When Medication Fails: What EEG Endophenotypes Reveal

Medication shouldn’t feel like guesswork, but for a lot of people it does, especially after a long string of “nothing worked.” We sit down with EEG and QEEG leader Jay Gunkelman to talk about a more grounded path: using brain endophenotypes to understand why the same diagnosis can respond to totally different medications, or to none at all.

We dig into what shows up when you look at incoming EEGs from people referred specifically for medication failure. Jay explains why focal slowing can be a sign that the problem is local and organic, not something you can fix by medicating the entire brain. We also unpack spindling excess beta and what “overarousal” looks like in the data, plus why certain common medication choices can accidentally push the nervous system in the wrong direction.

Then we get into the most overlooked conversation in psychiatry: epileptiform discharges without obvious seizures. Jay shares why spikes can still be clinically meaningful, how they can show up as false emotion or false memory, and why an empirical anticonvulsant trial can sometimes change everything. From addiction neurofeedback protocols (including alpha-theta and anterior cingulate targets) to ADHD subtypes tied to dopamine, norepinephrine, beta spindles, and discharges, the through-line stays the same: test first, then treat what you find.

If this helps you think differently about ADHD meds, OCD treatment response, precision psychiatry, or neurofeedback planning, subscribe, share this with a colleague, and leave a review so more people can find brain-based care that actually fits.

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Transcript

Welcome And Big Promise

SPEAKER_00 0:02

Welcome to the Transformative Neurotherapy Podcast with your host, Dr. Heather Pope, founder and executive director of Transformative Neurotherapy. This is the place where feelings happen faster. Because let's face it, your brain doesn't come with. Here we take a holistic approach to brain health, brain together styles, mind body harmonies, and the tools you need to optimize your well-being. Whether you're a high performer, athlete, hacker, or just someone tired of your brain for 50, Dr. Putney is here to help you unlock your full potential. From brain fog to chronic stress, we are covering it all so you can finally experience brain health, mind harmony, and total well-being. Ready to get on stock? Let's get started.

SPEAKER_01 0:56

Medication response can feel unpredictable, but brain endophenotypes bring clarity. Let's explore how phenotype-based insights guide smarter clinical decisions. Welcome everyone.

How Phenotypes Guide Medication Choices

SPEAKER_01 1:10

Back in the studio with the infamous Jay Gunkelman, a top leader in the field of EEG and QEG, and the um the I don't know, the the the father of um the world of phenotypes for you know an understanding and how to do that.

SPEAKER_02 1:29

And that's been and that been called worse.

SPEAKER_01 1:35

This is such a huge um gift to the field to understand phenotypes. So we talked a little bit about that in the last episode, how that can guide treatments, especially with like neurofeedback, neurotherapy type of things, but it also can have a huge implication in the medication arena. So can you tell me a little bit more what you've learned from your work about how this interacts with medications and how that can help practitioners like myself or others?

SPEAKER_02 1:59

One of my clients was a psychiatrist in Houston. And over a decade, I had done about 2,000 reports for them. And the the psychologist who is running the EEG, QEG portion of that psychiatrist's office practice, uh, met with me weekly to go over them one at a time. And when the EEG had something that suggested a medication based on the phenotype, I would make the recommendation. So they had my recommendations for a long period of time. And over that period of time, Ron Swatsina, who's the psychologist, um decided that he he wanted to get the IRB to approve access to the data that's de-identified for research because they had 2,000 patients' data. And so they they he went to the trouble of getting it all de-identified and going through the the hearing structure of the IRB to uh get it all cleared. And he called me one day and said, gee, I'm excited. We we got uh uh IRB approval to do research on it. What should we do? So and I said, Well, your psychiatrist is uh a uniquely positioned psychiatrist at the bottom of a funnel of psychiatric medication failure. Doctors who can't find a medication at work send their patients to your doctor to get it figured out. That's why you're doing this EEG stuff, you know.

Cluster Analysis On Medication Failures

SPEAKER_02 3:32

So find all the ones who came in with a referral of medication failure and look at their incoming EEG. And I want you to do a cluster analysis to add one more cluster and one more cluster and one more cluster until the cluster doesn't make EEG sense. And because cluster analysis will find another cluster. It's just a matter of it's gonna be, is it a reasonable real cluster, or is this just another one that's found? So it uh he found four. And focal slowing predicted medication failure about half the time. And when you have a focal slow problem in the EG, that's not a psychiatric, I mean, if this is a psychiatric patient. A focal slowing is something anatomically wrong with a local spot in the brain. And this is you can't medicate the whole brain to fix this one little spot that's not working. This is a prediction that you probably have a white matter lesion or that uh uh uh a Lyme insistment, uh uh a subdural hematoma. There's something organic, pathology of some sort there. And medication is really just not the approach. And that was the biggest one. Spindling excess beta. This is gigantic sinusoidal beta spindles, not just some beta mixed in. And spindling excess beta was a predictor as well. And for those they were grossly over aroused, and uh quite commonly they were given the wrong kind of medication in order to counterbalance things. Um epileptiform content, big spike discharges. Now, if you see a spike, you'd think, well, an anticonvulsant. But let's say you took this spiky discharge EEG and you ran to the next door neurology office and you said, Doctor, look, a spike discharge. They'd look, oh yeah, that's a spike discharge. Uh-huh. Well, would you medicate my client? Are they having a seizure? No, they're a psychiatric patient. Well, I'm sorry, we don't give anticonvulsants unless they're having convulsions. So they would deny the care that would be needed. Now, I made the recommendation

Spikes, Anticonvulsants, And 85% Wins

SPEAKER_02 6:05

for an empirical trial and an anticonvulsant because they had spikes in their EEG. Because the phenotype says anticonvulsant. Not diagnosis, but but the EEG. So they came in with a psychiatric diagnosis, no seizures at all, and we suggested an anti-con anticonvulsant for them, and 85% of the time they got better. That's an 85% hit rate that would be denied. That care would be denied by the neurology because they don't treat the spike. They will say, we don't treat the EG, we treat the patient. Yes. I come back at that every time I say, Well, who do you think made the EEG? I didn't take out a Sharpie and draw this, you know. Uh the uh come on. Uh uh, your patient has spikes in the EEG. Well, they're not all meaningful. You know, Yuri Kropotoff and I lectured together in Australia once. A neurologist took a CPT task, a go-no-go task, and uh recorded 20 minutes of EEG. I left the room, I've seen too many recordings, I caught up on my email and whatnot. I came back in and they're cleaning up the data. And I say, Oh, look, left frontally, there's an epileptoform discharge left frontally. Well, the guy's a neurologist, you know. And and and first of all, he says, I'm surprised anybody saw it. Well, like, I'm not gonna see it, you know. Uh uh, I've got a very sensitive eye, uh, and I I see things. So uh he said, but they're meaningless. That's that's a neurologist who sees his own epileptiform discharge and says it's meaningless. That's what he thought was real. But he just did a 20-minute CPT task. There were two omission errors, no commission errors, good reaction time, low variability, normal performance for an adult. The two discharges happened during the two omission errors. Now tell me that those discharges are meaningless, Doc. And he lost color. He went whiter than he was. He had a bit of a tan, you know. So but uh uh and and you know it it's it's hard to think of that pathology as a problem until you actually see the problem. And he thought it was just electrographic and meaningless, but they're not. Uh they're they're a disturbance in function, and you've got to fix that. Now, if it's disturbing you so much that you've got a psychiatric presentation, the discharges are significant enough to be clinical. You could have pseudoblubber affect, a false emotion, uh, a discharge in the hippocampus, a false memory, a discharge in the amygdala, a false emotion. And you could be reacting to those as though they were real for because for you they are. I mean, they they came out of your own brain, not from something outside yourself, objective reality. They came from your own internal reality, but you're gonna react to them. And you know, a fit of rage, a fit of laughter, a fit of crying that don't make sense objectively, and it's a discharge. And if you fix the discharge, they get rid of the psychiatric disturbance.

SPEAKER_01 9:28

So we 85% improvement in you know in the field of psychotherapy or or you know, psychiatry is just massive.

SPEAKER_02 9:38

I didn't do the math. Is that a significant value? Uh I should have done a P value somehow, some of the standard deviation. I don't know. Um, but 85% success for a medication is unheard of. You know, it really is. But that's the stats. I mean, that was an N of 76 people. It's not 85% of an N of 10. You know, you know, well, we got most of them, you know. But actually a good enough

Addiction Drives: Overarousal Vs Compulsion

SPEAKER_02 10:09

number. Now, uh in addiction, we we worked in addiction, and addiction's a DSM category. Um I consume something I shouldn't be consuming. I'm addicted to something and I'm taking it for some reason. Why are you taking it? Well, there's two drive mechanisms that we identified based on the phenotypes. Number one drive, the biggest drive, two-thirds of the people had over-arousal. I'm so agitated and over aroused, I have to take something and calm myself down, like the alcoholic who needs to saturate their GABA. And that's fast alpha, low voltage fast, or beta spindles. Those three phenotypes all are overarousal patterns, and all three of those are going to be addicted. And they need alpha theta to drop their arousal level. If they have beta spindrels, they get SMR, then alpha theta. If they're fast alpha, they go straight to alpha theta. If they have uh low voltage faster beta spindrels, they get SMR first and then alpha theta. But two-thirds of the people got alpha theta not because they were addicted, but because their EG phenotype told us that's what they needed. They came into the addiction treatment program, but we didn't think of them as addicts as a DSM category that needed a specific protocol. We looked at their EEG and it told us what to give them. And two-thirds of them said, I'm here for alpha theta. And uh that's what we gave them. And it worked wonderfully. The other one-third had an anterior singulate problem. Now, Penniston got 70% success. That's the two-thirds with the over arousal pattern. Uh, we got at the end of one year, Woodcock Johnson III repeat follow-up study. All the neurocognitive scores are improved by an average of 20 points, an IQ jump of 21 points. 21 points IQ jump from normal to superior. You know, and again, across the board, about 20 standard uh score points improvement neurocognitively. No neurocognitive category got worse at all. All of them improved significantly. And the one-third that didn't get alpha theta got trained at the anterior singlet because their drive was obsessive-compulsive. I'm not over aroused. I just really have this compulsion to consume this, whatever gas station heroin, you know. I mean, whatever stupid thing it is, they have an obsession with it and a compulsion to do it. And until you fix that, it's going to be symptom substitution. Oh, I can't get gas station heroin? Well, I will find something else. You know, if if you're just working on arousal and they have an OCD drive, they will be clean and sober, but maybe hooked on internet porn. You know, the the singlet is quite flexible. It's sex, drugs, and rock and roll, ready to go. You know, just it'll find something to drive its pleasure center with, you know, and if it the OCD uh for drugs isn't there, it'll find something else. If you fix the drive, you don't have a dry drunk. You have somebody who's cured. No drive, no behavior. Isn't that what they tell you in the books? If you get rid of the drive, the behavior associated with the drive is supposed to go away. And all we were doing is getting rid of the drive. Alpha theta to get rid of overarousal. And, you know, uh obviously that that's just the overarousal pattern. The anterior single people had to have frontal work trained. And alpha theta is done at the back of the head. Different people recommend different kinds of combinations, but it's all basically at the back of the head where alpha and alpha theta tend to

Why Alpha Theta Changes Access

SPEAKER_02 14:23

be. And the good thing about alpha theta is that you train the alpha up. So that's adult conscious awareness, and you hold enough of it during the theta, which is unconscious, preconscious material, and you're now consciously aware of your unconscious, so you can start to make changes in it. Most of the time, there's a kind of a hard barrier between our conscious and unconscious world, and alpha theta makes that barrier rather permeable. So it it it it does give us access to that.

SPEAKER_01 14:57

And uh, Jay, I've read a lot of your you know, papers and a lot of your work, and um, I know uh another uh the condition

ADHD Endophenotypes And Med Matching

SPEAKER_01 15:06

that is that you talk about a lot is ADHD with the endophenotypes and and and maybe how what you see with the endophenotypes um and how that predicts what you should be doing. Can you speak a little bit more to that? Because ADHD is a very hot topic, and a lot of people are interested in how to how to help themselves with that.

SPEAKER_02 15:23

So ADD ADHD is again a behavioral-based diagnosis, so it's not a uniform homogeneous group. You could have frontal theta. Frontalcentral theta means you have a dopamine deficit. That's probably DA2 genetics. Dopamine transferase is an enzyme that strips away dopamine in the frontal. And so if you have ADD in the family, it's probably that genetic ADD DAT, and you have frontalcentral theta. Methylphenidate's a dopamine reuptake inhibitor, it'll plug the leak basically to keep your dopamine around. So if you have frontalcentral theta, it means you need dopamine reuptake inhibitor to fix that leak. And if you don't have theta, but you have slow alpha, the dopamine isn't going to be something that fixes anything. Slow alpha in the back of your head could be simply from norepinephrine insufficiency, which you get from amphetamines or Stratera, which is a re-uptake inhibitor for norepinephrine. So you need norepinephrine to speed up your alpha. But you might have frontal alpha, not just slow alpha in the back, you might have frontal alpha. Then an antidepressant of some sort is probably going to be the thing that works. If it's slower than 10, a little bit, an SSRI will probably work great. In fact, if you have OCD and you have the alpha pattern, 85% positive response. If you have theta pattern, a slow pattern, 15% respond to the same med, same behavioral diagnosis. There's only one OCD in the DSM, you know, but there's three kinds in the EEG. The alpha pattern responds to that SSRI. The theta pattern or slow pattern doesn't respond, but you don't give a bad response, so you may stay on that medication just because they gave it to you. And but it you didn't you didn't react positively to it. If you have the beta pattern and they gave you that SSRI, you have a problem with it. Uh you're going to be way overroused because of the serotonin reuptake ever. So depending upon which your pattern you have, you may respond to the SSRI, but you may not respond, but not respond badly, but you might badly respond, depending upon the EEG. The beta pattern shouldn't have gotten that. In fact, Sandra Liu did a nice paper that says if you have theta, you get the methylphenidate, but if you have beta also, which you can have co-morbid, the both phenotypes, you have beta as well, you need guamphosine. Or if you're an adult, clonidine has been promoted for the same thing. They're norpinephrine reducers. They they block norpinephrine centrally in your nervous system and peripherally in your body. So in your body, it's going to drop blood pressure, and your brain is going to slow down the beta spindle so you're not spindling in beta. So there's meds that match the patterns. The theta needs methylphenidate, the slow alpha needs an amphetamine, the guanphaseine or clonidine for the beta spindling. There are one-third of the ADD ADHD kids that have epileptiform discharges. What do you think they get? An anticonvulsant, and maybe a stimulant or antidepressant or something as well. But you've got to stop the discharge if there's one or the other patterns there as well. You can't give the stimulant to them before you give the anticonvulsant because the stimulant drops the discharge threshold for the discharges, and you can have a worsening of the seizures. You can't give the antidepressant to them until you're treating the discharge, because it can make the discharges worse. You shouldn't ever give a discharge person an antipsychotic, regardless of how bad their behavior is, because their behavior may be being driven by false emotion, epileptroform content in the temporal area. And those would be worsened by the antipsychotic. If they're acting out behaviorally, look at the EG and see if it's epileptroform or psychosis. If they're acting crazy, it could be just epileptform

Discharges In Psychosis And Autism

SPEAKER_02 19:41

content. One-third of the psychotic individuals have epileptiform content. In the autism spectrum, the odds are 70%. 70%. Those are good odds. You know, the odds are better than even, you know, it's better than a 50-50 chance, you know. So the odds are, if you're working with autism, whether you know it or not, they probably have discharges in their EEG. The biggest study in the meta-analysis had over a thousand autistic kids in the study. They did a 24-hour EEG, including sleep, and they found 85%. Most of the studies were 60, 50 plus, you know. Historically, I was saying in our experience, it's 40% to 60%, somewhere in that range. And uh, but you know, sampling errors and whatnot, that you know what but it was it was uh it was a pretty good chance of seeing a discharge. And when the meta-analysis came out, it it looked even more probable.

SPEAKER_01 21:00

So I mean just hearing you talk about these different implications of you know understanding what the EG says and you know really can direct you towards or away from certain medications and you know I think reduce a lot of suffering with these clients while you're trying to get it right because it the the symptoms look the same, but the etiology is what's underneath is completely different.

Test First, Treat Second

SPEAKER_02 21:24

Yeah, exactly. If a cardiologist did his treatments based on symptom, everybody who came in complaining of chest pain would go get an angioplasty. Well, half of them had indigestion. You know, your story, your symptom story should tell you what to test, not how to treat. We're behaving very badly by listening to the story and figuring out how to treat based on the story. It doesn't guide you to the right answer. It might guide you to the right location. OCD. They'll get the right spot every time, but they don't know what they're looking at then. You know, that's one of three things. And the biggest one is alpha, so the the most common treatment is the one that fixes the alpha. And uh if you go to a psychiatrist and i the it's a classic OCD presentation, it'll be luvox, fluvoxamine. I mean, that's that's the one that they will give historically, like a knee-jerk response. And it works if you're the alpha type. If you're the beta type, you just melt it down for them right there in the office. Um if it's a slow type you made at home, and no big deal, can't tell a difference. But who knows, maybe I should be on it, you know. But being on meds that you shouldn't necessarily be on because there's no benefit for you isn't a good idea. Um medications end up shifting around other systems in your body, and if it's not the right medication for you, you you should be off of it. Uh if it's not uh a productive uh uh medication that's making a positive change, uh it could be making a slow negative change that takes years to end up uh manifesting. So you know, uh uh please be careful with the uh casual use of medication. In neurofeedback world, they tend to be kind of almost anti-medication, but I I have to say, I'm I live day to day on medications, you know. Uh uh, I don't have a pituitary at all. So uh uh I have to juggle hormones, any hormone I'm on, I'm taking. I I'm not making any. Um and for a male having no pituitary, the average life expectancy is 10 years. And I lost my pituitary somewhere in that surgical suite uh 34 years ago.

SPEAKER_01 23:53

Oh wow.

SPEAKER_02 23:53

So I've beat my odds by so much I stay alive to piss off their statistician.

SPEAKER_01 24:01

Well, we are so glad that you're here and for all your contributions to this field. And like I said, this really does, you know, provide some insights into more precision psychiatry, you know, and I I hope more people will hear about this and understand and look into your work um so that we can, you know, be more efficient and um you know make make better choices with what we choose to do. So before we sign off, Jay, any last any last things you want to say before we wrap up for today?

Supporting Students And The EEG Gathering

SPEAKER_02 24:31

Well, students are not only our future, they're the shoulders that we stand on. Every one of the giants in the field were students at one point. And if they hadn't been fostered, they wouldn't be there. So uh if you're not already helping students, please do. Um I uh I I I focus on that. Uh I can't travel anymore, but I have a birthday party once a year, and they have a little three-day EG meeting associated with that. Uh, but uh we we always do fundraising for students. And um you might see uh a short beard on me for the moment. Um uh I had one that was down almost to my navel a little while ago. Um there was a psychiatrist in Canada that heard I was gonna auction it off for money, and he thought that was just the craziest thing he'd ever heard. And uh so he came down from Canada with $5,000 in his pocket to shave me and uh donate the money to the students. And so uh of uh that long ago, um uh uh uh he came down and uh uh shaved me and uh donated five grand. Uh he gave me five thousand dollars, which I immediately uh sent down. A thousand of it went to University of North Texas. They have a group of students there that are doing some good stuff and they needed some assistance on some stuff, so we sent a thousand there. And uh I kept a thousand to assist some of the students that come to help at the event in October, uh, but that left three thousand that we split for uh uh two organizations for uh helping uh students that are going to APB and ISNR. And uh uh uh so uh I I I do whatever I can. Uh I actually for this year's event, yeah, there's I make these funny coins. You can see this has got an eye patch with a wavelet on it like me. And this last year they declared me the godfather of QEG.

SPEAKER_01 26:41

That's interesting.

SPEAKER_02 26:42

You can see the little puppeteer thing there, you know. So uh uh that I had I had a bunch of these made in silver. You know, silver at the time was under $20 somewhere, $12, $15, $18, I can't remember, uh an ounce, and now it's $75 an ounce. So these are going to be available for people who like to collect these kind of things at the meeting. And um uh uh we we plan on having a lot of fun. There's a pizza night with some uh uh uh world-class guitarists playing, and um uh we take over the yacht club for three days, and it's a little short walk from the hotel. And uh we we're uh a sociable group. Uh we're we take our science seriously, but that's about the end of it. The rest of it is just fun.

SPEAKER_01 27:32

So if you're if you're a clinician or someone wanting to learn more about delving into the world of EEG, then reach out to Jay and come to this meeting because it really is a great opportunity to learn from some of the greats out there. So thank you so much, Jay, for all that you do and for all that you've contributed and can continue to contribute to the field. We appreciate your time today.

SPEAKER_02 27:53

Thank you for the invitation.

Wrap Up And How To Work With Us

SPEAKER_00 27:58

You've been listening to the Transformative Neurotherapy Podcast with Dr. Heather Putney. Remember, your brain isn't supposed to hold you back, it's supposed to power you forward. So stop letting it crash your party and start letting it do its job. If you're ready to optimize brain health, sharpen your focus, and age like a fine wine, schedule your free consultation today at transformative neurotherapy.org. Or call us at 412-204-7397. Because here, healing happens faster. See you next time.com.