Risk of adverse behavioral effects with pediatric use of antidepressants

Goodman, Wayne K.; Murphy, Tanya K.; Storch, Eric A.

doi:10.1007/s00213-006-0642-6

Cited by 69 publications

(45 citation statements)

References 62 publications

(80 reference statements)

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“…Recent safety concerns have focused on the increased risk of suicidal behavior among children and adolescents treated with SSRIs (Hammad 2004;Whittington et al 2004;Leslie et al 2005). While suicidal ideation and attempts (SI=SA) are important adverse events, the development of behavioral adverse events from these medications is even more common among children and adolescents (Safer and Zito 2006;Goodman et al 2007). Although it has been speculated that behavioral adverse events, commonly referred to as ''activation,'' may be related to SI=SA, the evidence remains scant (Teicher et al 1993;Wong et al 2004).…”

Section: Introductionmentioning

confidence: 99%

Activation Adverse Events Induced by the Selective Serotonin Reuptake Inhibitor Fluvoxamine in Children and Adolescents

Reinblatt

dosReis

Walkup

et al. 2009

Journal of Child and Adolescent Psychopharmacology

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Objective: The aim of this study was to examine the prevalence of activation cluster adverse events (AC-AEs) in youths treated with the selective serotonin reuptake inhibitor (SSRI) fluvoxamine for anxiety and the relationship of AC-AEs to SSRI blood levels. Methods: Data from the Research Units on Pediatric Psychopharmacology (RUPP) Anxiety Study were examined for 45 youths (22 active fluvoxamine, 23 placebo) treated for Diagnostic and Statistical Manual for Mental Disorders, 4 th edition (DSM-IV) anxiety disorders at the Johns Hopkins University site with an 8-week forced-flexible titration schedule. As part of the double-blind placebo-controlled trial, AC-AEs were recorded by clinicians at weekly patient visits. AC-AEs were defined as hyperactivity, activation, and disinhibition. Demographic characteristics, daily doses, and week-8 blood levels were examined in relation to the presence of AC-AEs. The prevalence of AC-AE and time to first event were established for those who experienced this side effect. Results: AC-AEs were found in 10 of 22 participants (45%) receiving fluvoxamine and only 1 of 23 in the placebo group (4%). The onset of AC-AEs occurred from week 1 to week 8, with the majority occurring at or before week 4. The mean fluvoxamine blood level at week 8 in subjects with AC-AEs was higher than in subjects without AC-AEs (n ¼ 16, t ¼ À2.61, p ¼ 0.04). Neither the age of the participants nor family history of bipolar or anxiety disorder differed between those who did and did not develop an AC-AE. Conclusions: AC-AEs were common side effects of fluvoxamine, often appeared during the first 8 weeks of treatment, and were associated with higher fluvoxamine blood levels. Close monitoring for AC-AEs, not only when initiating SSRI treatment but also throughout dose titration, is recommended for early identification of activation.

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Section: Introductionmentioning

confidence: 99%

Activation Adverse Events Induced by the Selective Serotonin Reuptake Inhibitor Fluvoxamine in Children and Adolescents

Reinblatt

dosReis

Walkup

et al. 2009

Journal of Child and Adolescent Psychopharmacology

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“…Independent review of adverse events from data from 24 placebo-controlled trials of AD use in children and adolescents found that suicidality significantly increased with SSRI treatment compared to placebo, leading the FDA to issue a “black box” warning (see Brent, 2004; Goodman et al , 2007; Newman, 2004). Additional studies have likewise found evidence of increased suicidality with use of SSRIs in juveniles, suggesting that there may be an unfavorable risk to benefit ratio for SSRIs (with fluoxetine as a possible exception) (Bailly, 2008; Barbui et al , 2009; Bridge et al , 2007; Cipriani et al , 2005; Doggrell, 2005; Fergusson et al , 2005; Goodman et al , 2007; Hammad et al , 2006; Laughren, 2006; Mosholder and Willy, 2006; Olfson and Marcus, 2008; Olfson et al , 2006; Richmond and Rosen, 2005; Ryan, 2005; Scahill et al , 2005; Tiihonen et al , 2006; Vitiello and Swedo, 2004; Whittington et al , 2004; Wohlfarth et al , 2006). Many of these and other studies have pointed out difficulties in interpretation of the data and have stated that there is considerable risk for suicidality if pediatric patients are not adequately treated (e.g., Bridge et al , 2007; Mann et al , 2006).…”

Section: Discussionmentioning

confidence: 99%

Paroxetine-Induced Increase in Activity of Locus Coeruleus Neurons in Adolescent Rats: Implication of a Countertherapeutic Effect of an Antidepressant

West

Ritchie

Weiss

2010

Neuropsychopharmacol

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Concern that antidepressant (AD) drugs, especially selective serotonin reuptake inhibitors and paroxetine (PAR) in particular, can increase suicidality during the early treatment of juvenile patients (children and adolescents) has created a dilemma for clinicians treating depressives. Though preclinical research cannot resolve controversy in this area, our present findings may provide insight into how AD drugs might, under certain conditions, exacerbate rather than ameliorate the depressive state. Both clinical and preclinical evidence indicates that the principle noradrenergic cell group in the brain, the locus coeruleus (LC), is over-active in depressives and that, conversely, effective AD treatments decrease activity of LC neurons. We report here that short-term (2 and 4 day) administration of PAR produces an increase in the activity of LC neurons (spontaneous firing rate and sensory-evoked responses) in young rats, contrary to the “therapeutic” decrease in activity typically observed in adult rats. Blood levels of PAR were lower in young rats than in adult rats, though similar low blood levels produced by a lower dose of PAR in adult rats failed to produce an increase in LC activity. Additionally, activity of young rats in the swim test was determined to assess depressive-like responses. The same dose/durations of PAR which produced the largest increases in LC activity in young rats produced decreases in swim-test activity, indicating that brief administration of PAR in young rats can promote, rather than reduce, the depressive state. These results offer a model which may help screen potential adjunctive treatments to avoid early adverse effects of ADs.

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“…Unfortunately, efforts to enhance outcomes by combining CBT with SRI medications have been inconsistent, with some studies finding that the addition of SRIs does not lead to substantially stronger effects than would be obtained with CBT alone (e.g., Foa et al 2005). Furthermore, though SRIs are effective, concerns about suicidality and other symptoms of behavioral activation secondary to use (e.g., Goodman et al 2007;Whittington et al 2004) have prompted the need for alternative means of augmentation.…”

Section: Cognitive-behavioral Therapymentioning

confidence: 98%

D-Cycloserine Augmentation of Cognitive-Behavioral Therapy: Directions for Pilot Research in Pediatric Obsessive-Compulsive Disorder

Storch

McKay

Reid

et al. 2010

Child Youth Care Forum

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This paper discusses a recent translational success in combining behavioral psychotherapy with a novel medication, d-cycloserine (DCS), to augment cognitivebehavioral therapy (CBT) for anxiety disorders. The literature on behavioral theory of exposure-based therapies is provided, followed by a discussion of the role of DCS in enhancing extinction learning that is core to such therapies. As well, pragmatic issues such as dosing and timing are discussed. The manuscript is concluded with consideration of future directions in DCS augmentation in the form of a pilot trial investigating DCS augmentation of CBT in pediatric patients with obsessive-compulsive disorder.

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Risk of adverse behavioral effects with pediatric use of antidepressants

Abstract: Empirical studies are needed to identify the precursors of suicidality and to predict which individuals are most susceptible to adverse behavioral side effects of antidepressants.

Cited by 69 publications

References 62 publications

Activation Adverse Events Induced by the Selective Serotonin Reuptake Inhibitor Fluvoxamine in Children and Adolescents

Activation Adverse Events Induced by the Selective Serotonin Reuptake Inhibitor Fluvoxamine in Children and Adolescents

Paroxetine-Induced Increase in Activity of Locus Coeruleus Neurons in Adolescent Rats: Implication of a Countertherapeutic Effect of an Antidepressant

D-Cycloserine Augmentation of Cognitive-Behavioral Therapy: Directions for Pilot Research in Pediatric Obsessive-Compulsive Disorder

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