Another look at the citalopram trial

16 Jun

A recent study shows that Citalopram doesn’t control repetitive behaviors in people with Autism Spectrum Disorders. The failure of a drug trial usually leads to harsh criticism of the medical establishment from the biomedical community, but I haven’t seen much so far. Instead, Kev has already discussed this and made his opinion crystal clear. (As an aside–anyone who thinks bloggers here are somehow paid by pharmaceutical companies may want to read Kev’s post.)

The bottom line of the study was plain: citalopram doesn’t reduce repetitive behaviors in children with autism. Or, as Kev put it:

What the hell did they expect it to do? They expected it to reduce repetitive behaviours.


They put these kids on heavy duty SSRI’s because they flapped their hands and rocked back and forth. Excuse me for being a little rude here but so fucking what?

There is a good discussion of whether there is value in controlling repetitive behaviors in autistics in the comments to Kev’s post.

I had a different perspective on this–why did they expect citalopram to reduce repetitive behavior? The quoted rationale is that it works for obsessive compulsive disorder. I haven’t seen that many people with OCD, but repetitive behaviors in autism don’t seem all that similar to OCD traits to me.

On the other side of the question, repetitive behaviors are a measurable outcome. This may give some value to repetitive behaviors as a measure of success for autism treatments. This is something often missing from autism treatment trials–a clear, measurable outcome.

That aside, what else can we learn from this trial? The big answer: the placebo effect is alive and well. Consider this from the abstract:

There was no significant difference in the rate of positive response on the Clinical Global Impressions, Improvement subscale between the citalopram-treated group (32.9%) and the placebo group (34.2%)

Both the treatment group and the placebo group saw about 30% of the subjects improve. This was for a relatively short, 12 week, trial.

Citalopram has been used off-label for treatment on autistics for some time. I’ll admit that I was not aware of this, even though there are claims that a huge proportion of children with autism are on citalopram. The reason it is used–doctors believe it works.

The study authors expected there to be benefit for some subgroup:

“We didn’t expect it to work for everyone, but we were hoping that we’d be able to drill down into the population for whom it was very helpful and begin to identify the predictor of what a positive response would be,” he [Dr. Bryan King] said.

This part speaks well of Dr. King (at least to me). He went into this study with expectations of benefit. When the data said otherwise, he went with the data.

We need good trails of autism treatments. It is very easy for doctors and patients to believe there is benefit.

Does this trial mean that citalopram will be relegated to the dust heap of autism treatments? I somehow doubt it. Here is a quote from Dr. Andrew Zimmerman of the Kennedy Krieger Institute:

Zimmerman, the Baltimore autism specialist, said he’s successfully treated younger autistic children, ages 3 to 5, with the drug. He added that he uses smaller doses, which appear to not create as many side effects.

“If you start at a very low dose and build it up slowly, you see improvements in mood and decreases in repetitive behaviors,” he said. “The kids are more attentive.”

No, citalopram is not going away anytime soon.

6 Responses to “Another look at the citalopram trial”

  1. livsjourney June 16, 2009 at 04:25 #

    “On the other side of the question, repetitive behaviors are a measurable outcome. This may give some value to repetitive behaviors as a measure of success for autism treatments. This is something often missing from autism treatment trials—a clear, measurable outcome.”

    This part of the equation always makes my skin crawl a bit. Is the drug designed for the improvement of the condition of the patient, or is the trial designed for a measurable/quantifiable result, regardless of whether the behavior is a primary concern of the patient?

    Now what happens to those autistic patients who also may happen to also be OCD? Now, thanks mostly to the ‘autistification’ of diagnosing issues for people on the spectrum, this drug will probably be discarded for OCD issues on the spectrum. Whether OCD is more prevalent in the autism spectrum is an interesting idea, or should it be considered separately would be a good path to look down.

    But the label and the conglomeration of autism makes it a juicy target market for drug companies looking to cash in on the ‘wave’. Repetitive behaviors would not be the first thing I would be looking to ‘eliminate’, but it appears to be the only quantifiable one they could design a study around…

  2. Kev June 16, 2009 at 06:21 #

    Very good post and _excellent_ comment Bill. Very much agree.

  3. mccpdx June 16, 2009 at 16:36 #

    I do take issue with this post and the previous post on the subject. The truth is the science and the studies have not caught up with Autism yet. So what is a parent and practitioner to do? Wait until there is available science to definitively make a choice about what to do? That’s not really doing her or me any good now.

    So we do the next best thing: we try to make the best decisions about treatment based on small studies, flawed studies, case studies and whatever bits we can pull together, with the goal of not harming the child being top of mind.

    For us, some drugs have had good effects Risperdal has helped a lot and Lamictal is showing a lot of promise. One could have argued based on the logic presented in this article, that an anti-psychotic and an epilepsy drug shouldn’t be effective controlling some symptoms of Autism…but there it is all the same.

    I don’t think we are close to understanding how Autism affects the brain. Our experience SSRI actually increased aggressive mood swings and violence. This is like what one would expect to someone with bi-polar disorder to react when exposed to a SSRI. To me this suggests that some of the brain disorders my daughter has may have some commonalities with bi-polar disorder and maybe some treatment options for bi-polar disorder may be helpful. And some other parents have had good experience with SSRIs. It’s anecdotal to be sure, but it strongly suggests to me that depending on how Autism manifests itself, the condition may have significant differences and require individualized treatment options. This is just one example of how this disorder challenges conventional wisdom.

    We don’t even have the big studies to try and prove effectiveness of treatments across the board, let alone these subsets of Autism that appear to me to be completely overlooked using the current diagnoses criteria.

    So yeah, sometimes things may be tried that don’t make intuitive sense and I’m completely supportive with such efforts because I think the conventional wisdom should be challenged here. That’s not to say anything is game. I’m not going to go out and try a theories that have no basis in reality (GFCF, heavy metal treatments). But I have to do what I can now. I cannot wait for the science to catch up.

  4. livsjourney June 16, 2009 at 23:07 #

    Problem, in my mind, is not that we are trying SSRI’s to improve autistic quality of life, but that they are trying to invent studies that use somewhat facetious and dubious quantifiable outcomes to justify it’s use on an entire genre of diagnosis that now just happens to be 1% of the market segment…I mean patient population.

    “But I have to do what I can now. I cannot wait for the science to catch up.”

    Right there with you. My personal stake in this is that my youngest (5) has made some vast improvements over the past year with her communicative abilities and academic skills; to the point now that we have rethought where her deficits are. It came as an epiphany that what most holds her back today could be considered OCD, rather than the blanket diagnosis ASD.

    It gets me to thinking whether the criteria for ASD is hiding/masking/misdiagnosing other issues; or whether we have cocommitants within the spectrum. Personally, I think there’s a lot of the former in younger kids. We won’t find those differences drugging the entire grade school ASD population with SSRI’s in any event, which is what the pharmaceutical industry’s ultimate goal appears to be…

  5. mccpdx June 18, 2009 at 03:59 #

    I have to disagree across the board here on SSRIs. Now that’s not to say that the drugs companies are looking out for their own interests. I think we can agree that they are. However, their motivations are not important to me if the methodology is sound and negative results are not buried.

    If a child cannot learn because their OCD is in the way, if they are anxious, if they are depressed, and so on, then I think SSRIs might have some merit here. Your stand that the OCD behaviors we see don’t seem the same as traditional OCD behaviors to you, and therefore shouldn’t be studied is arrogant. I’m glad if that’s good enough for you. I would rather have the data there.

    Zimmerman’s observation of lower doses appearing to be more effective than larger doses reinforces what I’ve heard from many, including Dr. Temple Grandin. So yes, more studies with different doses should take place. If it doesn’t work, fine. If it does, great! No one study is going to cover all the bases. We do need a larger body of knowledge before we just start throwing things out.

    I don’t think there is any question that Autism is much more complex than the current diagnoses criteria. It’s a blanket we are throwing over something much larger because we simply don’t know enough. I completely believe the criteria we have now is going to be completely different in 20 years. We’ll shake our heads and wonder why we were content with such poor criteria for so long.

  6. rajensen088 June 18, 2009 at 19:20 #

    Eric Hollander, Director of Psychiatry at Mt. Sinai, has been promoting the use of Prozac (an SSRI) in the treatment of autistic children as young as two years old.

    Hollander published a small study in 2004 that saw improvement in a small group of autistic children treated with the form of Prozac that he and the manufacturer hold an orphan drug designation patent for.

    Hollander is also the director of treatment programs for Autism Speaks and as a result of their small positive initial study, Autism Speaks, conducted a multi-center trial for the use of this form of Prozac (NPL-2008). The study was funded by Neuropharm Group Plc also a co-holder of the patent.

    Autism Speaks published a press release for the study after its completion.

    “The study showed that repetitive behaviors were reduced when children were given either NPL-2008 or a placebo, but no differences between groups were found in terms of the level of reduction of repetitive behaviors. Thus, it was concluded that NPL-2008 was not more efficacious than the placebo”.

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