September 24, 2025 • 30 mins
Triple-board certified psychologist Dr. Heather Luing joins Dr. Erich Schramm to talk about depression. Major depressive disorder affects one in five Americans and ranks among the most disabling conditions worldwide. In spite of this, treatments for depression can be unsatisfying or ineffective for up to 1/3 of patients. The doctors discuss the symptoms, treatments, and biological underpinnings of depression. They move to advances in medications and devices and the possibilities that clinical trials hold for the not-too-distant future, including non-medical solutions like Transcranial Magnetic Stimulation and Vagus Nerve Stimulation for medication-resistant patients.
Be a part of advancing science by participating in clinical research.
Have a question for Dr. Koren? Email him at askDrKoren@MedEvidence.com
Listen on Spotify
Listen on Apple Podcasts
Watch on YouTube
Share with a friend. Rate, Review, and Subscribe to the MedEvidence! podcast to be notified when new episodes are released.
Follow us on Social Media:
Facebook
Instagram
X (Formerly Twitter)
LinkedIn
Want to learn more? Checkout our entire library of podcasts, videos, articles and presentations at www.MedEvidence.com
Music: Storyblocks - Corporate Inspired
Thank you for listening!
Mark as Played
Transcript
Episode Transcript
Available transcripts are automatically generated. Complete accuracy is not guaranteed.
Announcer (00:00):
Welcome to MedEvidence!, where we help you
navigate the truth behindmedical research with unbiased,
evidence-proven facts Hosted bycardiologist and top medical
researcher, Dr Michael Koren.
Dr. Erich Schramm (00:11):
Hello and welcome back to the MedEvidence
podcast.
I'm your host, Dr.
Erich Schramm, sitting in forDr.
Michael Koren today.
For those who don't know me,I'm a board-certified family
physician and long-term clinicalresearch investigator with the
ENCORE Clinical Research Groupand I'm very excited to be here
with my guest, Dr.
Heather Luing.
Dr.
Luing is an excellent clinicalpsychiatrist and I've had the
(00:35):
pleasure to get to know Dr.
Luing over the last two years.
We share a clinical space andalso an interest in clinical
research, so welcome to theMedEvidence! podcast, Dr.
Luing.
Dr. Heather Luing (00:46):
Thank you, Dr .
Schramm.
It's so exciting to be heretoday.
Dr. Erich Schramm (00:50):
Well, thank you, and we've got a very
interesting topic to discussmajor depressive disorder.
But before we do the deep diveinto that, perhaps you could
tell us a little bit about yourbackground, tell us, kind of
where you grew up and how youended up getting interested in
psychiatry and specificallyinterventional psychiatry that
(01:10):
you practice.
Dr. Heather Luing (01:12):
Okay, well, that's a big question.
I'm a native Floridian, so Igrew up in South Florida and
studied microbiology as myundergraduate degree and then
moved up to University ofFlorida and I did my medical
training there so medical schoolresidency and a fellowship in
forensic psychiatry so I'm nowtriple board certified in
(01:32):
general and forensic psychiatryas well as addiction medicine,
and I've done a lot of differentthings in my career.
So I started in communitymental health and worked there
for quite a while, did a littlebit of time working as a medical
director at a substance abusetreatment facility, and then
I've done a lot of inpatienthospital work and in 2017, I
started my private practice.
Dr. Erich Schramm (01:53):
Wow, that's very impressive.
Going back to your training,tell me a little bit about you.
Had a fellowship in forensicpsychiatry.
Okay, exactly what is that andwhat got you interested in that?
Dr. Heather Luing (02:06):
Forensic psychiatry is a subspecialty of
psychiatry, so it really focuseson the areas where psychiatry
and the law intersect, andthere's quite a few of those
when you think about it.
There's criminal-type work,when people are being evaluated
for sanity, and then there's alot of questions that come up in
civil cases that involvepsychiatry.
So a lot of it is acting as aconsultant and really an
(02:29):
educator to help peopleunderstand about psychiatry and
mental wellness and health.
Dr. Erich Schramm (02:34):
Right, and that's still an important part
of your practice today.
Dr. Heather Luing (02:38):
It's a percentage of the work that I do
.
I do enjoy speaking andconsulting and educating, and I
spend a lot of time still withpatients as well.
So I do a little bit ofeverything.
Dr. Erich Schramm (02:47):
Oh, that's terrific.
And talking a little bit aboutyour background, you actually
were involved in teachingresidents at one time in the
course of your training and yourwork at University of Florida.
Dr. Heather Luing (03:03):
Yeah, teaching has always been
important to me.
Right now, I work withpsychiatry residents from the
HCA Orange Park program, so Ialways have a third-year
resident who rotates through myclinic, which has been a lot of
fun.
It keeps you on your toes.
Dr. Erich Schramm (03:17):
Right and full disclosure.
When I do have opportunities tobe in the office with you, I'm
never against coming to pickyour brain on particular
patients or a condition, so Ithink I often see you in that
kind of teaching and supportrole, so that's really fantastic
(03:37):
.
Dr. Heather Luing (03:37):
Well, I think medicine is a team sport, right
?
So it takes a lot of members ofthe team to make things work.
Dr. Erich Schramm (03:42):
Wow.
Well, so today we have a reallyinteresting discussion on major
depressive disorder.
My background in familymedicine sees a lot of
depression, so you know, we cantalk a little bit, maybe a
little about epidemiology, ifyou could work us through a
little bit of major depressivedisorder 101.
Dr. Heather Luing (04:04):
Yeah, yeah.
I think it's so interesting inthe US that really the majority
of depression is treated byprimary care, so definitely the
important front lines and for alot of patients, the only doctor
or practitioner that they'regoing to see for their
depression journey.
So it's a kind of a rarepatient that actually gets to us
as psychiatrists.
Depression in general is suchan interesting condition, I
(04:27):
think partly because it's socommon.
So one in five Americans aregoing to deal with a major
depressive disorder at somepoint in their life, which, if
you think about it, it's a hugeamount.
Probably all of us either havegone through depression
ourselves or know somebody inour circle who has struggled
with it.
So it's very common.
However, you know, I've heardit referred to as the common
(04:49):
cold of psychiatry, andcertainly in its frequency it is
, but it's a common cold thatcould kill you.
It has a fatality rate rightand so it's a very serious
condition and besides the riskof suicide, it's a very
disabling condition.
So it's actually in the top oneor two disabling conditions
worldwide.
That keeps people not only fromworking occupationally but
(05:11):
functioning in their normalenvironment with relationships,
with just day-to-day activities.
Dr. Erich Schramm (05:17):
Wow, and really that's a great reflection
on the scope of the disease,the effect that it has on
patients and, like you said,it's debilitating, and so maybe
we could talk a little bit aboutyou know what are the kind of
typical symptoms that a lot ofpeople might be experiencing
with depression.
Dr. Heather Luing (05:38):
Yeah, I think depression is interesting,
because when you ask an averagelayperson about what is
depression, we all kind of havea little bit of an idea, right.
We recognize depression in somedegree when we see it, but I
think we tend to under-recognizeit.
And so the DSM-5 is ourDiagnostic and Statistical
Manual.
It has a very clear definitionof what depression is.
(06:00):
So in order to meet thecriteria for a major depressive
disorder, you have to have a lowmood and or anhedonia for at
least two weeks, and that has tohappen for at least most of the
days.
Now anhedonia is that conceptof lack of pleasure.
So it's where you used to enjoygoing to your son's baseball
game and you're still going, butyou're not getting pleasure out
(06:22):
of it anymore.
It's not enjoyable to you andit's one of really the key
diagnostic criterias ofdepression.
Dr. Erich Schramm (06:29):
Wow.
So you're there but you're notreally there.
Dr. Heather Luing (06:32):
Yeah
Dr. Erich Schramm (06:32):
You just feel like you're kind of going
through the moves and yeah, I'veseen a lot of patients like
that, so it's really such achallenge.
So with that, do you see otherthings being affected?
Sleep.
Dr. Heather Luing (06:46):
Yeah.
So besides those two criteria,there's a list of other things
that may be affected, and sleepis definitely one of those.
Now, sleep and appetite areinteresting is that for some
people they have less of them,right, maybe they have a hard
time sleeping, they're sufferingfrom insomnia, or their
appetite is just gone andthey're losing a lot of weight.
But for others, it reallyswings in the opposite direction
(07:08):
.
So we have people who havehypersomnia.
They have a hard time gettingout of bed, they spend many,
many more hours sleeping thanthey should and kind of use it
as an escape.
And we also have a subset ofpatients who will overeat as
something of their depression,so they may be gaining weight
rather than losing weight.
Other things that we seecommonly affected is energy.
So a lot of times when you'redepressed, you just don't have
(07:30):
much energy or motivation.
Concentration is one that I seea lot, and I have a lot of
adult patients who contact methinking maybe they have ADD or
ADHD, they're having a hard timestaying on task with their work
, but the reality is a lot oftimes it's depression.
So some of the symptoms ofdepression really can cross over
(07:51):
to other psychiatric disorders,which can be confusing.
Dr. Erich Schramm (07:55):
Boy.
That really resonates to me asa family practice physician
because again, I'm kind ofchecking off the boxes for the
patients that I see and you'vereally, really nailed down the
symptoms really, reallyaccurately.
So when you're seeing thesepatients, what kind of therapies
do you have to offer thesepatients?
Dr. Heather Luing (08:15):
Yeah, I always think in a really
holistic way.
So the first thing I want tothink about when somebody is
dealing with depression islifestyle.
Right, are you getting enoughsleep?
Is your diet sufficient?
Are you getting enough of someof the essential nutrients that
we know the brain really needsto function at its best?
What about exercise?
So many people, right, neglectexercise, but it's one of our
(08:36):
best antidepressants and thereally exciting things that the
studies show is that it doesn'ttake really extreme exercise to
get the mental health benefits.
Even something very low, verymoderate, can be helpful.
So I encourage patients trywalking around the block.
You know, take your dog out fora walk, take a bike ride.
You know, things like that canhave a profound effect on mental
(08:57):
health.
So we always start with thebasics.
After we make those lifestyleadjustments, then the next thing
I always think about ispsychotherapy.
Therapy is very safe.
You're not going to hurt anyonewith therapy and for a lot of
people it can be beneficial.
So that's the foundation webuild on.
For some people that'll beenough and then others are going
to need a more biological wayof treating depression.
(09:19):
So traditionally that's beenour antidepressant medications.
Dr. Erich Schramm (09:22):
Okay and I guess you know and each patient
is different, obviously to know.
Okay when all those in aholistic approach totally agree
with, because I'm a holisticphysician.
But of course, when somebodymight come in and maybe there's
some red flags or a higher levelof concern for a patient, then
(09:43):
you know, obviously you havepriorities that allow those
patients to seek, you know,maybe more intensive or more
appropriate treatments.
Dr. Heather Luing (09:51):
Absolutely, absolutely.
And the longer that I reallyspecialize in depression
treatment, the more I seedepression as an emergency.
So by taking a holisticapproach we certainly don't want
to slow down more aggressivetreatment if patient's
depression is severe andwarrants that.
The quicker we can get adepressive episode under control
, the better prognostically apatient is going to do so.
(10:12):
We don't want to waste a lot oftime trying treatments that
don't work or letting patientskind of get into this situation
where they have a partiallytreated depression.
And unfortunately that's what Isee really commonly is patients
who maybe have been started onan antidepressant, or maybe
they've tried some therapy alongwith it, but the symptoms
haven't resolved.
They're not in remission oftheir depression, it's just
(10:35):
improved a bit, but they stillhave a lot of lingering symptoms
, and so that's really what Iwant to work with in trying to
get patients into full remission.
Dr. Erich Schramm (10:43):
Wow, and thinking about your experiences,
not just in the clinic, but youactually have a good bit of
hospital-based experience whereyou would obviously be working
with a more acute and moresevere patient population in
terms of people that are havingsuicidal ideation or suicidal
(11:04):
attempts.
Is that right?
Dr. Heather Luing (11:05):
Yeah, absolutely Suicidal ideations
and attempts are one of the moresevere and concerning symptoms
of depression.
We always want to be watchingfor those and sometimes those
are what brings patients to thehospital and sometimes it's more
a profound level of dysfunction.
So patients with depression caneven go into a catatonic state
where they really just stopresponding like we would kind of
(11:28):
think of someone as respondingand might just sit immobile for
a period of time or have reallyprofound symptoms.
Dr. Erich Schramm (11:33):
Right and is there a concerted effort to try
to make that transition forthose hospitalized patients?
Do they typically come backinto your practice or do they
have to be referred out to otherprimary psychiatrists out there
?
Dr. Heather Luing (11:49):
No, frequently we'll see this type
of patient in our practice.
My goal is to treat depressioneffectively from the beginning
so patients ultimately don'thave to have hospitalization.
Hospitalization is kind of ourlast resort, right?
Nobody likes to be in apsychiatric hospital.
It's a challenging environment,and so we want to work to try
to find an effective treatmentas quickly as possible.
(12:11):
So hopefully things don't getto that level, but if they do,
absolutely they would return toour practice and we would do
everything to keep them at theirbest state.
Dr. Erich Schramm (12:20):
Well, again, I really love the continuity of
care.
You offer holistic approach andI do actually get to see your
patients and I think you'redoing a fantastic job.
Yeah, that's why I say.
I feel like you're reallyoutstanding in your field for
what you're offering thepatients a really very realistic
(12:42):
approach.
So thank you for being therefor that
Dr. Heather Luing (12:45):
Yeah absolutely.
Dr. Erich Schramm (12:46):
So let's get back, If we can talk about.
You're an interventionalpsychiatrist and you've already
alluded to that.
Obviously you're comfortablewith pharmaceutical approaches
to treating patients withdepression, but you're offering
something else as aninterventional psychiatrist, and
(13:08):
in our particular workspace youoffer TMS and the esketamine,
which is the Spravato, which Ifind interesting because, again,
I see these therapies beingapplied just about every day and
it's quite amazing.
So can you tell us a little bitabout some of those therapies?
Dr. Heather Luing (13:27):
Yeah, absolutely, and we can talk
about antidepressants, whichhave been kind of the backbone
of psychiatric treatment, butthe reality is there's about a
third of patients who thosemedications just haven't worked
for, and traditionally our oralantidepressants have targeted
primarily serotonin, to a lesserextent norepinephrine and
dopamine, and for some peoplethat can be a miracle, it can be
(13:48):
really, really effective.
But about a third of patients itjust doesn't work for them, and
so we have, as as a field,labeled that as a
treatment-resistant depression.
Now I personally wonder if inthe future, we don't consider
that more of a monoaminergic,treatment-resistant depression,
which is our serotonin system,but at this point we call it TRD
, and so the treatments that youmentioned are treatments for
(14:11):
TRD or treatment-resistantdepression.
So TMS is transcranial magneticstimulation.
It's an FDA-approved treatmentthat's been around for about 17
years at this point, so it's notnew.
But I think it's the best-keptsecret in psychiatry.
We just don't have enoughpeople who are really aware of
it as a treatment option, aswell as the efficacy that it
(14:33):
provides these patients.
What TMS does is it uses asmall high-powered magnet to
provide a focal stimulation to apart of the brain that we know
in depression tends to behypoactive and it's called the
left dorsolateral prefrontalcortex, so it's right about here
.
Dr. Erich Schramm (14:49):
Okay.
Dr. Heather Luing (14:50):
And that's a part of the brain that if you
image, you do PET studies orfunctional MRIs in patients with
depression, you'll see thatpart of the brain has kind of
gone to sleep.
It's just not doing its normalconnections with other parts of
the brain.
By stimulating it with magneticpulses we can generate
neuroplasticity, so we help makesome new connections that
(15:10):
ultimately help restore thebrain to its natural functioning
, rather than artificiallyadding a chemical or something
different to the brain.
So that's a great treatment.
The other kind of big advancewe've had in the last oh, six or
seven years in psychiatry isbringing in glutamate as a new
neurotransmitter that we'remodulating, and so Spravato, or
(15:34):
Esketamine, was our firstFDA-approved way of getting that
glutamatergic action forpatients' depression, and that's
been really a fantastictreatment for patients as well.
We now also have an oralantidepressant that has
glutamatergic activity that'savailable, called Auvelity.
So we're getting more and moreadvances and more options for
patients, which is fantastic.
Dr. Erich Schramm (15:56):
So, in terms of the glutamate, are we looking
at the possibility forneuroplasticity on that end, or
is that just a differentmechanism?
Dr. Heather Luing (16:06):
No, it's very similar actually.
So neuroplasticity is thoughtto be the endpoint that we're
looking at.
We kind of get there a littlebit of a different way, but
we're getting ultimately thesame results in the brain.
Dr. Erich Schramm (16:17):
Wow.
So very, very interesting.
And getting back to what you'resaying, that we have had TMS
for 17 years but it reallyhasn't moved into the forefront
and as a you know, as apracticing family physician for
20 years, you know I'd have toconsider that I really wasn't
fully aware of the capabilitiesuntil again I'd had an
(16:37):
opportunity to work with you andsee what a profound difference
it is for these patients.
And it isn't just oh, you know,this is a feel good.
This is actually kind of arewiring of the brain, which is
quite a bit different and moresophisticated than what we've
been using with our SSRIs thathave been around for I don't
know.
Dr. Heather Luing (16:57):
Yeah, since the late 1980s, I think.
Dr. Erich Schramm (17:00):
Yeah, yeah, I'd be like, wow, so it looks
like there is this kind of readyto move into this kind of whole
new technology.
Hopefully these therapies willbe coming more accessible to
patients and especially in theprimary care field and the
family medicine field.
I think you know.
(17:20):
Again, I feel that it's good tobe educating and say, look, you
know what are the options forpatients once they've kind of
they're reading their endpointwith their SSRI or similar.
So that's terrific.
I'd like to talk a little bitabout your fellow clinical
researcher and look forward toworking with you as part of the
(17:43):
ENCORE Clinical Research Group.
But maybe you could tell us alittle bit about your research
background.
What got you interested indoing clinical research?
Dr. Heather Luing (17:51):
Yeah, what got me interested in it is I'm
always looking for cutting edgetreatments and I want my
patients to really be able toassess those as early as
possible, because for somepatients it is a life or death
situation.
It is something where they needaccess to that.
So I got really interested invagus nerve stimulation, which
is another type of brainstimulation.
(18:13):
We have ECT, which we haven'treally talked about, but it's
kind of our older way oftreating depression with a
procedure.
We have TMS and now VNS as well.
And the interesting thing isvagus nerve stimulation was
actually approved at the end ofmy residency training, so we're
talking almost 20 years ago atthis point.
So we've known it worked, butwe didn't have a way of
(18:34):
accessing it through insuranceso that patients could actually
afford it.
So this trial came about,called the RECOVER trial, that
Liva Nova sponsored.
That was really to showMedicare and CMS that that VNS
was something worth paying forand that it was something that
could save lives and really helppatients with severe depression
.
So we had an opportunity tostart getting involved in that
(18:55):
trial and that's how I got myintroduction to clinical
research.
Dr. Erich Schramm (18:58):
Very interesting.
But you, I recall in yourbackground you had been involved
doing, even in your undergradyou'd been doing, you'd been
involved in research.
So it's.
Dr. Heather Luing (19:09):
I did some bench research.
Yeah, absolutely Back gettingmy chemistry degree.
It was pretty fun actuallyended up after.
When I was in medical school,one of the compounds that I
developed actually found promiseand ended up in a publication.
So that was kind of fun, butvery different from what I do
now with phase three and phasefour trials, working with
(19:30):
patients.
Dr. Erich Schramm (19:31):
Right, but certainly equally, if not more,
important, because you're thekind of where the rubber hits
the road right Every stage ofresearch is so important,
Otherwise we wouldn't have anyoptions for treating any disease
.
So you have treated the VNSpatients with the vagal nerve
stimulator.
You've treated TMS patients.
Do you see any similarities?
(19:53):
How would you compare andcontrast what you're seeing for
patients with those therapies?
Dr. Heather Luing (19:58):
TMS is a non-invasive treatment so it's
simply a matter of kind ofsitting in a recliner chair and
having a magnet placed againstyour head, so very easy for
patients.
Vns is a little bit more of acommitment in that you have to
have a procedure to implant adevice under your collarbone.
It's a minor procedurecertainly not a big surgery, but
it is a bit more of acommitment, I think from that
(20:21):
standpoint.
Now the interesting thing aboutthis VNS trial is a lot of
patients had already failedother treatments, including TMS
and esketamine, so a reallysevere group of patients as far
as resistance, and we've seenreally good effects.
So I think VNS we know it worksfrom those original trials
where it was FDA approved.
(20:42):
We just haven't had a chance toreally utilize it.
So I think you know all ofthese treatments for the right
individual have a lot of promiseand it's really a matter of
kind of navigating those risksand benefits and determining
what's the right fit for you asa patient.
Dr. Erich Schramm (20:56):
That's a great point to make.
And ultimately as researcherswe start thinking to ourselves
"gee that'd be nice if we couldfind a way yo compare, head to
head, TMS vagal nervestimulation.
" it would take a lot of work,you know, to try to see how we
could figure out how to make aplacebo arm in that.
(21:16):
But getting back to yourinterest in clinical research
and cutting edge technology, itreally resonates so that's
really cool.
So let's maybe talk a littlebit about kind of the newer
pharmaceutical options out therenow, and I think we're looking
at a study that's going to comeup, looking at a particular
(21:38):
compound, so maybe you couldtell us a little bit about that.
Dr. Heather Luing (21:41):
Yeah.
So you know we first discoveredthe first antidepressants by
accident.
It was serendipitous, right.
These were patients who werebeing treated for tuberculosis
and what they found is that whenthey were given a certain
medication they had improvementin their mood symptoms.
And so that's kind of where wegot this idea that serotonin was
(22:02):
the answer to treatingdepression.
And we have run with that as afield for 40 years.
The reality is now we havelearned that that may be kind of
a backdoor way of treatingdepression, because the reality
is I can deplete someonecompletely of serotonin by
removing an essential amino acidfrom their diet and they don't
get depressed.
(22:22):
So we know it's not just aserotonin deficiency that causes
depression.
We also know if we treatsomebody with a serotonergic
agent, it takes six to eightweeks for most patients to have
a clinical response.
That's very slow and what wesee is those serotonin levels
actually correct much before wesee the clinical improvement.
So that's led us as a field tothink well, what other things
(22:44):
could we modulate to help get aquicker and more effective
improvement of depressionsymptoms?
So glutamate has kind of beenthe first that's come to market,
come to fruition, and we'restill trying to figure out other
ways to affect theglutamatergic system.
And you know, glutamate andGABA are kind of they go hand in
hand, right.
It's the brakes and the gaspedal, kind of, if you think
(23:06):
about it.
So there's certainly yeahthere's certainly GABA agents
that are being investigatedright now.
One area that I'm particularlyinterested in is the kappa
opioid system.
So when we think of opiates,the first thing people think is
like bad right, you thinkopiates are something you're
artificially taking into yoursystem and causing our opiate
crisis.
But the reality is we have anendogenous opioid system, so
(23:30):
opioid system within us isnatural, right.
We have to figure out how canwe influence that system because
it seems to have a lot ofeffect on mood.
So the particular study that Ithink you're referring to is the
KOASTAL study looking atnavacaprant, and that's a new
novel agent that we think hasantidepressant effects and it is
(23:53):
a kappa opioid antagonist.
So that's a study that I'vebeen taking part in recently as
a PI and we're hoping that we'llfind new ways to positively
affect depressive symptoms.
Dr. Erich Schramm (24:05):
That's wonderful.
And getting back tounderstanding from a primary
care standpoint and talkingabout some of the problems
associated with serotonin-basedmedications.
We talked a little bit aboutthat, but we talked about
anhedonia as a not uncommoncircumstance where patients on
antidepressants but also thepotential for sexual side
(24:26):
effects, you know, possiblyweight gain.
So there are certainly barriersthat can come up with
compliance for those, and youmentioned that there's a high
rate for recurrence and so thissounds like this is a very
promising potential avenue fortreatment.
Dr. Heather Luing (24:47):
Yeah, you've highlighted a lot of reasons.
People don't like theirtraditional antidepressants
right, if you're depressed,getting fat and having problems
with your sexual life doesnothing to improve your
depressive symptoms, so thoseare never popular.
The other challenge withanhedonia and SSRIs is a lot of
patients just don't get animprovement in that anhedonic
tone or features that they have.
(25:09):
So what that means I kind ofdescribe it to patients is you
go through life looking atthings in black and white.
You don't really just see lifein technicolor that the rest of
us do, and so we want to try tofind medicines that are better,
better at targeting thatanhedonia, because it really is
a disabling and disruptivesymptom in patients' lives.
Dr. Erich Schramm (25:29):
So this is a receptor antagonist, so you are
affecting neurotransmitters inthat sense, but this wouldn't
necessarily be consideredsomething that would have
neuroplasticity, or does that?
Dr. Heather Luing (25:45):
It potentially could.
I think you know that's theexciting thing about clinical
research is we're learning,right, we're learning how are
things going to ultimately reactin the brain.
But I would highlight one ofthe nice things about being an
antagonist is you know you'renot influencing the opioid
system in a negative way likewe've been used to with opioid
medications, so we're notcausing any kind of reward and
(26:08):
because of that they're notcontrolled medications.
Dr. Erich Schramm (26:15):
And I think that's a really good and
important point to make becauseit is, you know I think a lot of
peope would think ok well,again, I'm familiar with what
opioids do for the opioidreceptors in patients to have
those to get that, but you know,gosh, here's this thing that is
(26:36):
regulating a lot of our moodand our pleasure centers and
reward centers.
So you know, and here we areback to research and that
cutting edge, looking at that.
So this is, I think, a terrificopportunity and you know, if
you think about now, compared to, you know, 20, 30 years ago,
now we're really being able tooffer patients a wide variety of
options to consider, whetherit's TMS or what's going to be
(26:57):
esketamine.
And now we look at glutamateand the KORA opioid receptor
antagonist.
So and we were talking earlierbefore because you know, we've
both been in research for a longtime and there was a period
where it seemed like therewasn't a lot of new things
coming down the pipe.
And you know we're like gosh,now we can see that there's
(27:20):
actually quite a bit opening uphere.
Dr. Heather Luing (27:22):
Yeah, it was so depressing as a new graduate
coming out of residency to seecompanies closing their CNS
divisions and knowing that,knowing that I was going to face
a career treating patientswithout getting new advances in
the ways that I would do that.
And it becomes verydiscouraging when you have a
patient in front of you, and youknow that after the second
(27:46):
antidepressant failure thatpatient has about a 14% chance
of having a response from one ofour traditional antidepressants
being used.
Third line and we learned thatfrom the STAR-D trial and we've
known that for a long time, butwe haven't had a whole lot of
alternatives.
So now we're at a point in timewhere it's so exciting that we
have many alternatives and Ithink what we have now is just
(28:07):
the tip of the iceberg.
I think there's a lot ofexciting things to come.
Dr. Erich Schramm (28:10):
Wow, you're saying everything I want to hear
right now so well, terrificHeather.
Thank you so much for giving usyour time.
Is there anything else you'dlike to add or any question?
I should have asked that.
I didn't ask you.
Dr. Heather Luing (28:24):
You know, I think the biggest thing is just
reminding everyone thatdepression is a treatable
disease and that people don'thave to live with these
disabling symptoms, that thereare effective and safe
treatments out there that areFDA approved.
Right, they have that clinicalresearch behind which gives us
information on efficacy andsafety, and most of the time
(28:46):
they're covered by insurance, sothey're affordable and
accessible.
So there's no reason to acceptdepression as a reality that you
have to endure.
Dr. Erich Schramm (28:52):
I love that.
And also I'll add that you know, we're kind of the one of our
themes here in clinical, thisclinical research office, to let
patients know that research isa very reasonable, you know,
care option.
You know we can't guaranteewhether you're going to get on
the study medication or placebo,but we know that patients just
coming into the office, you know, get a level of care that will
(29:16):
have a positive impact on theirhealth.
So we, you know again, I thinkthat's a point we like to make
here.
Dr. Heather Luing (29:21):
Absolutely.
We were kind of talking beforethe show too about some of the
challenge of depression.
Trials is a placebo response,and you know the reality as a
psychiatrist taking off myclinical research hat.
Placebos are fine, right, wejust want patients to feel
better.
So if somebody comes into aclinical trial and feels better,
no matter how, that's a win forthem as an individual.
(29:42):
I think that you know somethingto think about with research is
you're contributing to thefuture of science as well.
you may have family membersthat may have depression in the
future.
And helping find better trements
Dr. Erich Schramm (29:50):
Wow.
Great closing point, and thankyou so much, and maybe we'll do
another episode and we'll pick atopic and maybe we can talk
again on maybe anxiety or sleep.
So maybe we can do that in thefuture.
Dr. Heather Luing (29:55):
Absolutely, it's my pleasure being here
today
Dr. Erich Schramm (29:56):
My pleasure seeing you again.
Heather, take care,
Dr. Heather Luing (29:58):
Bye-bye,
Dr. Erich Schramm (29:59):
Bye.
Announcer (30:20):
Thanks for joining the MedEvidence podcast.
To learn more, head over toMedEvidence.
com or subscribe to our podcaston your favorite podcast
platform.
Welcome to MedEvidence!, where we help you
navigate the truth behindmedical research with unbiased,
evidence-proven facts Hosted bycardiologist and top medical
researcher, Dr Michael Koren.
Dr. Erich Schramm (00:11):
Hello and welcome back to the MedEvidence
podcast.
I'm your host, Dr.
Erich Schramm, sitting in forDr.
Michael Koren today.
For those who don't know me,I'm a board-certified family
physician and long-term clinicalresearch investigator with the
ENCORE Clinical Research Groupand I'm very excited to be here
with my guest, Dr.
Heather Luing.
Dr.
Luing is an excellent clinicalpsychiatrist and I've had the
(00:35):
pleasure to get to know Dr.
Luing over the last two years.
We share a clinical space andalso an interest in clinical
research, so welcome to theMedEvidence! podcast, Dr.
Luing.
Dr. Heather Luing (00:46):
Thank you, Dr .
Schramm.
It's so exciting to be heretoday.
Dr. Erich Schramm (00:50):
Well, thank you, and we've got a very
interesting topic to discussmajor depressive disorder.
But before we do the deep diveinto that, perhaps you could
tell us a little bit about yourbackground, tell us, kind of
where you grew up and how youended up getting interested in
psychiatry and specificallyinterventional psychiatry that
(01:10):
you practice.
Dr. Heather Luing (01:12):
Okay, well, that's a big question.
I'm a native Floridian, so Igrew up in South Florida and
studied microbiology as myundergraduate degree and then
moved up to University ofFlorida and I did my medical
training there so medical schoolresidency and a fellowship in
forensic psychiatry so I'm nowtriple board certified in
(01:32):
general and forensic psychiatryas well as addiction medicine,
and I've done a lot of differentthings in my career.
So I started in communitymental health and worked there
for quite a while, did a littlebit of time working as a medical
director at a substance abusetreatment facility, and then
I've done a lot of inpatienthospital work and in 2017, I
started my private practice.
Dr. Erich Schramm (01:53):
Wow, that's very impressive.
Going back to your training,tell me a little bit about you.
Had a fellowship in forensicpsychiatry.
Okay, exactly what is that andwhat got you interested in that?
Dr. Heather Luing (02:06):
Forensic psychiatry is a subspecialty of
psychiatry, so it really focuseson the areas where psychiatry
and the law intersect, andthere's quite a few of those
when you think about it.
There's criminal-type work,when people are being evaluated
for sanity, and then there's alot of questions that come up in
civil cases that involvepsychiatry.
So a lot of it is acting as aconsultant and really an
(02:29):
educator to help peopleunderstand about psychiatry and
mental wellness and health.
Dr. Erich Schramm (02:34):
Right, and that's still an important part
of your practice today.
Dr. Heather Luing (02:38):
It's a percentage of the work that I do
.
I do enjoy speaking andconsulting and educating, and I
spend a lot of time still withpatients as well.
So I do a little bit ofeverything.
Dr. Erich Schramm (02:47):
Oh, that's terrific.
And talking a little bit aboutyour background, you actually
were involved in teachingresidents at one time in the
course of your training and yourwork at University of Florida.
Dr. Heather Luing (03:03):
Yeah, teaching has always been
important to me.
Right now, I work withpsychiatry residents from the
HCA Orange Park program, so Ialways have a third-year
resident who rotates through myclinic, which has been a lot of
fun.
It keeps you on your toes.
Dr. Erich Schramm (03:17):
Right and full disclosure.
When I do have opportunities tobe in the office with you, I'm
never against coming to pickyour brain on particular
patients or a condition, so Ithink I often see you in that
kind of teaching and supportrole, so that's really fantastic
(03:37):
.
Dr. Heather Luing (03:37):
Well, I think medicine is a team sport, right
?
So it takes a lot of members ofthe team to make things work.
Dr. Erich Schramm (03:42):
Wow.
Well, so today we have a reallyinteresting discussion on major
depressive disorder.
My background in familymedicine sees a lot of
depression, so you know, we cantalk a little bit, maybe a
little about epidemiology, ifyou could work us through a
little bit of major depressivedisorder 101.
Dr. Heather Luing (04:04):
Yeah, yeah.
I think it's so interesting inthe US that really the majority
of depression is treated byprimary care, so definitely the
important front lines and for alot of patients, the only doctor
or practitioner that they'regoing to see for their
depression journey.
So it's a kind of a rarepatient that actually gets to us
as psychiatrists.
Depression in general is suchan interesting condition, I
(04:27):
think partly because it's socommon.
So one in five Americans aregoing to deal with a major
depressive disorder at somepoint in their life, which, if
you think about it, it's a hugeamount.
Probably all of us either havegone through depression
ourselves or know somebody inour circle who has struggled
with it.
So it's very common.
However, you know, I've heardit referred to as the common
(04:49):
cold of psychiatry, andcertainly in its frequency it is
, but it's a common cold thatcould kill you.
It has a fatality rate rightand so it's a very serious
condition and besides the riskof suicide, it's a very
disabling condition.
So it's actually in the top oneor two disabling conditions
worldwide.
That keeps people not only fromworking occupationally but
(05:11):
functioning in their normalenvironment with relationships,
with just day-to-day activities.
Dr. Erich Schramm (05:17):
Wow, and really that's a great reflection
on the scope of the disease,the effect that it has on
patients and, like you said,it's debilitating, and so maybe
we could talk a little bit aboutyou know what are the kind of
typical symptoms that a lot ofpeople might be experiencing
with depression.
Dr. Heather Luing (05:38):
Yeah, I think depression is interesting,
because when you ask an averagelayperson about what is
depression, we all kind of havea little bit of an idea, right.
We recognize depression in somedegree when we see it, but I
think we tend to under-recognizeit.
And so the DSM-5 is ourDiagnostic and Statistical
Manual.
It has a very clear definitionof what depression is.
(06:00):
So in order to meet thecriteria for a major depressive
disorder, you have to have a lowmood and or anhedonia for at
least two weeks, and that has tohappen for at least most of the
days.
Now anhedonia is that conceptof lack of pleasure.
So it's where you used to enjoygoing to your son's baseball
game and you're still going, butyou're not getting pleasure out
(06:22):
of it anymore.
It's not enjoyable to you andit's one of really the key
diagnostic criterias ofdepression.
Dr. Erich Schramm (06:29):
Wow.
So you're there but you're notreally there.
Dr. Heather Luing (06:32):
Yeah
Dr. Erich Schramm (06:32):
You just feel like you're kind of going
through the moves and yeah, I'veseen a lot of patients like
that, so it's really such achallenge.
So with that, do you see otherthings being affected?
Sleep.
Dr. Heather Luing (06:46):
Yeah.
So besides those two criteria,there's a list of other things
that may be affected, and sleepis definitely one of those.
Now, sleep and appetite areinteresting is that for some
people they have less of them,right, maybe they have a hard
time sleeping, they're sufferingfrom insomnia, or their
appetite is just gone andthey're losing a lot of weight.
But for others, it reallyswings in the opposite direction
(07:08):
.
So we have people who havehypersomnia.
They have a hard time gettingout of bed, they spend many,
many more hours sleeping thanthey should and kind of use it
as an escape.
And we also have a subset ofpatients who will overeat as
something of their depression,so they may be gaining weight
rather than losing weight.
Other things that we seecommonly affected is energy.
So a lot of times when you'redepressed, you just don't have
(07:30):
much energy or motivation.
Concentration is one that I seea lot, and I have a lot of
adult patients who contact methinking maybe they have ADD or
ADHD, they're having a hard timestaying on task with their work
, but the reality is a lot oftimes it's depression.
So some of the symptoms ofdepression really can cross over
(07:51):
to other psychiatric disorders,which can be confusing.
Dr. Erich Schramm (07:55):
Boy.
That really resonates to me asa family practice physician
because again, I'm kind ofchecking off the boxes for the
patients that I see and you'vereally, really nailed down the
symptoms really, reallyaccurately.
So when you're seeing thesepatients, what kind of therapies
do you have to offer thesepatients?
Dr. Heather Luing (08:15):
Yeah, I always think in a really
holistic way.
So the first thing I want tothink about when somebody is
dealing with depression islifestyle.
Right, are you getting enoughsleep?
Is your diet sufficient?
Are you getting enough of someof the essential nutrients that
we know the brain really needsto function at its best?
What about exercise?
So many people, right, neglectexercise, but it's one of our
(08:36):
best antidepressants and thereally exciting things that the
studies show is that it doesn'ttake really extreme exercise to
get the mental health benefits.
Even something very low, verymoderate, can be helpful.
So I encourage patients trywalking around the block.
You know, take your dog out fora walk, take a bike ride.
You know, things like that canhave a profound effect on mental
(08:57):
health.
So we always start with thebasics.
After we make those lifestyleadjustments, then the next thing
I always think about ispsychotherapy.
Therapy is very safe.
You're not going to hurt anyonewith therapy and for a lot of
people it can be beneficial.
So that's the foundation webuild on.
For some people that'll beenough and then others are going
to need a more biological wayof treating depression.
(09:19):
So traditionally that's beenour antidepressant medications.
Dr. Erich Schramm (09:22):
Okay and I guess you know and each patient
is different, obviously to know.
Okay when all those in aholistic approach totally agree
with, because I'm a holisticphysician.
But of course, when somebodymight come in and maybe there's
some red flags or a higher levelof concern for a patient, then
(09:43):
you know, obviously you havepriorities that allow those
patients to seek, you know,maybe more intensive or more
appropriate treatments.
Dr. Heather Luing (09:51):
Absolutely, absolutely.
And the longer that I reallyspecialize in depression
treatment, the more I seedepression as an emergency.
So by taking a holisticapproach we certainly don't want
to slow down more aggressivetreatment if patient's
depression is severe andwarrants that.
The quicker we can get adepressive episode under control
, the better prognostically apatient is going to do so.
(10:12):
We don't want to waste a lot oftime trying treatments that
don't work or letting patientskind of get into this situation
where they have a partiallytreated depression.
And unfortunately that's what Isee really commonly is patients
who maybe have been started onan antidepressant, or maybe
they've tried some therapy alongwith it, but the symptoms
haven't resolved.
They're not in remission oftheir depression, it's just
(10:35):
improved a bit, but they stillhave a lot of lingering symptoms
, and so that's really what Iwant to work with in trying to
get patients into full remission.
Dr. Erich Schramm (10:43):
Wow, and thinking about your experiences,
not just in the clinic, but youactually have a good bit of
hospital-based experience whereyou would obviously be working
with a more acute and moresevere patient population in
terms of people that are havingsuicidal ideation or suicidal
(11:04):
attempts.
Is that right?
Dr. Heather Luing (11:05):
Yeah, absolutely Suicidal ideations
and attempts are one of the moresevere and concerning symptoms
of depression.
We always want to be watchingfor those and sometimes those
are what brings patients to thehospital and sometimes it's more
a profound level of dysfunction.
So patients with depression caneven go into a catatonic state
where they really just stopresponding like we would kind of
(11:28):
think of someone as respondingand might just sit immobile for
a period of time or have reallyprofound symptoms.
Dr. Erich Schramm (11:33):
Right and is there a concerted effort to try
to make that transition forthose hospitalized patients?
Do they typically come backinto your practice or do they
have to be referred out to otherprimary psychiatrists out there
?
Dr. Heather Luing (11:49):
No, frequently we'll see this type
of patient in our practice.
My goal is to treat depressioneffectively from the beginning
so patients ultimately don'thave to have hospitalization.
Hospitalization is kind of ourlast resort, right?
Nobody likes to be in apsychiatric hospital.
It's a challenging environment,and so we want to work to try
to find an effective treatmentas quickly as possible.
(12:11):
So hopefully things don't getto that level, but if they do,
absolutely they would return toour practice and we would do
everything to keep them at theirbest state.
Dr. Erich Schramm (12:20):
Well, again, I really love the continuity of
care.
You offer holistic approach andI do actually get to see your
patients and I think you'redoing a fantastic job.
Yeah, that's why I say.
I feel like you're reallyoutstanding in your field for
what you're offering thepatients a really very realistic
(12:42):
approach.
So thank you for being therefor that
Dr. Heather Luing (12:45):
Yeah absolutely.
Dr. Erich Schramm (12:46):
So let's get back, If we can talk about.
You're an interventionalpsychiatrist and you've already
alluded to that.
Obviously you're comfortablewith pharmaceutical approaches
to treating patients withdepression, but you're offering
something else as aninterventional psychiatrist, and
(13:08):
in our particular workspace youoffer TMS and the esketamine,
which is the Spravato, which Ifind interesting because, again,
I see these therapies beingapplied just about every day and
it's quite amazing.
So can you tell us a little bitabout some of those therapies?
Dr. Heather Luing (13:27):
Yeah, absolutely, and we can talk
about antidepressants, whichhave been kind of the backbone
of psychiatric treatment, butthe reality is there's about a
third of patients who thosemedications just haven't worked
for, and traditionally our oralantidepressants have targeted
primarily serotonin, to a lesserextent norepinephrine and
dopamine, and for some peoplethat can be a miracle, it can be
(13:48):
really, really effective.
But about a third of patients itjust doesn't work for them, and
so we have, as as a field,labeled that as a
treatment-resistant depression.
Now I personally wonder if inthe future, we don't consider
that more of a monoaminergic,treatment-resistant depression,
which is our serotonin system,but at this point we call it TRD
, and so the treatments that youmentioned are treatments for
(14:11):
TRD or treatment-resistantdepression.
So TMS is transcranial magneticstimulation.
It's an FDA-approved treatmentthat's been around for about 17
years at this point, so it's notnew.
But I think it's the best-keptsecret in psychiatry.
We just don't have enoughpeople who are really aware of
it as a treatment option, aswell as the efficacy that it
(14:33):
provides these patients.
What TMS does is it uses asmall high-powered magnet to
provide a focal stimulation to apart of the brain that we know
in depression tends to behypoactive and it's called the
left dorsolateral prefrontalcortex, so it's right about here
.
Dr. Erich Schramm (14:49):
Okay.
Dr. Heather Luing (14:50):
And that's a part of the brain that if you
image, you do PET studies orfunctional MRIs in patients with
depression, you'll see thatpart of the brain has kind of
gone to sleep.
It's just not doing its normalconnections with other parts of
the brain.
By stimulating it with magneticpulses we can generate
neuroplasticity, so we help makesome new connections that
(15:10):
ultimately help restore thebrain to its natural functioning
, rather than artificiallyadding a chemical or something
different to the brain.
So that's a great treatment.
The other kind of big advancewe've had in the last oh, six or
seven years in psychiatry isbringing in glutamate as a new
neurotransmitter that we'remodulating, and so Spravato, or
(15:34):
Esketamine, was our firstFDA-approved way of getting that
glutamatergic action forpatients' depression, and that's
been really a fantastictreatment for patients as well.
We now also have an oralantidepressant that has
glutamatergic activity that'savailable, called Auvelity.
So we're getting more and moreadvances and more options for
patients, which is fantastic.
Dr. Erich Schramm (15:56):
So, in terms of the glutamate, are we looking
at the possibility forneuroplasticity on that end, or
is that just a differentmechanism?
Dr. Heather Luing (16:06):
No, it's very similar actually.
So neuroplasticity is thoughtto be the endpoint that we're
looking at.
We kind of get there a littlebit of a different way, but
we're getting ultimately thesame results in the brain.
Dr. Erich Schramm (16:17):
Wow.
So very, very interesting.
And getting back to what you'resaying, that we have had TMS
for 17 years but it reallyhasn't moved into the forefront
and as a you know, as apracticing family physician for
20 years, you know I'd have toconsider that I really wasn't
fully aware of the capabilitiesuntil again I'd had an
(16:37):
opportunity to work with you andsee what a profound difference
it is for these patients.
And it isn't just oh, you know,this is a feel good.
This is actually kind of arewiring of the brain, which is
quite a bit different and moresophisticated than what we've
been using with our SSRIs thathave been around for I don't
know.
Dr. Heather Luing (16:57):
Yeah, since the late 1980s, I think.
Dr. Erich Schramm (17:00):
Yeah, yeah, I'd be like, wow, so it looks
like there is this kind of readyto move into this kind of whole
new technology.
Hopefully these therapies willbe coming more accessible to
patients and especially in theprimary care field and the
family medicine field.
I think you know.
(17:20):
Again, I feel that it's good tobe educating and say, look, you
know what are the options forpatients once they've kind of
they're reading their endpointwith their SSRI or similar.
So that's terrific.
I'd like to talk a little bitabout your fellow clinical
researcher and look forward toworking with you as part of the
(17:43):
ENCORE Clinical Research Group.
But maybe you could tell us alittle bit about your research
background.
What got you interested indoing clinical research?
Dr. Heather Luing (17:51):
Yeah, what got me interested in it is I'm
always looking for cutting edgetreatments and I want my
patients to really be able toassess those as early as
possible, because for somepatients it is a life or death
situation.
It is something where they needaccess to that.
So I got really interested invagus nerve stimulation, which
is another type of brainstimulation.
(18:13):
We have ECT, which we haven'treally talked about, but it's
kind of our older way oftreating depression with a
procedure.
We have TMS and now VNS as well.
And the interesting thing isvagus nerve stimulation was
actually approved at the end ofmy residency training, so we're
talking almost 20 years ago atthis point.
So we've known it worked, butwe didn't have a way of
(18:34):
accessing it through insuranceso that patients could actually
afford it.
So this trial came about,called the RECOVER trial, that
Liva Nova sponsored.
That was really to showMedicare and CMS that that VNS
was something worth paying forand that it was something that
could save lives and really helppatients with severe depression
.
So we had an opportunity tostart getting involved in that
(18:55):
trial and that's how I got myintroduction to clinical
research.
Dr. Erich Schramm (18:58):
Very interesting.
But you, I recall in yourbackground you had been involved
doing, even in your undergradyou'd been doing, you'd been
involved in research.
So it's.
Dr. Heather Luing (19:09):
I did some bench research.
Yeah, absolutely Back gettingmy chemistry degree.
It was pretty fun actuallyended up after.
When I was in medical school,one of the compounds that I
developed actually found promiseand ended up in a publication.
So that was kind of fun, butvery different from what I do
now with phase three and phasefour trials, working with
(19:30):
patients.
Dr. Erich Schramm (19:31):
Right, but certainly equally, if not more,
important, because you're thekind of where the rubber hits
the road right Every stage ofresearch is so important,
Otherwise we wouldn't have anyoptions for treating any disease
.
So you have treated the VNSpatients with the vagal nerve
stimulator.
You've treated TMS patients.
Do you see any similarities?
(19:53):
How would you compare andcontrast what you're seeing for
patients with those therapies?
Dr. Heather Luing (19:58):
TMS is a non-invasive treatment so it's
simply a matter of kind ofsitting in a recliner chair and
having a magnet placed againstyour head, so very easy for
patients.
Vns is a little bit more of acommitment in that you have to
have a procedure to implant adevice under your collarbone.
It's a minor procedurecertainly not a big surgery, but
it is a bit more of acommitment, I think from that
(20:21):
standpoint.
Now the interesting thing aboutthis VNS trial is a lot of
patients had already failedother treatments, including TMS
and esketamine, so a reallysevere group of patients as far
as resistance, and we've seenreally good effects.
So I think VNS we know it worksfrom those original trials
where it was FDA approved.
(20:42):
We just haven't had a chance toreally utilize it.
So I think you know all ofthese treatments for the right
individual have a lot of promiseand it's really a matter of
kind of navigating those risksand benefits and determining
what's the right fit for you asa patient.
Dr. Erich Schramm (20:56):
That's a great point to make.
And ultimately as researcherswe start thinking to ourselves
"gee that'd be nice if we couldfind a way yo compare, head to
head, TMS vagal nervestimulation.
" it would take a lot of work,you know, to try to see how we
could figure out how to make aplacebo arm in that.
(21:16):
But getting back to yourinterest in clinical research
and cutting edge technology, itreally resonates so that's
really cool.
So let's maybe talk a littlebit about kind of the newer
pharmaceutical options out therenow, and I think we're looking
at a study that's going to comeup, looking at a particular
(21:38):
compound, so maybe you couldtell us a little bit about that.
Dr. Heather Luing (21:41):
Yeah.
So you know we first discoveredthe first antidepressants by
accident.
It was serendipitous, right.
These were patients who werebeing treated for tuberculosis
and what they found is that whenthey were given a certain
medication they had improvementin their mood symptoms.
And so that's kind of where wegot this idea that serotonin was
(22:02):
the answer to treatingdepression.
And we have run with that as afield for 40 years.
The reality is now we havelearned that that may be kind of
a backdoor way of treatingdepression, because the reality
is I can deplete someonecompletely of serotonin by
removing an essential amino acidfrom their diet and they don't
get depressed.
(22:22):
So we know it's not just aserotonin deficiency that causes
depression.
We also know if we treatsomebody with a serotonergic
agent, it takes six to eightweeks for most patients to have
a clinical response.
That's very slow and what wesee is those serotonin levels
actually correct much before wesee the clinical improvement.
So that's led us as a field tothink well, what other things
(22:44):
could we modulate to help get aquicker and more effective
improvement of depressionsymptoms?
So glutamate has kind of beenthe first that's come to market,
come to fruition, and we'restill trying to figure out other
ways to affect theglutamatergic system.
And you know, glutamate andGABA are kind of they go hand in
hand, right.
It's the brakes and the gaspedal, kind of, if you think
(23:06):
about it.
So there's certainly yeahthere's certainly GABA agents
that are being investigatedright now.
One area that I'm particularlyinterested in is the kappa
opioid system.
So when we think of opiates,the first thing people think is
like bad right, you thinkopiates are something you're
artificially taking into yoursystem and causing our opiate
crisis.
But the reality is we have anendogenous opioid system, so
(23:30):
opioid system within us isnatural, right.
We have to figure out how canwe influence that system because
it seems to have a lot ofeffect on mood.
So the particular study that Ithink you're referring to is the
KOASTAL study looking atnavacaprant, and that's a new
novel agent that we think hasantidepressant effects and it is
(23:53):
a kappa opioid antagonist.
So that's a study that I'vebeen taking part in recently as
a PI and we're hoping that we'llfind new ways to positively
affect depressive symptoms.
Dr. Erich Schramm (24:05):
That's wonderful.
And getting back tounderstanding from a primary
care standpoint and talkingabout some of the problems
associated with serotonin-basedmedications.
We talked a little bit aboutthat, but we talked about
anhedonia as a not uncommoncircumstance where patients on
antidepressants but also thepotential for sexual side
(24:26):
effects, you know, possiblyweight gain.
So there are certainly barriersthat can come up with
compliance for those, and youmentioned that there's a high
rate for recurrence and so thissounds like this is a very
promising potential avenue fortreatment.
Dr. Heather Luing (24:47):
Yeah, you've highlighted a lot of reasons.
People don't like theirtraditional antidepressants
right, if you're depressed,getting fat and having problems
with your sexual life doesnothing to improve your
depressive symptoms, so thoseare never popular.
The other challenge withanhedonia and SSRIs is a lot of
patients just don't get animprovement in that anhedonic
tone or features that they have.
(25:09):
So what that means I kind ofdescribe it to patients is you
go through life looking atthings in black and white.
You don't really just see lifein technicolor that the rest of
us do, and so we want to try tofind medicines that are better,
better at targeting thatanhedonia, because it really is
a disabling and disruptivesymptom in patients' lives.
Dr. Erich Schramm (25:29):
So this is a receptor antagonist, so you are
affecting neurotransmitters inthat sense, but this wouldn't
necessarily be consideredsomething that would have
neuroplasticity, or does that?
Dr. Heather Luing (25:45):
It potentially could.
I think you know that's theexciting thing about clinical
research is we're learning,right, we're learning how are
things going to ultimately reactin the brain.
But I would highlight one ofthe nice things about being an
antagonist is you know you'renot influencing the opioid
system in a negative way likewe've been used to with opioid
medications, so we're notcausing any kind of reward and
(26:08):
because of that they're notcontrolled medications.
Dr. Erich Schramm (26:15):
And I think that's a really good and
important point to make becauseit is, you know I think a lot of
peope would think ok well,again, I'm familiar with what
opioids do for the opioidreceptors in patients to have
those to get that, but you know,gosh, here's this thing that is
(26:36):
regulating a lot of our moodand our pleasure centers and
reward centers.
So you know, and here we areback to research and that
cutting edge, looking at that.
So this is, I think, a terrificopportunity and you know, if
you think about now, compared to, you know, 20, 30 years ago,
now we're really being able tooffer patients a wide variety of
options to consider, whetherit's TMS or what's going to be
(26:57):
esketamine.
And now we look at glutamateand the KORA opioid receptor
antagonist.
So and we were talking earlierbefore because you know, we've
both been in research for a longtime and there was a period
where it seemed like therewasn't a lot of new things
coming down the pipe.
And you know we're like gosh,now we can see that there's
(27:20):
actually quite a bit opening uphere.
Dr. Heather Luing (27:22):
Yeah, it was so depressing as a new graduate
coming out of residency to seecompanies closing their CNS
divisions and knowing that,knowing that I was going to face
a career treating patientswithout getting new advances in
the ways that I would do that.
And it becomes verydiscouraging when you have a
patient in front of you, and youknow that after the second
(27:46):
antidepressant failure thatpatient has about a 14% chance
of having a response from one ofour traditional antidepressants
being used.
Third line and we learned thatfrom the STAR-D trial and we've
known that for a long time, butwe haven't had a whole lot of
alternatives.
So now we're at a point in timewhere it's so exciting that we
have many alternatives and Ithink what we have now is just
(28:07):
the tip of the iceberg.
I think there's a lot ofexciting things to come.
Dr. Erich Schramm (28:10):
Wow, you're saying everything I want to hear
right now so well, terrificHeather.
Thank you so much for giving usyour time.
Is there anything else you'dlike to add or any question?
I should have asked that.
I didn't ask you.
Dr. Heather Luing (28:24):
You know, I think the biggest thing is just
reminding everyone thatdepression is a treatable
disease and that people don'thave to live with these
disabling symptoms, that thereare effective and safe
treatments out there that areFDA approved.
Right, they have that clinicalresearch behind which gives us
information on efficacy andsafety, and most of the time
(28:46):
they're covered by insurance, sothey're affordable and
accessible.
So there's no reason to acceptdepression as a reality that you
have to endure.
Dr. Erich Schramm (28:52):
I love that.
And also I'll add that you know, we're kind of the one of our
themes here in clinical, thisclinical research office, to let
patients know that research isa very reasonable, you know,
care option.
You know we can't guaranteewhether you're going to get on
the study medication or placebo,but we know that patients just
coming into the office, you know, get a level of care that will
(29:16):
have a positive impact on theirhealth.
So we, you know again, I thinkthat's a point we like to make
here.
Dr. Heather Luing (29:21):
Absolutely.
We were kind of talking beforethe show too about some of the
challenge of depression.
Trials is a placebo response,and you know the reality as a
psychiatrist taking off myclinical research hat.
Placebos are fine, right, wejust want patients to feel
better.
So if somebody comes into aclinical trial and feels better,
no matter how, that's a win forthem as an individual.
(29:42):
I think that you know somethingto think about with research is
you're contributing to thefuture of science as well.
you may have family membersthat may have depression in the
future.
And helping find better trements
Dr. Erich Schramm (29:50):
Wow.
Great closing point, and thankyou so much, and maybe we'll do
another episode and we'll pick atopic and maybe we can talk
again on maybe anxiety or sleep.
So maybe we can do that in thefuture.
Dr. Heather Luing (29:55):
Absolutely, it's my pleasure being here
today
Dr. Erich Schramm (29:56):
My pleasure seeing you again.
Heather, take care,
Dr. Heather Luing (29:58):
Bye-bye,
Dr. Erich Schramm (29:59):
Bye.
Announcer (30:20):
Thanks for joining the MedEvidence podcast.
To learn more, head over toMedEvidence.
com or subscribe to our podcaston your favorite podcast
platform.
Popular Podcasts
My Favorite Murder with Karen Kilgariff and Georgia Hardstark
My Favorite Murder is a true crime comedy podcast hosted by Karen Kilgariff and Georgia Hardstark. Each week, Karen and Georgia share compelling true crimes and hometown stories from friends and listeners. Since MFM launched in January of 2016, Karen and Georgia have shared their lifelong interest in true crime and have covered stories of infamous serial killers like the Night Stalker, mysterious cold cases, captivating cults, incredible survivor stories and important events from history like the Tulsa race massacre of 1921. My Favorite Murder is part of the Exactly Right podcast network that provides a platform for bold, creative voices to bring to life provocative, entertaining and relatable stories for audiences everywhere. The Exactly Right roster of podcasts covers a variety of topics including historic true crime, comedic interviews and news, science, pop culture and more. Podcasts on the network include Buried Bones with Kate Winkler Dawson and Paul Holes, That's Messed Up: An SVU Podcast, This Podcast Will Kill You, Bananas and more.
24/7 News: The Latest
The latest news in 4 minutes updated every hour, every day.
Dateline NBC
Current and classic episodes, featuring compelling true-crime mysteries, powerful documentaries and in-depth investigations. Follow now to get the latest episodes of Dateline NBC completely free, or subscribe to Dateline Premium for ad-free listening and exclusive bonus content: DatelinePremium.com