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>> Good evening.

I'm psychiatrist Jay Fawver live from Fort Wayne , Indiana.

Welcome to Matters of the Mind now in its 25th year, Matters of the Mind is a live call in program where you have the chance to choose the topic for discussion.

So if you have any questions concerning mental health issues ,give me a call here in the Fort Wayne area by dialing (969) 27 two zero or if you're calling Coast to coast you may dial toll free at 866- (969) to seven to zero now on a fairly regular basis we are broadcasting live every Monday night from our spectacular PBS Fort Wayne studios which lie in the shadows of the Purdue Fort Wayne campus.

>> And if you'd like to contact me with an email question that I can answer on the air, you may write me via the Internet at matters of the mind all one word at WSW Egg that's matters of the mind at WFA Big and I'll start tonight's program with an email I received this week.

>> It reads Dear Father I'm exploring as ketamine therapy.

>> That's bravado.

>> It's going to mean therapy for treatment resistant depression also known as to what percentage of people today are helped by this therapy?

How is it administered?

What factors into an average dosage and are there long term side effects?

>> Let me try to answer all of those questions.

What percentage of patients are helped with treatment resist depression with bravado or ketamine in the clinical trials about three out or four in my practice over 90 percent.

>> Now these are people who have failed on two or more different antidepressants and on the average they've failed on between five to ten different and a in the past it's bravado whereas ketamine is administered intranasal always under the watchful eye of a health care professional so you come into an office, you get back in a reclining chair and for two hours you're monitored twice a week.

>> The first month once a week, the second month than every other week and sometimes even less frequently as time goes on.

>> Our first provided treatment who we treated first time four years ago she's coming about every three months now so you just kind of stretch out the treatments as time goes on.

Think of this bravado US ketamine treatment as being kind of like watering new trees you're planning into the ground when you first get a tree from the tree factory the tree goes into the ground.

You're advised to water it every day for the first week five, six days a week, the second week, five days a week, the third week and so forth.

You decrease the frequency of the watering as time goes on.

If you think about us, academy is kind of like watering or fertilizing your brain and what happens is with chronic unresolved depression you'll have a shriveling up or shrinkage of the branching of your individual nerve cells.

>> Now there's a billion nerve cells up there and they all have anywhere between ten and one hundred thousand branches on them.

>> As you get more and more depressed you have less branching of your nerve cells and that's what causes people to have trouble with enjoyment, motivation, energy level concentration and so forth.

>> So what you want to do is make the little branches more fluffy and that's what is ketamine will do in some studies with ketamine at least it shows that branching starts to occur within four hours of each treatment.

We often will find that people notice a significant improvement within one or two treatments but we haven't given at least a month and ideally two months of treatment to really determine if it's going to work or not.

What determines the ideal dosing?

Basically we look for two side effects that might be problematic for people number one sedation number two the higher blood pressure both those will spike at about the 40 minute mark after somebody receives a of me so to see the spike in blood pressure not unlike if you exercising very intensely, if you're exercising intensely, you're on an exercise bike, you're on a treadmill, you're on an elliptical.

>> You're going to notice your blood pressure is increasing if you check it at about forty minutes into the exercising, that's what happens with us ketamine as well so that the blood pressure typically comes down in an hour and the time you leave at two hours the blood pressure is back to where it was at baseline before you had the treatment.

>> So the reason we would be reluctant to increase the dosage from fifty six milligrams to the highest dose he's eighty four milligrams would be if the sedation or the high blood pressure was a bit more excessive than would be thought to be tolerable.

>> Dissociation is what you often hear about as a side effect.

>> Association is not considered to be therapeutic so it's not going to help you have a therapist at your side during a set of mean treatments and deal with life events.

People sometimes get that confused with hallucinogenic treatment hallucinogenic treatment which will be available presumably with another year or two is where a therapist sits by your side sometimes for hours as a means of taking you through post traumatic events and dealing with a lot of life stressors.

So that's an entirely different type of treatment with as ketamine it's for the purpose of helping people with depression who have not been helped with other type of oral treatments.

>> Now you're advised to stay on some kind of oral medication while you're using this ketamine.

The reason being the oral medications might help some and you use the oral antidepressant medications with us ketamine they tend to give you added added effects.

>> Now why does that ketamine work?

Well, it's working directly on glutamate when we talk about the 16 or so different Orlanda presence that have come out over the past 30 years, those medications are primarily affecting serotonin, norepinephrine and dopamine.

So by affecting serotonin and norepinephrine and dopamine you kind of indirectly affect glutamate which is the major excitatory chemical in the brain.

>> Half the brain is influenced by glutamate.

>> So glutamate is an excitatory chemical that affects about half the brain indirectly glutamates affected by serotonin, norepinephrine and dopamine.

So if you think about serotonin, norepinephrine and dopamine, they're kind of like the passenger who's advising the driver to speed up or slow down whereas the accelerator is glutamate and the brake is gabb.

Those are the two chemicals were influencing when people are using a medication like us ketamine so it's ketamine is working within a matter of seconds after its administration again people are monitored for two hours in the chair basically because of the dissociation and sedation which tend to peak at about 40 minutes.

That's when the peak blood level occurs and the blood pressure tends to peak at about the 40 minute mark.

So people are monitoring during that time how long to somebody stay on it?

Well, it gets less frequent as time goes on but we do have some people who are still using after the a course of four years.

No long term side effects have been identified with four years of study in over a thousand patients in a formal study looking at difficulty with concentration, memory, any medical problems those were not seen to be problematic with long term use.

>> So the reason you don't use it every day the reason it spread out is for that very reason because glutamate in excess can be overly toxic.

So you don't want to give somebody too much of a glutamate enhancement because it's like putting too much fertilizer in your lawn.

A little bit of fertilizer is great for your lawn but if you put too much fertilizer in your lawn it'll fry it.

That's what happens with glutamate.

You want just the right amount of glutamate enhancement but not yet not excessive amounts.

So with that in mind as ketamine treatment is a medication that is affecting primarily glutamate, it's ideal dosing is eighty four milligrams older of people.

People who get into their 70s and 80s can use ketamine.

It's just that theoretically they metabolize that at half the rate.

But with all of our patients with whom we've for whom we've treated with, it's going to mean we have found that we get to eighty four milligrams without much problem again limit the dosage to just fifty six milligrams and not go higher if somebody had excessive sedation during the treatment itself or excessive high blood pressure during the treatment itself.

But sedation high blood pressure and association where people kind of have an out of body experience those are not predictive of somebody improving with depression.

>> Some people will have great effects even though they don't have those side effects.

A few people will have those kind of side effects and not do well enough with depression.

But generally in a real world setting I think you can pretty much count on over 90 percent of people having a pretty good response with this ketamine.

Now we want to give people a fair shake if you use a marijuana every day and you're having trouble with motivation, fatigue, poor concentration as ketamine is probably not going to help you, you need to get off the marijuana.

>> Same with alcohol, same with any drugs of abuse you probably need to deal with the drugs of abuse, get off of those for at least three months before you determine if this guy is going to help you if you're taking the so-called benzodiazepine medications every day Xanax, Klonopin, Ativan, Valium, those kind of medications used day by day by day can cause you to have trouble with prolonged depression.

So we'd want you to get off of those kind of medications as well to really see if the depression is still there.

And then we always look for underlying medical problems if somebody has sleep apnea where they're not getting enough air flow to the lungs at night, thereby decreasing oxygen to the brain if somebody has low thyroid, if they have diabetes, low iron those are all reasons why you might have depression that's just not improving with antidepressants.

>> So we want to give you a fair shot at the as with the academy and we want to rule out all these other factors that might be problematic.

>> Which antidepressant all antidepressants do you stay on?

You stay on the one that tends to work the best for you of all the ones you've tried to figure out which one to work the best for you and you probably stay on that.

>> Thanks for your email.

Let's go to our next e-mail question.

Our next e-mail question reads Dear Dr. Fauver, you emphasize the importance of sleep to mental and physical well-being.

>> I'm awaiting results of a sleep study I took six weeks ago.

>> How do you feel about the various remedies for overnight breathing issues overnight breathing issues would be sleep apnea which I just mentioned as a reason why people just might not feel well despite their being on the best antidepressant for them.

>> If you have sleep apnea where your oxygen level is dropping night by night for every few minutes or so that can cause you to have trouble with fatigue, poor concentration, low motivation and even depression.

So it's something that we have to identify in psychiatry.

Yeah, it's more of a pulmonary issue.

There's a sleep medicine especially itself.

>> But as psychiatrists, as mental health professionals it's very, very important that we try to at least screen those people and what we do is we'll order a home poly sonogram or a home sleep study test.

>> But then if sleep apnea is identified, the sleep medicine folks take over from there and they order the proper machinery for continuous positive airway pressure for automatic positive airway pressure.

>> This is a means by which air is forced into your lungs if you're not breathing deeply enough, if you're snoring it allows the air to be pushed back the closed throat or the trachea when you're snoring itself.

So it could be a highly, highly effective if you have untreated sleep apnea, not only are you more likely to have trouble with depression but you can have other medical issues such as heart disease, stroke, diabetes, higher likelihood of dementia if you have untreated sleep apnea, there's so many good reasons to get sleep apnea treated.

>> Now once you treat sleep apnea you might be able to lose a few pounds because sleep apnea will sometimes contribute to hire and unnatural amounts of cortisol which is a stress hormone because if you're pausing in your breathing and you're snoring and you're not getting adequate oxygen to the brain, your body senses that as being a stressful event and cortisol gets released on naturally a nighttime cortisol leads to increased deposition of fat around the belly and the neck and that can be a reason.

>> It's a vicious cycle, a reason why people with sleep sleep apnea will have more trouble losing weight.

So one reason why you could get sleep apnea treated would be to try to help you control weight in general.

But sleep apnea is something that we identify in psychiatry.

If we look for in as many as one out of six of our patients who come in with depression but you got to look for it.

It's like looking for mushrooms in the forest.

You know, you go out in the forest in looking for mushrooms.

You just don't look around and find the mushrooms.

You got to look under things because mushrooms often lurk under the dark leaves in the dark branches.

That's how sleep apnea is.

You have to look for it to really identify so you have to ask people questions.

>> Do you feel tired during the day?

Do you snore at night?

Do you pause in your breathing at night?

These are the kind of questions we're trying to to to ask as a means of identifying people with sleep apnea.

Sleep apnea will frequently be associated with higher blood pressure.

People have morning headaches upon awakening in the morning and many people will have gastric reflux where they have an Asadi feeling in the back of their throats.

>> That's all those are all possible symptoms of sleep apnea themselves.

Thanks for your email.

>> Let's go to our first caller.

Hello Ali.

Welcome to Matters of Mind .

Ali, you had asked about what is echolalia?

Echolalia is basically where a person simply repeats exactly what they've heard so they echo the language of people they have with whom they have just with whom they've heard speaking.

It's something that many people with psychosis will do.

They have trouble processing their own information so they simply repeat back to what somebody already said to them.

So it's considered to a thought processing disturbance where you're simply echoing what you have just heard.

>> Let's go to our next e-mail question.

Our next e-mail question reads as I take a sip there it is not a favor.

>> Can the brain grow when you treat people for strokes and depression?

What caused the brain to shrink kind of goes back to what I referred to previously.

When you have chronic stress and you're not coping with it and you're just overwhelmed, there's chemical called glutamate which is excitatory.

It's like putting on pushing the accelerator on your car.

>> It's speeding up the brain processing is great to a degree.

It's like in an automobile it's good to go down the road.

>> Sixty five even seventy miles an hour if you're under good control and traffic is relatively light but when you get up to a 90 and 100 miles per hour and you're in heavy traffic it can be kind of dangerous.

>> That's way glutamate is when it exceeds the amount you really need that's called glutamate spillover glutamate spillover goes to and underneath part of the individual neurons and will cause you to have a shrinkage a shriveled shriveled, shriveling of the individual neurons.

So if your neurons are supposed to have a hundred thousand branches for instance, that shriveling might go down forty or thirty thousand branches.

So it's like a tree that's not getting proper watering or proper fertilizing.

>> So how you bring that back will be sometimes with exercise diet can help as well.

>> Socializing can help make the neurons a little bit more fluffy but what will use medicinally will be medications that will block a particular receptor called NMDA receptors.

NMDA receptors are stimulated by glutamate and if you block NMDA receptor is more of the glutamate will no one go over these other glutamate receptors called AMPA receptors AMPA receptors turn on the sprinkler system for the brain and help you grow back those fluffy little branches so you want more glutamate to go into the AMPA receptors?

>> No, to want to block the NMDA receptors where the having the glutamate spill over it's kind of like a circuit breaker.

So imagine in your household having an electrical system where the electricity is going toward your ion, your television, your space heater but if you get too much electricity flowing flowing on one circuit you can have a fire unless you have a circuit breaker, the circuit breaker switches off and switches off the power for that particular circuit.

>> That's what blocking energy receptors will do and that's what we're seeing with medications like Ketamine Shadowman and now we have a medication called Veloute.

>> They're working in subtly different ways but they're all mainly affecting the NMDA receptors.

So that's how they're helping depression and potentially they're helping with neurotoxicity with excessive glutamate release now how do you block the excessive glutamate release if you have ongoing unmitigated stress?

If you have ongoing chronic depression, you can have an increased flow of glutamate that's just excessive.

And one way to deal with that is by giving a medication called Lamotrigine and Lamotrigine is an old anti epileptic medication also known as Lamictal and it's a medication that decreases the outflow of glutamate so it decreases the excessive amount of glutamate that's getting released when people to get under stress and we often will describe Lamotrigine as a medication that helps people put up with stuff better.

>> So in one hand it's decreasing glutamate outflow if it's excessive and then if you use ketamine or ketamine or valide on top of a it'll kind of balance out the glutamate outflow that way.

>> So it's an entirely different type of paradigm that we're using nowadays compared to the past thirty 40 even 60 years because for the past 60 years we've talked about the big three chemicals norepinephrine, serotonin and dopamine.

>> Now we're going a whole different direction.

We're talking about glutamate GABA which are reasons for which we're seeing very, very fast effects.

You might be hearing about this medication called Zurin alone coming out in a few months.

Zarein alone is a medication that affects effects GABA directly.

So you've got Valide it's got to be in ketamine affecting glutamate.

Zahradil It affects GABA and you can take one dose for fourteen days and in four to five cases with people who have on average been on four different antidepressants in the past you can get an 80 percent likelihood feeling a lot better with just 14 days of treatment.

So it's almost like taking an antibiotic for depression.

So we're really excited about what's going to be happening with Iran alone as we start using that later this year.

So it's an exciting time in psychiatry we're finally working.

We can help people in ways we had never dreamt of in the past.

>> Thanks for your question.

Let's go to next caller.

Hello Barry.

Welcome to Mars.

The mind.

>> Barry, you want to know what can I explain about about what stimming is in relationship to autism or ADHD?

I have no idea what you're referring to there, Barry.

>> With stimming autism and ADHD are conditions that are similar but yet they have some differences.

Autism is a condition where you have a difficult time being able to socially connect with other people because you lack these particular mirror neurons and the particularly the right front part of the brain and also with ADHD you'll have trouble I'm sorry I also with autism you'll have trouble putting up with stuff stresses will affect you in an exaggerated way compared to other people.

>> So you like continuity, you like consistency with autism when you're throwing off your consistency, when you're thrown off the continuity that will be for highly problematic for you.

Some people with autism also have attention deficit hyperactivity disorder so you can have both.

But with ADHD it's a condition where independent of the social disturbances you have with autism you have trouble with distractibility, have trouble focus.

People with ADHD will get especially annoyed and they have a they can have a very trigger temper that can be provoked in in various ways with ADHD you have a hard time getting things completed.

You'll get started on things but you won't get them completed.

You'll have a lot of distractibility whereas with autism yeah you'll have distractibility but it'll also be from over from overstimulation, from sensory input with autism sounds, noises, bright lights, flashing lights especially excessive sensory input can be highly problematic for you.

>> So autism or ADHD?

>> Yeah they have some similarities but they have some differences probably from a neurobiological standpoint they have several differences with autism.

>> The primary focus of research right now is the intranasal use of oxytocin because it's thought that people with autism lack the bonding hormone oxytocin.

Oxytocin is something that women will experience and increase in and it's volume by after childbirth because after childbirth the oxytocin levels in women will go up like eight to ten times whereas with men won't go up hardly at all for some reason after their loved one has a has a baby with oxytocin is the bonding hormone that is often lact with autism.

ADHD doesn't seem to be affected by that particular hormone itself with ADHD it's more a phenomenon associated with norepinephrine and dopamine and now we're starting to realize that glutamate is probably the end neurotransmitter with ADHD as well.

So autism ADHD there are some differences but a lot of similarities.

Thanks for your question.

Let's go to our next caller.

Hello Janice are Candice welcome to Matters of Mind.

>> Candice, you want to know the difference between how external processing works versus internal processing?

I'm trying to figure out how you're trying to to express that Qantas external processing .

I think you're referring to sensory input coming from the outside, sensory input coming from the outside is where you're trying to process information externally and it initially goes to the thalamus which is right in the middle of the brain.

The thalamus will take in information from the outside and try a process it accordingly.

It's got like a central operator where it's trying to then channel that information to various places I had mentioned earlier autism people with autism will have difficulty with processing outside stimuli because it just the thalamus just can't process at all.

We see the same kind of phenomena with schizophrenia.

People with schizophrenia when they're psychotic will have all sorts of disturbances processing that outside information internal processing has to do with thinking internal processing has to do with using the front part of your brain and logically thinking through step by step what's the best course of action for the situation around you now here's what happens Kandice you can have internal processing disturbances when the amygdala which is the anxiety volume control right up here hijacks the front part of the brain and your thinking is basically control you're thinking controls your your thinking is not able to work and your actions are basically influenced by your emotions.

So rather than thinking through what you should be doing and what's in your best interest using the front part of your brain, you use your emotional part of the brain and that leads to the immediate actions and that's why people get in trouble when they get angry, they get irritable, they get overly excited about different things.

>> They just don't use that part of their brain adequately when that's happening is this medial prefrontal cortex which is right in here that's underactive when that part of the brain is underactive, the media prefrontal cortex also known as the subgenera will argue gyrus that particular part of the brain in there is supposed to allow your front part of the brain to still have control over your actions if that part of the brain is not working so much, it's your anxiety, your emotional, your anger volume control that takes that over so internal processing can be influenced by your emotions and that's what we're trying to avoid in psychiatry when we treat people for anxiety and mood disturbances in psychiatry, we're trying to get them to a point where their front part of the brain is able to process information better and they're able to think through their current situation.

They compare their current situations to past experiences.

>> This is our coping works.

People who have endured past problematic and troublesome situations learn from those kind of experiences.

That's why in the Middle East conflicts with the with the battles that were fought over there, the American soldiers who had some past traumatic experiences before they became a soldier often held up better in battle compared to the soldiers who did.

In other words, if you had past traumatic experiences of various kinds, you are less likely to have post-traumatic stress disorder if you're once exposed to battle because it tends to sharpen the sword that way.

>> I mean if you've experienced conflicts in your life you're going to come out of it stronger and I'm often reminding people of that if they can get through their current life difficulties and especially if they journal about those current life difficulties they're going to realize when they encounter similar circumstances three years, five years, 10 years down the line they're going to remember they got over those kind of situations.

So that kind of dials down the anxiety volume control in itself.

But once your anxiety volume control starts turning on the what if circuit and the what if circuit just goes round and round and round you start to catastrophizing what's going to happen?

You worry about things in the future and that worry and anxiety leads to difficulty with sleep anxiety with difficulty with sleep leads to depression and depression is basically where you have trouble with motivation.

You can't concentrate.

You don't enjoy things you don't want to engage or interact with other people.

You have a hard time getting your conversations rolling and depression itself will be very incapacitating for people with their work social life going to school and we're trying to avoid the anxiety cascading to difficulty with sleep which thereby cascades into depression because it tends to occur on a continuum.

People sometimes ask me gee do I have anxiety?

Do I have depression?

It's not that clean anxiety depression often go hand in hand.

>> Candice, thanks for your call.

Unfortunately I'm out of time for this evening.

If you have any questions concerning mental health issues that I can answer on the air you may write me via the Internet at matters of the mind all one word at Edgard.

I'm psychiatrist Jeff Offer and you've been watching matters of mine on PBS for Wait God Willing and PBS will be back again next week.

>> Have a good evening.

Thanks for watching tonight