Search PubMed⌕ Search

Biomedical subjects

Graham J Emslie

Publications and source records attributed to Graham J Emslie.

26 records · Page 2Linked to original sources

Fluoxetine treatment for prevention of relapse of depression in children and adolescents: a double-blind, placebo-controlled study.

OBJECTIVE: To compare fluoxetine 20 to 60 mg/day with placebo for prevention of relapse of major depressive disorder in children and adolescents who had achieved Children's Depression Rating Scale, Revised scores of < or =28 during treatment with fluoxetine 20 to 60 mg. METHOD: In this 32-week relapse-prevention phase of a double-blind, multicenter, placebo-controlled 51-week study, 20 patients continued to receive their fixed dose of fluoxetine (F/F group), while 20 similar patients were switched to placebo (F/P group). Definition of relapse for the primary analysis was a Children's Depression Rating Scale, Revised score of >40 with a 2-week history of clinical deterioration or relapse in the opinion of the physician. Adverse events were compared between treatment groups to assess discontinuation-emergent adverse events. RESULTS: Mean time to relapse was longer in the F/F recipients than in the F/P recipients (p=.046). Relapse occurred in an estimated 34% in the F/F cohort and 60% in the F/P cohort. Incidence of adverse events and tolerability were similar in the F/F and F/P groups, suggesting that fluoxetine is not associated with significant discontinuation events. CONCLUSIONS: Fluoxetine 20 to 60 mg/day was well tolerated and can significantly delay relapse of major depressive disorder symptoms in children and adolescents.

Administration, Oral↗

Predictors of response to treatment in children and adolescents with mood disorders.

Depression and bipolar disorder are frequently chronic disorders, with onset often beginning in childhood. Mood disorders are becoming more recognized in children and adolescents, and treatment of these disorders has received much attention, particularly in the past 10 years. Recent studies have demonstrated efficacy of antidepressant medications (particularly SSRIs) and specific psychotherapies (primarily CBT). Rates of remission (little or no symptoms) in these studies, however, have remained quite low (35% to 40% in most acute studies). Furthermore, recurrence is common in this population, and affects 40% to 50%. Early onset mood disorders are also associated with increased risk of developing other psychiatric disorders, substance abuse, and suicide, and having poor academic, work, and social functioning. The lifelong implications are serious. Identifying factors that may predict response to treatment, both in general and to specific treatments, may lead to improved outcomes for these patients. Unfortunately, studies have typically been inconsistent. Most studies do not identify demographic variables as predictive of outcome, although older age has been associated with poor prognosis in several studies. Psychosocial factors have yielded some results, particularly with regard to family environments. Generally, intact families with positive interaction styles and less dysfunction have been associated with better outcomes. Psychiatric disorders among parents not only predicts the development of the disorder, but is also associated with poorer prognosis. Finally, several clinical factors have been linked to poorer outcome in children and adolescents with mood disorders. More frequent episodes, increased severity (particularly suicidality and psychosis), and comorbid disorders are likely to lead to fewer recoveries, longer episodes, and increased rate of recurrence. Recent attention has focused on mediators and moderators of outcomes to treatment. In general, the theory is that enumerable factors contribute to the course of an individual's mood disorder, but that by identifying some of the variables that have more impact may allow for more specific or modified treatments to improve outcome. Many of the predictive factors explored in this article are examples of mediators and moderators that affect outcome. Each one alone may not provide definitive answers for predicting response to treatment, but each must be taken into account at the outset of treatment. It is clear that treatments must be individualized for each patient. Furthermore, selecting only one treatment exclusively for patients may hinder progress. The first step is to attempt to identify some of the underlying causes and the consequences of the disorder itself (i.e., decreased social interaction). The next step in successful treatment is to address both the causes and consequences of the disorder, through medication, psychotherapy, skills training, family intervention, or any other methods needed to assist the child to begin functioning better in all domains (social, academic, work, family, and so forth). Such a biopsychosocial approach to treatment of these disorders will likely improve overall outcome.

Adolescent↗

A feasibility study of the children's medication algorithm project (CMAP) algorithm for the treatment of ADHD.

OBJECTIVE: To determine whether an algorithm for the treatment of attention-deficit/hyperactivity disorder (ADHD) can be implemented in a community mental health center. METHOD: Fifty child and adolescent patients at Texas community mental health centers who met criteria for ADHD were treated according to an algorithm-based disease management program for ADHD. Psychiatrists were trained in the use of the algorithm, and each subject underwent a baseline assessment consisting of a structured interview and standardized rating scales. Subjects were monitored for 4 months. At the end of treatment, the psychiatrists completed the Clinical Global Impression Scale (CGI) and the baseline rating scales were repeated. The primary variables of interest were psychiatrist and family adherence to the algorithm. To examine impact on treatment outcome, the CGI of the algorithm subjects was compared with CGIs based on chart reviews of 118 historical controls. RESULTS: Psychiatrists implemented the major aspects of the algorithm, but the detailed tactics of the algorithm (use of fixed titration of stimulants) were less well adhered to. CONCLUSIONS: An algorithm for the treatment of ADHD can be implemented in a community mental health center.

Adolescent↗

National Depressive and Manic-Depressive Association consensus statement on the use of placebo in clinical trials of mood disorders.

A consensus conference on the use of placebo in mood disorder studies consisted of expert presentations on bioethics, biostatistics, unipolar depression, and bipolar disorder. Work groups considered evidence and presented statements to the group. Although it was not possible to write a document for which there was complete agreement on all issues, the final document incorporated input from all authors. There was consensus that placebo has a definite role in mood disorder studies. Findings of equivalence between a new drug and standard treatment in active control studies is not evidence of efficacy unless the new drug is also significantly more effective than placebo. Add-on studies in which patients are randomized to standard therapy plus the investigational drug or standard therapy plus placebo are especially indicated for high-risk patients. Mood disorders in elderly and pediatric patients are understudied, and properly designed trials are urgently needed. Research is needed on the ethical conduct of studies to limit risks of medication-free intervals and facilitate poststudy treatment. Patients must fully understand the risks and lack of individualized treatment involved in research.

Bipolar Disorder↗

Sleep microarchitecture as a predictor of recurrence in children and adolescents with depression.

Although polysomnographic abnormalities are prevalent in adults with major depressive disorders (MDD), the findings in children and adolescents have been more equivocal. Polysomnographic measures may be of predictive value in assessing course of illness. The present study used standard sleep measures and temporal coherence of sleep electroencephalogram (EEG) rhythms to predict recovery and recurrence in a 1-yr naturalistic follow-up in 47 children and adolescents 8-18 yr of age with MDD. Standard sleep measures did not predict clinical course. On the other hand, temporal coherence measures discriminated between those who recovered, recovered but recurred, and those who did not recover from the index episode. Specifically, coherence between beta, theta and delta recorded in the right hemisphere was significantly lower in the no-recovery group. In addition, temporal coherence was strongly associated with both time to recovery and recurrence. Those with the lowest coherence were less likely to recover or recurred sooner. Significant sex differences were found with a stronger relationship between temporal coherence and clinical course in boys. This study supports the use of quantitative sleep EEG measures as a predictor of clinical course in depression.

Adolescent↗

Fluoxetine for acute treatment of depression in children and adolescents: a placebo-controlled, randomized clinical trial.

BACKGROUND: This report presents results from the acute treatment phase of a clinical trial designed to confirm efficacy of a fixed dose of 20 mg of fluoxetine in children and adolescents with major depressive disorder (MDD). METHOD: After a 3-week screening period, 122 children and 97 adolescents with MDD ( ) were randomly assigned to placebo or fluoxetine. After a 1-week placebo lead-in, fluoxetine-treated patients received fluoxetine 10 mg/day for 1 week, then fluoxetine 20 mg/day for 8 weeks. RESULTS: Fluoxetine was associated with greater mean improvement in Children's Depression Rating Scale-Revised (CDRS-R) score than placebo after 1 week ( <.05) and throughout the study period. Significantly more fluoxetine-treated patients (41%) met the prospectively defined criteria for remission than did placebo-treated patients (20%) ( <.01). More fluoxetine- (65%) than placebo-treated (53%) patients met the prospectively defined response criterion of > or =30% decrease in CDRS-R score, but this difference was not significant ( =.093). Significantly more fluoxetine-than placebo-treated patients completed acute treatment ( =.001). There were no significant differences between treatment groups in discontinuations due to adverse events ( =.408). CONCLUSION: Fluoxetine 20 mg daily appears to be well tolerated and effective for acute treatment of MDD in child and adolescent outpatients. Fluoxetine is the only antidepressant that has demonstrated efficacy in two placebo-controlled, randomized clinical trials of pediatric depression.

Adolescent↗

Citalopram in children and adolescents with depression or anxiety.

OBJECTIVE: To investigate the efficacy and tolerability of citalopram in children and adolescents. METHOD: Retrospective chart review of 17 outpatients treated with citalopram at a tertiary care center. Subjects were diagnosed with a depressive or anxiety disorder with or without comorbidities and may have received concurrent medications. The primary outcome measure was the Clinical Global Impression Improvement Scale (CGI-I). Secondary outcome measures were the Children's Depression Rating Scale-Revised (CDRS-R), Inventory of Depressive Symptomatology, and Screen for Child Anxiety-Related Emotional Disorders (SCARED). Adverse effects were assessed via chart documentation. RESULTS: Patients were treated with a mean citalopram dose of 22.4 +/- 7.3 mg for 12 weeks. Thirteen patients (76%) had CGI-I scores </=2: 8 of 12 patients with depression and 5 of 5 patients with an anxiety disorder. The mean time to response was 7.6 +/- 3.6 weeks. Additionally, 6 of 8 patients had >/=50% reduction from baseline CDRS-R score, with 3 patients (38%) meeting criteria for remission. Three of 4 patients had a >50% reduction for baseline SCARED-parent score. Overall, adverse effects appeared minor and transient. One patient discontinued citalopram due to intolerable adverse effects, and 1 patient required dose reduction. CONCLUSIONS: Citalopram appears to be effective and well tolerated in this group of children and adolescents with depressive or anxiety disorders and a high degree of comorbidity. Controlled studies in this patient population are indicated.

Adolescent↗

Efficacy of atomoxetine versus placebo in school-age girls with attention-deficit/hyperactivity disorder.

OBJECTIVE: The efficacy of atomoxetine was assessed in school-age girls with attention-deficit/hyperactivity disorder (ADHD). Atomoxetine is a potent inhibitor of the presynaptic norepinephrine transporter with minimal affinity for other noradrenergic receptors or for other neurotransmitter transporters or receptors. METHODS: A total of 291 children who were 7 to 13 years of age and met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for ADHD participated in 1 of 2 combined, double-blind, placebo-controlled, multisite, identical clinical trials. This intent-to-treat subset analysis examined the effects of atomoxetine versus placebo in 51 girls who were randomized to atomoxetine (n = 30) or placebo (n = 21) for 9 weeks. ADHD symptoms were assessed using parent- and investigator-rated scales. RESULTS: Atomoxetine was superior to placebo on the following measures: the Attention-Deficit Hyperactivity Disorder Rating Scale-IV-Parent Version: Investigator Administered and Scored Total Score; the Inattentive and Hyperactive/Impulsive subscales of the Attention-Deficit Hyperactivity Disorder Rating Scale-IV-Parent Version: Investigator Administered and Scored Total Score; the ADHD Index subscale of the Conners' Parent Rating Scale-Revised: Short Form; and the Clinical Global Impressions of Severity of ADHD. Statistically significant efficacy was seen 1 week after randomization and remained so for the duration of the study. One patient from each of the atomoxetine and placebo groups discontinued the study as a result of an adverse event. CONCLUSION: Atomoxetine was found to be effective and well tolerated for the treatment of ADHD in school-age girls.

Adolescent↗