Fluoxetine 40–60 mg versus Fluoxetine 20 mg in the Treatment of Children and Adolescents with a Less-Than-Complete Response to Nine-Week Treatment with Fluoxetine 10–20 mg: APilot Study

The purpose of the present paper was to identify, from the voluminous literature on efficacy and safety in new-generation antidepressants (NGAs) with depressed children and adolescents, practical clinical strategies for acute phase treatment. To this end a pragmatic survey of studies and reviews was undertaken. Meta-analyses of randomized controlled trials of NGAs in depressed children and adolescents have noted a comparative lack of efficacy, and a weak but statistically significant increased risk of self-harm and suicidal thoughts. But NGA prescription rates and youth suicide rates are generally inversely related, and ensuing 'black box' warnings about NGAs, by deterring NGA prescribing, have possibly contributed to rising youth suicide rates. In moderate-severe depression, benefits for fluoxetine and possibly other NGAs demonstrably outweigh risks. NGAs are not present in adolescents who die by suicide. Concern about NGA risks must be balanced against risks of non-treatment. While mild depression entails regular review, psychoeducation, self-care strategies and psychological interventions, NGAs should be administered concurrently with psychological treatments if depression is moderate- to severe, or if mild depression persists. Patients should be warned about off-label status of NGAs in depression, serious side-effects such as 'activation', suicidality, emotional blunting and manic switches, the need for adherence and avoiding abrupt discontinuation. They should be monitored early and regularly. Better evidence is required regarding psychological treatments, clinical course, and clinical practice trends. In moderate-severe depression the risk of suicide if NGAs are not used may outweigh any risk of self-harm associated with them.

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“…An adequate trial lasts at least 4 weeks at the minimum effective dose [102]. Some patients may require 60 mg [54], [104].…”

Section: Antidepressant Treatment Guidelinesmentioning

confidence: 99%

New-Generation Antidepressants, Suicide and Depressed Adolescents: How Should Clinicians Respond to Changing Evidence?

Dudley

Hadži-Pavlović

Andrews

et al. 2008

Aust N Z J Psychiatry

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“…Once daily dosing, compared with twice daily dosing, has been shown to improve medication adherence in the treatment of chronic psychiatric illness [ 172 ]. Moreover, fluoxetine uniquely has evidence to suggest that increased dosages may benefit those who do not respond to lower doses [ 173 ], and therefore we are allowing flexible dosing for fluoxetine in this protocol. Finally, extensive discussions with leaders of our pediatric primary care network have suggested that the once-daily dosing, the wide range of doses over which fluoxetine administration is deemed safe in pediatric patients, and the simple upward titration in 10 mg increments will facilitate the training and comfort of pediatricians in prescribing medication in this study.…”

Section: Methodsmentioning

confidence: 99%

A Sequential Multiple Assignment Randomized Trial (SMART) study of medication and CBT sequencing in the treatment of pediatric anxiety disorders

et al. 2021

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Background Treatment of a child who has an anxiety disorder usually begins with the question of which treatment to start first, medication or psychotherapy. Both have strong empirical support, but few studies have compared their effectiveness head-to-head, and none has investigated what to do if the treatment tried first isn’t working well—whether to optimize the treatment already begun or to add the other treatment. Methods This is a single-blind Sequential Multiple Assignment Randomized Trial (SMART) of 24 weeks duration with two levels of randomization, one in each of two 12-week stages. In Stage 1, children will be randomized to fluoxetine or Coping Cat Cognitive Behavioral Therapy (CBT). In Stage 2, remitters will continue maintenance-level therapy with the single-modality treatment received in Stage 1. Non-remitters during the first 12 weeks of treatment will be randomized to either [1] optimization of their Stage 1 treatment, or [2] optimization of Stage 1 treatment and addition of the other intervention. After the 24-week trial, we will follow participants during open, naturalistic treatment to assess the durability of study treatment effects. Patients, 8–17 years of age who are diagnosed with an anxiety disorder, will be recruited and treated within 9 large clinical sites throughout greater Los Angeles. They will be predominantly underserved, ethnic minorities. The primary outcome measure will be the self-report score on the 41-item youth SCARED (Screen for Child Anxiety Related Disorders). An intent-to-treat analysis will compare youth randomized to fluoxetine first versus those randomized to CBT first (“Main Effect 1”). Then, among Stage 1 non-remitters, we will compare non-remitters randomized to optimization of their Stage 1 monotherapy versus non-remitters randomized to combination treatment (“Main Effect 2”). The interaction of these main effects will assess whether one of the 4 treatment sequences (CBT➔CBT; CBT➔med; med➔med; med➔CBT) in non-remitters is significantly better or worse than predicted from main effects alone. Discussion Findings from this SMART study will identify treatment sequences that optimize outcomes in ethnically diverse pediatric patients from underserved low- and middle-income households who have anxiety disorders. Trial registration This protocol, version 1.0, was registered in ClinicalTrials.gov on February 17, 2021 with Identifier: NCT04760275.

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“…This recommendation is based on meta-analysis of adult antidepressant trials that have demonstrated a significant but modest improvement in depression symptoms with higher doses of SSRI pharmacotherapy (Jakubovski, Varigonda, Freemantle, Taylor, & Bloch, 2016). Additionally, a previous trial that examined 29 children who had not responded adequately to 20 mg of fluoxetine at 9 weeks of treatment suggested that raising the dose of fluoxetine to 40-60 mg (response rate 71%) was more effective than maintaining the dose at 20 mg (response rate 36%; Heiligenstein et al, 2006).…”

Section: Defining Adequate Treatmentmentioning

confidence: 99%

Annual Research Review: Defining and treating pediatric treatment‐resistant depression

Dwyer

Stringaris

Brent

et al. 2020

Child Psychology Psychiatry

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Background Adolescent major depressive disorder (MDD) is a significant health problem, associated with substantial morbidity, cost, and mortality. Depression is a significant risk factor for suicide, which is now the second leading cause of death in young people. Up to twenty per cent of adolescents will experience MDD before adulthood, and while a substantial proportion will improve with standard‐of‐care treatments (psychotherapy and medication), roughly one third will not. Methods Here, we have reviewed the literature in order to discuss the concept of treatment‐resistant depression (TRD) in adolescence, examine risk factors, diagnostic difficulties, and challenges in evaluating symptom improvement, and providing guidance on how to define adequate medication and psychotherapy treatment trials. Results We propose a staging model for adolescent TRD and review the treatment literature. The evidence base for first‐ and second‐line treatments primarily derives from four large pediatric clinical trials (TADS, TORDIA, ADAPT, and IMPACT). After two medications and a trial of evidence‐based psychotherapy have failed to alleviate depressive symptoms, the evidence becomes quite thin for subsequent treatments. Here, we review the evidence for the effectiveness of medication switches, medication augmentation, psychotherapy augmentation, and interventional treatments (i.e., transcranial magnetic stimulation, electroconvulsive therapy, and ketamine) for adolescent TRD. Comparisons are drawn to the adult TRD literature, and areas for future pediatric depression research are highlighted. Conclusions As evidence is limited for treatments in this population, a careful consideration of the known risks and side effects of escalated treatments (e.g., mood stabilizers and atypical antipsychotics) is warranted and weighed against potential, but often untested, benefits.

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Fluoxetine 40–60 mg versus Fluoxetine 20 mg in the Treatment of Children and Adolescents with a Less-Than-Complete Response to Nine-Week Treatment with Fluoxetine 10–20 mg: APilot Study

Cited by 35 publications

References 27 publications

New-Generation Antidepressants, Suicide and Depressed Adolescents: How Should Clinicians Respond to Changing Evidence?

New-Generation Antidepressants, Suicide and Depressed Adolescents: How Should Clinicians Respond to Changing Evidence?

A Sequential Multiple Assignment Randomized Trial (SMART) study of medication and CBT sequencing in the treatment of pediatric anxiety disorders

Annual Research Review: Defining and treating pediatric treatment‐resistant depression

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