Psychiatric and seizure medicines for autism: what 'works' best

The paper by Devon Coleman and colleagues [1] represents pretty good scientific value for money by my reckoning. Describing the results of a 'survey' called the "National Survey on Treatment Effectiveness for Autism" created by the researchers, the aim was to provide "separated... scales for overall benefits and overall AEs [adverse effects]" for a wide range of interventions used in the context of autism.

The focus this time around was on "Psychiatric and Seizure medications data" but it looks like there may be quite a bit more to see from this group in future with regards to data on "supplements, diets, therapies, and educational interventions" also collected during this initiative. Before continuing on with this paper I have to hat-tip the authors for mentioning a great and much under-valued resource in autism circles: "the Parent Ratings of Behavioral Effects of Biomedical Interventions Survey,... conducted by the Autism Research Institute (ARI) and published in 2008." Indeed, in other posts talking about the medicines cabinet and autism (see here) I've expressed my positive views of the ARI resource albeit with caveats.

Anyhow: "we report ratings of 26 psychiatric and seizure medications by 505 participants." Researchers actually noted that nearly 900 people completed their survey; most of whom were described as the "Primary caregiver of an individual with autism." Some people might um-and-ah about the lack of 'authentic autistic representation' in this study, but one needs to bear in mind that most participants - about three-quarters - were under 18 years of age, most diagnosed with autism and not autism spectrum disorder (described as "less severe than a diagnosis of autism") and most were currently described as having mild, moderate or severe autism. I know this won't be enough for some people, but there you have it.

Then to the medicines that were 'graded', which fell into "five general categories: stimulants (four medications), SSRIs [selective serotonin reuptake inhibitors] (five medications), antipsychotics (four medications), seizure (nine medications), and other (four medications)." There's a lot of data included in the Coleman paper which really is too much for a blog post. I'll direct you to Figure 8 of the Coleman paper which provides a handy 'net benefit score' taking into account an 'overall benefit score' and an 'overall adverse score' for each medicine. When it came to SSRI medicines - typically indicated for treating depression - sertraline came top. When it came to antiepileptic medicines - primarily used to manage epilepsy and/or seizures - lamotrigine came top. When it came to antipsychotic medicines, aripiprazole came top. I was also interested to see that buspirone, a medicine typically indicated for anxiety, also did pretty well according to the Coleman results, which kinda ties in with some continuing research interest in this medicine with autism in mind (see here). Researchers also provide a handy 'medications for symptoms' overview as a consequence of their results (see Table 7) covering various symptoms from aggression/agitation to tics/abnormal movements. I can see this being particularly useful when it comes to physicians having to make big medication decisions (which should never be entered into lightly).

There's a couple of other details that are also mentioned in the Coleman paper outside of those 'how was medicine rated?' sentiments. Some details are not likely to make many friends in some quarters. So, around 2% of participants were described as follows: "No current diagnosis, but he/she was on the autism spectrum previously." Yes folks, such data once again harks back to the idea that for some people at least, autism is not a lifelong diagnosis (see here and see here). And also: "Thirty-four percent of participants had early onset of symptoms, but 56% had normal development followed by a plateau or regression." Regression accompanying autism is not the 'dirty' concept that it used to be (see here). Indeed, in the few years that I've been blogging about autism research, I've seen it become a lot more commonplace to talk about regression and autism (see here) even to the point that some now talk about it being 'the rule rather than the exception' (see here). Interesting.

And then there's something even more controversial in the Coleman paper: "The perceptions of possible causes of the regression are listed in Table 2." So we have things like high fever, illness, seizure and then... vaccination. I know this takes us into some uncomfortable territory, but the authors report that 51% of respondents to their survey who cited regression as part of the clinical picture mentioned vaccination as the 'perceived cause' whether singly or in conjunction with other factors. Of course I'm going to provide a link to what the population-based science says on this matter (see here) with the caveat that such 'perceived cause' data perhaps needs objective and dispassionate follow-up (see here and see here).

The Coleman results are not without their limitations as per author comments such as: "The survey is retrospective and based on respondent memory which reduces the accuracy" and "The results are subject to “placebo effect” since it represents clinical data without a placebo control, so the real benefit is likely less than the perceived benefit." But let's not take too much away from the findings and how they may, as well as informing clinical practice, also hopefully lead to further inquiry to make medicines safer and more reliable for those on the autism spectrum who access them.

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[1] Coleman DM. et al. Rating of the Effectiveness of 26 Psychiatric and Seizure Medications for Autism Spectrum Disorder: Results of a National Survey. J Child Adolesc Psychopharmacol. 2019 Feb 6.

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On the recent report suggesting that US autism rates "appear to be stabilizing"

The research letter by Guifeng Xu and colleagues [1] is making some New Year's headlines following their finding that: "In a large, nationwide population based study, the estimated ASD [autism spectrum disorder] prevalence was 2.41% among US children and adolescents in 2014-2016, with no statistically significant increase over the 3 years."

Based on data derived from the National Health Interview Survey (NHIS), researchers have kinda repeated what was reported in a recent NCHS data brief [2] that provided some blogging fodder here a few weeks ago (see here). On that occasion as this, the data reported an increasing percentage of families positively responding to the question: "Has a doctor or health professional ever told you that [sample child] had Autism, Asperger’s disorder, pervasive developmental disorder, or autism spectrum disorder?" year on year, but nothing to say that the percentage increase is statistically significant.

Unlike the Xu data, the previous data brief by Zablotsky and colleagues [2] also asked some questions about diagnoses 'around the edges of autism'  such as 'other developmental delay' alongside a composite measure called 'developmental disability' that included ASD, intellectual disability and other developmental delay. The stats for that composite measures were deemed statistically significant in terms of the increase in percentages of children/young adults being diagnosed year on year.

Whilst there may be some optimism that the rates of autism/ASD might be 'stabilising' based on the NHIS research format, I'd like to see a lot more data before anyone calls an end to the quite phenomenal increase in the numbers of children/young adults being diagnosed over the past few decades. I believe we should be due some updated CDC figures later this year (2018) on the basis of other data reported on a once-every-2-years basis with autism in mind (see here). And hopefully, the moves to "estimate ASD case status on the basis of both DSM-5 and DSM-IV-TR" in the next CDC figures, should provide some additional talking points too (see here)...

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[1] Xu G. et al. Prevalence of Autism Spectrum Disorder Among US Children and Adolescents, 2014-2016. JAMA. 2018; 319: 81-82.

[2] Zablotsky B. et al. Estimated prevalence of children with diagnosed developmental disabilities in the United States, 2014–2016. NCHS Data Brief, no 291. Hyattsville, MD: National Center for Health Statistics. 2017

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Low birth weight and autism: rise of the population attributable risk

RIP Cheggers.

"LBW [low birth weight] accounted for 6.0% of all ASD [autism spectrum disorder] cases, 2.4% of BCD [behaviour and conduct disorder], and 6.8% of LD [learning disability] among the study population."

Those were the observations made by Sandie Ha and colleagues [1] and with it, another example of the use of the population attributable risk/fraction in the context of autism (see here for another occasion). Published in 2014 but only recently appearing on PubMed, Ha et al report results based on data from the 2011 (US) National Survey of Children’s Health, (NSCH) - a "random-digit-dial phone survey conducted between February 2011 and June 2012" - where data on birth weight and receipt or not of a diagnosis of "attention deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), behavior and conduct disorder (BCD) and learning disability (LD)" were available. As an aside, I've talked about the other studies arising from the NSCH program before on this blog (see here and see here for examples).

Including data pertinent to around 81,000 children aged between 2 and 17 years of age, researchers reported that around 9% of the cohort were "born with a LBW as reported by their parent" in response to the question: "What was [sampling child’s] birth weight?" There were some interesting correlates alongside those responses regarding LBW status: "children who were female, non-Hispanic black, had single mothers, had less educated mothers, were poorer, lacked insurance, were exposed to in-home smoking, or born prematurely were more likely to have LBW compared to those with normal BW."

Insofar as 'neurobehavioural disorders' (ND) also asked about: "The weighted prevalence of parent-reported ND among children ages 2 to 17 was approximately 9.9% for ADHD, 2.3% for ASD, 4.1% for BCD, and 10.6% for LD." Yes, this was a telephone-based survey where "both exposure and outcome are based on parental reporting, and thus the information may not represent actual diagnoses" but with the size of the participant numbers included, these prevalence/frequency figures still make for important reading.

Then to the main event - the population-attributable risk percentage (PAR%) and the finding headlining this post: "LBW [low birth weight] accounted for 6.0% of all ASD [autism spectrum disorder] cases, 2.4% of BCD [behaviour and conduct disorder], and 6.8% of LD [learning disability] among the study population." The authors caution that "maternal age at delivery, gestational age, and pregnancy complications could be important confounders" and were not taken into account in their analyses and could be "potential reasons for LBW" alongside undetected "congenital anomalies or genetic disorders." Caution is required.

It's not new news that birth weight might impact on something like autism risk (see here and see here). One also has to bear in mind that something like LBW may not necessarily appear in isolation to other pregnancy or birth events (see here) so a wider research agenda perhaps needs to be followed. But the size of the PAR% talked about by Ha and colleagues is not easily ignored. Taking into account that LBW for some may very well have some 'genetic' influences, one is left asking whether those more 'social' variables linked to LBW might be to some degree 'influenced' with a corresponding effect on neurodevelopmental 'consequences' reported. I say this in the context that poverty as a variable, has already been linked to some diagnoses included in the Ha study (see here)...

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[1] Ha SU. et al. Population attributable risks of neurobehavioral disorders due to low birth weight in US children. Adv Pediatr Res. 2014;1. pii: 2.

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US National Health Interview Survey (NHIS) on autism rates and beyond

The US National Center for Health Statistics (NCHS) has recently released a data brief [1] covering the topic of diagnosed developmental disabilities and specifically: "the latest prevalence estimates for diagnosed autism spectrum disorder, intellectual disability, and other developmental delay among children aged 3–17 years from the 2014–2016 National Health Interview Survey (NHIS)."

The figures show a number of trends in relation to various diagnoses; not least that the prevalence of autism spectrum disorder (ASD) rose year on year between 2014 and 2016, albeit not significantly. In 2014, the percentage of positive responses to the question: "Has a doctor or health professional ever told you that [sample child] had Autism, Asperger’s disorder, pervasive developmental disorder, or autism spectrum disorder?" was 2.24%; in 2015 it was 2.41% and in 2016 it was 2.76%. I might add that we already knew what the 2014 data showed given other publications (see here).

When it came to the categorisation of developmental disability - "A composite measure of children with a diagnosis of autism spectrum disorder, intellectual disability, or any other developmental delay" - the figures were rather more significant. So: "During 2014–2016, the prevalence of children aged 3–17 years who had ever been diagnosed with a developmental disability increased from 5.76% to 6.99%." The categorisation 'other developmental delay' seemed to be the main driver of the [statistically significant] increase in that composite measure (2014: 3.57%; 2015: 3.56%; 2016: 4.55%).

There are a few additional details to mention about the report by Benjamin Zablotsky and colleagues. Boys, yet again, were the over-represented group when it came to all and total categories and race/ethnicity seemed to show some important differences such as a typically lower percentage estimate being present for most diagnoses in Hispanic children compared to other groups.

What can we make of these recent statistics? Well, it's pretty evident that, for whatever reason(s), there is still an upward trend when it comes to a diagnosis of autism and various other developmental labels. It's worthwhile pointing out that the current report used "a more restrictive definition for a developmental disability that does not include conditions such as attention-deficit/hyperactivity disorder or learning disabilities" so the figures might also not be entirely reflective of the 2014-2016 situation. I also had a question in mind about what the difference was between 'intellectual disability' (shown) and 'learning disability' (not shown) given their interchangeable meaning at least here in Blighty (see here).

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[1] Zablotsky B. et al. Estimated prevalence of children with diagnosed developmental disabilities in the United States, 2014–2016. NCHS Data Brief, no 291. Hyattsville, MD: National
Center for Health Statistics. 2017

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"the importance of considering how autism acceptance could contribute to mental health in autism"

The quote heading this post comes from the findings reported by Eilidh Cage and colleagues [1] (open-access) who sought to examine how "experiences and perceptions of autism acceptance could impact on the mental health of autistic adults."

Using an on-line survey "to test the relationship between perceived autism acceptance and mental health (specifically, depression, anxiety and stress)" findings are reported based on responses from over 110 people diagnosed as on the autism spectrum. I say 'diagnosed as on the autism spectrum' but as with any internet survey, there is always a degree of 'trust' that autism diagnoses are being reported faithfully just as it is with other labels that were under study: "a high proportion of participants reported additional diagnoses." Indeed, I also note that "11 participants reported that they did not currently have a formal diagnosis of autism" and were still included in some of the analyses...

No mind, the authors sought to 'quantify' autism acceptance given no measure currently exists by asking various questions including "whether they felt that society (specified as the general public, made up of people who did not personally know them) generally accepted them, with “yes”, “no”, “sometimes” and “prefer not to say” as response options." Responses were also sought to statements such as "over the past week, I have felt accepted by society as an autistic person/person with autism" and onward "perceptions of autism acceptance from different sources." This was complemented by responses to the Depression, Anxiety and Stress Scale (DASS-21).

Results: "depression was predicted by autism acceptance from external sources (society, family and friends) and personal acceptance" but anxiety was not seemingly *linked* to autism acceptance. Drilling down further into their results, researchers observed that "greater personal autism acceptance predicted lower depressive symptoms" indicating that variables such as self-esteem might mediate any risk of presenting with depressive signs and symptoms [2] (see here for my take). This is something that perhaps tallies with other research talking about autistic traits and wellbeing [3].

The author has also written a piece for The Conversation on her research study (see here).

I'm not quite sure why the ever-fluffy psychological concept of 'Theory of Mind' (ToM) needed to be introduced into the Cage paper given that no measure of ToM was actually included in the study. A quick search of other published research from these authors reveals that ToM is a feature there too [4]. The authors talk about how "Theory of Mind ability may impact on perceptions of autism acceptance" but I'm not so sure that this is particularly important. It's kinda like suggesting that society is completely autism aware and accepting/accommodating but those on the spectrum 'don't seem to understand it' as a result of any ToM issues, which is of course, a nonsense. ToM also still requires a bit more investigation into what it actually means and covers (see here) including the idea that issues with ToM might themselves be 'impaired' as a result of something like depression (see here). I'd also point out that quite a few other over-represented diagnoses potentially appearing alongside autism also seem to present with ToM issues [5] too...

"There is still a long way to go in understanding and tackling the high prevalence of mental health difficulties in autism, but we believe that the social model approach is a useful and positive lens through which mental health outcomes could be improved." That was the conclusion reached by authors on the basis of their findings. I would agree that there is still a long way to go on the topic of mental health and autism and the social model approach - "disability is caused by the way society is organised, rather than by a person’s impairment or difference" - is an option for further research of this kind. But I would also caution that one needs to balance such a perspective with others too (see here), and accept that the organisation of society is not always the most disabling aspect of a person's disability, particularly when it comes to something like depressive symptoms. Indeed, to say that depressive symptoms accompanying autism might merely be a facet of a 'lack of acceptance' or a lack of understanding from society or the individual themselves, risks plunging autism back into some pretty dark times (see here) and is likely to conflict with various other views. From a clinical point of view, it ignores some very serious research on the wide spectrum that is depression potentially present for all-manner of different reasons, being relevant to the equally wide spectrum that is autism (see here for a discussion on how depression might actually be something rather more fundamental to some autism over just being 'comorbidity'). At worst, it may even delay or put people off from seeking timely recognised treatments when depression becomes 'clinical', which could be a rather dangerous path to start down (see here).

Having said all that, I don't however think too many people would argue with the idea that personal perception(s) whether positive or negative are likely to impact on a person's mental (and physical?) health and wellbeing. If one is constantly feeling like an 'outsider' or excluded or feels that ones needs are not being met, added to a possible history of being bullied or loneliness or indeed, with other clinical labels also potentially being present for example, one is likely to build up a mindset appropriate to such a situation which probably includes some advanced risk for depressive signs and symptoms. From that point of view, much more needs to be done to look at the ways and means of impacting those personal perceptions; possibly taking into account other relevant research which has some [evidence-based] suggestions on things like societal inclusion and increasing access to it (see here) for those who want this option, alongside other complementary strategies where some [peer-reviewed] evidence is present (see here) and continues to be produced (Google the 'HUNT Cohort Study' to see what I mean). I say all this reiterating that something like chronic loneliness can very much be a major contributor to issues like depression.

I also understand the calls to make society more autism-accepting which I think most people would support as being pertinent across the ENTIRE autism spectrum (see here). I'm however, a little unsure of the real-life plan and details of the plan attempting to achieve this goal; particularly in the current climate when even getting a timely diagnosis seems to be an uphill struggle and when also many on the autism spectrum are seemingly left to fend for themselves post-diagnosis. Society it seems, is getting much more autism aware (for good or bad based on current media portrayals for example) but not necessarily getting more autism accommodating nor necessarily putting important words into actions. Indeed, one could argue that other societal factors like unemployment and financial hardship readily experience by those with autism are probably as, if not more, important to their experiences of something like depression yet little appears to be done to improve such issues for the vast majority...

As for the "experiences of “camouflaging” [that] could relate to higher rates of depression" also mentioned in the Cage article, I have quite a lot of time for this area of autism research (see here). Particularly the idea that camouflaging is not necessarily an all-female pursuit in the context of autism (see here) and how truly energy-sapping it can be for many, many people on the spectrum...

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[1] Cage E. et al. Experiences of Autism Acceptance and Mental Health in Autistic Adults. J Autism Dev Disord. 2017. Oct 25.

[2] McCauley JB. et al. Self-Esteem, Internalizing Symptoms, and Theory of Mind in Youth With Autism Spectrum Disorder. J Clin Child Adolesc Psychol. 2017 Oct 19:1-12.

[3] Rodgers JD. et al. Brief Report: Personality Mediates the Relationship between Autism Quotient and Well-Being: A Conceptual Replication using Self-Report. J Autism Dev Disord. 2017 Sep 16.

[4] Cage E. et al. Reputation management: evidence for ability but reduced propensity in autism. Autism Res. 2013 Oct;6(5):433-42.

[5] Wang Y-Y. et al. Theory of mind impairment and its clinical correlates in patients with schizophrenia, major depressive disorder and bipolar disorder. Schizophrenia Res. 2017. Nov 7.

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The autism numbers game: now 1 in 45 (estimated)

I want to (briefly) draw your attention to the findings reported by Benjamin Zablotsky and colleagues [1] (open-access) recently on the topic of the (estimated) autism prevalence rate. Specifically the figure that seems to be making some media headlines: "The estimated ASD [autism spectrum disorder] prevalence was 2.24% (1 in 45) in 2014."

Based on data derived from the 2014 US National Health Interview Survey (NHIS) designed with the purpose "to monitor the health of the United States population through the collection and analysis of data on a broad range of health topics" researchers turned their eyes towards the question of "the lifetime prevalence of ASD, intellectual disability (ID), and any other developmental delay (other DD)." The added interest in this latest version of the NHIS was the inclusion of a "standalone question" to respondents about autism/ASD along the lines of "Did a doctor or health professional ever tell you that [child's name] had autism, Asperger's disorder, pervasive developmental disorder, or autism spectrum disorder?" In previous times, the survey only included autism/ASD among a list of various other health-related conditions including Down syndrome and cerebral palsy.

Taking into account the change in format to the current (2014) survey bringing autism/ASD to the forefront, Zablotsky et al report something of a considerable shift in the number of people reporting a positive response to that question. So based on the estimated prevalence of 2.2% this time around, researchers noted that this was "a significant increase" compared with previous versions of the NHIS (2011-2013) where the figure was 1.25% or an estimated 1 in 80 children (aged 3-17 years old) with autism/ASD. At the same times as an increase in reports of autism/ASD/Asperger syndrome/PDD, there was a significant decrease in the number of reports of 'other developmental delay' (this question being standalone in both the 2011-2013 and 2014 surveys). Reports on the frequency of intellectual (learning) disability were not significantly different between the 2011-2013 and 2014 data (1.2% vs. 1.1% respectively). More discussion about the study can be read here.

The authors (and some of the media) have made quite a bit of the change in questioning format as being a primary variable to account for the estimated prevalence. I would tend to agree that how one asks the question and specifically the prominence of the question, is likely to impact on what responses one gets from these kinds of surveys, also bearing in mind that this was not a 'go out there and objectively screen' kind of autism prevalence study. That being said, I am open to the idea that part of the percentage increase in reports of autism/ASD may also reflect other factors not limited to just something like diagnostic substitution for example.

Whilst the 1 in 45 figure might be a shock to some/many people, I personally am not that surprised. Only this year (2015) I've talked about a figure of 1 in 46 coming out of Canada (see here) making the previous 1 in 68 estimate from the CDC look a little conservative in the context of the North American experience taking into account differences in ascertainment (see here). Irrespective of the discussions around what factors might be contributory to reported autism rates (estimated and actual), such findings suggest that quite a bit more planning and resources may need to be put into catering for the needs of this ever-growing population both in childhood and indeed, beyond.

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[1] Zablotsky B. et al. Estimated Prevalence of Autism and Other Developmental Disabilities Following Questionnaire Changes in the 2014 National Health Interview Survey. National Health Statistics Reports. 2015; 87. Nov 13.

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Benjamin Zablotsky, Lindsey I. Black, Matthew J. Maenner, Laura A. Schieve, & Stephen J. Blumberg (2015). Estimated Prevalence of Autism and Other Developmental Disabilities Following Questionnaire Changes in the 2014 National Health Interview Survey National Health Statistics Reports