seen for adjunctive brexpiprazole (compared with adjunctive placebo) in both anxiety definition subgroups. For patients with anxious distress, the least squares mean difference (95% CI) at week 6 was -3.00 (-4.29, -1.71; P<0.0001) and, for those without anxious distress, was -1.38 (-2.71, -0.05; P=0.043). For patients with anxious depression, the difference was -2.19 (-3.60, -0.78; P=0.0023), compared with -2.34 (-3.58, -1.10; P=0.0002) for those without anxious depression. The most common TEAEs among patients with anxiety symptoms receiving ADT + brexpiprazole were akathisia, headache, restlessness, somnolence, and weight increase. There were no clinically meaningful differences in the rates of these TEAEs according to the presence or absence of anxiety symptoms. CONCLUSION: Adjunctive brexpiprazole 2-3 mg/day may be efficacious in reducing depressive symptoms, and was well tolerated, in patients with clinically relevant anxiety symptoms.
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OBJECTIVE: To analyze the effect of brexpiprazole on metabolic parameters and body weight in adults with schizophrenia, including clinically relevant sub-groups of patients, based on data from two pivotal phase 3 studies (NCT01393613; NCT01396421) and a long-term extension study (NCT01397786). METHODS: The short-term studies were randomized, double-blind, placebo-controlled, fixed-dose (2 and 4 mg/day), 6-week phase 3 studies. The long-term study was an open-label 52-week study, recruiting de novo patients and those completing either short-term study. Maximum exposure to brexpiprazole was 58 weeks. Fasting metabolic parameters and weight were measured throughout the studies. Metabolic values were characterized as normal, borderline, or high (cholesterol, triglycerides, and glucose) and low or normal (HDL), using commonly reported thresholds. The incidences of all possible shifts in metabolic parameters were measured from baseline to any time post-baseline during the first 6 weeks, first 6 months, and last 6 months of treatment. RESULTS: In short-term studies, the proportion of brexpiprazole-treated patients with unfavorable shifts in metabolic parameters was low and like that of placebo-treated patients; the incidence of these shifts was not dose-dependent. During both short- and long-term treatment, the incidence of unfavorable shifts with brexpiprazole was lower than that of favorable shifts. During short-term studies, the mean increase in body weight was 1.2 kg with brexpiprazole treatment and 0.2 kg with placebo. The mean increase in body weight during long-term treatment was 3.2 kg at week 58. CONCLUSIONS: Brexpiprazole treatment was associated with moderate weight gain and small changes in metabolic parameters during both short- and long-term treatment.
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Antipsicóticos/uso terapêutico , Quinolonas/uso terapêutico , Esquizofrenia/tratamento farmacológico , Tiofenos/uso terapêutico , Adulto , Ensaios Clínicos Fase III como Assunto , Método Duplo-Cego , Glucose/metabolismo , Humanos , Estudos Longitudinais , Ensaios Clínicos Controlados Aleatórios como Assunto , Triglicerídeos/sangue , Aumento de Peso/efeitos dos fármacosRESUMO
BACKGROUND: Patients with major depressive disorder (MDD) who do not adequately respond to antidepressant treatment (ADT) may benefit from adjunctive atypical antipsychotics; however, certain agents target specific symptoms of depression and not the full syndrome. The aim of this analysis was to examine the effects of brexpiprazole, adjunct to ADT, on the core symptoms of MDD, defined using Montgomery-Åsberg Depression Rating Scale (MADRS) items. METHODS: This was a post hoc analysis of data from two 6-week, randomized, double-blind studies of adjunctive brexpiprazole in patients with MDD and inadequate response to ADTs (n = 1056). Efficacy was assessed using the MADRS core symptom subscale (MADRS6) and individual items (apparent sadness, reported sadness, inner tension, lassitude, inability to feel, and pessimistic thoughts). RESULTS: At Week 6, adjunctive brexpiprazole showed a greater effect than adjunctive placebo on the MADRS6 (within-group Cohen's d effect sizes: brexpiprazole, 1.05; placebo, 0.71; p < 0.001 between groups) and on each of the six core symptoms (effect sizes: brexpiprazole, 0.64-0.94; placebo, 0.39-0.64; all p < 0.001). At Week 2, adjunctive brexpiprazole already showed a greater effect than adjunctive placebo on the MADRS6, and on five of the core symptoms (all p < 0.01). LIMITATIONS: This was a post hoc analysis of studies that were not designed for this purpose. Correction for multiple comparisons was not performed. CONCLUSIONS: Brexpiprazole, as adjunct to ADT, produced a statistically significant and clinically meaningful improvement on the core symptoms of MDD. Brexpiprazole is thought to exert its effects in MDD by treating the core symptoms of the disease.
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Antidepressivos/uso terapêutico , Antipsicóticos/uso terapêutico , Transtorno Depressivo Maior/tratamento farmacológico , Quinolonas/uso terapêutico , Serotoninérgicos/uso terapêutico , Tiofenos/uso terapêutico , Adulto , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
The aim of this analysis was to explore the effects of brexpiprazole and aripiprazole on body weight when used as monotherapy to treat schizophrenia and as adjunctive treatment to antidepressant treatment (ADT) for major depressive disorder (MDD) in short-term (4/6 weeks) and long-term (≤52 weeks) studies. Body weight data were obtained from the clinical studies of each drug (brexpiprazole and aripiprazole), in schizophrenia and adjunctive treatment of MDD. Data were pooled and analyzed to assess the mean change in body weight and to determine the incidence of a clinically relevant change in body weight from baseline (≥7% increase or decrease, at any time) in each treatment group. The overall weight profiles for brexpiprazole and aripiprazole in the short-term and long-term treatment of schizophrenia, and MDD (adjunctive to ADT), were similar. In short-term schizophrenia studies, the mean weight increase was 1.2 kg for brexpiprazole and 0.6 kg for aripiprazole. In short-term MDD studies (adjunctive to ADT), the mean weight increase was 1.5 kg for brexpiprazole and 1.6 kg for aripiprazole. In the long-term schizophrenia studies, at week 52, the mean weight increase was 2.1 kg for brexpiprazole and 3.0 kg for aripiprazole. In long-term MDD studies (adjunctive to ADT), at week 52, the mean weight increase was 3.2 kg for brexpiprazole and 4.0 kg for aripiprazole. Clinically relevant increases or decreases in body weight were also similar for brexpiprazole and aripiprazole. Overall, in the treatment of schizophrenia, and in adjunctive treatment of MDD, brexpiprazole and aripiprazole have a similar effect on body weight over the course of 1 year.
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Antipsicóticos/efeitos adversos , Aripiprazol/efeitos adversos , Transtorno Depressivo Maior/tratamento farmacológico , Quinolonas/efeitos adversos , Esquizofrenia/tratamento farmacológico , Tiofenos/efeitos adversos , Aumento de Peso/efeitos dos fármacos , Adulto , Antipsicóticos/uso terapêutico , Aripiprazol/uso terapêutico , Feminino , Humanos , Estudos Longitudinais , Masculino , Metanálise como Assunto , Pessoa de Meia-Idade , Quinolonas/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Tiofenos/uso terapêuticoRESUMO
OBJECTIVE: Patients with major depressive disorder (MDD) with inadequate response to antidepressant treatment (ADT) may suffer a prolonged loss of functioning. This review aimed to determine if self-rated functional measures are informative in randomized placebo-controlled studies of adjunctive therapy in patients with MDD and inadequate response to ADT. METHODS: This was a systematic literature review of articles in any language from the MEDLINE database published between January 1990 and March 2017. Eligible studies met the following criteria: patients with MDD; inadequate response to at least one ADT; adjunctive therapy (pharmacological or otherwise) to ADT; placebo control group; randomized controlled trial or a post hoc analysis of a randomized controlled trial; reported a self-rated functioning scale. Study characteristics and functioning efficacy data were extracted. RESULTS: A total of 2,090 discrete records were screened, 293 full-text articles were assessed for eligibility, and 26 studies were included. All studies were acute (6-12 weeks) except for one 52-week study. The only self-rated functioning scale used in the included studies was the Sheehan Disability Scale (SDS). Of the 13 adjunctive agents identified, aripiprazole, brexpiprazole, edivoxetine, and risperidone improved functioning versus placebo (p<0.05), as measured by the SDS total or mean score. On the SDS "work/studies" item, only aripiprazole had a statistically significant benefit, in one study out of four. Thus, where a benefit was observed on the SDS total or mean, this was generally driven by improvement on the "social life" and "family life" items. A limitation of the review is that it only considered published literature from one database. CONCLUSION: The SDS, a self-rated functional measure, is informative in acute randomized placebo-controlled studies of adjunctive therapy in patients with MDD and inadequate response to ADT. However, the item that measures work performance may be less relevant to this population than the items that measure social and family life.
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BACKGROUND: Randomized controlled clinical trials have demonstrated that escitalopram is efficacious in a range of mood and anxiety disorders, but the individual trials are insufficiently large to allow a full exploration of its tolerability. OBJECTIVE: To assess the tolerability and safety of escitalopram through analysis of all randomized controlled clinical trials in major depressive disorder and anxiety disorders. METHODS: Analyses of tolerability were based on data from all available randomized, double-blind, controlled studies completed by December 2006 in which escitalopram was compared with placebo or active compounds (citalopram, fluoxetine, paroxetine, sertraline, venlafaxine). Adverse events (AEs) that occurred more frequently with escitalopram than with placebo were listed, and tolerability and safety were evaluated. RESULTS: Nausea was the only AE with an incidence greater than or equal to 10% and 5 percentage points greater than with placebo during short-term treatment. In general, AEs were mild to moderate in severity. AEs related to sexual dysfunction were similarly frequent with escitalopram and citalopram, but were higher with paroxetine. No suicide occurred among escitalopram-treated patients, and there were no significant differences between escitalopram and placebo in incidence of suicidal behavior, measured by self-harm and suicidal thoughts. The 8 week withdrawal rate due to AEs was higher with escitalopram than with placebo (7.3% vs 2.8%; p < 0.001) but lower than with paroxetine (6.6% vs 9.0%; p < 0.01) or venlafaxine (6.1% vs 13.2%; p < 0.01) (Fisher's Exact test, 2 tailed). Compared with paroxetine, escitalopram resulted in significantly fewer discontinuation symptoms (average increase in Discontinuation Emergent Signs and Symptoms Scale of 1.6 vs 3.9; p < 0.01). There were no clinically relevant changes in clinical laboratory values in patients treated with escitalopram. Mean weight change after 6 months of treatment with escitalopram (0.58 +/- 2.63 kg) was similar to that with placebo (0.15 +/- 2.33 kg). The incidence of cardiovascular events was similar to that with placebo. The risk of AEs was no higher in special patient populations, such as the elderly (> or =65 y of age) or those with hepatic dysfunction. CONCLUSIONS: Based on data from randomized controlled trials involving more than 4000 escitalopram-treated patients, escitalopram (10-20 mg/day) is safe and well tolerated in short- and long-term treatment.
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Transtornos de Ansiedade/tratamento farmacológico , Citalopram/uso terapêutico , Transtorno Depressivo Maior/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Transtornos de Ansiedade/epidemiologia , Transtornos de Ansiedade/psicologia , Citalopram/efeitos adversos , Transtorno Depressivo Maior/epidemiologia , Transtorno Depressivo Maior/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Náusea/epidemiologia , Ensaios Clínicos Controlados Aleatórios como Assunto/métodosRESUMO
PURPOSE: Patients with a bipolar I disorder (BD-I) manic episode meeting the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5), criteria for "with mixed features" have a high incidence of suicide attempts and of anxiety, irritability, and agitation (AIA) symptoms. The aim of this analysis was to explore the relationship between suicidality and AIA symptoms in patients with BD-I experiencing mania with depressive symptoms, using data from a previous naturalistic study. PATIENTS AND METHODS: Psychiatrists completed an online questionnaire about their adult patients who had a current BD-I manic episode. Questions covered the DSM-5 "with mixed features" specifier, the severity of AIA symptoms, the frequency and controllability of suicidal ideation, and the number of suicide attempts. RESULTS: Of 1,035 patients with BD-I mania who were included in the analyses, 348 (33.6%) met the criteria for the DSM-5 "with mixed features" specifier (three or more depressive symptoms). These patients were further stratified according to the severity of their AIA symptoms: "mild AIA" (zero or one AIA symptom above a severity threshold; 105 patients) or "severe AIA" (all three AIA symptoms above a severity threshold; 167 patients). A greater incidence of suicidal ideation was observed in the severe AIA group (71.9%) than in the mild AIA group (47.6%). Twice as many patients had easily controlled suicidal ideation than difficult-to-control suicidal ideation in both subgroups. The mean number of suicide attempts was higher in the severe AIA group than in the mild AIA group, during the current episode (0.84 vs 0.34 attempts, respectively; P<0.05) and over the patient's lifetime (1.56 vs 1.04 attempts, respectively). CONCLUSION: The high risk of suicide among BD-I mania patients with depressive symptoms is further increased when they experience severe AIA symptoms. Recognizing AIA symptoms in BD-I mania could provide a means of identifying patients with depressive symptoms, as well as those who may be suicidal, thereby allowing for appropriate, tailored treatment.
RESUMO
BACKGROUND: Anxiety symptoms are prevalent in major depressive disorder (MDD) and are associated with greater illness severity, suicidality, impaired functioning and poor response to antidepressant treatment (ADT). The efficacy and safety of brexpiprazole - a serotonin-dopamine activity modulator - as adjunctive treatment in patients with MDD was recently evaluated in two phase 3 studies. We here present a post-hoc analysis of the efficacy of adjunctive brexpiprazole in patients with MDD and symptoms of anxious distress, defined using proxies for DSM-5 criteria. METHODS: Eligible patients were randomized to 2mg brexpiprazole+ADT or placebo+ADT (NCT01360645); or 1mg brexpiprazole+ADT, 3mg brexpiprazole+ADT, or placebo+ADT (NCT01360632), respectively. Patients were defined as having anxious distress if they had ≥2 of the symptoms tension (MADRS item 3 score ≥3), restlessness (IDS item 24 score ≥2), concentration (MADRS item 6 score ≥3), or apprehension (HAM-D item 10 score ≥3). Primary efficacy endpoint was change in MADRS total score from baseline to Week 6. RESULTS: 55% of the patients had anxious distress at baseline. Adjunctive brexpiprazole showed greater improvement than adjunctive placebo on the primary efficacy endpoint in both patients with (least square mean difference to placebo+ADT: 2mg+ADT: -2.95, p=0.0023; 3mg+ADT: -2.81, p=0.0027); and without anxious distress (1mg+ADT: -2.37, p=0.0093; 3mg+ADT: -2.23, p=0.0131). Brexpiprazole in patients with anxious distress was not associated with an increased incidence of activating adverse events (e.g., akathisia). CONCLUSIONS: Adjunctive brexpiprazole 2-3mg may be efficacious in reducing depressive symptoms and is well tolerated, in patients with MDD and anxious distress.
Assuntos
Antidepressivos/uso terapêutico , Transtornos de Ansiedade/tratamento farmacológico , Transtorno Depressivo Maior/tratamento farmacológico , Quinolonas/uso terapêutico , Serotoninérgicos/uso terapêutico , Tiofenos/uso terapêutico , Adulto , Transtornos de Ansiedade/fisiopatologia , Depressão , Transtorno Depressivo Maior/fisiopatologia , Agonistas de Dopamina/uso terapêutico , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Agitação Psicomotora/tratamento farmacológico , Agitação Psicomotora/fisiopatologia , Resultado do TratamentoRESUMO
The aim of this study was to explore the effects of brexpiprazole and aripiprazole on efficacy, cognitive functioning, and safety in patients with acute schizophrenia. Patients who would benefit from hospitalization/continued hospitalization for acute relapse of schizophrenia were enrolled and randomized (2 : 1) to target doses of open-label brexpiprazole 3 mg/day or aripiprazole 15 mg/day for 6 weeks. Outcomes included change from baseline to week 6 in the Positive and Negative Syndrome Scale total score, Barratt Impulsiveness Scale 11-item score, and Cogstate computerized cognitive test battery scores. Patients treated with brexpiprazole (n=64) or aripiprazole (n=33) showed reductions in symptoms of schizophrenia as assessed by Positive and Negative Syndrome Scale total score (-22.9 and -19.4, respectively). A modest reduction in impulsivity was observed with brexpiprazole, but not aripiprazole (mean change in the Barratt Impulsiveness Scale 11-item total score: -2.7 and 0.1, respectively). No change in Cogstate scores was observed for either treatment. Brexpiprazole was well tolerated and the incidence of akathisia was lower in patients treated with brexpiprazole (9.4%) than aripiprazole (21.2%). Clinically relevant improvements in psychopathology were observed in patients with acute schizophrenia treated with brexpiprazole or aripiprazole. Brexpiprazole was well tolerated, with a lower incidence of akathisia than aripiprazole.
Assuntos
Antipsicóticos/uso terapêutico , Aripiprazol/uso terapêutico , Quinolonas/uso terapêutico , Esquizofrenia/diagnóstico , Esquizofrenia/tratamento farmacológico , Serotoninérgicos/uso terapêutico , Tiofenos/uso terapêutico , Doença Aguda , Adulto , Acatisia Induzida por Medicamentos/diagnóstico , Antipsicóticos/efeitos adversos , Aripiprazol/efeitos adversos , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Quinolonas/efeitos adversos , Serotoninérgicos/efeitos adversos , Tiofenos/efeitos adversos , Resultado do Tratamento , Aumento de Peso/efeitos dos fármacosRESUMO
Brexpiprazole, a serotonin-dopamine activity modulator, is a partial agonist at 5-HT1A and dopamine D2 receptors, and antagonist at 5-HT2A and noradrenaline α1B and α2C receptors, all at similar potency. Efficacy of brexpiprazole was evaluated in patients with acutely exacerbated schizophrenia in three short-term, randomized, double-blind, placebo-controlled studies. In a Phase 2 study, patients were randomized to brexpiprazole 0.25mg (fixed dose), 1.0±0.5mg, 2.5±0.5mg, 5.0±1mg (flexible-dose ranges), placebo, or aripiprazole 15±5mg. In two Phase 3 studies, patients were randomized to fixed-dose brexpiprazole 0.25mg, 1mg, 2mg, or 4mg, or placebo. For this review, brexpiprazole 2mg and 4mg arms from the Phase 3 studies were combined. Primary efficacy endpoint was change in Positive and Negative Syndrome Scale (PANSS) total score from baseline at week 6; key secondary endpoint was change in Clinical Global Impression-Severity of illness (CGI-S) score at week 6. Primary outcome moderator analyses explored effects of sex, age, race, and illness duration. There were no statistically significant differences vs. placebo in the Phase 2 brexpiprazole and aripiprazole groups for primary and key secondary endpoints. Combined brexpiprazole 2mg (n=359) and 4mg (n=359) were superior to placebo (n=358) in change in PANSS total score (least square mean difference from placebo: -5.46, p=0.0004, and -6.69, p<0.0001, respectively) and CGI-S (-0.25, p=0.0035, and -0.38, p<0.0001, respectively). Changes from baseline in efficacy endpoints were minimal in the 0.25mg group, while the 1mg group exhibited suboptimal improvement. No relevant moderators were identified. Meta-analysis of the pivotal studies indicates brexpiprazole 2mg and 4mg are effective in treating acute schizophrenia.
Assuntos
Antipsicóticos/uso terapêutico , Quinolonas/uso terapêutico , Esquizofrenia/tratamento farmacológico , Tiofenos/uso terapêutico , Doença Aguda , Ensaios Clínicos Fase II como Assunto , Ensaios Clínicos Fase III como Assunto , Humanos , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Second-generation antipsychotics have demonstrated efficacy for patients with schizophrenia but are associated with wide-ranging side effects. Brexpiprazole, a serotonin-dopamine activity modulator, has demonstrated efficacy in adult patients with schizophrenia. This paper provides an overview of the safety and tolerability of brexpiprazole in patients with schizophrenia through examination of pooled safety data from one Phase 2 and two Phase 3 6-week, short-term studies, and two open-label, 52-week, long-term studies. In the short-term studies, there were no reports of treatment-emergent adverse events (TEAEs) with an incidence≥5% and twice that of placebo in patients treated with brexpiprazole 2-4mg. In the long-term studies, TEAEs reported by ≥5% of patients were schizophrenia (10.7%), insomnia (8.0%), weight increase (7.7%), headache (6.0%), and agitation (5.2%). Akathisia rates were low in the short- (5.8%, pooled brexpiprazole group) and long-term studies (4.6%). Sedation rates were low in the short- (2.3%, pooled brexpiprazole group) and long-term studies (0.9%). Mean body weight increase was 1.1kg in both short- and long-term studies. For all studies, changes from baseline to last visit in laboratory parameters, electrocardiogram values, and vital signs were small and not clinically relevant. Changes in lipid profiles or other metabolic parameters were also small. Collectively, these studies suggest that brexpiprazole was well tolerated, with a favorable safety profile that does not exhibit significant rates of important adverse events that can be seen with existing antipsychotics (akathisia, sedation, weight gain, or QTc prolongation), and therefore may provide a useful treatment option for patients with schizophrenia. ClinicalTrials.gov: NCT00905307; NCT01396421; NCT01393613; NCT01649557; NCT01397786.
Assuntos
Antipsicóticos/efeitos adversos , Antipsicóticos/uso terapêutico , Quinolonas/efeitos adversos , Quinolonas/uso terapêutico , Esquizofrenia/tratamento farmacológico , Tiofenos/efeitos adversos , Tiofenos/uso terapêutico , Ensaios Clínicos Fase II como Assunto , Ensaios Clínicos Fase III como Assunto , Humanos , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
BACKGROUND: Major depressive disorder (MDD) is a common, debilitating disorder with substantial socioeconomic burden. Many patients with MDD experience symptoms that impair functioning and productivity, often negatively affecting work or educational pursuits. This Phase 3b open-label study evaluated adjunctive brexpiprazole in young adults with MDD, who were in work or study. METHODS: Young patients (18-35 years) with MDD (inadequate responders to 1-3 antidepressant treatments [ADT] for their current episode) received brexpiprazole 1-3mg/day (target dose, 2mg/day) adjunctive to the same stable dose of ADT for 12 weeks. RESULTS: Depressive symptoms improved during treatment with adjunctive brexpiprazole (primary endpoint, least squares [LS] mean change from baseline in Montgomery-Åsberg Depression Rating Scale [MADRS] total score, -18.1 [p<0.0001]). Reductions from baseline in Sheehan Disability Scale Score (SDS; LS mean change -11.2 [p<0.0001]) and Work Limitations Questionnaire (WLQ; p<0.0001) indicated improvements in the effects of patients' symptoms on functioning (work/school, social life, and home responsibilities). Changes from baseline in additional measures supported improvements in patient functioning and depression symptoms. The most common adverse events were headache (21.3%), weight increase (17.0%), and somnolence (17.0%); reported rates of akathisia were low (6.4%). Clinically relevant increases in weight (≥7%) occurred in 10.5% of patients. LIMITATIONS: Open-label design; absence of comparator. CONCLUSIONS: Brexpiprazole may represent an effective therapy for adjunctive treatment strategy of young adults with MDD who are working or studying. The observed improvements in work/school functioning in patients with MDD, whose depression was treated with ADT+brexpiprazole, suggests potential to reduce socioeconomic burden.