Thursday, November 17, 2011

The RIght Med for the Right Brain - Not There Yet

Yesterday’s piece, Brain Science and Recovery, ran through a list of some of my favorite psychiatric genes, which - quite ironically - may signal the end of psychiatry as we know it. The exercise sent me back to my old notes, from an eye-opening session at the NAMI Convention in Chicago in early July.

“Emerging Technologies to Improve Care,” read the name of the session in my program book. I waltzed in late, trying to shake myself awake, prepared to make a hasty exit.

“The way psychiatrists practice right now,” I heard one of the panelists say, “is all trial and error.”

Suddenly, I was wide awake. I flipped through my program for the name of the speaker -  Jay Lombard MD, chief scientific officer at a Norfolk company called Genomind. Its website says:

Many patients complain of mood disturbances, including depression and anxiety. However, despite the commonality of these complaints, there is significant biochemical heterogeneity regarding the etiology of mood disorders, which may account for the high rate of treatment failures or adverse side effects.

OK, here’s the English translation. A depression is not just a depression. There are many biological-environmental causes, which makes one-size-fits-all treatments such as antidepressants not only a joke, but lamentably bad medicine.

Dr Lombard reeled off some of the same genes I listed in yesterday’s piece. A quick review:

Serotonin transporter gene: Regulates serotonin reuptake. A variation results in a hyperactive amygdala that results in over-reaction to stimulae, with downstream anxiety, depression, and other conditions.

BDNF: Regulates cell maintenance and survival, neural growth and connectivity. A variation results in inefficiencies in these processes, leading to moodiness and anxiety.

COMT: Breaks down dopamine. A variation impacts signaling in a way that raises the risk of schizophrenia.

MAO-A: Breaks down dopamine. A variation results in a hyperactive amygdala and low-responding cortical areas, resulting in difficulties controlling impulses, leading to aggressive behavior.

In addition, Dr Lombard noted three more, namely:

DRD2: Antipsychotics bind to this receptor. A variation results in poor binding and a bad med response.

Methylfolic acid gene: Breaks down folic acid. A variation results in B vitamin deficiencies that may lead to depression.

Calcium channel gene: Regulates the intake of calcium into the neuron. A variation results in too much calcium which ramps up excitability, with risk of bipolar, schizophrenia, and treatment-resistant depression.

So -  maybe if we can pinpoint the actual physical malfunction that is contributing to our bad moods and behaviors, we can target our treatments accordingly. This would represent a quantum leap over our current mindset of throwing meds at diagnostic labels. 

Daniel Hoffman MD, president and chief medical officer at the Denver-based CNS Response, put it this way: “The world wants buckets of symptom clusters and it doesn’t work.” He quoted Thomas Insel, head of the NIMH to the effect that the DSM is 100 percent reliable but zero percent valid.

In other words, doctors may all be in agreement on what schizophrenia or bipolar may look like, but they may also be unanimously wrong. “Why we’re spending so much time on the DSM-5 is beyond me,” he went on to say.

Instead of symptom clusters, we need to be looking at neurological outcomes that correlate to specific parts of the brain. Otherwise, “we are doing harm.”

He wasn’t through. Citing STAR*D (which most unequivocally demonstrated the limited efficacy of antidepressants), he observed: “What Pharma told us about these meds didn’t pan out.”

Maybe you can see where this is going, real diagnostics based on bio-markers: A saliva kit to tease out problematic genes, a blood test to differentiate bipolar from schizophrenia, qEEG to read brain waves. All of these are just about ready for prime time. The biggest issue is getting the insurance companies to reimburse.

About one third of patients diagnosed with ADHD, said Dr Hoffman, don’t have the neuropathology for it. Kids with ADHD have very specific EEG patterns. But we don’t give up on the non-ADHD kid. In essence, we are looking for “the right drug for the right brain.”

What a novel thought.


Lizabeth said...

We can only pray we live long enough to see some of this hit the market. I probably won't even complain about the prices. I like these last two columns better than the ones about Whitaker.

I got his book on my Kindle, read about half of it and had an anxiety attack like I have not had since the last time I was in Hospital. I am a big believer in reading before commenting but in this case I can't---husband got furious at me and wanted to know why I was reading it when my meds are working just fine. So I won't comment on the book.
I will say we are not the only group that has gone thru often ineffective or marginal treatments before medical science got it right.
People with TB used to be sent to sanitariums. And their pallor was much admired. Lots of cancers (there is no such thing as one over-all cancer) are still hit or miss. And of course there is the AIDs/HIV combo,Type One diabetes (bad--thats the one that hits kids) and asthma and assorted breathing difficulties. Also cardiac problems and inborn defects-my older sister died as a baby before I was born from one they can fix now.
So we are unfortunately, not alone. And I still hope to live long enough to see the real world hit your last two columns.

John McManamy said...

Hey, Lizabeth. I fully appreciate where you are coming from. Just so there is no misunderstanding: I validate where Whitaker is coming from without endorsing him. I wish psychiatry would constructively engage with him in good faith, and I find it highly disturbing that they don't.

That leaves any intelligent commentary to we who live with mental illness. So I would love to hear from you. This would guide me, and inform our community. I see this issue as a "conversation." You're in a safe place here.

Re your other point: You took the words right out of my mouth. I'm a great believer in medical science eventually getting it right, and I'm so glad to have this validated by you. Sometimes I feel all alone talking about brain science. Whitaker is very deficient in his appreciation of what's going on under the hood. If you were upset at the first part of his book, you will be incensed at his last chapter. He must have had Mad Pride ghost-write it for him.

Heather said...

Brain science for the win(usually!) Your articles and blogs posts are greatly appreciated, John. Please don't feel alone in your curiosity or investigation of the swirling mass of brain research. I find it fascinating and validating, especially around the non-medical and more recovery-based principles and practices. I have been avidly reading your sites for over a year now and attribute significant strides forward in my own recovery to your ability in providing information, insight and wicked good humor.

John McManamy said...

Many thanks, Heather. I couldn't imagine doing any other kind of writing - and you just told me why. :)

Herb said...

Hi John,

I hope all is going well with you and yours.

I extend my additional compliments to you on your recent Brain Science writings. I couldn’t agree with you more. As the science and investigation of the brain into its genetics and relationships, although too slowly for me, they’ll find the same possible answers and/or treatments as they are currently doing for cancer.

I recently was invited by a close friend to attend an Awareness Luncheon sponsored by the Moffitt Cancer Center in Tampa, FL. My friend, a Multiple Myeloma survivor lectured along with Eric B. Haura, MD – Thoracic cancer specialist. I recorded the event but more importantly I was fascinated by Dr. Haura and his team’s unique and individualized research into patient faulty genes and their treatment approach.

I think you might find Dr. Haura’s presentation to the lay-person of interest as I think this same approach will be applicable someday to those suffering serve mental illnesses.

One last point as I chuckled to myself when you wrote, “The way psychiatrists practice right now,” I heard one of the panelists say, “is all trial and error.” Some five decades ago I coined the phrase, “The Trial and Error Approach to Wellness”. Sadly it still is practiced that way today but hopefully in the near future the correct brain treatment will be applied to the right patient.

I hope you had a good Thanksgiving as I wish you and yours and all those reading you’re very worthwhile posts, wellness and all the good you’d wish for yourselves as well as a Happy Chanukah, Merry Christmas and a Happy, Healthy, Prosperous and Peaceful New Year.


John McManamy said...

Hey, Herb. Good to hear from you again. :)