Use of Selective Serotonin Reuptake Inhibitors during Pregnancy and Risk of Autism

Autism and its causes have been a heavily discussed issue.  This study specifically concerns the issue of the use of antidepressants during pregnancy and increased risk of autism spectrum disorders.  The study was conducted in Denmark and looked at live births from 1996 to 2005.  It looked at the use of SSRIs by the mother before and during pregnancy, autism spectrum disorders that were diagnosed and any other potential confounders.

The results of the study showed that there was no increased risk of autism spectrum disorders associated with use of SSRIs during pregnancy when compared to no SSRI use both before and during pregnancy.  While no significant association could be found, based on the upper boundary of the confidence interval relative risk of up to 1.61 could exist.  Therefore, the study concluded that more research had to be conducted to determine a conclusive answer.

I found this article interesting because of how much attention is being paid to autism and its potential causes.  I think it is extremely important to always do your research before making a claim or even sharing an article on Facebook.  So many people are willing to accept inaccurate information, especially if its explains something in their life that was previously unexplainable.

Hviid A, Melbye M, and Pasternak B. Use of Selective Serotonin Reuptake Inhibitors during Pregnancy and Risk of Autism. N Engl J Med. 2013;369(25): 2406-415.

http://www.nejm.org/doi/full/10.1056/NEJMoa1301449

Buspirone and Autism

A study was done to look at the effects of buspirone in various doses in treating children with autism spectrum disorder. Over the course of 24 weeks, 166 children between the ages of 2 and 6 were randomly given a placebo, 2.5 mg or 5 mg of buspirone twice a day. The first phase was followed by a second 24-week phase, in which the patients were re-randomized to receive again the placebo, 2.5 or 5 mg of buspirone. The efficacy of the drugs at varying doses was assessed every 24 weeks. Every child in the study were diagnosed with autism spectrum disorder based on the Autism Diagnostic Interview Review and Autism Diagnostic Observation Schedule. Following the full 48 week study, there was significant evidence of behavioral improvement in the group of patients whom received the 2.5 mg, however the placebo and 5 mg showed no change over the course of the study.

Understanding the importance of dosing and its effect on the patients is crucial as a medical professional. Without the study, there would be a common misconception that an increase in dose would produce an increased effect, however the study proves that a low-dose buspirone would in fact be more effective and successful in improving the behavior of children with autism spectrum disorder. It would definitely be worth conducting a follow up study to research why the higher dose is less effective and how to, in needed cases, one can increase efficacy without increasing dose.

JAMA.2016;170(45-53)

Decreased Brain Levels of Vitamin B12 in Aging, Autism and Schizophrenia

Vitamin B12 is crucial for brain development and function. This is because vitamin B12’s active metabolites are important cofactors for two reactions. One reaction involves the metabolite methylcobalamin (MeCbl), and it is folate dependent methylation of HCY to methionine by methionine synthase in the cytoplasm. The other metabolite, adenosylcobalamin (AdoCbl), is used as a cofactor for the conversion of methylmalonylCoA to succinylCoA by methylmalonyl CoA mutase in mitochondria. Despite us knowing this, vitamin B12’s role in the brain across the lifespan has not been investigated until this study.

In this study, the levels of five vitamin B12 species in postmortem human frontal cortexes of 43 control subjects were measured. These cortexes ranged from those of 19 week old fetuses to those of 80 year old individuals. Of the subjects, twelve of them were autistic and nine of them were schizophrenic.

The results of this study showed that total B12 levels were significantly lower in the front cortexes of the older control subjects 60 years and older. This reflected over a ten fold age dependent decline in the B12 metabolite MeCbl. Levels of another B12 metabolite, cyanocobalamin (CNCbl) were much higher in fetal brain samples, further showing that vitamin B12 levels decrease with age. The levels of MeCbl and AdoCbl in autistic and schizophrenic subjects were more than three fold lower than the controls that were the same age as these subjects, but who did not have autism or schizophrenia.

This study is interesting to me because it makes me wonder whether taking vitamin B12 supplements would help with aging, or improve the mental state of those with autism or schizophrenia. I feel that it may be beneficial for pharmacists to recommend these supplements to patients with autism or schizophrenia. However, it is important that if they do begin doing this that they counsel these patients or their caregivers on the common side effects of taking vitamin B12 supplements. Some of these side effects include joint pain, dizziness, headache, and nasopharyngitis.

PLoS ONE. 2016;11(1): 1-19.

http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0146797

Prescription Use Among Children with Autism Spectrum Disorders

The purpose of this article is to focus on the difference between prescription medications given to children with autism spectrum disorders versus children in the general population. Published in February 2016, this article focuses on a study that was conducted during the years 2007-2010. This study was a cross-sectional study of ambulatory prescription fills from Maine, Vermont and New Hampshire.

Autism Spectrum Disorders, or ASDs, affect more children than we may think. In fact, during this study, there were 13,100 children diagnosed with ASD, compared to the 936,721 children without ASD diagnosis. That means that about 1 in every 71 children is diagnosed with ASD. Also, along with the ASD diagnosis comes prescription medications. Furthermore, this study showed that children with ASDs consume more prescription drugs than the general pediatric population.

The overall prescription fill rate was about 4-fold higher in children with ASD compared to the children without ASD. First, psychotropic use among children with ASD was 9-fold higher than the general population rate. The children with ASD made up about 2% of the pediatric population, but received a little over 15% of the psychotropics being prescribed to those pediatric patients. Next, nonpsychotropic drug use was also higher in the population with ASD, particularly in those children age 3 or younger. Furthermore, antibiotic use was 2-fold higher and antacid use was nearly 5-fold higher than the general population.

This increase in drug use was not only observed in the community settings, but also seen in the hospital settings. Antacid and alpha-agonist uses in hospital settings were about 3-fold higher in the ASD population, and benzodiazepines reached nearly 4-fold higher for the ASD population in the hospital setting.

As you can see, autism spectrum disorders really affect the medication use in the pediatric population. There is an overall increase in psychotropic and nonpsychotropic prescription medications in the ASD population, followed by an increase in other prescription drugs as well. There is still more research to be done in this category; however, the correlation is shown relating ASD with prescription drug use as compared to the general population.

Prescription Use among Children with Autism Spectrum Disorders in Northern New England: Intensity and Small Area Variation. House, Samantha A. et al. The Journal of Pediatrics , Volume 169 , 277 – 283.e2

http://www.jpeds.com/article/S0022-3476(15)01199-3/fulltext

Antidepressants Taken by Pregnant Woman and the Risk of Autism in her Child

Autism spectrum disorder has no known single cause for its occurrence, but it is known to result from some sort of abnormality in the brain. Some studies suggest that it is genetic, however, a gene has not been identified to cause autism. It is also thought that babies may be born susceptible to autism, but there is no trigger that has been identified. One theory of autism is mothers using harmful substances while pregnant.

This study aims to uncover if antidepressants in pregnant mothers constitutes a harmful substance to the baby and therefore causes autism. This is a controversial topic, because the mother is put in a tough spot. The study was register-based of an ongoing population-based cohort in Quebec from January 1, 1998 to December 31, 2009. 145, 456 babies were born during this time. The study classified the different antidepressants into class as well as what trimesters they were used in. The average age of the children studied was 6.24 years old. About 1,054 of these children had a diagnosis of autism, which is about 0.7%. There were 4 boys to every 1 girl diagnosed. 31 infants were exposed to antidepressants during the second or third trimester, and the hazard ratio was 1.87. Specifically, 22 infants were exposed to SSRIs, and this caused the health ratio to be 2.17. It was concluded that antidepressants, especially SSRIs, do increase the risk of having an autistic child if the medication is taken during the second or third trimester. More research is needed to figure out why.

I think this is such a hard decision for a mother that suffers from depression, because she needs to decide if she can handle her mental health without medication for the sake of her child. Relapse into depression may also be harmful for her baby though. The percentage of babies born with autism was relatively small, however, I would not want to take that risk with my baby. Would you choose to suffer depression or take your chances with your baby? Are there other treatment options for depression that would not harm the baby?

Boukhris T, Sheehy O, Mottron L, Bérard A. Antidepressant Use During Pregnancy and the Risk of Autism Spectrum Disorder in Children. JAMA Pediatr. 2016;170(2):117-124. doi:10.1001/jamapediatrics.2015.3356.