Antidepressants - No Good In Autism?

Children with autism often shown repetitive behaviours, ranging from repeated movements to compulsively collecting or arranging objects and desiring that daily routines are always done in the exact same way. Repetitive behaviour is often considered one of the three core features of autistic disorders (alongside difficulties in social interaction, and difficulties in communication).

SSRI antidepressants are often used to try to treat repetitive behaviours. Unfortunately, they don't work, at least according to a new study - Lack of Efficacy of Citalopram in Children With Autism Spectrum Disorders and High Levels of Repetitive Behavior.

The trial included 149 American children with autism aged from 5 to 17 years old, all of whom had moderate or severe repetitive behaviours. They were randomly assigned to get either citalopram, an SSRI, or placebo, and were followed up for 12 weeks to see if it had any effect on their repetitive behaviours. The dose of citalopram started at 2.5 mg and gradually increased to, in most cases, 20 mg, which is the dose that an adult person with depression would most commonly take - for a kid, this is a high dose.

The results were unequivocal - citalopram had absolutely no benefit over placebo. Zilch. On the other hand, it did cause side effects in some children - gastrointenstinal problems like diarrehea, skin rashes, and, most worryingly, hyperactivity - "increased energy levels", insomnia, "Attention and concentration decreased", and so forth. (Two children in the citalopram group also experienced seizures, but it's not clear that this was related to the drug, as citalopram is not known for causing seizures in adults.)

So, citalopram was not just useless, but actually harmful, in these children. This is the largest trial of an SSRI for repetitive behaviours in autism so far; there have been a few others, including one double-blind study of Prozac finding some benefit, but this is by far the most compelling.

But there's a big question here - why would anyone think that citalopram would work? Citalopram was designed to treat adults with... depression. Hence why it's called an antidepressant. Depression in adults is no more like compulsive behaviour in autistic children than is having a broken leg or heart disease. They're completely different conditions.

The main reason why SSRIs are used to try to treat repetitive behaviour is that they also work quite well against obsessive-compulsive disorder (OCD). People with OCD have repetitive behaviours, "compulsions". They might wash their hands ten times after going to the toilet. Or check that the fridge door is closed and the oven is switched off every time they leave the kitchen. Or count up to one hundred in their head whenever they see the number 13. And so forth.

SSRIs do work against OCD. Does this mean that they ought to also work against the repetitive behaviors in autism? Only if you think all repetitive behaviours are the same, with the same causes.

People with OCD feel compelled to perform their ritualistic behaviours as a way of coping with their "obsessions" - intrusive, unpleasant thoughts that they can't otherwise get out of their heads. Someone might be obsessed with the thought of germs and disease whenever they go to the toilet, and the only way to feel clean is to wash their hands 10 times. They might be obsessed with the idea that their family will die whenever they see the unlucky number 13, unless they "cancel it out" by counting to 100. The repetitive behaviours, in other words, are a consequence of the obsessions, which are unwanted, anxiety-provoking thoughts. SSRIs probably work by making the obsessions seem less troubling, so there is less need for the compulsions.

People with autism are often described as having "obsessions" too, but in the sense of "Things they are very interested in", not "Thoughts they cannot get rid of". Likewise, autistics may show "compulsive behaviours", but not as a way of dealing with obsessions. The words are the same, but the reality is different.

Maybe autistic people just like sameness and routine. That's part of who they are, and it's not something that can be treated with drugs. People with OCD hate having it - they don't like their obsessions or compulsions, they feel stuck with them. The compulsions are a coping mechanism. But in autism, at least most of the time, that's not how it works. An autistic child "compulsively" playing with the same toy over and over, or reading yet another book about their "obsession", dinosaurs, may be perfectly happy. In which case, why give them happy pills? And this is what the authors of the paper eventually suggest -

It may be that the repetitive behavior in children with ASDs is fundamentally different from what is observed among children with obsessive-compulsive disorder in its behavioral picture and in its biologic underpinnings.

Bryan H. King, MD; Eric Hollander, MD; Linmarie Sikich, MD; James T. McCracken, MD; Lawrence Scahill, MSN, PhD; Joel D. Bregman, MD; Craig L. Donnelly, MD; Evdokia Anagnostou, MD; Kimberly Dukes, PhD; Lisa Sullivan, PhD; Deborah Hirtz, MD; Ann Wagner, PhD (2009). Lack of Efficacy of Citalopram in Children With Autism Spectrum Disorders and High Levels of Repetitive Behavior Arch Gen Psychiatry, 66 (6), 583-590