Lack of evidence for antidepressants – Instead of benefit, some evidence of serious harm

Antidepressants commonly prescribed to people with autistic spectrum disorders cannot be recommended based on current evidence, a new study by Cochrane Researchers concludes. Despite some evidence of benefits in adults diagnosed with autism, they say there is no evidence for any benefits associated with selective serotonin reuptake inhibitors (SSRIs) in children, who may suffer serious adverse effects as a result of taking the drugs.

Autistic spectrum disorders are difficult to treat because of the range of symptoms experienced by patients, including difficulties with social interactions and communication. SSRIs are among the most commonly prescribed medications, although none have been specifically approved by any drug authority for use in autism. In the UK, most antidepressants are not approved for children for any condition. The rationale behind the use of SSRIs in autism is that they act on serotonin, the same chemical in the body that is responsible for some of the psychological processes affected by the condition.

The researchers included a total of seven trials, involving 271 patients, in their study. The trials evaluated fluoxetine, fluvoxamine, fenfluramine and citalopram. Overall, the researchers found no benefit in the five trials in children and some evidence of serious harm, including one child who suffered a prolonged seizure after taking citalopram. The two trials in adults were very small and thus, although there was some evidence for improvement in symptoms, the authors concluded there was too little evidence for the drugs to be recommended. A major problem with analysing the results was that all the trials used different measures for assessing the drugs’ effects.

“We can’t recommend SSRIs as treatments for children, or adults, with autism at this time. However, decisions about the use of SSRIs for co-occurring obsessive-compulsive disorder, aggression, anxiety or depression in individuals with autism should be made on a case by case basis,” said lead author Katrina Williams of the School of Women’s and Children’s Health at the University of New South Wales & Sydney Children’s Hospital in Sydney, Australia.

“Not all the SSRIs currently in use have undergone controlled trials for autistic spectrum disorders, but parents are often anxious to try treatments regardless of the lack of evidence. It’s important that doctors are open about the lack of evidence, and explain any risks fully, before prescribing these treatments.”

Reference: Wiley-Blackwell, Autism: Lack of evidence for antidepressants, August 7, 2010

Related Articles:

1. Antidepressants Offer No Relief for Repetitive Behaviors in Children with Autism
2. Children with Autism show slower pupil responses, study finds
3. Autism – Do terbutaline- and mold-associated impairments of the brain and lung relate to autism?
4. Neuroimaging: New insights in the pathophysiological mechanisms of Autism
5. A prospective study of prenatal mercury exposure from maternal dental amalgams and autism severity

Autism affects an estimated 1 in 150 children today, making it more common than childhood cancer, juvenile diabetes and pediatric AIDS combined. Despite its widespread effect, autism is not well understood and there are no objective medical tests to diagnose it. Recently, University of Missouri researchers have developed a pupil response test that is 92.5 percent accurate in separating children with autism from those with typical development. In the study, MU scientists found that children with autism have slower pupil responses to light change. 

“No comprehensive study has been conducted previously to evaluate the pupils’ responses to light change, or PLR, in children with autism,” said Gang Yao, associate professor of biological engineering in the MU College of Agriculture, Food and Natural Resources and the College of Engineering. “In this study, we used a short light stimulus to induce pupil light reflexes in children under both dark and bright conditions. We found that children with autism showed significant differences in several PLR parameters compared to those with typical development.” 

In the study, scientists used a computerized binocular infrared device, which eye doctors normally use for vision tests, to measure how pupils react to a 100-millisecond flash light. A pupil reaction test reveals potential neurological disorders in areas of the brain that autism might affect. The results showed that pupils of children diagnosed with autism were significantly slower to respond than those of a control group. 

“There are several potential mechanisms currently under study,” Yao said. “If these results are successfully validated in a larger population, PLR response might be developed into a biomarker that could have clinical implications in early screening for risks of autism. Studies have shown that early intervention will improve these children’s developmental outcome.” 

Yao’s study, completed with Xiaofei Fan, post-doctoral fellow at MU, Judith Miles, professor and William S. Thompson Endowed Chair in Child Health, and Nicole Takahashi, senior research specialist at MU’s Thompson Center for Autism and Neurological Disorders, has been published in the Journal of Autism and Developmental Disorders. In October, the scientists received a grant from the National Institutes of Health for the next phase. For this study, the researchers hope to amplify the earlier study’s measurements and investigate any correlation between PLR and several other medical conditions that could be associated with autism. 

Reference:

Xiaofei Fan, Judith H. Miles, Nicole Takahashi and Gang Yao. Abnormal Transient Pupillary Light Reflex in Individuals with Autism Spectrum Disorders. Journal of Autism and Developmental Disorders, 2009; 39 (11): 1499 DOI: 10.1007/s10803-009-0767-7 

Adapted from materials provided by University of Missouri-Columbia, via EurekAlert! Nov. 11, 2009

Picture: University of Missouri

Among dietary factors, learning and behavior are influenced not only by nutrients, but also by exposure to toxic food contaminants such as mercury that can disrupt metabolic processes and alter neuronal plasticity. 

Neurons lacking in plasticity are a factor in neurodevelopmental disorders such as autism and mental retardation. Essential nutrients help maintain normal neuronal plasticity. Nutritional deficiencies, including deficiencies in the long chain polyunsaturated fatty acids eicosapentaenoic acid and docosahexaenoic acid, the amino acid methionine, and the trace minerals zinc and selenium, have been shown to influence neuronal function and produce defects in neuronal plasticity, as well as impact behavior in children with attention deficit hyperactivity disorder. 

Nutritional deficiencies and mercury exposure have been shown to alter neuronal function and increase oxidative stress among children with autism. These dietary factors may be directly related to the development of behavior disorders and learning disabilities. 

Mercury, either individually or in concert with other factors, may be harmful if ingested in above average amounts or by sensitive individuals. High fructose corn syrup has been shown to contain trace amounts of mercury as a result of some manufacturing processes, and its consumption can also lead to zinc loss. Consumption of certain artificial food color additives has also been shown to lead to zinc deficiency. Dietary zinc is essential for maintaining the metabolic processes required for mercury elimination.

Since high fructose corn syrup and artificial food color additives are common ingredients in many foodstuffs, their consumption should be considered in those individuals with nutritional deficits such as zinc deficiency or who are allergic or sensitive to the effects of mercury or unable to effectively metabolize and eliminate it from the body. 

Reference:

Dufault R, Schnoll R, Lukiw WJ, Leblanc B, Cornett C, Patrick L, Wallinga D, Gilbert SG, Crider R., Mercury exposure, nutritional deficiencies and metabolic disruptions may affect learning in children, Behav. Brain Funct. 2009 Oct 27;5(1):44.

Increased prevalence of the autism spectrum disorders (ASD) and the failure to find genetic explanations has pushed the hunt for environmental causes. These disorders are defined clinically but lack objective characterization.

 To meet this need, we measured neurobehavioral and pulmonary functions in eight ASD boys aged 8 to 19 years diagnosed clinically and compared them to 145 unaffected children from a community with no known chemical exposures. As 6 of 35 consecutive mold/ mycotoxin (mold)-exposed children aged 5 to 13 years had ASD, we compared them to the 29 non-ASD mold-exposed children, and to the eight ASD boys. Comparisons were adjusted for age, height, weight, and grade attained in school. 

The eight ASD boys averaged 6.8 abnormalities compared to 1.0 in community control boys. The six mold-exposed ASD children averaged 12.2 abnormalities. The most frequent abnormality in both groups was balance, followed by visual field quadrants, and then prolonged blink reflex latency. 

Neuropsychological abnormalities were more frequent in mold-exposed than in terbutaline-exposed children and included digit symbol substitution, peg placement, fingertip number writing errors, and picture completion. Profile of mood status scores averaged 26.8 in terbutaline-exposed, 52 in mold exposed, and 26 in unexposed. The mean frequencies of 35 symptoms were 4.7 in terbutaline, 5.4 in mold/ mycotoxins exposed and 1.7 in community controls. 

Reference:   Kilburn KH, Thrasher JD, Immers NB., Do terbutaline- and mold-associated impairments of the brain and lung relate to autism?, Toxicol Ind Health. 2009 Sep 30.

Neuroimaging studies done by means of magnetic resonance imaging (MRI) have provided important insights into the neurobiological basis for autism. The aim of this article is to review the current state of knowledge regarding brain abnormalities in autism. Results of structural MRI studies dealing with total brain volume, the volume of the cerebellum, caudate nucleus, thalamus, amygdala and the area of the corpus callosum are summarised. In the past 5 years also new MRI applications as functional MRI and diffusion tensor imaging brought considerable new insights in the pathophysiological mechanisms of autism. Dysfunctional activation in key areas of verbal and non-verbal communication, social interaction, and executive functions are revised. Finally, we also discuss white matter alterations in important communication pathways in the brain of autistic patients. 

Reference: Verhoeven JS, De Cock P, Lagae L, Sunaert S., Neuroimaging of autism, Neuroradiology. 2009 Sep 15.