I've decided I am rooting for neuronal survival during the NFL SuperBowl today.
I've decided I am rooting for neuronal survival during the NFL SuperBowl today.
Almost by definition there is something wrong with the mental health of mass shooters like the Aurora cinema guy, the Sikh Temple shooter and the one who just killed 20 elementary school children, 6 staff members, his own mother and ultimately himself.
In parallel with the calls for better gun control in the US we experience calls for improved health care for the brain. But the failing is not the provision of care so much as it is the detection of mental health problems that might lead to mass shootings.
We will never get to a one to one prediction of who is about to become the next news cycle. But then, we don't know who will heal eventually from a given infection, who will recover from stroke without a given intervention...or who will get heart attack save for the cholesterol meds, statins and what not.
So we go with the odds.
And we detect problems with broad screening (annual checkups), acute responses (minor cardiac event perhaps)...and crowdsourcing.
If someone were bleeding in front of you, chances are decent that you would know whether to get a bandaid (even a 5 year old knows to add the antibiotic cream) or stick a finger on the vein while yelling for help. In a crowd? Someone would know CPR if a person stops breathing...in a pinch you'd have a go based only on what you remember from teevee shows.
What about when someone shows signs of a mental health problem? How does the crowd and pre-FirstResponse do with those situations?
I have only recently been made aware of Mental Health First Aid.
It intrigues me.
Hard on the heels of something I just learned about at a recent conference, the NIMH issued a Press Release for a new clinical trial they funded.
A drug that works through the same brain mechanism as the fast-acting antidepressant ketamine briefly improved treatment-resistant patients’ depression symptoms in minutes, with minimal untoward side effects, in a clinical trial conducted by the National Institutes of Health. The experimental agent, called AZD6765, acts through the brain’s glutamate chemical messenger system.
Interesting. The background is that prior studies* have shown that the dissociative anesthetic ketamine is capable of the rapid (within hours) amelioration of depressive symptoms. Yes, ketamine. The recreational drug known as Special K and the veterinary anesthetic they've used on your pet cat or dog. Same ketamine that is approved for human use in pediatric anesthesia, emergency medicine in some cases and for tricky clinical situations.
The same ketamine that has been widely used for decades in humans and nonhuman animals. It has established efficacy, mechanism of action and a huge therapeutic index. A big distance between effective doses and the dose that will kill you. Whether effect is recreational, medical or veterinary. Meaning it is safe.
So why are the studies (cited below*) of effect in depression so exciting? Because traditional drug therapy for depression takes weeks to have effect. Weeks of daily dosing. Selective Serotonin Reuptake Inhibitors (SSRIs) like Prozac are broadly familiar to most of my Readers, I would assume. Efficacy with these front-line meds takes up to three weeks to see effect on depressive symptoms. Trouble is, some cases of depression are acutely suicidal--they may just kill themselves before any SSRI has a chance to make them feel better. And hell, who wants to wait three weeks if another med could make you feel better by tomorrow? Prior to the ketamine work, the only other thing that seemed to have such a rapid effect was ECT. Yeah, ElectroConvulsive Therapy. Which has come a loooooong way from the One Flew Over the Cuckoo's Nest era....but still. A single ketamine dosing seems quite preferable.
So.....on to the me-too drug development! Woot!
Zarate CA Jr, Mathews D, Ibrahim L, Chaves JF, Marquardt C, Ukoh I, Jolkovsky L, Brutsche NE, Smith MA, Luckenbaugh DA. A Randomized Trial of a Low-Trapping Nonselective N-Methyl-D-Aspartate Channel Blocker in Major Depression. Biol Psychiatry. 2012 Nov 30. pii: S0006-3223(12)00941-9. doi: 10.1016/j.biopsych.2012.10.019. [Epub ahead of print][Publisher, PubMed]
This AZD6765 compound is, as you might deduce from the letters, property of AstraZeneca Pharmaceuticals and indeed one of the authors lists this as his affiliation. The rest of the folks are from the NIMH intramural program which, presumably, provided the majority of the funding for the study.
The conclusions appear to be that this novel compounds, with a similar mechanism of action as ketamine worked but less well. From the Presser:
About 32 percent of 22 treatment-resistant depressed patients infused with ASD6765 showed a clinically meaningful antidepressant response at 80 minutes after infusion that lasted for about half an hour – with residual antidepressant effects lasting two days for some. By contrast, 52 percent of patients receiving ketamine show a comparable response, with effects still detectable at seven days. So a single infusion of ketamine produces more robust and sustained improvement, but most patients continue to experience some symptoms with both drugs.
However, depression rating scores were significantly better among patients who received AZD6765 than in those who received placebos. The researchers deemed this noteworthy, since, on average, these patients had failed to improve in seven past antidepressant trials, and nearly half failed to respond to electroconvulsive therapy (ECT).
So this is good. Anything that shows promise as a rapid-alleviator of depression is good by my lights.
But why is NIMH spending taxpayer dollars to develop me-too drugs? Look, I recognize that drugs within a class of pharmacological mechanism, like the SSRIs, may be differentially effective for different patients. And it is a good thing if we have more options to tailor medication to the individual patient. ADHD is another situation where an array of monoamine transporter inhibitors, including methylphenidate and amphetamine, are used with success and failure. One drug works for one patient, another works for a different patient....and they might describe the other medication as even worse than not being treated. So...great.
But make no mistake. The central feature driving me-too drug development is profit. Drug companies decide they can take a big enough slice of the market away from the market-leader to make it worth their while. Perhaps they had development in parallel and had sunk enough cost in by the time their competitor gained FDA approval that there was no turning back. Whatever. Point being that they are in it for the money and not for some noble cause of serving that subset of patients that do not gain relief from their competitor's drug.
Over the past few years the side-chatter about the ketamine effect on depression has frequently been a lament about the lack of financial motive for companies to push forward with ketamine. Push forward with specific clinical trials to gain on-label approval for the indication of depression. Push forward with marketing campaigns. Push forward with physician education and stroking like they do with their proprietary stuff.
The Zarate paper took a stab at claiming the reason for developing something else was an attempt to avoid the adverse effects of ketamine. The dissociative type effects can be unpleasant and recovery doesn't look fun. So there's some toehold there to claim one is motivated to find a "perfect" drug which somehow produces the therapeutic effect with nothing else. Color me skeptical, given what I know about existing NMDA channel blockers like ketamine (and PCP, did I mention that? Yeah, angel dust might work for depression....).
So I smell profit motive in this effort.
What I don't understand is why NIMH is involved with this. Why not just pursue the evidence body for ketamine?
*References pulled out of the paper
R.M. Berman, A. Cappiello, A. Anand, D.A. Oren, G.R. Heninger, D.S. Charney et al. Antidepressant effects of ketamine in depressed patients. Biol Psychiatry, 47 (2000), pp. 351–354
N. Diazgranados, L. Ibrahim, N.E. Brutsche, A. Newberg, P. Kronstein, S. Khalife et al. A randomized add-on trial of an N-methyl-D-aspartate antagonist in treatment-resistant bipolar depression. Arch Gen Psychiatry, 67 (2010), pp. 793–802
C.A. Zarate Jr, N.E. Brutsche, L. Ibrahim, J. Franco-Chaves, N. Diazgranados, A. Cravchik et al. Replication of ketamine’s antidepressant efficacy in bipolar depression: A randomized controlled add-on trial Biol Psychiatry, 71 (2012), pp. 939–946
G.W. Valentine, G.F. Mason, R. Gomez, M. Fasula, J. Watzl, B. Pittman et al. The antidepressant effect of ketamine is not associated with changes in occipital amino acid neurotransmitter content as measured by [(1)H]-MRS Psychiatry Res, 191 (2011), pp. 122–127
M. aan het Rot, K.A. Collins, J.W. Murrough, A.M. Perez, D.L. Reich, D.S. Charney et al. Safety and efficacy of repeated-dose intravenous ketamine for treatment-resistant depression Biol Psychiatry, 67 (2010), pp. 139–145
Gurdur has an excellent post on "How not to criticize psychiatry". It's a must read.
Many psychomedications - just like many medications in general - can have bad side-effects. So do you for example recommend vaguely against antibiotics or cortisone or aspirin because in each case there can be bad side-effects? Or how about whether Lipitor (a statin, used to lower cholesterol level) can cause memory loss or not? Or chemotherapy meds that can really go to town in side-effects? This is yet again the hurdle of lack of exactness; a very vague accusation made without context or consideration. There is also the factor that a severe mental dysfunction is itself very dangerous to the sufferer - and as with many other conditions, such as the also-as-yet-poorly-understood autoimmune conditions, it becomes a matter of weighing risks and effects of a medication against risks and effects of the original illness.
Likely because like most people, most skeptics etc. simply don't know enough about psychiatry - or medicine in general. Access to good healthcare is an even more important issue, and includes psychiatry, yet just how many skeptics, atheists etc. cover health and healthcare issues in any detailed depth? Very few indeed. SC is right to say psychiatry should be a concern for the left, for skeptics, for everybody. But then so too should immunology, paediatrics, and practically every other branch of medicine. Health care is a pressing concern, and often very much a class issue too.
I invite you to put the new blog of Professor J. David Jentsch on your list. At the unlikely activist you will find fare such as:
If they are remarkably lucky and have proper medical and psychological support, they may return to a healthy life and never use again. But for most, their freedom is only temporary, and they will relapse again days, weeks, months or even years later, returning them to their suffering and to their fateful spiral. You see, drugs kill. They are powerful toxins that can stop breathing or a heart. If they are injected, they can bring infectious diseases like hepatitis and HIV along with them. And because they intoxicate the mind, they lead to reckless driving and other behaviors that risk the lives of the addict and those around them.
Put differently, juveniles and teens have a brain fully capable of feeling powerful emotions (like anger), but their ability to resist those emotions and to behave in a socially appropriate manner (like to inhibit aggressive reactions) is not at adult levels. The 5 justices who struck down harsh penalties for child offenders recognized this; it was a crucial part of their logic in this, and the earlier death penalty, case.
But like a frightening number of people in our society, the other 4 justices viewed the science as either being wrong or irrelevant. Their own ethical or philosophical views about crime and punishment appeared to trump their interest in scientific principles and facts. In this regard, they are not unlike strident animal rights activists opposed to biomedical and behavioral research involving animals.
In the fall of 2010, an animal rights extremist sent me razor blades and heinous threats to cut my throat in the mail. It became a national news story, again highlighting the abject cruelty of some in the anti-vivisection movement. During this time, I turned on my phone one evening to see that I had received a voice mail. Anticipating the worst – yet another cruel, rabid and profane threat from my opponents – I found something quite different. I have kept this communication private for long enough. Now, at the wishes of the caller, I am sharing it with the broader community to demonstrate that support for humane animal research is everywhere…. It comes not from greed or ignorance, but from love and a hope that no one should ever suffer the same loss as the caller.
VoiceofSupport (click on this link to listen to this .wav file)
Don't forget DrZen's comment:
Freud was a comparative neuroanatomist who made significant discoveries: http://bit.ly/vf3qK
A letter to the editor has recently been published in the Journal of Neurophysiology by authors Ringach and Jentsch. You may recall that these individuals are neuroscience researchers who have come under attack by extremist animal rights activists. These brave investigators have been stepping up in public to defend the conduct of animal research. The letter asks for your help, DearReader, as do I. Ringach and Jentsch conclude their letter as follows:
Despite being in the spotlight, our work is not different from the majority of articles appearing in the pages of this Journal and has always been in compliance with all the regulations on the use of animals in research. Investigators using primates, mice, or flies have been assaulted, so nobody can feel at ease. With an expanding list of investigators listed in the extremists' crosshairs, it is clear that anybody could be next.
Enough is enough! We believe time has come to express our outrage at the activities of animal rights extremists and to request from our political representatives the security we and our families need to carry out our work. We believe that time has also come to discuss, debate, and express our opinions on the importance and ethics of animal research. Perhaps, most important, the time has also come to defend our research collectively and not to let only those under attack confront their plight alone.
One place to start is to stay aware. Follow @RaisingVoices and read / bookmark the Speaking of Research pages on ARA activities / talking points and research facts.
Sign the Pro-Test petition in support of the use of animals in well-regulated and responsible research.
Greg Laden has an absolutely fantastic post up on "The Falsehoods" in which he observes:
Biology is harder to learn than quantum physics. Why? Because most people think they totally get biology, but everyone knows nobody gets quantum physics. Therefore, any effort to explore quantum physics will result in new learning, but people rarely learn new biology. The bottom line is that our brains are full of biology, which would be good if most of it did not consist of falsehoods.
This is great stuff.
The CSR directives assure us that the priority scores for our grants will be available on eRA Commons within 3 working days of the conclusion of the study section meeting. Of course, we have generally been waiting 4-5 months after initial submission for the study section to be held for a given grant.
Why do we do this?
The man who constituted one of the best explored case studies in cognitive psychology, perhaps the best explored case study ever, has passed away. As reported in the Montreal Gazette:
The 82-year-old man scientists have known only as HM died of heart failure Tuesday after decades in a Connecticut chronic care home, unaware of what he gave to science.
In short, H.M. suffered intractable epilepsy for which he underwent a removal of large portions of his temporal lobes. Although successful in curbing his seizures, the procedure resulted in a anterograde memory loss resulting in an individual stuck in time. The rather selective nature of his impairment led to a huge number of investigations and information on the neuronal basis of various processes that we think of under the general term"memory".
RIP, H.M., voluntarily or not you are a lion of science.
[additional here; h/t: PP]