Fluoxetine for Acute Treatment of Depression in Children and Adolescents: A Placebo-Controlled, Randomized Clinical Trial

Emslie, Graham J.; Heiligenstein, John H.; Wagner, Karen Dineen; Hoog, Sharon L.; Ernest, D.; Brown, Eileen; Nilsson, Mary; Jacobson, Jennie G.

doi:10.1097/00004583-200210000-00010

Cited by 489 publications

(319 citation statements)

References 25 publications

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“…TCAs have not been shown to be effective in general in adolescents (Geller et al, 1999;Hazell et al, 2002), or in depressed adolescents with atypical features whereas SSRIs have generally not been effective for depressive illness in children (Mandoki et al, 1997;Keller et al, 2001;Whittington et al, 2004;Wagner et al, 2006) except fluoxetine (Emslie et al, 1997;Emslie et al, 2002;Whittington et al, 2004). The early onset of depressive illness in patients suffering from atypical features likely results in an increased percentage of atypical depression among depressed teenagers, perhaps accounting for these findings.…”

Section: Discussionmentioning

confidence: 99%

DSM-IV Depression with Atypical Features: Is It Valid?

Stewart

McGrath

Quitkin³

et al. 2009

Neuropsychopharmacol

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Atypical features were incorporated into the American Psychiatric Association's Diagnostic and Statistical Manual, Fourth Edition (DSM-IV, 1994) as an illness specifier for major depression and dysthymia. The validity of depression with atypical features was supported by differences relative to depression with melancholic features in syndromal symptoms, course of illness, biology, family history, and treatment response. This paper reviews post-DSM-IV literature relevant to the validity of depression with atypical features. Most studies support the pre-DSM-IV findings. Again, course of illness, biological, family, and treatment differences are shown between melancholia and depression with atypical features. Several biologic studies report nondepressed controls have mean values between depressed subjects having atypical features and other depressed patients. This suggests atypical depression is a distinct depressive group rather than a milder form of melancholia. In addition, some studies show distinctions between depressed subjects with atypical features and those having neither atypical nor melancholic features. As depression with atypical features separates not only from melancholia but also from other depressed groups and controls over a range of meaningful distinctions, we conclude it is a valid clinical syndrome, useful both heuristically and in driving treatment decisions.

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Section: Discussionmentioning

confidence: 99%

DSM-IV Depression with Atypical Features: Is It Valid?

Stewart

McGrath

Quitkin³

et al. 2009

Neuropsychopharmacol

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“…Racemic fluoxetine is an antidepressant with well-documented efficacy (Emslie et al, 2002;Cheer and Goa, 2001), pharmacokinetics (Bergstrom et al, 1992(Bergstrom et al, , 1993, and therapeutic dose range Schmidt et al, 2002). Despite its widespread use, fluoxetine's inhibition of the cytochrome P450 IID6 isoenzyme (CYP2D6), implicated in drug interactions with certain other medications, and its side effects (eg sexual dysfunction, apathy) have demonstrated the need for antidepressant agents with shorter elimination half-lives, fewer drug-drug interactions, and a more benign side effect profile (Vandel, 2003).…”

Section: Introductionmentioning

confidence: 99%

A Comparison of Brain and Serum Pharmacokinetics of R-Fluoxetine and Racemic Fluoxetine: A 19-F MRS Study

Henry

Schmidt

Hennen

et al. 2005

Neuropsychopharmacol

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Racemic fluoxetine consists of R-and S-fluoxetine, which are metabolized to R-and S-norfluoxetine, respectively. This study was designed to compare brain levels achieved with R-fluoxetine to those achieved with racemic fluoxetine in healthy subjects using fluorine-19 (19-F) magnetic resonance spectroscopy (MRS). In all, 13 healthy volunteers received study drug for 5 weeks using a dosing schedule designed to achieve steady state for 20 mg/day racemic fluoxetine, 80 mg/day R-fluoxetine, or 120 mg/day R-fluoxetine. The resulting brain drug levels were measured using 19-F MRS. At 5 weeks, the racemate, 80 and 120 mg/day R-fluoxetine groups had mean brain levels of 25.5, 34.9, and 41.4 mM, respectively. In the serum, R-norfluoxetine, which is thought to be an inactive metabolite, accounted for 17, 71, and 63% of the fluoxetine/norfluoxetine concentration, respectively. When the relative proportion of active to total species in serum are taken into account, the data suggest that doses of R-fluoxetine greater than 120 mg/day would be needed to achieve brain levels of active drug comparable to 20 mg/day of racemate. The 120 mg/day R-fluoxetine group experienced a mean increase in QTc interval of 44 ms, with one individual having an increase of 89 ms, which suggests that higher doses may not be tolerable. While these data support the use of MRS to aid in defining the therapeutic dose range for drug development, they also highlight the need for additional studies with concurrent animal models to establish the validity of using serum drug/metabolite ratios to interpret MRS determined brain drug levels.

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“…We compared the performance and psychometric properties of the CDRS-R and the MADRS in a group of children (n=96) enrolled in a 9-week, randomized, double-blind, placebocontrolled trial (Emslie et al 2002) for which CDRS-R was the primary outcome.…”

Section: Discussionmentioning

confidence: 99%

“…This report is based on a dataset generated in a previously reported 9-week acute trial (Emslie et al 2002) of children and adolescents (n=219) with nonpsychotic major depressive disorder (MDD) (single or recurrent) who were randomized to fluoxetine or placebo. For this report, we focus on children (ages 8 to 11 inclusive) (n=96).…”

Section: Methodsmentioning

confidence: 99%

“…The participants had normal cardiograms, hematological and blood chemistry studies, and urinalyses at baseline with no significant medical comorbidities. Participants with first-degree relatives with history of bipolar disorder were excluded, as were those who had used neuroleptic or monoamine oxidase inhibitors within two weeks prior to study entry (Emslie et al 2002). Parents or legal guardians of all participants provided written informed consent prior to study entry.…”

Section: Participantsmentioning

confidence: 99%

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A Psychometric Evaluation of the CDRS and MADRS in Assessing Depressive Symptoms in Children

Jain

Carmody

Trivedi

et al. 2007

Journal of the American Academy of Child & Adolescent Psych

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Objective-This study compared the psychometric properties of the Children's Depression Rating Scale-Revised (CDRS-R) and the Montgomery-Asberg Depression Rating Scale (MADRS) in children with major depressive disorder (MDD).Method-Children (n=96) (8-11 years inclusive) with nonpsychotic MDD were enrolled. Participants were part of a multisite, outpatient, randomized, placebo-controlled, 9-week trial of fluoxetine (10 mg/day for the first week and 20 mg/day thereafter). The CDRS-R and MADRS were completed based on clinician interviews with both parents and children. Classical Test Theory and Item Response Theory analyses were conducted. Results-The MADRS and CDRS-R total scores were correlated at baseline (r=0.51) and at study exit (0.85). The Cronbach's alpha was 0.86 (CDRS-R) and 0.82 (MADRS) at exit. The effect sizes for change from baseline to exit between the fluoxetine and placebo groups were 0.78 (CDRS-R) and 0.61 (MADRS). Agreement between the CDRS-R and MADRS in the declaration of treatment response (50% improvement from baseline to exit) occurred in 84.2% of children. Test information function favored the CDRS-R. Conclusion-The CDRS-R showed greater effect size for differentiating drug and placebo and better test information than the MADRS in this study of depressed children.

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Fluoxetine for Acute Treatment of Depression in Children and Adolescents: A Placebo-Controlled, Randomized Clinical Trial

Cited by 489 publications

References 25 publications

DSM-IV Depression with Atypical Features: Is It Valid?

DSM-IV Depression with Atypical Features: Is It Valid?

A Comparison of Brain and Serum Pharmacokinetics of R-Fluoxetine and Racemic Fluoxetine: A 19-F MRS Study

A Psychometric Evaluation of the CDRS and MADRS in Assessing Depressive Symptoms in Children

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