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

Differential Impact of Selective Serotonin Reuptake Inhibitors on Platelet Response to Clopidogrel: A Randomized, Double-Blind, Crossover Trial

SSRIs and other antidepressant medications constitute one of the most commonly prescribed drug classes that pharmacists will see in the community setting. When taken alone, any one of these medications can be a good treatment option for patients experiencing depression; however, these drugs can cause a patient who is taking multiple drugs  to experience significant interactions with his/her other medications. For this reason, it is crucial to know how the effects of other medications can be altered through this therapy.  This study analyzed the effects of two SSRIs (citalopram and fluvoxamine) on the blood thinning medication clopidogrel. These medications all work on the same CYP enzyme (CYP2C19)  and have opposing effects. Researches tested these medications on healthy individuals and found that fluvoxamine was the only drug that caused significant inhibition of clopidogrel action.

I think this is important to note because these medications are commonly utilized by patients and thus there is a high likelihood that they may be taken together. As pharmacists, we should be able to provide adequate care in response to possible drug-drug interactions. To do this, we have to be able to recognize when there could potentially be a problem in medication therapy. By taking the proper precautions when these situations arise, pharmacists will be more likely to help patients avoid adverse medical events associated to drug therapy methods.

Dose-Response Relationship of Selective Serotonin Reuptake Inhibitors in Major Depressive Disorder

Selective serotonin reuptake inhibitors are generally accepted as a class of drugs that should be prescribed to those with major depressive disorder, especially in the most severe cases. There is really not much debate about this fact, however, there is still question and uncertainty about how to dose these medications. The APA guidelines today call for optimizing the dose as long as the side effects can be tolerated because it has been shown that the there is a flat dose-response curve within the therapeutic range for antidepressant medications in major depressive disorder. The authors of this meta-analysis believe that this statement may be flawed for two reasons. One, the data that supports this statement includes all antidepressants not just SSRIs, and the researchers from the previous meta-analysis that produced this guideline looked at dose as a categorical outcome instead of continuous which could have reduced their power to determine what the dose-response relationship is really like. This meta-analysis set out to determine whether higher doses of SSRIs really improved outcomes or not.

The authors of this paper only included very specific studies to ensure that they came to the most accurate conclusion. The inclusion criteria were data for both SSRI and placebo treated patients and used standardized, validated outcome measurements for depression. The exclusion criteria included patients less than 19 or older than 60, use of a cross-over design, dual diagnoses, non-SSRIs, not randomized, not placebo-controlled, and psychotherapy was given to either the control or active group. In the end, the team of authors concluded that SSRIs show a significant increase in efficacy when higher doses were administered. The analysis also found that the higher doses are associated with reduced tolerability because more people dropped out of the trials due to side effects at high doses of SSRIs. These results differed from the previous meta-analysis, showing that the dose response curve did not level-off until the very end of the dosing range. This new finding could possibly affect how doctors prescribe SSRIs because there could be evidence to indicate prescribing higher doses than the minimum therapeutic range could be more effective for patients but also more harmful.

 

Jakubovski E, Varigonda AL, Freemantie N, et al. Systematic Review and Meta-Analysis: Dose-Response Relationship of Selective Serotonin Reuptake Inhibitors in Major Depressive Disorder. Am J Psychiatry. 2016; 173: 174-83.

 

After reading this article, it makes me wonder how physicians in charge of treating a patient’s major depressive disorder would react. Would more physicians start their patients off at a dose in the middle of the dose response curve, or would they start off higher? If they started in the middle and their patient did not see any improvement, would they feel more comfortable increasing the dose or would the potential side effects still keep them from doing this?