fluvoxamine and Autistic-Disorder

Autism spectrum disorders (ASD) are characterised by abnormalities in social interaction and communication skills, as well as stereotypic behaviours and restricted activities and interests. Selective serotonin reuptake inhibitors (SSRIs) are prescribed for the treatment of conditions often comorbid with ASD such as depression, anxiety and obsessive-compulsive behaviours.. To determine if treatment with an SSRI:1. improves the core features of autism (social interaction, communication and behavioural problems);2. improves other non-core aspects of behaviour or function such as self-injurious behaviour;3. improves the quality of life of adults or children and their carers;4. has short- and long-term effects on outcome;5. causes harm.. We searched the following databases up until March 2013: CENTRAL, Ovid MEDLINE, Embase, CINAHL, PsycINFO, ERIC and Sociological Abstracts. We also searched ClinicalTrials.gov and the International Clinical Trials Registry Platform (ICTRP). This was supplemented by searching reference lists and contacting known experts in the field.. Randomised controlled trials (RCTs) of any dose of oral SSRI compared with placebo, in people with ASD.. Two authors independently selected studies for inclusion, extracted data and appraised each study's risk of bias.. Nine RCTs with a total of 320 participants were included. Four SSRIs were evaluated: fluoxetine (three studies), fluvoxamine (two studies), fenfluramine (two studies) and citalopram (two studies). Five studies included only children and four studies included only adults. Varying inclusion criteria were used with regard to diagnostic criteria and intelligence quotient of participants. Eighteen different outcome measures were reported. Although more than one study reported data for Clinical Global Impression (CGI) and obsessive-compulsive behaviour (OCB), different tool types or components of these outcomes were used in each study. As such, data were unsuitable for meta-analysis, except for one outcome (proportion improvement). One large, high-quality study in children showed no evidence of positive effect of citalopram. Three small studies in adults showed positive outcomes for CGI and OCB; one study showed improvements in aggression, and another in anxiety.. There is no evidence of effect of SSRIs in children and emerging evidence of harm. There is limited evidence of the effectiveness of SSRIs in adults from small studies in which risk of bias is unclear.

Topics: Adult; Age Factors; Autistic Disorder; Child; Child Development Disorders, Pervasive; Citalopram; Fenfluramine; Fluoxetine; Fluvoxamine; Humans; Obsessive-Compulsive Disorder; Randomized Controlled Trials as Topic; Selective Serotonin Reuptake Inhibitors

Autism spectrum disorders (ASD) are characterised by abnormalities in social interaction and communication skills, as well as stereotypic behaviours and restricted activities and interests. Selective serotonin reuptake inhibitors (SSRIs) are prescribed for the treatment of co-morbidity associated with ASD such as depression, anxiety and obsessive-compulsive behaviours.. To determine if treatment with an SSRI: 1. improves the core features of autism (social interaction, communication and behavioural problems); 2. improves other non-core aspects of behaviour or function such as self-injurious behaviour; 3. improves the quality of life of children and their carers; 4. has short and long term effects on outcome; 5. causes harms.. We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library 2009, Issue 4), MEDLINE ( December 2009), EMBASE (December 2009), CINAHL (December 2009), PsycINFO (December 2009) and ERIC (December 2009), without language restrictions.. Randomised controlled trials (RCTs) of any dose of oral SSRI compared with placebo, in participants with autism spectrum disorders. Trials must have included at least one standardised outcome measure.. Two authors independently selected and appraised studies for inclusion and risk of bias. All data were continuous. Meta-analysis, where possible, used a random-effects model.. Seven RCTs with a total of 271 participants were included. Four SSRIs were evaluated: fluoxetine (two studies), fluvoxamine (two studies), fenfluramine (two studies) and citalopram (one study). Five studies included only children and two studies included only adults. Varying inclusion criteria were used with regard to diagnostic criteria and intelligence of participants. Seventeen different outcome measures were reported. Although more than one study reported data for Clinical Global Impression (CGI) and obsessive-compulsive behaviour (OCB), different tool types or components of these outcomes were used in each study. As such, data were unsuitable for meta-analysis. One large, high quality study in children showed no evidence of positive effect of citalopram. Two small studies in adults showed positive outcomes for CGI and OCB; one study showed improvements in aggression and another in anxiety.. There is no evidence of effect of SSRIs in children and emerging evidence of harm. There is limited evidence of the effectiveness of SSRIs in adults from small studies in which risk of bias is unclear.

Topics: Adult; Age Factors; Autistic Disorder; Child; Citalopram; Fenfluramine; Fluoxetine; Fluvoxamine; Humans; Obsessive-Compulsive Disorder; Randomized Controlled Trials as Topic; Selective Serotonin Reuptake Inhibitors

To review literature describing use of selective serotonin-reuptake inhibitors (SSRIs) in the management of functional impairments associated with autistic disorder.. EMBASE (1980-3rd quarter of 2003), International Pharmaceutical Abstracts (1970-August 2003), and MEDLINE (1966-August 2003) were searched. Search terms included autism, autistic disorder, citalopram, fluoxetine, fluvoxamine, paroxetine, selective serotonin-reuptake inhibitors, and sertraline.. Studies and case reports evaluating treatment outcomes associated with the use of SSRIs in managing impairments of autism were reviewed. Multiple SSRI dosing ranges were evaluated in autistic patients of different ages with various functional impairments. No specific SSRI or dose range has been shown to improve a specific autistic symptom although some patients have demonstrated improvements.. Benefits with SSRIs in treating functional impairments in autism have been observed. Response to therapy and adverse effects are individualized. Current evidence does not support selection of one SSRI over another for any impairment associated with autism.

Topics: Autistic Disorder; Citalopram; Clinical Trials as Topic; Fluoxetine; Fluvoxamine; Humans; Paroxetine; Retrospective Studies; Selective Serotonin Reuptake Inhibitors; Sertraline

We studied the correlation between response to fluvoxamine and serotonin transporter gene promoter region polymorphism (5-HTTLPR). Eighteen children with autistic disorder completed a 12-week double-blind, placebo-controlled, randomized crossover study of fluvoxamine. Behavioral assessments were obtained before and at 12 weeks of treatment. 5-HTTLPR (long (l) or short(s)), was analyzed by the PCR method. Ten out of 18 patients responded to fluvoxamine treatment; allele type analysis revealed that clinical global effectiveness was noted significantly more in the l allele than in the s allele. However, with respect to language use, a significant effectiveness was noted in the s allele. 5-HTTLPR may influence the individual responses to fluvoxamine administration.

Topics: Alleles; Autistic Disorder; Child; Child, Preschool; Cross-Over Studies; Double-Blind Method; Fluvoxamine; Gene Expression; Genotype; Humans; Polymorphism, Genetic; Promoter Regions, Genetic; Selective Serotonin Reuptake Inhibitors; Serotonin Plasma Membrane Transport Proteins

Autistic disorder is characterized by a fundamental disturbance in social interaction, impairments in communication, and a markedly restricted repertoire of activities and interests. Abnormalities in the serotonin neurotransmitter system have been identified in some persons with autism. No consistently effective and safe drugs have been developed for treating the symptoms of autism.. Thirty adults with autistic disorder completed a 12-week double-blind, placebo-controlled trial of the potent and selective serotonin uptake inhibitor fluvoxamine maleate. Behavioral ratings were obtained at baseline and after 4, 8, and 12 weeks of treatment.. Eight (53%) of 15 patients in the fluvoxamine-treated group were categorized as responders compared with none of 15 in the placebo group (P = .001). Fluvoxamine was superior to placebo in reducing repetitive thoughts and behavior (P < .001), maladaptive behavior (P < .001), and aggression (P < .03), and in improving some aspects of social relatedness (P < .04), especially language usage (P < .008). Treatment response was not correlated with age level of autistic behavior, or full-scale IQ. Other than mild sedation and nausea in a few patients, fluvoxamine was well tolerated. No dyskinesias, adverse cardiovascular events, or seizures occurred.. 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.

Topics: Adolescent; Adult; Autistic Disorder; Double-Blind Method; Female; Fluvoxamine; Humans; Male; Middle Aged; Placebos; Psychiatric Status Rating Scales; Selective Serotonin Reuptake Inhibitors; Treatment Outcome

Selective serotonin re-uptake inhibitors (SSRIs) have recently been applied to the children with autistic disorder. To create better treatment, we studied here clinical adverse effects of fluvoxamine and correlated them with genetic polymorphism of two genes, the promoter region of serotonin transporter gene (5-HTTLPR) and serotonin 2A receptor gene (5-HT2AR). Twenty-eight subjects, consisting of 23 boys and 5 girls, aged from 3 to 18 years old diagnosed as having autistic disorder were analyzed during fluvoxamine administration. The dosages and duration of fluvoxamine treatment are 1.5 to 3 mg/kg/day and 2 weeks to 17 months (mean 7.9 months), respectively. There were several clinical adverse effects such as sleep disturbance in 9 cases, climb up to high places in 8, gastrointestinal symptoms in 6, hyperactivities in 5, excitement in 4, general fatigability in 2 and urticaria in 1. Medication was discontinued in 2 patients with fatigability and 1 with sleep disturbance, diarrhea and poor appetite. There was no significant correlation between genetic polymorphism in 5-HTTLPR and the occurrence of clinical adverse effects of fluvoxamine. However hyperactivity was significantly more frequent in the subjects with 102T/102T polymorphism of 5-HT2AR, and patients with sleep disturbance were significantly less frequent in the subjects with 102C/102C polymorphism. We conclude that the clinical adverse effects such as climb up to high places and hyperactivity during fluvoxamine treatment may be relatively specific in children, and that genetic polymorphism of 5-HT2AR may be related to the appearance of clinical adverse effects.

Topics: Adolescent; Autistic Disorder; Carrier Proteins; Child; Child, Preschool; Female; Fluvoxamine; Humans; Male; Membrane Glycoproteins; Membrane Transport Proteins; Nerve Tissue Proteins; Polymorphism, Genetic; Promoter Regions, Genetic; Receptor, Serotonin, 5-HT2A; Receptors, Serotonin; Selective Serotonin Reuptake Inhibitors; Serotonin Plasma Membrane Transport Proteins

Pediatric populations, including those with autistic disorder or other pervasive developmental disorders, increasingly are being prescribed selective serotonin reuptake inhibitors (SSRIs). Little is known about the age-related brain pharmacokinetics of SSRIs; there is a lack of data regarding optimal dosing of medications for children. The authors used fluorine magnetic resonance spectroscopy ((19)F MRS) to evaluate age effects on whole-brain concentrations of fluvoxamine and fluoxetine in children taking SSRIs.. Twenty-one pediatric subjects with diagnoses of autistic disorder or other pervasive developmental disorders, 6-15 years old and stabilized with a consistent dose of fluvoxamine or fluoxetine, were recruited for the study; 16 successfully completed the imaging protocol. Whole-brain drug levels in this group were compared to similarly acquired data from 28 adults.. A significant relationship between dose and brain drug concentration was observed for both drugs across the age range studied. Brain fluvoxamine concentration in the children was lower, consistent with a lower dose/body mass drug prescription; when brain concentration was adjusted for dose/mass, age effects were no longer significant. Brain fluoxetine concentration was similar between age groups; no significant age effects on brain fluoxetine drug levels remained after adjustment for dose/mass. Observations of brain fluoxetine bioavailability and elimination half-life also were similar between age groups.. These findings suggest that fluvoxamine or fluoxetine prescriptions adjusted for dose/mass are an acceptable treatment approach for medicating children with autistic disorder or other pervasive developmental disorders. It must be determined whether these findings can be generalized to other pediatric populations.

Topics: Adolescent; Adult; Age Factors; Autistic Disorder; Brain; Brain Chemistry; Child; Child Development Disorders, Pervasive; Depressive Disorder; Dose-Response Relationship, Drug; Fluorine; Fluoxetine; Fluvoxamine; Half-Life; Humans; Magnetic Resonance Spectroscopy; Middle Aged; Obsessive-Compulsive Disorder; Panic Disorder; Selective Serotonin Reuptake Inhibitors

Five autistic children underwent fluovoxamine administration. Their self-injury and aggressive behaviors did not respond psychotherapy and other medication with haloperidol, carbamazepine. The improvement of the behaviors was excellent in two patients, and partial in one patient. In a patient who received a combination of haloperidol and fluvoxamine, fluvoxamine treatment was discontinued because of severe drowsiness and could not continue. The other patients showed no obvious side effects. These results suggest that fluvoxamine treatment may be indicated for self-injury and aggressive behaviors in autistic children.

Topics: Aggression; Autistic Disorder; Child; Child Behavior; Child, Preschool; Fluvoxamine; Humans; Male; Selective Serotonin Reuptake Inhibitors; Self-Injurious Behavior

The serotonin system has been implicated in the pathoetiology of autistic disorder. To examine the clinical effects of fluvoxamine, a selective serotonin reuptake inhibitor (SSRI) in children with autistic disorder, eighteen patients underwent a cross-over, double-blind trial of fluvoxamine treatment after a written informed consent was obtained from patients' parents. Fluvoxamine treatment resulted in significant improvements in some clinical findings such as eye contact and language use, as tested by behavioral assessment scores consisting of twenty items (p < 0.05). The improvement in language use was also confirmed by parental assessments. Clinical Global Impression Scale was improved in approximately half of the patients. No severe adverse effect was observed during the trial. Thus SSRI treatment in autistic children may be of value.

Topics: Autistic Disorder; Child; Child, Preschool; Cross-Over Studies; Double-Blind Method; Female; Fluvoxamine; Humans; Male; Selective Serotonin Reuptake Inhibitors

The case of a 20 year old autistic woman with disabling repetitive behaviour that responded dramatically to treatment with fluvoxamine is reported. The connection between repetitive symptoms in autism and obsessive-compulsive disorder is considered, and the need for further evaluation of selective serotonin reuptake inhibitors in autism is discussed.

Topics: Adult; Autistic Disorder; Behavior; Female; Fluvoxamine; Follow-Up Studies; Humans; Obsessive-Compulsive Disorder; Treatment Outcome

This is a single-case report of fluvoxamine treatment of comorbid autistic disorder (AD) and obsessive-compulsive disorder (OCD). Psychological, neuroanatomical, and neurochemical parallels are drawn between AD and OCD. The implications of this case of coincident AD and OCD, as well as the response to fluvoxamine, are discussed with respect to nosology, pathophysiology, and treatment of these disorders.

Topics: Adult; Autistic Disorder; Dose-Response Relationship, Drug; Fluvoxamine; Humans; Male; Neurocognitive Disorders; Obsessive-Compulsive Disorder; Oximes; Serotonin Antagonists