度洛西汀治疗抑郁症及广泛性焦虑障碍临床应用指导建议

抑郁症及广泛性焦虑障碍都是常见的负性情绪障碍,具有患病率高、复发率高、致残率高的特点,目前倡导全病程治疗。新型抗抑郁药均能治疗抑郁症及广泛性焦虑障碍,度洛西汀作为5-羟色胺与去甲肾上腺素再摄取抑制剂类抗抑郁药物的一种,有大量临床证据表明,其在抗抑郁、抗焦虑治疗方面具有起效快、临床治愈率高及安全性好、不良反应少等特点。本文重点介绍近年来国内外在度洛西汀临床应用中的治疗学和循证医学研究进展,结合广大专家的用药经验,为临床医生提供更客观、更规范的治疗选择和治疗方案,以进一步改善患者预后,促进患者回归社会。     

Assessing remission in major depressive disorder and generalized anxiety disorder clinical trials with the discan metric of the Sheehan disability scale

Relatively little research has focused on the relationship between functional remission and symptomatic remission in mood and anxiety disorders. This study investigates the relationship and synchrony between symptomatic and functional remission in outpatients with major depressive disorder (MDD) and generalized anxiety disorder (GAD). Using data from three MDD (N=1419) and four GAD (N=1847) randomized, placebo-controlled duloxetine studies, we calculated the percentages of patients meeting symptomatic, functional, and combined functional-symptomatic remission criteria for each disorder. We also calculated mean depression [17-item Hamilton depression rating scale (HAMD??), Montgomery-Asberg depression rating scale] scores and mean anxiety (Hamilton anxiety rating scale) scores for patients meeting Sheehan disability scale (SDS) functional remission and the mean SDS scores for patients with symptomatic remission. Among the patients with MDD, 38% achieved symptomatic remission (HAMD?? ≤ 7), 32% achieved functional remission (SDS ≤ 6), and 23% achieved combined functional-symptomatic remission. Mean HAMD?? and Montgomery-Asberg depression rating scale scores for patients with functional remission were approximately 6. Mean SDS total scores for patients with symptomatic remission were 7.1 (patients with HAMD?? ≤ 7) and 8.6 (patients with Montgomery-Asberg depression rating scale ≤ 10). Among the patients with GAD, 30% achieved symptomatic remission (Hamilton anxiety rating scale ≤ 7), 45% achieved functional remission (SDS ≤ 6), and 25% achieved combined symptomatic-functional remission. The mean Hamilton anxiety rating scale score in GAD was approximately 8 for patients with functional remission and the mean SDS total score was approximately 4 in patients with symptomatic remission. The study shows that functional remission does not always move in tandem with symptom remission and provides useful anchor points or rules of thumb for evaluating symptomatic and functional remission in MDD and GAD.     

Impact of escitalopram treatment on Quality of Life Enjoyment and Satisfaction Questionnaire scores in major depressive disorder and generalized anxiety disorder

Administration of the same Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) in major depressive disorder (MDD) and in generalized anxiety disorder (GAD) before and after treatment allowed us to compare quality of life enjoyment and satisfaction in these two disorders and to compare outcome based on symptoms versus functioning. Q-LES-Q and symptom-specific Montgomery-Asberg Depression Rating Scale (MADRS) and Hamilton Anxiety Scale (HAMA) data from eight randomized, 8-week, double-blind, placebo-controlled clinical trials with escitalopram were used. MDD (n=1,140) or GAD (n=1,045) patients report a substantial degree of quality of life enjoyment and satisfaction impairment (baseline scores 64% and 76% of community norm, respectively). Treatment resulted in statistically and clinically significant improvement in quality of life enjoyment and satisfaction. The improvement was greater in patients treated with escitalopram than with placebo. In MDD, the majority of remitters (MADRS相似文献   

Anterior cingulate volume predicts response to psychotherapy and functional connectivity with the inferior parietal cortex in major depressive disorder

In major depressive disorder (MDD), the anterior cingulate cortex (ACC) has been associated with clinical outcome as well as with antidepressant treatment response. Nonetheless, the association between individual differences in ACC structure and function and the response to cognitive behavioral therapy (CBT) is still unexplored. For this aim, twenty-five unmedicated patients with MDD were scanned with structural and resting state functional magnetic resonance imaging before the beginning of CBT treatment. ACC morphometry was correlated with clinical changes following psychotherapy. Furthermore, whole-brain resting state functional connectivity with the ACC was correlated with clinical measures. Greater volume in the left subgenual (subACC), the right pregenual (preACC), and the bilateral supragenual (supACC) predicted depressive symptoms improvement after CBT. Greater subACC volume was related to stronger functional connectivity with the inferior parietal cortex and dorsolateral prefrontal cortex. Stronger subACC-inferior parietal cortex connectivity correlated with greater adaptive rumination. Greater preACC volume was associated with stronger functional connectivity with the inferior parietal cortex and ventrolateral prefrontal cortex. In contrast, greater right supACC volume was related to lower functional connectivity with the inferior parietal cortex. These results suggest that ACC volume and its functional connectivity with the fronto-parietal cortex are associated with CBT response in MDD, and this may be mediated by adaptive forms of rumination. Our findings support the role of the subACC as a potential predictor for CBT response.     

Etizolam in the treatment of generalized anxiety disorder associated with depressive symptoms

A double-blind study was carried out in 30 female patients with generalized anxiety disorders associated with depressive symptoms to compare the effectiveness and tolerability of etizolam and alprazolam. Patients were allocated at random to receive one or other drug at a dosage of 0.5 mg twice daily for 5 weeks. Assessments were made on entry and after 3 and 5 weeks of treatment using the Hamilton rating scales for anxiety and for depression. The results showed that both drugs had marked anxiolytic and antidepressive activity, there being significant reductions after treatment in mean total rating scores compared to baseline. Although there was no statistically significant difference between the two drugs, there was a trend for etizolam to be more effective in relieving anxiety somatization symptoms. Apart from moderate daytime drowsiness in a few patients, both drugs were considered to be extremely well tolerated.     

Etizolam in the treatment of generalized anxiety disorder associated with depressive symptoms

Summary

A double-blind study was carried out in 30 female patients with generalized anxiety disorders associated with depressive symptoms to compare the effectiveness and tolerability of etizolam and alprazolam. Patients were allocated at random to receive one or other drug at a dosage of 0.5?mg twice daily for 5 weeks. Assessments were made on entry and after 3 and 5 weeks of treatment using the Hamilton rating scales for anxiety and for depression. The results showed that both drugs had marked anxiolytic and antidepressive activity, there being significant reductions after treatment in mean total rating scores compared to baseline. Although there was no statistically significant difference between the two drugs, there was a trend for etizolam to be more effective in relieving anxiety somatization symptoms. Apart from moderate daytime drowsiness in a few patients, both drugs were considered to be extremely well tolerated.     

Alterations in effective connectivity anchored on the insula in major depressive disorder

Recent work has identified disruption of several brain networks involving limbic and cortical regions that contribute to the generation of diverse symptoms of major depressive disorder (MDD). Of particular interest are the networks anchored on the right anterior insula, which binds the cortical and limbic regions to enable key functions that integrate bottom-up and top-down information in emotional and cognitive processing. Emotional appraisal has been linked to a presumed hierarchy of processing, from sensory percepts to affective states. But it is unclear whether the network level dysfunction seen in depression relates to a breakdown of this presumed hierarchical processing system from sensory to higher cognitive regions, mediated by core limbic regions (e.g. insula). In 16 patients with current MDD, and 16 healthy controls, we investigated differences in directional influences between anterior insula and the rest of the brain using resting-state functional magnetic resonance imaging (fMRI) and Granger-causal analysis (GCA), using anterior insula as a seed region. Results showed a failure of reciprocal influence between insula and higher frontal regions (dorsomedial prefrontal cortex) in addition to a weakening of influences from sensory regions (pulvinar and visual cortex) to the insula. This suggests dysfunction of both sensory and putative self-processing regulatory loops centered around the insula in MDD. For the first time, we demonstrate a network-level processing defect extending from sensory to frontal regions through insula in depression. Within limitations of inferences drawn from GCA of resting fMRI, we offer a novel framework to advance targeted network modulation approaches to treat depression.     

Associations between compulsive buying and substance dependence/abuse,major depressive episodes,and generalized anxiety disorder among men and women

The objective of this study was to examine the associations between compulsive buying and substance dependence/abuse, major depressive episodes, and generalized anxiety disorder at the mean age of 43. Participants came from a community-based random sample of residents in 2 New York counties in 1975 (N = 548). The participants were followed from adolescence to early midlife. The mean age of participants at the most recent interview was 43.0 (standard deviation = 2.8). Of the participants, 55% were females. Over 90% of the participants were Caucasian. The prevalence of substance dependence/abuse, major depressive episodes, and generalized anxiety disorder (during the past 5 years before the interviews) was 6.6, 13.7, and 11.5%, respectively. Logistic regression analyses showed that compulsive buying was significantly associated with substance dependence/abuse (adjusted odds ratio = 1.60), major depressive episodes (adjusted odds ratio = 1.70), and generalized anxiety disorder (adjusted odds ratio = 1.63), despite controlling for substance dependence/abuse, major depressive episodes, and generalized anxiety disorder, respectively, at the mean age of 37, and demographic factors. Since the study sample is limited to predominantly Caucasian participants (over 90%) with a close association to a small geographic area, the findings may not be generalizable to racial/ethnic minority groups or individuals living in other parts of the country. Nevertheless, it is important that clinicians treating substance dependence/abuse, major depressive episodes, and generalized anxiety disorder consider the role of compulsive buying.     

Selegiline transdermal system: in the treatment of major depressive disorder

The monamine oxidase (MAO) inhibitor selegiline is selective for MAO-B at the low oral dosages used in the treatment of Parkinson's disease. However, MAO-A is also inhibited at the high oral dosages needed to effectively treat depression (not an approved indication), necessitating a tyramine-restricted diet. The selegiline transdermal system was designed to deliver antidepressant drug concentrations to the CNS, without substantially impairing small intestine MAO-A activity. At the target dose of 6 mg/24 hours, tyramine dietary restrictions are not needed. Short-term treatment with fixed (6 mg/24 hours) or flexible (6, 9 or 12 mg/24 hours) doses of selegiline transdermal system was superior to placebo on most measures of antidepressant activity in 6- or 8-week, randomised, double-blind, multicentre studies in adult outpatients with major depressive disorder (MDD). Likewise, long-term treatment with a fixed dose of selegiline transdermal system 6 mg/24 hours was superior to placebo as maintenance therapy in a 52-week, randomised, double-blind, multicentre, relapse-prevention trial in patients with MDD. Selegiline transdermal system therapy was generally well tolerated in placebo-controlled studies; application site reactions, mostly of mild to moderate severity, were the most commonly reported adverse events. The incidence of sexual adverse effects and weight gain was low and similar to that with placebo.     

Critical appraisal of selegiline transdermal system for major depressive disorder

ABSTRACT

Introduction: Although safer and easier to use antidepressants (ie.,SSRIs/SNRIs) have largely displaced MAOIs, these medications still have a role in difficult to treat conditions. Efforts to improve MAOIs benefit-risk profile resulted on the reversible MAOI and in the first antidepressant patch (selegiline transdermal delivery system-STS). The later had been available in the US since 2006. Thus a review on its safety profile and comparative efficacy is timely.

Areas covered: This review provides an overview of STS’s clinical pharmacology and summarizes what has been learned across nearly a decade of experience. Product labels and the search engine PubMed were used to obtain relevant information.

Expert opinion: STS remains a unique treatment option. It is the only FDA-approved antidepressant for patients with significant problems ingesting, tolerating, or absorbing oral medications. It remains the only MAOI that can be initiated without dietary restrictions at a therapeutic dose and has a low incidence of side effects when compared to other MAOIs. STS also provides an interesting option for depressed patients suffering from Parkinson’s disease. However these advantages are counterweighted by drawbacks including the need for wash-out periods and the lack of convincing data illustrating its utility for treatment of more severe, treatment refractory depression.     

Use of duloxetine in patients with an anxiety disorder,or with comorbid anxiety and major depressive disorder: a review of the literature

Importance of the field: Except for generalized anxiety disorder, few reports have been published on the efficacy, safety and tolerability of duloxetine in patients with anxiety disorders individually or in comorbidity with major depressive disorder (MDD).

Areas covered in this review: The literature search in Medline (dating back to 1966) and Embase (dating back to 1988) databases was conducted using the OVID interface on 9 April 2009, restricted to any article or abstract in English, per title, reporting any information on the use of duloxetine in patients with any anxiety disorder with or without concomitant MDD. A systematic review approach was taken.

What the reader will gain: The reader will gain knowledge of the current data available on the use of duloxetine to treat patients with anxiety disorders individually or in comorbidity with MDD.

Take home message: Duloxetine could be considered an effective treatment option in the treatment of anxiety disorders individually or in comorbidity with each other, or with MDD; however, apart from the well-demonstrated efficacy, tolerability and safety of duloxetine in the treatment of MDD with or without anxiety and GAD, data on this subject are preliminary and very limited, and more research is warranted.     

Pharmacological treatment of generalized anxiety disorder

Introduction: Generalized anxiety disorder (GAD) is a chronic, relapsing, debilitating disorder, associated with markedly impaired social and occupational functioning. Pharmacological treatment is considered standard care and several drug classes are now FDA approved for the treatment of GAD. While there are clear data for the efficacy of short-term acute treatment, long-term treatment and treatment-resistant GAD remain challenging.

Areas covered: This article describes current pharmacological treatment options for GAD, with focus on benzodiazepines, azapirones, antidepressants and anticonvulsant and antipsychotic drugs. Recent findings from placebo-controlled clinical trials are reviewed and evidence-based clinical implications are discussed. A PubMed search was completed using the terms: ‘generalized anxiety disorder AND treatment’ and ‘generalized anxiety disorder AND therapy’. Additional pivotal trials were included for a historical perspective (older landmark trials that established efficacy and safety for older drug classes in the treatment of GAD).

Expert opinion: Efficacy for treatment of GAD has been established for several different drug classes. At present, based on clear efficacy and good tolerability, first-line treatment with either a selective serotonin reuptake inhibitor (SSRI) or a serotonin-norepinephrine reuptake inhibitor (SNRI) is indicated. If an initial, at least moderate, clinical response is achieved under antidepressant therapy, treatment should be at least continued for 12 months.     

A critical appraisal of the selegiline transdermal system for major depressive disorder

The selegiline transdermal system (STS) is the first antidepressant transdermal medication approved by the US FDA for the treatment of major depressive disorder. Its unique antidepressant delivery system allows for steady release of selegiline over 24 h with minimal fluctuation in drug serum levels. It is able to deliver high enough central nervous system concentrations required for an antidepressant effect without substantially inhibiting Monoamine oxidase-A in the gastrointestinal and hepatic system, thereby reducing the risk of tyramine hypertensive crises especially at the lowest doses. Patient adherence theoretically could be improved due to ease of use and once-daily dosing when compared to oral counterparts’ need for multiple daily doses. Clinical trials have established that doses between 6 and 12 mg over 24 h have been effective for major depressive disorder and tolerated among patients. Episodes of hypertensive crisis with STS have been minimally reported thus far. Overall, STS appears to be an effective agent for major depressive disorder when held to regulatory standards and post marketing analyses. This paper reviews the pharmacologic characteristics of STS and results of studies investigating its clinical efficacy and safety.     

Joint trajectories of cigarette smoking and depressive symptoms from the mid-20s to the mid-30s predicting generalized anxiety disorder

The current study examines longitudinal patterns of cigarette smoking and depressive symptoms as predictors of generalized anxiety disorder using data from the Harlem Longitudinal Development Study. There were 674 African American (53%) and Puerto Rican (47%) participants. Among the 674 participants, 60% were females. In the logistic regression analyses, the indicators of membership in each of the joint trajectories of cigarette smoking and depressive symptoms from the mid-20s to the mid-30s were used as the independent variables, and the diagnosis of generalized anxiety disorder in the mid-30s was used as the dependent variable. The high cigarette smoking with high depressive symptoms group and the low cigarette smoking with high depressive symptoms group were associated with an increased likelihood of having generalized anxiety disorder as compared to the no cigarette smoking with low depressive symptoms group. The findings shed light on the prevention and treatment of generalized anxiety disorder.     

Agomelatine for the treatment of generalized anxiety disorder

Introduction: Agomelatine is a melatonergic antidepressant, approved for the treatment of Major Depressive Disorder (MDD) in Europe and Australia, but not in the United States. This compound seems to be promising in the short-term and maintenance treatment of Generalized Anxiety Disorder (GAD).

Areas covered: This paper presents an evaluation of the available data about the clinical efficacy and tolerability of agomelatine in the treatment of GAD.

Expert opinion: First-line GAD treatments are limited by high rates of lack of clinical response. Preliminary data would indicate agomelatine as a safe compound, and with a higher rate of clinical response in the short-term and an earlier improvement of symptoms with respect to Selective Serotonine Reuptake Inhibitors (SSRIs) and Selective Serotonin Noradrenaline Reuptake Inhibitors (SNRIs). In addition, agomelatine has not been associated with potential risk of abuse as in case of pregabalin and with long-term metabolic side effects similar to quetiapine. The major limitation of the results presented is that little data has come from long-term or comparative trials. Furthermore, some caution should be reserved in case of liver impairment (e.g. in subjects with alcohol abuse).     

Duloxetine for the treatment of major depressive disorder

>55% were observed in two of the studies, while in a third study the probability of remission with duloxetine treatment was nearly three times that observed with placebo (44% versus 16%). Duloxetine also produced significant improvement in painful physical symptoms compared with placebo, in many cases after only 2 weeks of treatment. The discontinuation rate due to adverse events (14.6%) was similar to those observed with selective serotonin reuptake inhibitors. The most frequently reported adverse events were nausea, dry mouth, fatigue, and insomnia. Conclusion. Duloxetine was demonstrated to be safe and effective in the treatment of MDD. The starting dose with the best balance of efficacy and tolerability is 60 mg QD.