But another trend has been happening over the same time period - or so it seems to me. This is the rise of small companies who offer techniques for diagnosing mental illness, or predicting which drugs will work best. Generally (it seems) partnerships between venture capitalists and psychiatry (ex-)researchers, these enterprises might be dubbed "Little Pharma".
The latest is a company called AssureRx Health, Inc. According to a paper just published, they offer
a pharmacogenomic algorithm designed to improve the safety and efficacy of prescribing antidepressant and antipsychotic medication... based on the genotyping of both copies of five genes.From this, you end up with a report giving each drug a rating of green, yellow, or red (see above).
The price is not provided on their website.
According to the paper, they gave 26 depressed patients normal treatment at the discretion of their psychiatrist, while 25 got treatment guided by the AssureRx algorithm. It was non-randomized, and unblinded so there's a clear possibility of a placebo effect.
Anyway, the results were...
For the first 4 weeks of treatment, there was no difference between the two groups whatsoever in terms of depression symptom scores - they both improved. But then by week 8, the unguided patients abruptly got worse, while the AssureRx-guided ones continued to benefit. This is an unusual pattern of improvement in an antidepressant trial.
Previously, I wrote about another Little Pharma antidepressant prediction scheme. It used a different approach, measuring brain electrical activity using a technique called "rEEG", rather than genetics. But the basic idea is the same... and so are the problems.
As I said last time:
There were two groups and they got entirely different sets of drugs. One group also got rEEG-based treatment personalization. That group did better, but that might have nothing to do with the rEEG: they might have done equally well if they'd just been assigned to [those drugs] by flipping a coin. We cannot tell, from these data, whether rEEG offered any benefits at all.In the AssureRx paper, we can't even tell whether the two groups got different kinds of drugs, because the meds used aren't reported, but if they did differ then that would offer an alternative explanation for the differences in outcome: maybe the 'guidance' just recommended better drugs overall, with the genes being just a sideshow. Or maybe it's a placebo, as I said.
Moving on, I also wrote...
What's curious is that it would have been very simple to avoid this issue. Just give everyone rEEG, but shuffle the assignments in the control group, so that everyone was guided by someone else's EEG. So you'd give control Patient 2 the drugs that Patient 1 should have got, and vice versa; swap 3 and 4, 5 and 6, etc.It is odd that Little Pharma never seem to do such real vs. muddled prediction studies, as they'd be really informative as to whether their approach is a helpful innovation as opposed to an expensive, meaningless red herring. Hmm.
This would be a genuinely controlled test of the personalization, because both groups would get the same kinds of drugs... and it would allow the trial to be double-blind: in this study the investigators knew which group people were in, because it was obvious from the drug choice...
Hall-Flavin, D., Winner, J., Allen, J., Jordan, J., Nesheim, R., Snyder, K., Drews, M., Eisterhold, L., Biernacka, J., and Mrazek, D. (2012). Using a pharmacogenomic algorithm to guide the treatment of depression Translational Psychiatry, 2 (10) DOI: 10.1038/tp.2012.99
9 comments:
Drives me nuts to see these quasi RCTs being interpreted as more than they actually are; it's like when someone does a RCT for a psychotherapy and compares it to wait-list control and trumpets that fact. It's a low bar to jump over to make sure your therapy isn't hurting someone.
I wonder what the reasons were behind not doing a proper RCT?
Authors have to pay to get their stuff published in Translational Psychiatry. The journal’s website states “Authors are charged an article processing fee of £2,200/$3,600/€2,600 (plus VAT where applicable).” Caveat lector.
Actually I'm not too bothered by that - it's common & sensible for Open Access journals to charge authors, and there are loads of terrible journals that will publish any old rubbish without charging for it. So in my view it's the paper not the journal that's questionable, here.
http://www.plosmedicine.org/article/info%3Adoi%2F10.1371%2Fjournal.pmed.1001326
///(...)After quality control, a dataset of 1,790 individuals with high-quality genome-wide genotyping provided adequate power to test the hypotheses that antidepressant response or a clinically significant differential response to the two classes of antidepressants could be predicted from a single common genetic polymorphism. None of the more than half million genetic markers significantly predicted response to antidepressants overall, serotonin reuptake inhibitors, or noradrenaline reuptake inhibitors, or differential response to the two types of antidepressants (genome-wide significance p<5×10−8). No biological pathways were significantly overrepresented in the results. No significant associations (genome-wide significance p<5×10−8) were detected in a meta-analysis of NEWMEDS and another large sample (STAR*D), with 2,897 individuals in total. Polygenic scoring found no convergence among multiple associations in NEWMEDS and STAR*D.
Conclusions
No single common genetic variant was associated with antidepressant response at a clinically relevant level in a European-ancestry cohort.
Editors'snote: (...)What Do These Findings Mean?
This study was large enough that it should have been possible to find common genetic variants that by themselves could predict a clinically meaningful response to SRIs and/or NRIs, had such variants existed. The fact that the study failed to find such variants suggests that such variants do not exist. It is still possible, however, that variants that are less common could predict response, or that combinations of variants could. To find those, if they do exist, even larger studies will need to be done.///
That study tried to adress the bigest question mark for any psychiatrist with ethics:
Can genetic testing predict if antidepressant drugs will help that person or will you provide him(her)with side-effects and withdrawal symptoms vicious circles only-if that person trusts you and take the pills long enough?
This is mainly off topic, but since it relates somewhat to improving accuracy of treatment, I would like to mention an under reported "coincidence". Borderline personality disorder following concussion and TBI. What is sometimes the case is that when the mysterious symptoms of BPD appear (perhaps not long after an undiagnosed concussion) they are usually treated an-historically, medicated randomly, and maybe compensated for cognitively. I wonder if there have been any studies on this coincidence? Case in point : Football Player Brandon Marshall
Bernard,
Always precious to have you providing a much needed worldly view on some researchers, sincerely.
By the way, has not Pr Charles Nemeroff been given a fabulous grant in order to answer the question the post is about- using an hormonal dosages instead of genetic testing?
retrun,
I am afraid what you report applies to most mental sufferers in the rich western world. We just lack knowledge and the article that post is about didn't really improved that sad reality.The American footballers's brains bank scientists will be a good bet in my opinion on your issue.
@ Ivana Fulli: Dr. Nemeroff got a large grant award from NIMH for a problematic project concerning PTSD. Problem is the validity of the PTSD diagnoses is suspect. See my comment on the Nature News blog: http://tinyurl.com/8exut3p
Where was Thomas Insel, director of NIMH?
26 subjects is not enough especially given depression is so diverse in behavioral manifestation thus suggesting that there are multiple and somewhat independent physiological processes that gives rise to depressive symptoms.
The "bump" in the chart is suspicious to say the least.
Another study not worth publishing.
I wouldn't put too much trust in these weird little studies; but on the other hand I wouldn't do an RCT of a psychoactive drug. Since pharmacogenetic tests have a lot to offer on some fronts (such as sorting out initial doses of warfarin in atrial fibrillation), I would like to see more of them in psychiatry. Getting onto the right medication for an individual is like picking out where to land a plane using a pin on the map. As a long term sufferer from depression, I've been tried on most things that have been invented since reserpine. I'm now happy & without side effects on Venlafaxine, provided I also take daily high-dose fish oils & extra Vitamin D3. I'm sure the high doses I usually require for any response at all on anti depressants is due to some sort of P450 genetic liver factor- I just learnt I could not write off pills until I had tried them for 2 months (unless they sent me to sleep or made me really agitated). I'd love it if there was a way to predict what dose I would need from the start, & I'm sure a lot of others might stick with their pills if they got good advice on dose. I'm keeping a good eye on the researchers at Melbourne University (Australia) who are working on pharmacogenetic prediction of psychiatric drugs.
Post a Comment