The selective serotonin-reuptake inhibitor (SSRI) citalopram (Celexa, Forest Pharmaceuticals) appears to be no more effective than placebo at reducing repetitive behaviors in children with autism spectrum disorders (ASD) — a finding that calls into question the currently widespread practice of prescribing SSRIs in this patient population in the absence of scientific evidence.
A multicenter, randomized, placebo-controlled trial showed no significant difference in the rate of positive response on the Clinical Global Impressions (CGI) Improvement subscale between the citalopram-treated group (32.9%) and the placebo group (34.2%).
Furthermore, children in the active-treatment group were significantly more likely than those in the placebo group to experience at least 1 treatment-related adverse event — 97.3% vs 86.8%.
"Adverse symptoms were common in both groups, probably reflecting common childhood ailments as well as the changing nature of symptoms associated with ASD. However, reports of increased energy, impulsiveness, decreased concentration, hyperactivity, diarrhea, insomnia, and dry skin were more common in the citalopram group," lead author Bryan H. King, MD, from Seattle Children's Hospital, in Washington, said in a statement.
The study is published in the June issue of Archives of General Psychiatry.
Multibillion Dollar Market
ASDs are characterized by impaired social interaction, communication problems, unusual preoccupations, and repetitive behavior. Repetitive behaviors, which can involve stereotypic movements, inflexible routines, repetitive play, and perseverative speech, are the strongest predictors that an early ASD diagnosis will endure, the authors note.
Previous research has suggested there are similarities between ASDs and obsessive-compulsive disorder (OCD). As a result, antiobsessional agents such as SSRIs have been of interest.
However, the authors point out, there are currently no Food and Drug Administration–approved agents to treat the core symptoms of ASDs. Despite this, medication use in this population has become increasingly common, with SSRIs accounting for 59% of a global market for autism therapeutics that is estimated to be between $2.2 and $3.5 billion.
"There is growing recognition that children and adolescents with ASDs have serious behavioral problems and psychiatric symptoms that may be appropriate targets for pharmacotherapy. To date, there are few large-scale trials to guide clinical practice, so clinicians are left to address these problems with inadequate information."
However, the investigators point out that "despite the relative dearth of evidence supporting their use, SSRIs are among the most frequently used medication for children with autism, partially because of their perceived safety."
The goal of the study was to assess the safety of citalopram as well as its efficacy in improving global functioning by reducing repetitive behaviors.
Sponsored by the National Institutes of Health, the Studies to Advance Autism Research and Treatment (STAART) network undertook the 12-week, placebo-controlled trial, which included 149 volunteers age 5 to 17 years with ASDs, Asperger's disorder, or pervasive developmental disorder not otherwise specified.
All participants had at least moderate illness measured on the CGI Severity of Illness Scale and scored at least moderate on compulsive behaviors as measured with the Children's Yale-Brown Obsessive Compulsive Scales modified for pervasive developmental disorders.
The study's primary end point was defined as a score of much improved or very much improved on the CGI Severity of Illness Scale. Subjects were randomized to receive citalopram (n = 73) or placebo (n = 76). Citalopram subjects received a maximum daily dose of 20 mg by mouth.
Urgent Need for Large, Multicenter Trials
At the end of the study, roughly 1 out of 3 children in both groups — 32.9% in the citalopram group and 34.2% in the placebo group — showed fewer or less severe repetitive symptoms.
According to the researchers, these findings may challenge the underlying premise that repetitive behaviors in children with ASD are similar to repetitive and inflexible behaviors in OCD.
"The results of this trial indicate that citalopram is not an effective treatment for children having ASDs with moderate or greater repetitive behavior. The results also highlight the urgent need for placebo-controlled trials of medications commonly used for children with ASDs to determine whether the risks of specific drugs substantially outweigh their benefits," the authors write.
In an accompanying editorial, Fred R. Volkmar, MD, from the Yale Child Study Center, in New Haven, Connecticut, said the study is "an important step that addresses this major gap in the literature."
Dr. Volkmar pointed out that the study by Dr. King and colleagues is the largest randomized medication trial in children with autism and ASDs.
"We need more studies of this kind to advance research and guide clinical practice. The commitment of the National Institutes of Health to support well-designed multisite clinical trials should be applauded. Conducting such studies today, when there are so many constraints on funding, will be difficult but no less important," writes Dr. Volkmar.
0 comments:
Post a Comment