A Placebo Controlled Crossover Trial of Liquid Fluoxetine on Repetitive Behaviors in Childhood and Adolescent Autism

Hollander, Eric; Phillips, Ann; Chaplin, William F.; Zagursky, Karen; Novotny, Sherie; Wasserman, Stacey; Iyengar, Rupa

doi:10.1038/sj.npp.1300627

Cited by 344 publications

(221 citation statements)

References 26 publications

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“…In the author's opinion, the sub-threshold OC symptoms detected in our AS sample might be read as the sign of a phenomenological and possibly neurobiological overlap between ASD and OCD according to the concept of a broader spectrum of OC-related disorders, in line with previous bibliography [4]. This model seems sustained by some evidence derived from the association between ASD and OCD in family studies [1,14] and by some findings from clinical trials of a positive pharmacologic treatment response to SRIs in ASD [15,24,25].…”

Section: Resultssupporting

confidence: 82%

“…Higher prevalence of autistic traits has been found in OCD samples both in adults [5,6] and children [16], and some evidence suggests that treatments effective for OCD may be effective for repetitive thoughts and behaviours in ASD as well [15,19,24,25]. Also, family studies have reported an association between restrictive or repetitive behaviours in probands with autism and obsessive-compulsive features in parents both in multiplex [14] and sporadic autism families [1].…”

Section: Introductionmentioning

confidence: 99%

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Obsessive–compulsive traits in children and adolescents with Asperger syndrome

Ruta

Mugno

D'Arrigo

et al. 2009

Eur Child Adolesc Psychiatry

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The objective of this study is to examine the occurrence and characteristic features of obsessive-compulsive behaviours in children and adolescents with Asperger syndrome (AS), with respect to a matched obsessive compulsive disorder group (OCD) and a typically developing control group (CG). For this purpose, 60 subjects (20 OCD; 18 AS; 22 CG), aged 8-15 years, matched for age, gender and IQ were compared. AS and OCD patients were diagnosed according to the DSM-IV-TR criteria. The Autism Diagnostic Interview-Revised and the Autism Diagnostic Observation Schedule were used to assist in the AS diagnosis; the WISC-R was administered to assess IQ. Obsessive and compulsive symptoms were evaluated by using the Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS). None of the AS children received a formal diagnosis of OCD. The AS group presented significantly higher frequencies of Hoarding obsessions and Repeating, Ordering and Hoarding compulsions compared to CG. The OCD group, in turn, reported significantly higher frequencies of Contamination and Aggressive obsessions and Checking compulsions compared to both the AS group and CG. As expected, the OCD group displayed a higher severity of symptoms (Moderate level of severity) than did the AS group (Mild level of severity). Finally, in our sample, neither the OCD group nor the AS group demonstrated a completely full awareness of the intrusive, unreasonable and distressing nature of symptoms, and the level of insight did not differ between the OCD group and CG, although an absence of insight was observed in the AS group. Children with AS showed higher frequencies of obsessive and compulsive symptoms than did typically developing children, and these features seem to cluster around Hoarding behaviours. Additionally, different patterns of symptoms emerged between the OCD and AS groups. Finally, in our sample, the level of insight was poor in both the OCD and the AS children. Further research should be conducted to better understand the characteristics of repetitive thoughts and behaviours in autism spectrum disorders, and to clarify the underlying neurobiological basis of these symptoms.

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Section: Resultssupporting

confidence: 82%

Section: Introductionmentioning

confidence: 99%

Obsessive–compulsive traits in children and adolescents with Asperger syndrome

Ruta

Mugno

D'Arrigo

et al. 2009

Eur Child Adolesc Psychiatry

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“…8,9 In addition, selective serotonin reuptake inhibitors (SSRIs) and atypical antipsychotic medications, which are often effective in autism to treat disruptive anxiety-related behaviors and aggression, respectively, act on the serotonin system. 10,11 Data thus suggest that at least some of the serotonin dysregulation in autism families is not secondary to autism, but rather may inform us about a heritable predisposing factor.…”

Section: Introductionmentioning

confidence: 99%

Variation in ITGB3 is associated with whole-blood serotonin level and autism susceptibility

et al. 2006

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Autism is a pervasive developmental disorder affecting more males than females. Heritability estimates for autism can rise above 90%, and genes influencing the serotonin system are strong candidates for autism susceptibility genes, as drugs selectively acting on the serotonin system are some of the most effective treatments for maladaptive behaviors seen in autism. ITGB3 was recently identified as a male quantitative trait locus (QTL) for whole-blood serotonin levels in the Hutterites (P ¼ 0.0003). Here, we demonstrate associations between variation in ITGB3 and serotonin levels in two outbred samples (P ¼ 0.010 and 0.015). Lastly, we show that a coding variant of ITGB3 is associated with autism susceptibility in a large multiplex sample (P ¼ 0.00082), and that this variation has different effects in males and females (P ¼ 0.0018).

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“…35 Three of these 5 published trials reported a statistically significant benefit of SRI treatment in ASD. [46][47]49 Two published trials and the 1 available unpublished trial reported some or no benefit of antidepressant treatment. 35,48,50 Efficacy of SRI Treatment of Autism Our literature search first alerted us to the presence of 5 completed studies that were possibly eligible for inclusion in this meta-analysis but remained unpublished at the time the manuscript was put together, thus suggesting the presence of publication bias in the field.…”

Section: Included Studiesmentioning

confidence: 99%

“…Table 1 presents the characteristics of the 5 published trials [46][47][48][49][50] and the 1 unpublished trial included in this meta-analysis. 35 Three of these 5 published trials reported a statistically significant benefit of SRI treatment in ASD.…”

Section: Included Studiesmentioning

confidence: 99%

Pharmacologic Treatment of Repetitive Behaviors in Autism Spectrum Disorders: Evidence of Publication Bias

2012

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WHAT'S KNOWN ON THIS SUBJECT: Although several randomized trials have examined the efficacy of serotonin receptor inhibitors in the treatment of repetitive behaviors, there still remains clinical uncertainty as to whether these agents are effective in treating such behaviors in children and adults with autism spectrum disorders. WHAT THIS STUDY ADDS:The goal of this meta-analysis was to examine randomized trials of serotonin receptor inhibitors for treating repetitive behaviors in autism spectrum disorders. Although a small but significant effect of these agents was observed, this effect is likely due to the selective publication of trial results.abstract OBJECTIVE: The goal of this study was to examine the efficacy of serotonin receptor inhibitors (SRIs) for the treatment of repetitive behaviors in autism spectrum disorders (ASD). METHODS:Two reviewers searched PubMed and Clinicaltrials.gov for randomized, double-blind, placebo-controlled trials evaluating the efficacy of SRIs for repetitive behaviors in ASD. Our primary outcome was mean improvement in ratings scales of repetitive behavior. Publication bias was assessed by using a funnel plot, the Egger' s test, and a metaregression of sample size and effect size. RESULTS: Our search identified 5 published and 5 unpublished but completed trials eligible for meta-analysis. Meta-analysis of 5 published and 1 unpublished trial (which provided data) demonstrated a small but significant effect of SRI for the treatment of repetitive behaviors in ASD (standardized mean difference: 0.22 [95% confidence interval: 0.07-0.37], z score = 2.87, P , .005). There was significant evidence of publication bias in all analyses. When Duval and Tweedie' s trim and fill method was used to adjust for the effect of publication bias, there was no longer a significant benefit of SRI for the treatment of repetitive behaviors in ASD (standardized mean difference: 0.12 [95% confidence interval: -0.02 to 0.27]). Secondary analyses demonstrated no significant effect of type of medication, patient age, method of analysis, trial design, or trial duration on reported SRI efficacy.CONCLUSIONS: Meta-analysis of the published literature suggests a small but significant effect of SRI in the treatment of repetitive behaviors in ASD. This effect may be attributable to selective publication of trial results. Without timely, transparent, and complete disclosure of trial results, it remains difficult to determine the efficacy of available medications. Pediatrics 2012;129:e1301-e1310

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A Placebo Controlled Crossover Trial of Liquid Fluoxetine on Repetitive Behaviors in Childhood and Adolescent Autism

Cited by 344 publications

References 26 publications

Obsessive–compulsive traits in children and adolescents with Asperger syndrome

Obsessive–compulsive traits in children and adolescents with Asperger syndrome

Variation in ITGB3 is associated with whole-blood serotonin level and autism susceptibility

Pharmacologic Treatment of Repetitive Behaviors in Autism Spectrum Disorders: Evidence of Publication Bias

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