Escitalopram prevents relapse in older patients with major depressive disorder.

OBJECTIVE: The present study investigated the efficacy and tolerability of escitalopram in the prevention of relapse of major depressive disorder (MDD) in older patients who had responded to acute treatment with escitalopram. METHOD: A total of 405 patients who were aged 65 years or older with a primary diagnosis of MDD (according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria) and a Montgomery-Asberg Depression Rating Scale (MADRS) total score of 22 or more received 12-week, open-label escitalopram 10 or 20 mg per day treatment. Remitters (MADRS 相似文献   

Escitalopram in the long-term treatment of major depressive disorder.

BACKGROUND: Escitalopram has been proven safe and efficacious in the treatment of major depressive disorder (MDD) in short-term studies. The long-term clinical tolerability and response to treatment are presented from a 12-month open-label study with a total exposure time to escitalopram of 486 patient years. METHODS: Patients (n = 590) with MDD entered the study after completing one of two 8-week, double-blind, placebo-controlled, lead-in studies in primary care. Escitalopram was administered at doses of 10 or 20 mg/day (dose based on physician's clinical judgement) with an average exposure to escitalopram of 315 days. The primary efficacy parameter was the Montgomery Asberg Depression Rating Scale (MADRS) total score. RESULTS: The overall withdrawal rate was 26%; and the withdrawal rate due to adverse events was 9%. The most common adverse events were headache, back pain, upper respiratory tract infection, rhinitis and nausea, with an incidence ranging from 11% to 17%. No new types of adverse events were seen after the acute period of 8 weeks, and the incidence declined with time. At baseline (entry into the 12-month study), patients had a mean MADRS total score of 14.2, which decreased to 10.5 after 8 weeks and 7.2 after 52 weeks (LOCF). The percentage of patients in remission (MADRS total score 相似文献   

Evidence of treatment for depressive episodes of bipolar disorder

In recent years, many papers on the treatment of the depressive phase of bipolar disorder (bipolar depression), especially bipolar I disorder, with high-level evidence, have been reported. The results of meta-analyses have also been reported for some medications. In the pharmacotherapy for bipolar depression, quetiapine (300 mg/day), lithium (more than 0.8 mEq/L), olanzapine (5-20 mg/day) and lamotrigine (200 mg/day) are effective, with high-level evidence. The combination of lithium and lamotrigine is also effective for bipolar depression. There is no evidence for effectiveness of the combination of mood stabilizers and antidepressants for bipolar depression. This paper presents the evidence data of quetiapine, lithium, olanzapine, lamotrigine, carbamazepine, valproate, aripiprazole, antidepressants, a combination of medications, and electroconvulsive therapy for bipolar depression, based on large-size randomized controlled studies and meta-analyses. The first-line medications for bipolar depression in the practice guidelines published for the last three years are also included.     

Escitalopram in the long-term treatment of major depressive disorder in elderly patients

AIM: The primary aim was to investigate the long-term safety and tolerability of escitalopram (10 or 20 mg/day) treatment of elderly patients suffering from major depressive disorder. The secondary aim was to examine response to treatment, as measured by change in the Montgomery-Asberg Depression Rating Scale (MADRS) total score from study entry to each visit, using observed cases. METHOD: This extension trial included 225 patients who had completed an 8-week, double blind, placebo-controlled lead-in study, which was performed in outpatients in primary care and in specialist clinics. The intent-to-treat population comprised 223 patients. RESULTS: The overall withdrawal rate was 24%. The most common reason for withdrawal was adverse events (9%). The 5 most common adverse events were accidental injury, rhinitis, weight increase, arthralgia and coughing, with an incidence ranging from 8 to 13%. No new types of adverse events were reported in this extension study compared to the 8-week lead-in study. The mean weight increased from 69.7 kg at study entry to 70.3 kg at endpoint. The percentage of patients in remission (MADRS total score < or = 12) increased from 48% at study entry to 72% by week 52. CONCLUSION: Escitalopram demonstrated a favourable tolerability profile during 52 weeks of open-label treatment of elderly patients, with further improvement in depressive symptoms.     

Reboxetine, a unique selective NRI, prevents relapse and recurrence in long-term treatment of major depressive disorder.

BACKGROUND: The long-term efficacy and tolerability of the antidepressant reboxetine, a unique selective norepinephrine reuptake inhibitor (selective NRI), were assessed in an international study. METHOD: Two hundred eighty-three patients with recurrent DSM-III-R major depression who responded to 6 weeks of reboxetine treatment (> or =50% decrease in Hamilton Rating Scale for Depression [HAM-D] total score) were randomly assigned to receive reboxetine or placebo for 46 weeks in a double-blind phase. Relapse (> or =50% increase in HAM-D total score and/or a HAM-D total score > or =18) rate was the principal assessment criterion and included patients who experienced relapse or recurrence. Only patients who remained relapse-free at the end of the first 6-month treatment period were included in the relapse rate assessment at the end of the second 6-month treatment period. RESULTS: Reboxetine was associated with a markedly lower relapse rate than placebo (22% vs. 56%; p<.001) and a greater cumulative probability of a maintained response (p = .0001) during long-term treatment. Patients in remission (HAM-D total score < or =10) at the time of random assignment were less likely to relapse (16% reboxetine, 48% placebo; p<.001). The proportion of patients who were relapse-free and therefore remained in the study was significantly (p< or =.001) higher among those on reboxetine treatment than on placebo at the end of the first (61% vs. 40%) and second (88% vs. 59%) 6 months of treatment. Additional efficacy measures supported these findings. The incidence of adverse events with reboxetine was low and comparable with that for placebo. Discontinuation due to adverse events occurred infrequently. CONCLUSION: Reboxetine treatment over 1 year is more effective than placebo in the prevention of relapse in patients with recurrent depression. The low relapse rates at the end of the second 6 months of treatment further suggest that reboxetine effectively prevents recurrence of depressive symptoms following episode resolution. Reboxetine is well tolerated in long-term treatment of depression, a finding that bodes well for long-term patient compliance.     

Subtypes of depressive episodes according to ICD-10: prediction of risk of relapse and suicide

BACKGROUND: The long-term predictive ability of the ICD-10 subtypes of depression with melancholic syndrome and depression with psychosis has not been investigated. SAMPLING AND METHODS: All patients in Denmark who had a diagnosis of a single depressive episode at their first ever discharge during a period from 1994 to 1999 were identified. The risk of relapse leading to readmission and the risk of committing suicide were compared for patients discharged with an ICD-10 diagnosis of a single depressive episode with and without melancholic syndrome and for patients with and without psychotic symptoms, respectively. RESULTS: In all, 1,639 patients had a diagnosis of depressive episode without psychotic symptoms, 1,275 patients a diagnosis with psychotic symptoms, 293 a diagnosis without melancholic syndrome, and 248 a diagnosis with melancholic symptoms at first discharge. The risk of relapse leading to readmission was greater for patients with psychotic symptoms than for patients without, but no difference was found between the two groups in the risk of committing suicide during follow-up. No differences were found in the risk of relapse leading to readmission or suicide between patients with and without melancholic syndrome. CONCLUSIONS: The ICD-10 categorization into depression with and without psychotic symptoms seems to be clinically and prognostically useful, whereas the ICD-10 subtyping into melancholic and non-melancholic syndrome does not seem to have any long-term predictive value.     

艾司西酞普兰治疗抑郁症伴焦虑的疗效分析

目的评价国产艾司西酞普兰片治疗抑郁症伴焦虑的疗效及安全性。方法本研究为6周的多中心开放性研究,共入组符合CCMD-3诊断标准的抑郁症(同时HAMD≥17分、HAMA≥14分)患者173例,服用国产艾司西酞普兰片的剂量为10mg-20mg/d,分别在治疗前及第1、2、4、6周末以汉密尔顿抑郁量表17项(HAMD)、汉密尔顿焦虑量表(HAMA)和临床总体印象量表CGI(包括病情严重程度评分CGI-SI、疗效评分CGI-GI)评定疗效,以不良事件记录表、体格检查、实验室检查评估用药安全性。结果共169例患者完成研究,经6周治疗后显示,HAMD、HAMA、CGI-SI评分呈现一致的减分趋势,各时点HAMD-17、HAMA、CGI-SI的总分与治疗前比较,差异均有显著性(P<0.05),总体有效率为81.1%、痊愈率是63.9%。不良反应发生率为10.06%,一般可以耐受。结论国产艾司西酞普兰片治疗抗抑郁及焦虑作用确切,可用于治疗抑郁症伴焦虑障碍。     

Predictors of relapse during fluoxetine continuation or maintenance treatment of major depression

BACKGROUND: The goal was to examine predictors of relapse during continuation/maintenance treatment of major depression that had remitted following 12 to 14 weeks of fluoxetine therapy. METHOD: The study utilizes data collected in a collaborative clinical trial including patients with DSM-III-R major depression at 5 university-affiliated outpatient psychiatry clinics. Three hundred ninety-five patients who remitted with fluoxetine therapy were randomly assigned to 1 of 4 treatments: fluoxetine for 14 weeks followed by placebo for 36 weeks, fluoxetine for 38 weeks followed by placebo for 12 weeks, fluoxetine for 50 weeks, or placebo for 50 weeks. Cox proportional hazard models were used to identify predictors of time to relapse. RESULTS: In addition to the previously reported longitudinal pattern of response during acute treatment, neurovegetative symptom pattern was a predictor of fluoxetine benefit compared with placebo. Greater chronicity predicted poorer survival, which was not differential by treatment. The most robust advantage of fluoxetine was seen for patients with endogenous vegetative symptoms, chronic depression, and acute treatment response characterized by onset in the third week or later and persistence of response once attained. CONCLUSION: Both nonspecific pattern of response and neurovegetative symptoms characteristic of atypical depression were predictive of lack of fluoxetine efficacy in continuation/ maintenance treatment. These findings have importance for both clinical management and analyses of future maintenance trials.     

Duloxetine in the acute and continuation treatment of major depressive disorder

Duloxetine is a serotonin-noradrenaline reuptake inhibitor with indications for use in the short term, continuation and maintenance treatment of major depression. Although clinicians currently have access to a range of medications for the treatment of depression, a significant number of patients fail to respond or remit from their illness despite adequate trials of treatment with multiple agents. A developing concept is that antidepressant strategies that combine multiple mechanisms of action may have advantages over agents with single mechanisms (i.e., selective serotonin reuptake inhibitors). As a dual-acting agent, duloxetine offers the promise of advantages in terms of efficacy over selective serotonin reuptake inhibitors while retaining a favorable safety and tolerability profile in comparison to older agents. Likewise, duloxetine is of interest in the treatment of certain conditions commonly seen in conjunction with major depression, particularly anxiety and pain, both of which may respond more favorably to agents that act on both serotonin and noradrenaline neurotransmitter systems.     

Escitalopram is more effective than citalopram for the treatment of severe major depressive disorder

BACKGROUND: Escitalopram is a highly selective serotonin reuptake inhibitor (SSRI). It is the therapeutically active S-enantiomer of citalopram. It has been shown, compared with placebo, to be an effective and well-tolerated treatment for major depressive disorders (MDD) in both primary and specialist care settings. A recent meta-analysis has found that escitalopram-treated patients showed significant higher response rates and increased mean change from baseline in the Montgomery-Asberg Depression Rating Scale (MADRS) total scores at weeks 1 and 8 compared with citalopram-treated patients. Each of these active drugs shares similar safety profiles. Although the efficacy of newer antidepressants has been well established for the treatment of mild-to-moderate depression, there are very few studies concerning severe depression. OBJECTIVE: To determine if escitalopram is more effective than citalopram in patients with severe depression. METHODS: Data were pooled from three different clinical trials, each similar in design and inclusion/exclusion criteria, primary endpoints and assessment schedules. This analysis was exhaustive because it included all trials in which the maximum dose for escitalopram (20 mg) could be administered. According to the cut-off point taken to define severe depression based on the MADRS total score ( 30), 506 patients were considered as severely depressed patients and so included in this analysis. Among them, 169 received escitalopram, 171 received citalopram and 166 received the placebo. The primary efficacy parameter was the mean change from baseline to end of treatment in MADRS total score between escitalopram and citalopram groups, based on last-observation-carried-forward method. The change from baseline to endpoint of the Hamilton rating scale for Depression (HAM-D) and the Clinical Global Impression of Improvement and Severity (CGI-I and CGI-S) were also analysed as secondary criteria. Clinical response was defined by at least a 50% reduction in baseline MADRS total score or by at least a 60% reduction in baseline HAM-D score or by a score of 1 (very much improved) on the CGI scale, and remission by a MADRS total score pound 12. RESULTS: Results showed that the mean change from baseline in the MADRS total score was significantly higher in the escitalopram group compared with the citalopram group (- 17.3 vs - 13.8 respectively, p=0.003). This significant difference was observed as early as week 1 (p=0.01). Response rates were significantly higher for escitalopram than for citalopram (56% vs 41% respectively, p=0.007). A borderline significant difference was found for remission rate in the observed-cases analysis (43% vs 33% respectively, p=0.07). Analyses of the HAM-D, CGI-I and CGI-S scores revealed consistent results. DISCUSSION: This study shows that the new SSRI escitalopram has better efficacy in the treatment of severe depression than citalopram, its racemic parent. Mean differences between treatments groups were in favour of escitalopram for all scales. The benefits of escitalopram compared with citalopram, as demonstrated by both magnitude of effect and time of onset, are superior to the benefits of citalopram, an antidepressant drug with proven efficacy. This evidence clearly supports the use of escitalopram as a legitimate first-line treatment for MDD.     

Severity of depressive episodes during the course of depressive disorder

BACKGROUND: It is not clear whether the severity of depressive episodes changes during the course of depressive disorder. AIMS: To investigate whether the severity of depressive episodes increases during the course of illness. METHOD: Using a Danish nationwide case register, all psychiatric in-patients and out-patients with a main ICD-10 diagnosis of a single mild, moderate or severe depressive episode at the end of first contact were identified. Patients included in the study were from the period 1994-2003. RESULTS: A total of 19 392 patients received a diagnosis of a single depressive episode at first contact. The prevalence of severe depressive episodes increased from 25.5% at the first episode to 50.0% at the 15th episode and the prevalence of psychotic episodes increased from 8.7% at the first episode to 25.0% at the 15th episode. The same pattern was found regardless of gender, age at first contact and calendar year. CONCLUSIONS: The increasing severity of depressive episodes emphasises the importance of early and sustained prophylactic treatment.     

Duloxetine treatment of major depressive episodes in the course of psychotic disorders

During the course of psychotic disorders, patients often suffer from intercurrent major depressive episodes (MDEs), and suicides frequently occur. This constellation challenges further improvements in psychopharmacological therapy. The antidepressant duloxetine was recently introduced as a novel reuptake inhibitor of serotonin and noradrenaline. We provide the first reports on duloxetine treatment of MDEs in the course of psychotic disorders. In two cases this substance was successfully involved as an add-on to antipsychotic treatment consisting of clozapine or amisulpride. We achieved a response of the MDEs, as reflected by psychopathological rating scales. A significant rise in the clozapine serum level was detected, most likely because of pharmacokinetic interactions. Overall, the application of duloxetine was well tolerated; therefore, further investigations in prospective studies seem to be recommendable.     

Residual sleep disturbance and risk of relapse during the continuation/maintenance phase treatment of major depressive disorder with the selective serotonin reuptake inhibitor fluoxetine

Background  

Relapse of major depressive disorder (MDD) is a common clinical problem. This study was designed to determine whether residual sleep disturbance (insomnia and hypersomnia) predict risk of relapse during the continuation and maintenance treatment of MDD.     

Pituitary-adrenal regulation over multiple depressive episodes

Pituitary-adrenal activity was evaluated with the dexamethasone suppression test in 11 patients over their multiple hospitalizations for major depression. All six patients who were suppressors during their index admission had one subsequent admission over the period of study during which they were again suppressors. Of five patients who were nonsuppressors during their index admission, three had one subsequent admission and two had three subsequent admissions. Four of these patients were again nonsuppressors during a subsequent admission. For patients who were nonsuppressors during some but not all admissions for depression, pituitary-adrenal activity appeared related to the persistence of the depressive episodes.     

Type of residual symptom and risk of relapse during the continuation/maintenance phase treatment of major depressive disorder with the selective serotonin reuptake inhibitor fluoxetine

Relapse of major depressive disorder (MDD) is a common clinical problem. Identifying relapse predictors could lead to strategies that reduce relapse risk. This study is designed to determine whether residual symptoms predict relapse risk during the continuation/maintenance treatment of MDD. 570 MDD patients received open-label fluoxetine for 12 weeks. Under double blind conditions, 262 patients who responded by week 12 were randomly assigned to continue fluoxetine or switch to placebo for 52 weeks or until relapse. Residual symptoms were measured using the Symptom Checklist-90 and the Symptom Questionnaire. The relationship between residual symptom severity and relapse risk was assessed. Without adjusting for overall residual symptom severity, a greater severity of residual obsessive-compulsive and phobic anxiety symptoms predicted greater relapse risk. After adjusting for overall residual symptom severity, only severity of phobic anxiety symptoms predicted relapse risk. The predictive value of phobic anxiety symptoms with respect to relapse risk was independent of treatment assignment. The results indicated that there may be a specific pattern of residual symptoms associated with depressive relapse during antidepressant continuation/maintenance, which is unrelated to treatment assignment. Future studies are needed to further explore the relationship between residual symptoms and relapse risk in MDD. Clinical implications: (1) It is important to treat residual symptoms among antidepressant responders/remitters in order to decrease relapse risk. (2) Clinicians should target residual phobic anxiety symptoms in order to decrease relapse risk. (3) Clinicians should target residual obsessive-compulsive symptoms in order to decrease relapse risk. Limitations: (1) limited generalizability due to inclusion/exclusion criteria; (2) lack of active comparator treatment group; (3) post hoc analysis.