Adolescent depression: A placebo-controlled fluoxetine treatment study and follow-up

doi:10.1016/0278-5846(90)90050-Q

Progress in Neuro-Psychopharmacology and Biological Psychiatry

Volume 14, Issue 5, 1990, Pages 791-795

https://doi.org/10.1016/0278-5846(90)90050-Q Get rights and content

Abstract

Forty patients aged 13 to 18 years participated in a placebo-controlled double-blind study of fluoxetine. Fifteen subjects in each group completed the eight week study. Approximately two-thirds of the patients showed marked or moderate clinical global Improvement with both fluoxetine and placebo. Fluoxetine was superior to placebo on all clinical measures except for sleep disorder, but the differences were not statistically significant. Thirty-two of the patients and their parents were interviewed after a mean follow-up Interval of 24 months (range: 8–46 months). Mean age at follow-up was 18 years (range: 15–22 years). Both groups had shown further improvement at follow-up but there were no significant group differences. Independent of the study, 19 patients (59%) had received intervening treatment following study termination and nine patients (28%) were still in treatment. Adolescent depression appears to respond to treatment but both mood disturbance and psychosocial adaptation problems persist, requiring active follow-through.

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Dropout Prevalence and Associated Factors in Randomized Clinical Trials of Adolescents Treated for Depression: Systematic Review and Meta-analysis
2017, Clinical Therapeutics
Citation Excerpt :
The characteristics of each study are presented in the Table.27–76 The evaluation of study quality using the Jadad scale revealed that 82% were of high quality27–31,33,35–49,51–54,56,58–60,62–68,71–76 and 18% were of low quality32,34,50,55,57,61,69,70 (see Supplemental Table I in the online version at http://dx.doi.org/10.1016/j.clinthera.2017.03.017). No study achieved a grade of 8 (or good quality) on the Cochrane Handbook for Systematic Review scale.
Depression currently affects 350 million people, and its prevalence among adolescents is 4% to 8%. Adolescents who abandon antidepressant treatment or drop out of clinical trials are less likely to recover or experience a remission of symptoms because they are not being followed up by a medical team. The objective of this study was to analyze the dropout rates of randomized clinical trials of depressed adolescents receiving treatment with antidepressant drugs and the factors associated with nonadherence by summarizing this information in a systematic review and meta-analysis.
Articles were retrieved from MEDLINE, EMBASE, Cochrane, Clinical Trial, PsycINFO, and Web of Science using the MeSH terms “depressive disorder,” “randomized trials,” and “adolescents.” The evaluation of study quality was performed by using the Cochrane Handbook for Systematic Reviews of Interventions and the Jadad scale.
The final sample included 50 articles, of which 44 presented dropout rates. The overall dropout prevalence was 23% (95% CI, 20–27; P < 0.0001). Participants aged ≥16 years, those treated with serotonin norepinephrine reuptake inhibitors, and those receiving medication only exhibited the highest dropout prevalence, respectively (33% [95% CI, 27-39], 45% [95% CI, 31–64], and 15% [95% CI, 13-17]). The adverse effects most associated with dropout were attempted suicide followed by mania, skin rash, and headache. Problems relating to clinical trials and family arbitration were also related with dropout.
Serotonin/norepinephrine reuptake inhibitor treatment, adolescent age >16 years, and receiving medication were the only factors demonstrating a higher association with dropout rates. Selective serotonin reuptake inhibitors were linked to the lowest prevalence, probably due to fewer perceived problems with related adverse effects and higher efficacy in adolescents. Cognitive-behavioral therapy combined with pharmacotherapy produced a lower nonadherence prevalence; this approach can be an alternative to avoid dropouts and relapse. Prospero identifier: CRD42014013475.
Psychopharmacological Treatment for Depression in Children and Adolescents: Promoting Recovery and Resilience
2016, Positive Mental Health, Fighting Stigma and Promoting Resiliency for Children and Adolescents
Depressive disorders are prevalent in youth, and these conditions are not benign, often leading to significant impairment in functioning. Efficacious evidenced-based psychosocial and psychopharmacological treatments are available for depressed youth, but many do not receive sufficient treatment, in part due to stigma and other barriers to care. This chapter will provide a clinical framework for fighting stigma, enhancing wellness, and promoting resiliency in depressed youth by (1) summarizing the foundation necessary to assess depression and partner with youth and their families, (2) reviewing systematic psychopharmacological treatment strategies, and (3) focusing on achieving wellness, not simply symptom reduction.
A meta-analysis and model of the relationship between sleep and depression in adolescents: Recommendations for future research and clinical practice
2014, Sleep Medicine Reviews
Citation Excerpt :
Adolescents who reported notable depressive symptoms were 50% more likely to develop sleep problems than those who did not report symptoms. In contrast, Simeon and colleagues included sleep disturbance as an outcome measure in their double-blind, placebo-controlled study for the treatment of adolescent depression with fluoxetine [27]. Although two-thirds of the adolescents treated with fluoxetine showed a marked clinical improvement on the majority of outcome measures (e.g., symptoms of depression and anxiety), sleep disturbance remained unchanged immediately following treatment and at a 24-mo follow-up.
The purpose of this review was to quantify the strength of evidence for a directional relationship between sleep disturbance and depression in adolescents.
A literature search was conducted to identify research investigating the relationship between sleep disturbance and depression in adolescent samples (12–20 y). Twenty-three studies were identified; 13 explored associations between depression and sleep disturbance; seven examined the prospective role of sleep disturbance in the development of depression; and three investigated the role of adolescent depression in the development of subsequent sleep disturbance. Average weighted mean differences in sleep/depression-related outcome variables were calculated between adolescents with depression, and non-clinical adolescents, or those in remission.
Adolescents with depression experienced significantly more wakefulness in bed (sleep onset latency, wake after sleep onset, number of awakenings and sleep efficiency), lighter sleep (more stage 1), and reported more subjective sleep disturbance. Overall effect sizes from longitudinal and treatment studies suggest sleep disturbance acts as a precursor to the development of depression. At follow-up, depressed adolescents had significantly longer sleep onset, more wake after sleep onset, and lower sleep efficiency compared to adolescents who were non-clinical, or had undergone remission. Little support was found for a predictive role of depressive symptoms in the development of sleep disturbance. Based on these findings we propose a model to understand the development of depression from initial sleep disturbance, provide recommendations for clinicians and recommendations for future research.
Antidepressants in children and adolescents: Update on efficacy and safety
2012, Neuropsychiatrie de l'Enfance et de l'Adolescence
Au cours des dernières années, la nécessité de disposer d’essais thérapeutiques spécifiques à la population pédiatrique est apparue comme un enjeu important, du fait des particularités cliniques de cette population et des profils de tolérance et de sécurité qui montrent des différences significatives par rapport à ceux de l’adulte. Cela s’applique, en particulier, aux antidépresseurs, pour lesquels des effets psychocomportementaux spécifiques à l’âge ont été observés dans une proportion faible mais non négligeable de jeunes patients. Cet article propose une mise au point des données actuelles d’efficacité et de tolérance concernant les antidépresseurs chez l’enfant et l’adolescent. Le développement d’études collaboratives multicentriques en psychopharmacologie pédiatrique a permis de mieux comprendre la place des antidépresseurs parmi les autres stratégies thérapeutiques dans un certain nombre de troubles internalisés de l’enfant et de l’adolescent. Dans la dépression de l’enfant, la fluoxétine a obtenu l’autorisation de mise sur le marché (AMM) dans les troubles dépressifs majeurs de l’enfant à partir de huit ans. L’efficacité des inhibiteurs sélectifs de la recapture de la sérotonine (ISRS) est documentée dans le trouble obsessionnel compulsif (TOC) de l’enfant, avec une AMM pour la sertraline et la fluvoxamine en France dans cette indication. Des arguments existent en faveur de l’efficacité des ISRS et de la venlafaxine dans les troubles anxieux – hors TOC – de l’enfant et de l’adolescent, mais sans AMM actuellement dans ces indications. Les données de tolérance et de sécurité (effets psychocomportementaux, incluant les idées et comportements suicidaires, tolérance à long terme, risque léthal) sont également passées en revue. Il s’ensuit des propositions de décision incorporant l’ensemble des modalités thérapeutiques disponibles pour les trois indications considérées : dépression, TOC et autres troubles anxieux de l’enfant et de l’adolescent.
The evidence of the past years has shown that specific studies in children and adolescents were mandatory, as important differences in the efficacy and safety profiles of psychopharmacological drugs have been documented between pediatric and adult populations. This applies in particular to antidepressants, in which age-dependent psychobehavioral effects have been shown in a small but significant proportion of young patients. Our review focuses on current efficacy and tolerability data on antidepressants in children and adolescents. Recent collaborative multicenter trials in pediatric psychopharmacology have provided evidence-based data on the use of antidepressants as part of the treatment strategies for internalized disorders in children and adolescents. Fluoxetine has been shown effective in pediatric major depression, with a label for children above eight years old. The efficacy of specific serotonin reuptake inhibitors (SSRIs) has been documented in obsessive-compulsive disorder (OCD), with some SSRIs labeled for children and adolescents in this indication in both the USA. and Europe. In non-OCD anxiety disorders, clinical trials support efficacy for a number of SSRIs and venlafaxine in children and adolescents, although none has a pediatric label in these indications. We also review available data on tolerability and safety (psychobehavioral effects, including treatment-induced suicidality, long-term tolerance, lethal risk). In conclusion, we suggest decision options including all treatment modalities available for depression, OCD and other anxiety disorders in children and adolescents.
Restoring the two pivotal fluoxetine trials in children and adolescents with depression
2022, International Journal of Risk and Safety in Medicine
Meta-Analysis: Pediatric Placebo Response in Depression Trials Does Not Replicate in Anxiety and Obsessive-Compulsive Disorder Trials
2021, Journal of Child and Adolescent Psychopharmacology

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Adolescent depression: A placebo-controlled fluoxetine treatment study and follow-up

Abstract

Primary Depression or Primary Anxiety? A Possible Approach to a Diagnositc Dilemma

Clin. Neuropharmacol.

Fluoxetine Versus Trazodone in the Treatment of Outpatients with Major Depression

J. Clin. Psychiatry

The Hopkins Symptom Checklist (HSCL): A Self-Report Symptom Inventory

Behav. Sci.

A Fixed-Dose Clinical Trial of Fluoxetine in Outpatients with Major Depression

J. Clin. Psychiatry