Thursday, 28 July 2011

SSRIs and autism

I start this post with a disclaimer or two. I am not a Medic or healthcare professional. I am not giving medical advice. Please speak to your prescribing physician if you have any worries, complaints or comments about any current or planned medication regime. Please don't shoot the messenger.

In this post I want to discuss some of the research done on the use of, and 'possible' relationship between, selective serotonin reuptake inhibitors (SSRIs) and autism. SSRIs are, in as few words as possible, a class of drugs which are believed to act upon the serotonergic system, and in particular inhibiting the removal of serotonin so allowing more serotonin to be available. The theory is that serotonin among its many jobs seems to have some connection to enhancing mood; hence more serotonin = sustained better mood. There are various types of SSRIs available, approved mainly for use for things like depression; although also used for conditions like various anxiety disorders.

SSRIs, whilst quite a successful class of medication for many people, have not been without their problems down the years as can be seen here on the MHRA website and for those in the UK, the link here to those BBC Panorama investigations a few years back. I don't want to become embroiled in any of these debates given them being outside my area of competence and am not offering any opinion either way on the various issues suggested.

A few things brought me to this entry on SSRIs and autism. The recent study looking at maternal antidepressant use during pregnancy and risk of autism (here) and the conclusions drawn from the 2010 Cochrane review on SSRI use in autism (here) are perhaps the main articles. SSRI use as part of the pharmacotherapeutic management of certain behaviours/conditions associated/co-morbid with autism, although perhaps not commonplace, is fairly widespread. Up until the 2010 Cochrane Review, the data seemed to suggest that the various SSRI drugs used were quite successful and fairly well tolerated assuming correct medicines management. Even then however, questions were being asked about the drug profiles in terms of benefits and costs.

No matter how you look at it, the 2010 Cochrane Review of SSRI use for autism does not make great reading. For those who don't know about the Cochrane Reviews and Library, Cochrane represents a database of systematic reviews on various health and medical research - a kind of one-stop shop for meta-analyses and reviews. A selection of their other reviews on autism can be found here and here (there is also a review of dietary intervention from 2008 here). Anyhow, the 2010 report suggested that based on the current evidence, there was little indication of effect for SSRI use with children with autism, and only limited evidence for effect for adult use. I should perhaps temper the children's use statement by saying that several SSRIs are not currently licensed for use with pediatric populations so perhaps were not intended for this age-group anyway.

The paper by Lisa Croen and colleagues was published in the Archives of General Psychiatry, the same journal as the recent twin study which has received so much comment. Their findings: out of nearly 300 children diagnosed with an autism spectrum condition, mums of 6.7% reported taking antidepressant medication in the year prior to birth, compared with only 3.3% of 1507 randomly selected controls. I say antidepressants but this included various medications including the SSRIs; indeed of the 20 mums reporting medication use, 13 were prescribed SSRI monotherapy and a further two used SSRIs in combination with another antidepressant. The remaining 5 mums reported using non-SSRI pharmacotherapy. These medication combination percentages were roughly the same as that of the control group. The authors concluded that maternal use of SSRIs a year before delivery, so covering pre-natal and peri-natal stages, was associated with just over double the risk of her child presenting with autism. The risk increased if medication was being taken during the first trimester of pregnancy, with an odds ratio of 3.8 (CI 1.8-7.8).

Dr Croen and her colleague Judith Grether have quite a long history in looking at various 'risk' factors and autism. Their various research topics include: autism and ultrasound scans (here), parental age (here) and outdoor air quality (here). There was even some early hinting at their involvement in looking at twins and autism (here). The OR of 3.8 mentioned in their SSRI-autism study seems to represent quite a risk when taking into account their other data on environmental factors such as air pollutants and paternal age.

Given the leaning towards environmental factors potentially being associated with autism, I do wonder where we go from here in terms of what the evidence is suggesting. The authors state that the use of anti-depressants such as the SSRIs was comparatively low in their participants group, and certainly the advice (so far) about using such drugs during pregnancy is airing on the side of cautious monitoring rather than a complete ban. I have blogged about the concept of risk previously and how, because there are still so many gaps in the research literature, one has to be careful how research like this is translated. I should give mention that SSRI use associated with raised serotonin levels had been speculatively suggested as being a risk factor for autism a few years back.

With all due respect, I do find it interesting that some mums of children later diagnosed with autism were perhaps at greater risk of requiring medication for depression (assuming that was what it was being used for) prior to the birth of their child, which has been mentioned in the research literature previously. With my science hat on, could one perhaps argue for some effect from maternal depression serious enough to require medication as itself being a risk factor for autism as has recently been suggested with asthma? Does maternal depression translate into immune effects for example? Caution as always needs to be applied to such research. Caution that the dark times of the blame game do not re-emerge as a result of such observations and that the concept of risk is put into context.

Enough of all this talk about risk and boiling people down into numbers and odds ratios. How about a spot of The Housemartins to finish? (the singing doesn't start until about 45 seconds into the video so be patient)