Anxiety symptom severity and functional recovery or relapse.

Background: Anxiety disorders are associated with significant disability. There is growing interest in the question of whether pharmacotherapy that effectively reduces symptoms can also restore function. Recovery could potentially be defined as a lack of disability, with an associated reduction in symptom severity. Conversely, relapse could potentially be defined in terms of either increased disability or increased symptoms.Methods: We analyzed a database of randomized controlled trials of escitalopram in generalized anxiety disorder (GAD) and social anxiety disorder (SAD), focusing on the relationship between disorder-specific severity scales, and the Sheehan Disability Scale (SDS). In short-term studies, cut-points on symptom scales were derived for recovered function. In relapse prevention studies, the effects of defining relapse in terms of increased disability scores were examined.Results: In GAD and SAD, there is a close correlation between primary symptom severity scales and the SDS, both in the short term and during relapse prevention. Thus, functional recovery is associated with relatively low symptom severity scores, and rates of relapse—defined in terms of increased disability—are significantly lower on escitalopram than on placebo.Conclusions: These data indicate that recovery and relapse can potentially be defined either in terms of symptom severity or functioning. Thus, the concept of functional recovery and relapse may be useful in defining treatment outcomes. Longer-term treatment of anxiety disorders is needed to ensure functional recovery.<br/

How are symptom severity and functional recovery/relapse related? An analysis of the escitalopram database

Background: Anxiety disorders are associated with significant disability. There is growing interest in the question of whether pharmacotherapy that effectively reduces symptoms also restores function. Recovery could be defined as a lack of disability, with associated reduction in symptom severity. Conversely, relapse could be defined in terms of either increased disability or increased symptoms.Methods: We analysed a database of randomised controlled trials of escitalopram in generalised anxiety disorder (GAD) and social anxiety disorder (SAD), focusing on the relationship between disorder-specific severity scales, and the Sheehan Disability Scale (SDS). In short-term studies, cut-points on symptom scales were derived for recovered function. In relapse prevention studies, the effects of defining relapse in terms of increased disability scores were examined.Results: In GAD and SAD, there is a close correlation between primary symptom severity scales and the SDS, both in the short-term and during relapse prevention. Thus, a lack of disability is associated with relatively low symptom severity scores, and rates of relapse - defined in terms of increased disability - are significantly lower on escitalopram than on placebo.Conclusion: These data indicate that improvement in primary symptom scales in anxiety disorders is accompanied by improvement in functioning, and vice versa. Recovery and relapse can therefore be defined either in terms of symptom severity or in terms of functioning. Longer-term treatment of anxiety disorders is needed to ensure recovery

Improvement of quality of life in panic disorder with escitalopram, citalopram, or placebo

Background: It has been argued that measurement of outcome in panic disorder should not be limited to monitoring the number of panic attacks, but should include all domains that affect patient quality of life. Methods: Data from a randomized prospective comparison of escitalopram, citalopram, and placebo in patients with DSM-IV panic disorder were analyzed with regard to measurements of impairment of quality of life. The subscales of the Panic and Agoraphobia Scale (P&amp;A) (Panic Attacks, Agoraphobic Avoidance, Anticipatory Anxiety, Functional and Social Disability, and Worries about Health) and the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) were analyzed. Results: Treatment with escitalopram was associated with significant improvement on all 5 subscales of the P&amp;A. Citalopram was significantly different from placebo in 3 subscales. Escitalopram and citalopram were significantly better than placebo in improving quality of life (measured by the total score of the Q-LES-Q Scale). Escitalopram was superior to placebo on 12 of 16 items of the Q-LES-Q, while citalopram was superior on 7 items. Conclusion: The P&amp;A scale was more robust than measurement of panic frequency in differentiating medication from placebo. Escitalopram treatment was associated with improvement on all assessed domains that impair quality of life in panic disorder. Measurement of clinical improvement should not be solely based on panic attack frequency, but should also include assessment of a broad range of domains that affect patient quality of life

Sleep and daytime psychomotor performance during acute and continuation treatment of major depressive disorder: double-blind randomised controlled trial of escitalopram vs paroxetine

Introduction. Disturbed sleep is a common depressive symptom which often persists despite otherwise successful pharmacological or psychological treatment, and is associated with increased risks of recurrence. As both worsened insomnia and daytime drowsiness are reported as treatment-emergent adverse effects with antidepressants, we wished to evaluate the effects of acute and continuation treatment on sleep and daytime psychomotor performance. Method. International, randomized, flexible-dose, parallel-group, comparator-controlled study involving 36 centres in 6 countries. Patients met DSM-IV criteria for current major depressive episode, with a baseline score of 22-40 on the Montgomery-Åsberg Depression Rating Scale (MADRS). After a single-blind one-week placebo run-in, patients were randomized to escitalopram (ESC) (10-20 mg/day) or paroxetine (PAR) (20-40 mg/day) for 8 weeks of acute treatment: those who were significantly improved could continue fixed-dose double-blind treatment for a further 19 weeks. Sleep and early morning behaviour were assessed by the Leeds Sleep Evaluation Questionnaire (LSEQ), psychomotor performance by Critical FIicker Fusion (CFF) and Choice Reaction Time, and cognitive function by the Cognitive Failures Questionnaire (CFQ). Assessments were undertaken at baseline and weeks 4, 8, 16 and 27. Results. 323 patients (ESC, 165; PAR, 158) started acute treatment and received at least one dose of study medication. There were no significant differences between treatment groups in reduction of depressive symptoms from baseline to week 8, but in severely depressed patients (baseline MADRS &gt;30) escitalopram was superior (p&lt;0.05; ANCOVA) to paroxetine at week 27. Sleep and daytime performance improved as depressive symptoms reduced. Two patients withdrew from the study due to the adverse effect of insomnia, and 1 due to somnolence. There were no significant differences between treatment groups in change from baseline on the LSEQ subscales for ‘getting to sleep’, ‘awakening from sleep’, or ‘behaviour following sleep’ although at week 4 ESC was superior (p&lt;0.01; ANCOVA) to PAR on ‘quality of sleep’. There were no significant differences between treatment groups in the change from baseline in CFF, recognition or motor reaction times, or CFQ total score, at any of the scheduled assessments. Conclusion. In this study, only a small number of patients withdrew from antidepressant treatment due to adverse effects on sleep or daytime alertness. Repeated assessments of sleep and daytime performance indicated a steady improvement during acute and continuation treatment of major depressive disorder with both escitalopram and paroxetine. Source of funding. The overall randomised controlled trial was sponsored by Lundbeck Ltd

What is the threshold for symptomatic response and remission for major depressive disorder, panic disorder, social anxiety disorder, and generalized anxiety disorder?

Objective: Symptom-free remission is a goal for treatment in depression and anxiety disorders, but there is no consensus regarding the threshold for determining remission in individual disorders. We sought to determine these thresholds by comparing, in a post hoc analysis, scores on the Clinical Global Impressions scale (CGI) and disorder-specific symptom severity rating scales from all available studies of the treatment of major depressive disorder, panic disorder, generalized anxiety disorder, and social anxiety disorder with the same medication (escitalopram). We also sought to compare the standardized effect sizes of escitalopram for these 4 psychiatric disorders. Data Sources and Study Selection: Raw data from all randomized, double-blind, placebo-controlled, acute treatment studies sponsored by H. Lundbeck A/S (Copenhagen, Denmark) or Forest Laboratories, Inc. (New York, N.Y.), published through March 1, 2004, with patients treated with escitalopram for DSM-IV major depressive disorder (5 studies), panic disorder (I study), generalized anxiety disorder (4 studies), or social anxiety disorder (2 studies) were compared with regard to the standardized effect sizes of change in CGI score and scores on rating scales that represent the "gold standard" for assessment of these disorders (the Montgomery-Asberg Depression Rating Scale, the Panic and Agoraphobia Scale, the Hamilton Rating Scale for Anxiety, and the Liebowitz Social Anxiety Scale, respectively). Data Synthesis: In all indications, treatment with escitalopram showed differences from placebo in treatment effect from 0.32 to 0.59 on the CGI-S and CGI-I and standardized effect sizes from 0.32 to 0.50 on the standard rating scales. There were no significant differences among the different disorders. Moderate to high correlations were found between scores on the CGI and the standard scales. The corresponding standard scale scores for CGI-defined "response" and "remission" were determined. Conclusion: Comparison of scores on the standard scales and scores on the CGI suggest that the traditional definition of response (i.e., a 50% reduction in a standard scale) may be too conservative