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Biomedical subjects

Moira Rynn

Publications and source records attributed to Moira Rynn.

10 recordsLinked to original sources

Early response and 8-week treatment outcome in GAD.

Our objective was to compare the predictive value of early response to treatment outcome in patients with generalized anxiety disorder (GAD) treated with benzodiazepines, serotonin receptor (5HT-1A) partial agonists, or placebo. Data from two double-blind GAD studies were combined. Subjects were evaluated with the Hamilton Anxiety Scale (HAM-A) and the Clinical Global Impression of Improvement (CGI-I) scale over 8 weeks. Categories of response at weeks 1 and 2 were defined by the HAM-A total score. Analyses of covariance and Kaplan-Meier survival analyses were the primary analyses used to assess 8-week end point treatment outcomes as a function of early improvement. HAM-A change from baseline to weeks 1 and 2 significantly predicted last observation carried forward (LOCF) response at week 8 for both medications and for placebo (P<.001). Early improvement was a strong predictor for treatment outcome irrespective of whether active medication or placebo was the treatment agent.

Adult↗

Sertraline in children and adolescents with major depressive disorder.

OBJECTIVE: To explore time to first response and time to first persistent response of sertraline versus placebo and compare these parameters between children (6-11 years old, n = 177) and adolescents (12-17 years old, n = 199) with major depressive disorder. METHOD: A 10-week placebo-controlled treatment was followed by a 24-week open-label sertraline treatment. The double-blind studies were not powered to detect efficacy differences between age groups. A post hoc analysis explored time to first response and first persistent response using the Children's Depression Rating Scale-Revised and Clinical Global Impressions-Improvement predefined criteria. RESULTS: There were no statistically significant differences in time to first response or first persistent response between sertraline and placebo in children, except for time to first response on Clinical Global Impressions-Improvement. Sertraline had a significantly faster time to first persistent response in adolescents compared to placebo. Within treatment groups, children had a significantly faster time to first response than adolescents, whether treated with placebo or sertraline, but not on time to first persistent response. Both age groups showed similar improvement over 34 weeks of treatment. CONCLUSION: In the double-blind studies, children and adolescents had different patterns of response with sertraline vs. placebo.

Adolescent↗

Remission of generalized anxiety disorder: a review of the paroxetine clinical trials database.

OBJECTIVE: Paroxetine is a potent selective serotonin reuptake inhibitor with antidepressant and anxiolytic activity that is effective in the treatment of generalized anxiety disorder (GAD), improving the core symptoms of anxiety, worry, and tension. The majority of patients with GAD have chronic symptomatology and significant comorbid mood and anxiety disorders that often require ongoing pharmacotherapy. This article reviews the efficacy and tolerability of paroxetine in the short- and long-term treatment of GAD including remission data. DATA SOURCES: Data from more than 1800 outpatients with DSM-IV-defined GAD were analyzed from 3 short-term (8-week) studies and a longer (6-month) relapse prevention study. These studies were all randomized, double-blind, placebo-controlled trials of paroxetine. DATA SYNTHESIS: The results emphasize the benefit of paroxetine treatment in GAD, enabling a substantial proportion of patients to achieve clinical remission and preventing relapse. Long-term treatment with paroxetine also shows good tolerability with no evidence of weight gain. CONCLUSION: Given the high comorbidity of psychiatric depression and anxiety, the long-term efficacy and tolerability of paroxetine are important considerations when selecting a first-line therapy for patients with GAD.

Adult↗

Sertraline treatment for generalized anxiety disorder: a randomized, double-blind, placebo-controlled study.

OBJECTIVE: This study assessed the efficacy and safety of sertraline in the treatment of generalized anxiety disorder (GAD). METHOD: The study was conducted from April 2000 to May 2002. Outpatients with DSM-IV GAD (N = 326) who satisfied inclusion/exclusion criteria and completed a 1-week screening phase were randomly assigned to 10-week double-blind treatment with flexible dosing of sertraline (50-200 mg/day) or placebo. The primary efficacy measure was change from baseline in Hamilton Rating Scale for Anxiety (HAM-A) total score. Response was defined as a 50% or greater decrease in HAM-A total score at endpoint. RESULTS: Sertraline produced a statistically significant reduction in anxiety symptoms, as measured by HAM-A total change scores (p = .032), HAM-A psychic anxiety subscale (p = .011), and Hospital Anxiety and Depression Scale-anxiety subscale (p = .001). Response rates were significantly higher (p = .05) for the sertraline group (59.2%) compared to the placebo group (48.2%). Sertraline was well tolerated, with only sexual side effects reported significantly more often by subjects receiving sertraline than those receiving placebo. CONCLUSION: Despite the relatively small between-group differences, study findings suggest a role for sertraline in the acute treatment of GAD.

Adult↗

Explanatory style change in supportive-expressive dynamic therapy.

Change in explanatory style (measured by the Attributional Style Questionnaire [ASQ]) has often been considered specific to cognitive therapy (CT). We used data from 59 patients who had received supportive-expressive (SE) dynamic therapy after meeting DSM-III-R criteria for a depressive spectrum disorder and who had completed the ASQ at intake and termination of treatment. We found that depressive symptoms decreased significantly and that explanatory style became more optimistic over the course of treatment. Furthermore, change in ASQ correlated with change in depression. There was some evidence suggesting that ASQ at termination predicted level of depression at follow-up.

Adult↗

Cognitive behavioral and attachment based family therapy for anxious adolescents: Phase I and II studies.

The goals of these two studies were to assess the acceptability and feasibility as well as to gather preliminary efficacy data on a modified combination cognitive behavioral (CBT) and attachment based family therapy (ABFT) for adolescents (ages 12-18), with the primary diagnosis of generalized (GAD), social phobia (SP), and separation (SAD) anxiety disorders. In Phase I, CBT was modified for an adolescent population and ABFT was modified for working with anxious adolescents in combination with CBT. Therapists were trained for both conditions and eight patients were treated as an open trial pilot of combined CBT-ABFT with positive results. In Phase II, 11 adolescents were randomly assigned to CBT alone or CBT and family based treatment (CBT-ABFT). Participants were evaluated at pre, post, and 6-9 months follow-up assessing diagnosis, psychiatric symptoms and family functioning. Results indicated significant decreases in anxiety and depressive symptoms by both clinical evaluator and self-reports with no significant differences by treatment. Sixty-seven percent of adolescents in CBT no longer met criteria for their primary diagnosis at post treatment as compared to 40% in CBT-ABFT with continued improvement of 100 and 80% at follow-up with no significant differences between treatments. Both CBT and CBT-ABFT appear to be promising treatments for anxious adolescents and more treatment development and evaluation is needed.

Adolescent↗

Efficacy of sertraline in the treatment of children and adolescents with major depressive disorder: two randomized controlled trials.

CONTEXT: The efficacy, safety, and tolerability of selective serotonin reuptake inhibitors (SSRIs) in the treatment of adults with major depressive disorder (MDD) are well established. Comparatively few data are available on the effects of SSRIs in depressed children and adolescents. OBJECTIVE: To evaluate the efficacy and safety of sertraline compared with placebo in treatment of pediatric patients with MDD. DESIGN AND SETTING: Two multicenter randomized, double-blind, placebo-controlled trials were conducted at 53 hospital, general practice, and academic centers in the United States, India, Canada, Costa Rica, and Mexico between December 1999 and May 2001 and were pooled a priori. PARTICIPANTS: Three hundred seventy-six children and adolescents aged 6 to 17 years with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-defined MDD of at least moderate severity. INTERVENTION: Patients were randomly assigned to receive a flexible dosage (50-200 mg/d) of sertraline (n = 189) or matching placebo tablets (n = 187) for 10 weeks. MAIN OUTCOME MEASURES: Change from baseline in the Children's Depression Rating Scale-Revised (CDRS-R) Best Description of Child total score and reported adverse events. RESULTS: Sertraline-treated patients experienced statistically significantly greater improvement than placebo patients on the CDRS-R total score (mean change at week 10, -30.24 vs -25.83, respectively; P =.001; overall mean change, -22.84 vs -20.19, respectively; P =.007). Based on a 40% decrease in the adjusted CDRS-R total score at study end point, 69% of sertraline-treated patients compared with 59% of placebo patients were considered responders (P =.05). Sertraline treatment was generally well tolerated. Seventeen sertraline-treated patients (9%) and 5 placebo patients (3%) prematurely discontinued the study because of adverse events. Adverse events that occurred in at least 5% of sertraline-treated patients and with an incidence of at least twice that in placebo patients included diarrhea, vomiting, anorexia, and agitation. CONCLUSION: The results of this pooled analysis demonstrate that sertraline is an effective and well-tolerated short-term treatment for children and adolescents with MDD.

Adolescent↗

Imipramine and buspirone in patients with panic disorder who are discontinuing long-term benzodiazepine therapy.

Pretreatment with imipramine, buspirone, or placebo was compared in 40 patients meeting the Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition criteria for panic disorder and in patients who were discontinuing long-term benzodiazepine use. The average duration of benzodiazepine use was 75 +/- 64 months, and the average benzodiazepine intake expressed as diazepam equivalents was 25.7 +/- 19 mg/d. We hypothesized that pretreatment with either imipramine or buspirone, in contrast to pretreatment with placebo, would lead to a significant decrease of symptoms of anxiety and depression before tapering benzodiazepines, thus making the taper process easier to complete. All 3 treatments (imipramine, buspirone, and placebo) caused a reduction in anxiety and depression symptoms as measured by changes in the Hamilton Anxiety Rating Scale and Hamilton Depression Rating Scale. Neither discontinuation severity nor taper-free status 12 weeks posttaper differed between the 3 treatment groups.

Adult↗

Pharmacotherapy of generalized anxiety disorder.

Less than one third of people afflicted with generalized anxiety disorder (GAD) experience spontaneous remission, and the symptoms of GAD wax and wane throughout a person's life. The burden of GAD may be reduced with psychopharmacologic therapy. The medications with the most evidence of efficacy in GAD are the benzodiazepines, including a new long-acting formulation of alprazolam. These drugs have a low incidence of side effects but may cause physical dependence, withdrawal, and sedation. Antidepressants are also efficacious in GAD but act less quickly than benzodiazepines. Tricyclic antidepressants such as imipramine may substantially reduce symptoms of anxiety but are not considered a first-line therapy because of their side effects spectrum. The extended-release formulation of venlafaxine and selective serotonin reuptake inhibitors such as paroxetine and sertraline are also efficacious in GAD. While their association with sexual dysfunction may be intolerable for some adults, these drugs may be more appropriate than the benzodiazepines because their chronic use does not lead to dependence. Buspirone also significantly reduces symptoms of GAD and is associated with less sexual dysfunction than SSRIs and less sedation than benzodiazepines. Combining antidepressant and benzodiazepine therapy or medication treatment and psychotherapy may lead to an increase in improvement in patients not responding to 1 treatment approach alone. The most effective treatment for managing the recurrent symptoms of this chronic disorder will remain unknown until more long-term studies using both drug and nondrug therapies are conducted. Remission rates are still only about 40%, signifying the need for improved treatment interventions.

Algorithms↗

Long-term sertraline treatment of children and adolescents with major depressive disorder.

OBJECTIVE: The aim of this study was to assess the long-term safety, tolerability, and efficacy of sertraline 50-200 mg once-daily in children (6-11 year olds) and adolescents (12-18 year olds) with a Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) diagnosis of major depressive disorder (MDD). METHODS: This study consisted of a 24-week open-label observational study of children and adolescents who had completed either of two 10-week double-blind, placebo-controlled trials. The Children's Depression Rating Scale-Revised (CDRS-R) was the primary measure of efficacy. RESULTS: Two hundred ninety nine (299) patients completed the acute studies and were eligible for the extension study. Of these, 226 enrolled, but 5 did not receive treatment. Of 221 patients (107 children and 114 adolescents), 62.4% completed the study. The endpoint mean daily dose was 109.9 mg/day. The mean decrease in CDRS-R score from double-blind baseline was 34.8 points (p < 0.001), with patients showing continued improvement in CDRS-R scores regardless of which treatment they received in the double-blind studies. At endpoint, 86% of patients met CDRS-R responder and 58% CDRS-R remitter criteria. CONCLUSIONS: Sertraline appears to be well tolerated and safe over 24 weeks of treatment in children and adolescents with MDD. Children and adolescents treated with sertraline appear to have increased improvement over that seen in the first 10 weeks of treatment. These findings need confirmation in placebo-controlled studies.

Adolescent↗