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Sep. 18th, 2010 01:16 am![[personal profile]](https://www.dreamwidth.org/img/silk/identity/user.png){kind=small}
urocyonThis was just one of the links I was going to point out, but I had more to say about this one than expected. ;)
Via the disability news section at BBC Ouch!:
New drug eases symptoms of autism
A better writeup: Seaside Therapeutics Reports Positive Data from Phase 2 Study of STX209 in ASD
Argh, just argh. I had somehow managed to miss the attempts at using arbaclofen "to rebalance the brain chemistry of those with autism." (Quotes from the first link.) How exactly using a muscle relaxant for "reductions in agitation and tantrums" is supposed to differ from the use of "anti-depressants and anti-psychotics for particular symptoms", I have no idea. Other than that the researchers want us to believe that it's somehow different.
Here's more on Arbaclofen. It is basically jiggered-with, R-isomer-only baclofen. Apparently, the uses for which it was developed were pretty much the same as baclofen: as a muscle relaxant and for certain GI problems. The side effects are apparently pretty much the same as for baclofen, including "Drowsiness -- in up to 63 percent of people" (pretty much what I'd expect from a muscle relaxant). This is being touted to treat agitation. Hmm...
Fromwhat appears to be the same trial a different trial connected to SeaSide Therapeutics, LLC (???)*--presented at International Meeting for Autism Research earlier this year, we find out that what they were really trying it out on was Fragile X syndrome--according to the beforementioned paper, "the most common known genetic cause of autism, and about 25% of males with FXS meet full criteria for autism", they say--i.e., some people with Fragile X show some behavior similar to some autistic behavior. In this trial, "Of 63 subjects randomized, 55 were male", and they were specifically trying to treat irritability. Apparently, "[i]t is hypothesized that other etiologies of autism may also be characterized by “synapsopathies” (disorders of synaptic function)." So it's all somehow totally the same and safe to generalize.
Why? (Emphasis mine.)
Erm, OK.
What particularly caught my eye in that paper?
One of the well-known problems with baclofen? Nasty withdrawal. They were giving both adults and kids as young as 6 a slightly tinkered-with version of something known to cause physical dependency, then acting surprised when subjects showed "deterioration" going off it. See Acute Intrathecal Baclofen Withdrawal: A Brief Review of Treatment Options: "numerous complications which may require neurocritical care expertise such as respiratory failure, refractory seizures, delirium, and blood pressure lability...Critical care practitioners should be prepared to treat this potentially devastating and often refractory complication of ITB therapy." (also a problem with oral administration). More on withdrawal at Wikipedia.
I have muscle spasticity, and was given benzodiazepines instead of baclofen for it because of the lower (!) risk of physical dependency. I can't find rates for baclofen, since most of the search results apply to the use of baclofen to minimize withdrawal from other substances (alcohol, cocaine, etc.).
Idly looking for previous uses of baclofen for ASDs, I found one from the same conference: Effect of Intrathecal Baclofen On Severe Tactile Defensiveness and Symptoms of Autism Spectrum Disorder, in which a teenager with an ASD got a traumatic brain injury, and the sequelae of that injury were conflated with his ASD. Another with SeaSide Therapeutics, LLC involved: Patent application title: Methods of treating mental retardation, down's syndrome, fragile X syndrome and autism, using--surprise!--baclofen. Gosh, they're getting even less selective here. And they're claiming to treat all this with baclofen "without significant side effects"!
Unfortunately, I have to wonder how many poorly-coping parents will try to get their kids on baclofen, based on reading the reporting in the Daily Fail. Or, about as good, from even less substantive coverage on parentdish.co.uk, New autism drug 'opens doors to treating the disorder', or TheMedGuru's New autism drug offers hope: "However, the small number of people tested in the trail and findings not compared against a placebo drug, come across as negatives. Also, the assessment of the children was purely subjective." Or...
It is probably a good idea for me to link to an older disclaimer post, Psychiatry, freedom, and noninterference. Also a rather good piece (not mine) on How to Recognize Pseudoscience.
_________
* I'm a little confused, but I am trying to read and write through some serious brain fog tonight. The more recently reported one sounds like at least a very similar trial with an expanded subject pool. But, they seem to be looking at the same measures, and the way people with FXS and ASDs keep getting conflated, it's really hard to tell. Confirmed by looking at Seaside Therapeutics' site ("creating new drug treatments to correct or improve the course of
Fragile X Syndrome, autism and other disorders of brain development"), they are different. I can only assume that the conflation was not enough to get eventual approval to flog arbaclofen at people with ASDs instead of FXS.
Via the disability news section at BBC Ouch!:
New drug eases symptoms of autism
A better writeup: Seaside Therapeutics Reports Positive Data from Phase 2 Study of STX209 in ASD
Argh, just argh. I had somehow managed to miss the attempts at using arbaclofen "to rebalance the brain chemistry of those with autism." (Quotes from the first link.) How exactly using a muscle relaxant for "reductions in agitation and tantrums" is supposed to differ from the use of "anti-depressants and anti-psychotics for particular symptoms", I have no idea. Other than that the researchers want us to believe that it's somehow different.
Here's more on Arbaclofen. It is basically jiggered-with, R-isomer-only baclofen. Apparently, the uses for which it was developed were pretty much the same as baclofen: as a muscle relaxant and for certain GI problems. The side effects are apparently pretty much the same as for baclofen, including "Drowsiness -- in up to 63 percent of people" (pretty much what I'd expect from a muscle relaxant). This is being touted to treat agitation. Hmm...
From
Why? (Emphasis mine.)
The rationale for studying arbaclofen (the active entantiomer of racemic baclofen) in FXS and autism is multifold. First, racemic baclofen anecdotally improves behavior in both FXS and autism. Second, racemic baclofen ameliorates abnormal phenotypes in several animal models of FXS, including audiogenic seizures and hyperactivity in the FXS mouse. Third, transcranial magnetic stimulation studies show that racemic baclofen modulates cortical plasticity in healthy control subjects. Lastly, in both human and animal studies, arbaclofen appears better tolerated and more efficacious than racemic baclofen.
Erm, OK.
What particularly caught my eye in that paper?
The interim safety review determined that adverse events were predominantly attributed to pre-existing conditions or viral infections, and none were unanticipated, given the known side effects of baclofen. One subject experienced a serious adverse event, increased irritability, when tapering off study medication (subsequently unblinded and determined to be arbaclofen). Other subjects showed similar deterioration when blinded study medication was titrated downward. On the independent monitor's recommendation, enrollment was then extended to age 6.
One of the well-known problems with baclofen? Nasty withdrawal. They were giving both adults and kids as young as 6 a slightly tinkered-with version of something known to cause physical dependency, then acting surprised when subjects showed "deterioration" going off it. See Acute Intrathecal Baclofen Withdrawal: A Brief Review of Treatment Options: "numerous complications which may require neurocritical care expertise such as respiratory failure, refractory seizures, delirium, and blood pressure lability...Critical care practitioners should be prepared to treat this potentially devastating and often refractory complication of ITB therapy." (also a problem with oral administration). More on withdrawal at Wikipedia.
I have muscle spasticity, and was given benzodiazepines instead of baclofen for it because of the lower (!) risk of physical dependency. I can't find rates for baclofen, since most of the search results apply to the use of baclofen to minimize withdrawal from other substances (alcohol, cocaine, etc.).
Idly looking for previous uses of baclofen for ASDs, I found one from the same conference: Effect of Intrathecal Baclofen On Severe Tactile Defensiveness and Symptoms of Autism Spectrum Disorder, in which a teenager with an ASD got a traumatic brain injury, and the sequelae of that injury were conflated with his ASD. Another with SeaSide Therapeutics, LLC involved: Patent application title: Methods of treating mental retardation, down's syndrome, fragile X syndrome and autism, using--surprise!--baclofen. Gosh, they're getting even less selective here. And they're claiming to treat all this with baclofen "without significant side effects"!
Unfortunately, I have to wonder how many poorly-coping parents will try to get their kids on baclofen, based on reading the reporting in the Daily Fail. Or, about as good, from even less substantive coverage on parentdish.co.uk, New autism drug 'opens doors to treating the disorder', or TheMedGuru's New autism drug offers hope: "However, the small number of people tested in the trail and findings not compared against a placebo drug, come across as negatives. Also, the assessment of the children was purely subjective." Or...
It is probably a good idea for me to link to an older disclaimer post, Psychiatry, freedom, and noninterference. Also a rather good piece (not mine) on How to Recognize Pseudoscience.
_________
* I'm a little confused, but I am trying to read and write through some serious brain fog tonight. The more recently reported one sounds like at least a very similar trial with an expanded subject pool. But, they seem to be looking at the same measures, and the way people with FXS and ASDs keep getting conflated, it's really hard to tell. Confirmed by looking at Seaside Therapeutics' site ("creating new drug treatments to correct or improve the course of
Fragile X Syndrome, autism and other disorders of brain development"), they are different. I can only assume that the conflation was not enough to get eventual approval to flog arbaclofen at people with ASDs instead of FXS.
