A Double-blind, Placebo-Controlled Study of Fluvoxamine in Adults With Autistic Disorder

McDougle, Christopher J.; Naylor, Susan T.; Cohen, Donald J.; Volkmar, Fred R.; Heninger, George R.; Price, Lawrence H.

doi:10.1001/archpsyc.1996.01830110037005

Cited by 501 publications

(255 citation statements)

References 49 publications

(2 reference statements)

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“…This suggests that the effect may be clinically meaningful. However, prior findings in adults with autism with fluvoxamine (McDougle et al, 1996b) and clomipramine (Gordon et al, 1993) were even more robust, showing statistical separation in parallel design studies of similar sample size, whereas our study did not reach statistical significance in a post hoc comparison of the first phase only. Since this study was conducted with children and adolescents, dosing levels were kept low, and were thus much lower than doses typically used in adult trials.…”

Section: Discussioncontrasting

confidence: 89%

“…In the only double-blind study of an SSRI in adult autism to date, McDougle et al (1996b) conducted a placebo-controlled study of fluvoxamine and found that 8/15 (53%) patients were responders compared to 0/15 in the placebo group. Significant improvements in repetitive thoughts and behavior, maladaptive behavior, aggression, social relatedness and language usage were reported.…”

Section: Introductionmentioning

confidence: 99%

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

Hollander

Phillips

Chaplin

et al. 2004

Neuropsychopharmacol

344

214

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Repetitive behaviors are a core symptom domain in autism that has been linked to alterations in the serotonin system. While the selective serotonin-receptive inhibitor fluvoxamine has been shown to be effective in adults with autism, as yet no published placebo controlled trials with these agents document safety and efficacy in children with autism. This study examines the selective serotonin reuptake inhibitor liquid fluoxetine in the treatment of repetitive behaviors in childhood and adolescent autism spectrum disorders (ASDs). In total, 45 child or adolescent patients with ASD were randomized into two acute 8-week phases in a double-blind placebocontrolled crossover study of liquid fluoxetine. Study design included two randomized 8-week fluoxetine and placebo phases separated by a 4-week washout phase. Outcome measures included measures of repetitive behaviors and global improvement. Low-dose liquid fluoxetine (mean final dose: 9.974.35 mg/day) was superior to placebo in the treatment of repetitive behaviors by CY-BOCS compulsion scale. The effect size was in the moderate to large range, and the doses used were low. Liquid fluoxetine was only slightly, and not significantly, superior to placebo on CGI autism score partially due to a phase order effect. However, fluoxetine was marginally superior to placebo on a composite measure of global effectiveness. Liquid fluoxetine did not significantly differ from placebo on treatment emergent side effects. Liquid fluoxetine in low doses is more effective than placebo in the treatment of repetitive behaviors in childhood autism. Limitations include small sample size and the crossover design of the study. Further replication and long-term maintenance trials are needed.

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Section: Discussioncontrasting

confidence: 89%

Section: Introductionmentioning

confidence: 99%

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

Hollander

Phillips

Chaplin

et al. 2004

Neuropsychopharmacol

344

214

View full text Add to dashboard Cite

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“…In accordance with previous hypotheses, the results of our study suggest that serotonergic mechanisms may play a role in the pathophysiology of autism. As described in the Introduction, evidence that the serotonergic system is involved in the pathophysiology of autism comes from pharmacological studies with SSRIs (McDougle et al 1996a), behavioral research, such as results of tryptophan depletion techniques (McDougle et al 1996b), molecular biology (Cook and Leventhal 1996;Cook et al 1997) and brain imaging (Chugani et al 1997(Chugani et al , 1999.…”

Section: Discussionmentioning

confidence: 99%

“…Selective 5-HT reuptake inhibitors (SSRIs), have beneficial effects in the treatment of some individuals with autism (McDougle et al 1996a). Tryptophan depletion techniques result in a significant increase in autistic behaviours (McDougle et al 1996b). PET-scan studies revealed decreased 5-HT synthesis in frontal cortex and thalamus, but elevated 5-HT synthesis in the contra-lateral dentate nucleus (Chugani et al 1997).…”

Section: Serotonin (5-ht)mentioning

confidence: 99%

Peripheral Markers of Serotonergic and Noradrenergic Function in Post-Pubertal, Caucasian Males with Autistic Disorder

Croonenberghs

Delmeire²,

Verkerk³

et al. 2000

Neuropsychopharmacology

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Some studies have suggested that disorders in the peripheral and central metabolism of serotonin (5-HT) and noradrenaline may play a role in the pathophysiology of autistic disorder. This study examines serotonergic and noradrenergic markers in a study(5-15 per 10.000) and is four times more common in boys than in girls. Research on the biological pathophysiology of autism has found some evidence for a role of the turnover of serotonin (5-HT) and catecholamines.

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“…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%

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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A Double-blind, Placebo-Controlled Study of Fluvoxamine in Adults With Autistic Disorder

Abstract: Fluvoxamine is more effective than placebo in the short-term treatment of the symptoms of autistic disorder in adults. Controlled studies of fluvoxamine and other potent and selective serotonin uptake inhibitors seem warranted in children and adolescents with autism.

Cited by 501 publications

References 49 publications

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

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

Peripheral Markers of Serotonergic and Noradrenergic Function in Post-Pubertal, Caucasian Males with Autistic Disorder

Obsessive–compulsive traits in children and adolescents with Asperger syndrome

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