Yale Psychiatry Grand Rounds: September 29, 2023

September 29, 2023

Information

Innovations in Research for Treatments of PTSD and Substance Use Disorders: The Next Decade in Combined Pharmacotherapy and Behavioral Approaches

Speaker: Denise Hien, PhD, Distinguished Professor; Helen E. Chaney Endowed Chair in Alcohol Studies; Vice Provost of Research; Director, Center of Alcohol and Substance Use Studies, Rutgers-New Brunswick

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00:00Here to be here
00:03and I'm just letting everyone know.
00:05I'm pipelining in from my private
00:07practice office in New York City where
00:10I maintain a very small practice.
00:12And despite the the various other
00:14things that I spend my time doing.
00:17Because I, you know, and I say that
00:19because I'm a clinician obviously,
00:20as well as a scientist and very pleased to
00:25be able to talk to you today about the,
00:29you know, sort of the state of science
00:33in our field and you know where
00:36where I think the field is going,
00:38hopefully the signal will hold.
00:41We're in the midst of a giant rainstorm,
00:44which I think is affecting you guys as well.
00:46But we just had a flash flood warning.
00:49So I'm going to share my screen now
00:52and spend some time talking about the
00:55landscape and then hopefully we'll have
00:58some time for some questions and discussion.
01:01So let's see.
01:04Are you guys seeing my presentation now?
01:07Yes, yes. OK, fantastic.
01:09I'm just going to get you
01:12out of my way a little bit.
01:13And then will take it away.
01:16So I've spent the bulk
01:18of my career as is mini,
01:20you know introduced it doing clinical
01:23multi single site and multi site trials.
01:26The single site trials I spent most
01:29of my career in New York City,
01:31working with agencies and
01:33communities in Harlem and Fort
01:36Washington and Upper Manhattan,
01:38mostly minoritized populations and
01:40testing different types of interventions,
01:44both behavioral and also combined
01:48pharmacotherapy interventions to
01:50address trauma, post traumatic stress,
01:53and substance use disorder.
01:54So the bulk of what I'm talking about
01:57kind of comes from my experiences here,
02:00although I have moved into the sphere
02:02of data science and using big data,
02:05which in our field you know constitutes
02:09pooling together clinical trials
02:11that are usually somewhere between
02:1350 and 100 participants per trial.
02:17So the big data allows us to look
02:20at sample sizes of like 4500 and
02:23and going up into the future.
02:25So I'll be talking about that
02:27as I think a promising Ave.
02:29for the future in before I get fully started.
02:34First of all,
02:35want to do a small land acknowledgement,
02:38just that where I am in New Jersey
02:41and also in New York City where we
02:43do our scholarship and research,
02:45it stands on the land that is ancestral
02:48territory of the Lenape peoples.
02:50And we pay respect to indigenous
02:53peoples throughout this diaspora,
02:55past, present and future,
02:57honoring all those who've been historically
03:00and systematically disenfranchised
03:02And acknowledge that New York,
03:04New Jersey and the United States
03:07was founded upon exclusions and
03:08erasures of indigenous peoples.
03:10And that's the disclosure that
03:11I would like to make.
03:13I have no other disclosures other than
03:16my my career long funding with the
03:20the National Institutes of Health.
03:23So just to bring us right to the our,
03:25our who we work with and what you
03:29know what it feels like for patients,
03:31for individuals with lived experience
03:34who have both traumatic stress related
03:37problems and also substance use problems.
03:40I know it ravages my life.
03:43But when I'm high I don't have to feel it.
03:45The trauma in my body, in my soul.
03:49I can disappear a few hours,
03:51a few days, a few weeks,
03:53a break from those relentless memories.
03:56Well, at least I'll know exactly how
03:58I will feel when I use substances,
04:01good, bad or ugly.
04:03Otherwise,
04:04I'm all over the place.
04:05These are some of the sentiments
04:08of individuals who we strive
04:11to help with their conditions.
04:14And I'm very happy to say as as a
04:18starting point that we have a lot
04:21of answers that we didn't have.
04:23You know,
04:23in over the decades of all of us who've
04:26been and doing research in this these areas,
04:29it's really led to a groundswell of
04:32knowledge that I'm going to share with you.
04:35You know sort of the big picture of what do
04:37we know in terms of comorbidity and
04:39consequences, what do we know in terms
04:42of the science of integrated PTSD&amp;SUD
04:45care and then how do we apply it
04:48in integrated treatment frameworks.
04:50And really the challenge for all of
04:52us who are are continuing to work
04:55in this field is dissemination,
04:57dissemination, adoption, dissemination.
04:58Because even though we know a lot,
05:02there is still a gap and a barrier
05:05between what we do know as from our
05:07science and from our clinical trials and
05:10what is being practiced in the community.
05:12Even though we do know a lot more.
05:15And you know from your agencies and working
05:18with agencies the concepts of trauma,
05:19informed care and the importance of
05:21doing work in these spaces and bringing
05:24together people with substance use
05:26and mental health issues broadly.
05:28But we still have a lot of,
05:32a lot of room to still do work and
05:37understand more about dissemination
05:38and implementation.
05:39So first,
05:40what do we know about the scope
05:42of the problem And this is a slide
05:44that everyone has seen that speaks
05:46to opioid overdose deaths,
05:48which is one way that we have,
05:50you know, come to understand this,
05:52the significance of the problem
05:55of addiction in our country.
05:58And these numbers,
05:59you know are now upwards of 100,000
06:02deaths per year through due to opioids,
06:06prescription drugs, synthetics, fentanyl.
06:07It's really shifted over to fentanyl
06:10and now other other substances.
06:13But you know,
06:16we and and as a nation we've come to
06:19some understanding of the importance of,
06:21you know,
06:22D stigmatizing addiction as as the
06:25rates of deaths of white young men
06:29actually were rising most dramatically.
06:31And I think really tapped the
06:35nation's understanding in a way
06:37that the substance use, you know,
06:40criminalization of substance use and
06:42problems that have faced our black
06:45and brown communities, you know,
06:47have been going on for decades.
06:48You know as since the Rockefeller
06:50laws were in place, you know,
06:52prior to Nixon,
06:53you know,
06:53so it's been going on for a long time.
06:56But it I still think it's good
06:57that we have more recognition about
06:59the importance of addiction and
07:01and facing addiction.
07:03And just to show that in
07:06in the curves that we see,
07:08there's sort of it's there's a coming
07:10down in terms of opioid overdose deaths.
07:13It's still a steep increase
07:16for for white populations.
07:18But what we see is that the
07:21rise for individuals,
07:24you know from Latinx and African American
07:27backgrounds continues to steeply increase.
07:30And with the fentanyl and also cocaine
07:33combinations that have really been lethal,
07:37this is not a problem that we've cracked
07:39the code on and we still need to do
07:42much more and really be focusing in
07:45on our our black and brown communities.
07:48So more broadly,
07:49however,
07:50than mortality,
07:51we also need to understand more
07:55about the epidemiology of substance
07:58use in its relationship to other
08:00mental health conditions.
08:02M5 allows us to have a more
08:04of a continuum
08:05model when we think about how substance
08:08use what role it plays in the lives of
08:11individuals in our country, for example.
08:14And so we have a more continuous model
08:16that has helped us look at categories
08:18of impaired control, social problems,
08:21risky use and physical dependence.
08:24And we also can think about levels of
08:27severity of use from at risk all the
08:30way up through severe severe addiction.
08:33And this continuum model has helped us
08:36to re to understand how many people in
08:39our country are affected by substance
08:42use of all kinds and we include
08:44alcohol here and illicit drug use,
08:47cannabis use disorders down the line.
08:50But you see that we're,
08:51we're dealing with 40 million people who,
08:57you know are part of our our,
08:59our pool of individuals who are
09:02struggling with substance use
09:05at some level of of harmfulness.
09:08And I show this even though
09:10it's a little bit old,
09:11older with a different definition
09:14of substance use.
09:15So it's a much lower number from 2016,
09:18but basically to show the disparity
09:20between those who are struggling with
09:23substance use problems and those are
09:25actually receiving any kind of care,
09:28which is a small fraction.
09:31And that continues to this day,
09:34including medications for opioid use
09:37treatment and other kinds of treatment.
09:39And and it still remains true
09:41that people don't seek treatment.
09:42A lot of people don't seek treatment
09:45because they're not ready to stop
09:47using a lot of barriers that
09:49have to do with access to care.
09:53And then stigma is another huge,
09:56huge area that we need to do
09:58better to sort of help, you know,
10:01encourage people to seek treatment.
10:03Because we do have a lot of
10:05treatments that actually work,
10:07whether they're from a medication point of
10:09view or from behavioral or combination,
10:11which I'm going to tell you about.
10:13So people,
10:14another reason that people don't
10:16seek or receive adequate care is that
10:20people who have comorbidities often
10:22don't get the care that they need.
10:24So those who live with a mental illness,
10:26for example,
10:27are at a much higher likelihood of using
10:30drugs and alcohol than those who don't.
10:33So here this is,
10:36you know 50% of those with SMI and
10:3940% of those with acute mental
10:43illness disorders have used illicit
10:45drugs in the past year compared to
10:48only 17% of adults 18 years of age
10:51or older with no mental illness.
10:53So this is recent.
10:55And so the,
10:57the main point to get across the big
10:59elephant in the room that unfortunately
11:01continues to be you know plague ourselves.
11:04Our systems,
11:05our systems of care are not set
11:07up to address comorbidity,
11:09but comorbidity is the norm,
11:12not the exception.
11:14And so we need to really get
11:17that through to you know,
11:20in terms of our thinking in order
11:22to really be able to address
11:24our nation's problem.
11:25So for example, even in,
11:27you know,
11:28the big rollout of medications
11:30for opioid use disorders,
11:33most of the people that have
11:35opioid use disorders also have severe
11:38trauma and trauma related conditions
11:40and depression and other mental health
11:42conditions and as well as physical problems.
11:46But our our care systems are really not
11:48set up to deliver these kinds of things.
11:51So if we can deliver medications,
11:53which is really lifesaving and very
11:56important, don't get me wrong.
11:58But we still have to figure out how
12:01to get mental health interventions
12:03that work into these populations and
12:05also how to work with those 50% of
12:09people who aren't ready to get help.
12:11And so I just was heard a talk from one
12:14of our postdocs at Columbia University,
12:16Manesh Gopal Dus,
12:17who does work on adherence and looks at,
12:21looked at one of the CTN Xbox
12:23studies and looked at adherence to
12:26opioid use treatment in the study.
12:31And basically, you know,
12:32people were adherent early on
12:34and then over the course of time
12:36became less and less adherent.
12:38And those only those who actually got
12:42stayed with some types of medications.
12:46The the rates of other treatments
12:49increased dramatically.
12:49And I suspect that those other treatments
12:52were some of the behavioral other
12:55interventions for mental health conditions
12:57that may have helped them along the way.
12:59But we we we don't have a
13:01magic bullet at this point.
13:03And so we need to kind of
13:05have all hands on deck.
13:07The other thing I will just mention
13:09that we learn from the pandemic,
13:11all of us learned in real time
13:13is that there was this collision
13:15And so we all know about the
13:18inequalities and access to care for
13:21for COVID related health conditions.
13:26We also were dealing with the
13:29epidemic of opioid,
13:31of the opioid epidemic and we were
13:34all aware of the epidemic of racism
13:37with George Floyd's killing and others
13:40that you know brought our attention.
13:42So we've talked about the idea that these
13:46were really a condition of syndemic,
13:49which is the collision of multiple epidemics.
13:52And I,
13:53you know,
13:54we've argued that traumatic stress
13:56really forms one of the core elements
13:59that we hear a lot of people now
14:01talking about social determinants of
14:03health influencing the likelihood
14:04that people are going to get
14:06the kind of care that they need.
14:08And certainly when we think of
14:10social determinants of stress,
14:11we also have to recognize that trauma
14:14goes part and parcel with with those
14:17social determinants like lack of,
14:19you know, access to healthcare,
14:21housing,
14:22poverty,
14:22nutrition and all those things that
14:26people who are of color and also come
14:28from lower socioeconomic circumstances are,
14:32are dealing with and facing.
14:34So turning our attention to one of
14:36the bigger trauma related conditions
14:38that many of you here I know are very
14:41interested in and it contributed
14:43greatly to the science of this is
14:46one of the problem Post traumatic
14:49stress affects 8 million people
14:51in the United States.
14:53I'm not going to go into all
14:54of the criterion risk factors,
14:56but we know that you know social
14:59determinants are are some of them and
15:02also you know the predisposition and
15:05I'll talk a little bit about some of
15:08the pathways to addiction that overlap
15:09for those with PTSD and substance use.
15:12But we also know that more women than men
15:16develop PTSD when exposed to a trauma Puma.
15:19But still it cost.
15:21It exacts a huge toll on our economy and
15:27the kinds of symptoms we're talking about.
15:30You know, when we think about, you know,
15:32certainly the hallmark symptoms of
15:34PTSD are being haunted by memories of
15:38and triggers of the traumatic event.
15:41We also see intrusion symptoms and
15:45particularly avoidance symptoms that can
15:48include and often do include the use of
15:52substances as well as the HPA access,
15:55arousal and guilt feelings and
15:58cognitive and dissociative symptoms.
16:00So it's a it's a pick.
16:02It's a real mix of of diagnosis
16:06and what we are are symptoms that
16:08people are struggling with.
16:10But often I think it's important to
16:13mention people who have PTSD or trauma
16:15don't necessarily think that they do.
16:17So part of our interventions,
16:20many of our interventions focus
16:22on providing identification and
16:24psychoeducation around the problem.
16:27And the fact that these disparate
16:29symptoms that are very dysregulating
16:31for a person actually constitutes
16:34something that is a a common
16:37reaction to an uncommon event.
16:39So even though many people
16:42could develop PTSD,
16:44most people are quite resilient and don't.
16:47But for those who do, we we,
16:50we know that there are,
16:52you know,
16:53the the likelihood of them developing
16:55more than one condition is actually
16:58again more common than not.
17:00And so some of the numbers that
17:03you know well are and it doesn't
17:06matter what kind of study you do,
17:08whether it's an epidemiologic study
17:10like the epidemiologic catchment area
17:12or knees arc or that you guys you
17:16know obviously know very well or it
17:19is clinical trials in communities
17:22or its community assessments in
17:24addiction related facilities or
17:26assessments in mental health facilities.
17:30No matter which way you scratch it,
17:32you know,
17:33basically we know that the two
17:35conditions Co occur and are ubiquitous.
17:38And so here are some of the numbers.
17:41And we know that six people that
17:43have PTSD are 6 times more likely
17:46to develop alcohol use disorders,
17:482 1/2 times more likely to develop
17:50a substance use disorder.
17:52And here you see for men,
17:5460% are likely to have at least more
17:58than three cooccurring diagnoses
18:00and similarly not not quite as
18:03a high rates for women.
18:05But.
18:05So when we're working with
18:07someone with either trauma,
18:09PTSD or substance use,
18:11we can know that they're likely
18:14more likely than not may have the
18:16cooccurring condition and then
18:18they may also struck be struggling
18:21with another depression mood
18:22disorder or an anxiety disorder.
18:24So how we understand the relationship
18:28between PTSD and substance use,
18:30We've made a lot of gains in that regard.
18:33And the two most common ways we
18:36think about the relationship
18:37are self medication model,
18:40which is the idea that substance
18:42use is used to
18:43manage the PTSD symptoms.
18:45So like the avoidance symptoms,
18:46the hyper arousal, the nightmares,
18:49people may use particular substances
18:51to help tamp down those symptoms.
18:54The high risk model is the idea of
18:57susceptibility that you know if
18:59you're a substance user you may be
19:01for whatever various of reasons
19:03more likely to be traumatized.
19:05Let's say you you're are doing high risk
19:07things and you're in in the company
19:09of others who are doing harvesting.
19:11So you then may be victimized either
19:15related to drug related crime or you
19:19know assaults and things like that and
19:22that would then lead you to develop PTSD.
19:24The studies that have really attempted
19:27to look at comparisons between the self
19:30medication model and susceptibility
19:33models largely continue to come
19:35back to self medication as the most
19:39likely the most common pathway.
19:42But what we do know is that there
19:45is a convergent, rich,
19:47multidisciplinary literature that
19:50describes cross sensitization of
19:52stress and reward neural pathways
19:55that promote and then maintain the
19:58relationship between PTSD and Sud.
20:00The role that early life adversity
20:03and the dysregulation of HBA access
20:06and dopaminergic systems that
20:09predisposes individuals to internalizing
20:12and externalizing disorders and
20:15behavioral styles.
20:16And personalities that are shared
20:18between the two disorders and not to
20:21mention G wash studies that indicate
20:25that polymorphisms are kindling for
20:28the relationship between PTSD&amp;SUD.
20:30And there have been a couple of
20:33great review papers that you know
20:35kind of cover the sort of pathway
20:39pathways that we can understand.
20:40But the bottom line is this is
20:43these are complicated problems,
20:44they require all hands on deck and
20:47there's room for everyone doing.
20:49You know,
20:50you can find some piece of yourself in,
20:52in many of these explanatory pathways.
20:54And this is true for other you know,
20:56conditions,
20:57mental health conditions that we're
20:58trying to study and understand more about.
21:01But it's certainly true for for
21:04this comorbidity.
21:05And so regardless of the, you know,
21:08you know, the explanatory pathways,
21:10what we do know is that people
21:13that have both have more severe
21:15psychiatric problems.
21:16They are of course less likely to seek help.
21:19They have higher dropout rates.
21:22When they do seek help,
21:25they probably have less access to
21:27care because of the barriers between
21:30our separated funding structures
21:32and and and the way that our our
21:35programs are set up and thus are
21:38at increased rates of relapse.
21:41And finally and to close off the
21:44epidemiology kind of section of this talk,
21:48you know it's often the case that
21:50people with substance use present
21:52with the most complex trauma profile.
21:54So the I CD10 and 11 have have
21:59complex trauma in it.
22:00Our system DSM55 do does not but
22:04regardless because of all the
22:06dysregulation and other symptoms that
22:09I've described our our clients also
22:13have complicated lives with ongoing trauma.
22:18There's interpersonal trauma IPVI.
22:20Know that that at Yale
22:22you have many folks here,
22:24Kate Walsh,
22:25Tammy Sullivan and their their
22:27teams that have been working for
22:30decades on trying to address
22:33IPV, specifically in relation
22:35to substance use disorder,
22:38difficulties in relationships
22:40and trust impairments and emotion
22:43regulation and dissociative disorders
22:46that kind of complicate the picture
22:49and make it a challenge to treat.
22:52Nonetheless, I'm here to tell
22:54you the good news that all of our
22:58efforts have not been in vain and
23:00over decades we actually have a
23:03robust science in of of integrated
23:07PTSD Sud care that I'm going to do
23:11my best to summarize you know for
23:14us in the next section of the talk.
23:17I will say that we,
23:19we are all familiar with the concept
23:23of trauma informed care which sort
23:26of speaks to making agencies and
23:29providers and institutions recognize
23:31that many of the clients who come to
23:35us for whatever different reasons in
23:38in through through many different
23:40doors come to us with trauma.
23:43And that the way that we organize
23:46our program, our programming,
23:48the way that we present ourselves
23:50to our clients as as caregivers,
23:53you know should have recognition of that.
23:56Whether it's how your waiting room
23:59looks or how the the consulting
24:01room looks or how you approach,
24:04you know how you train your staff.
24:06Because also you know particularly
24:08now with a peer driven system that
24:11we have for delivering a lot of
24:13the first line care for people
24:16with substance use disorders.
24:18We're talking about people
24:19who have lived experience,
24:20who also have their own trauma
24:23histories and backgrounds and
24:25so being mindful of how they are
24:28potentially being re traumatized and
24:30also need support is very important.
24:33What I'm going to be talking about
24:35is not that but actually the evidence
24:38based and treatment development
24:40that we've done over over time.
24:43So when, you know,
24:44I first started in the field in
24:47the late 90s and early 2000s,
24:51the concept of phase based
24:54approaches for PTSD was key.
24:56For those of you who may not have read,
25:01you know, Judith Herman's book,
25:03I I still recommend it as a kind
25:07of encyclopedia of of understanding
25:09you know trauma and it and and the
25:13way that we can think about
25:14conceptualizing the care.
25:16And so she emphasized a stage
25:19model that first you would work
25:21on stabilization and these kinds
25:23of skills would do,
25:24would be involved in psychoeducation.
25:26As I spoke about skills training,
25:30affect regulation, distress tolerance,
25:33the processoriented second phase is
25:36really the delving into the trauma more
25:39specifically and that involves the
25:42trauma focused treatment approaches
25:45such as prolonged exposure in which you
25:48are working in a manualized fashion
25:52very systematically to desensitize
25:54the individual through you know sort
25:57of exposure to the traumatic memory
26:00and then working on a bottom up,
26:04you know allowing the person to experience
26:06the fear and to live through it.
26:09And I didn't realize in a systematic
26:13fashion that their their symptoms
26:16can reduce through fear habituation
26:18and that exposure based approach or
26:22cognitive treatments that are more
26:24top down that focus on addressing
26:27like cognitive processing therapy.
26:29That this meanie Petrakis has
26:31employed a great deal and to great
26:34success in her interventions that
26:36are pharmacotherapy combinations.
26:38But where you're addressing the
26:41cognitive distortions that come
26:44from PTSD and helping the person to
26:48reexamine their assumptions and work
26:50towards managing the trauma that way.
26:52But it's a very active and trauma,
26:55you know in both cases people are
26:58identifying their specific traumas
26:59and delving into them very deeply.
27:02And then we also have somatosensory
27:05approaches where people are doing
27:08EMDR and other kinds of, you know,
27:12somatosensory approaches that help to
27:15address trauma on a physical level.
27:17And so these these process the idea
27:20had been early on that we would do
27:23stabilization first and processing next,
27:26but that the assumption was that
27:29with PTSD and substance use that
27:32sequential care was necessary and
27:34that you couldn't start working
27:36on trauma until the person was
27:39abstinent from their substance use.
27:42And so that's how our systems
27:44have been set up.
27:45And even though there have been some changes,
27:48we're still sort of tackling the fact that
27:51there are structural barriers to doing
27:54what I'm going to talk about in a moment,
27:56which is the idea of integrated care.
27:59And more and more,
28:00our science has really showed us that
28:03the siloed care is quite harmful.
28:05So sending a patient over,
28:07you know, like OK,
28:08sorry,
28:08you can't get any treatment for your
28:11PTSD until you go to this substance
28:13use treatment facility that has
28:15an absence based model and you
28:16have to get clean first before you
28:19can start addressing any of those
28:21other mental health conditions.
28:23Well,
28:23it doesn't make sense if the mental
28:27health condition is a driver of
28:29the substance used to expect that
28:32the patient can heal themselves
28:34before you've actually helped to to
28:36deal with the underlying problem.
28:38So we do know that the siloed
28:42approaches do not have not worked
28:44as well and patients tend to drop
28:46out of treatment and don't, don't,
28:48you know, complete their care.
28:50And what we don't now know is that
28:53concurrent PTSD care is safe and effective.
28:56So patients can't are not as fragile
28:59as we thought them to be And in
29:02fact the first treatment model
29:04that many of us started working on
29:06early on and and you know and it
29:08made perfect sense that we would
29:10employ a skill based model first.
29:13The Seeking Safety model is a 24 session
29:16skills based model that integrates and
29:20talks about PTSD and substance use,
29:23you know,
29:23in sessions.
29:24At the same time,
29:27there's a lot of sessions on relapse
29:29prevention that are incorporated.
29:31There's sessions on psychoeducation
29:33about PTSD and the symptoms.
29:35There's sessions on safety.
29:37It's organized around helping
29:38the patient to focus on safety.
29:41It it's turned out to be a very
29:44adoptable intervention that's feasible.
29:46You can train people so that they
29:49even now there's an app peer peer
29:51individuals have been trained to
29:53be able to deliver seeking safety
29:55and it's been well tolerated.
29:58So patients like it.
30:01So that was very good for us to get started
30:04in the field to really show that yes,
30:06you don't have to wait to treat
30:08the trauma and here are some
30:10approaches that can be used and
30:12delivered safely and without harm.
30:14What we have found over the
30:17last really decade is very clear
30:21evidence that treating trauma with
30:24a trauma focused intervention.
30:27So that's stage two model that I was
30:30talking about is also safe and tolerable
30:33and effective for people with substance use.
30:36So that's a new sort of
30:39relatively newer finding.
30:40And so those those are what we call
30:43trauma focused interventions and the
30:45most commonly tested one has been the
30:48COPE treatment which is an integrated
30:51treatment that focuses on some relapse
30:54prevention as well as as well as you
30:58know a prolonged exposure cognitive
31:01processing therapy is another trauma
31:03focused treatment that has been used.
31:05EMDR has been used effectively and and
31:10basically we have one you know more
31:12recent clinical trial that was done by
31:15Sonia Norman and her colleagues with
31:18veterans that was published in JAMA
31:21Psychiatry right before the pandemic
31:24really showing superiority of the of
31:27of in a headtohead comparison between
31:30cope and seeking safety treatment.
31:34So suggesting that that although
31:39you know the the more stabilization
31:42focused treatments seem to do
31:44no harm and may do some good.
31:46We're seeing stronger outcomes and I'll
31:49be showing you some more data that
31:52helps helps us to pretty confidently
31:54say that it's important to think
31:57about the the COPE interventions
31:58and then one of our trials.
32:01So, you know,
32:01should we wait to treat PTSD for those
32:05who have PTSD said absolutely not.
32:09And we can.
32:10We we know that that these treatments
32:12are tolerable,
32:13safe and effective.
32:14And what we see is that if we treat PTSD,
32:18we see greater substance use improvement.
32:23And that is coming from now there
32:27are four or five systematic reviews
32:30that pretty rigorously and and
32:34definitively are showing that greater
32:38PTSD reduction is also associated with
32:41greater substance use improvements.
32:44And the opposite is less true.
32:47And I'll show you one of our
32:50trials where we compared COPE,
32:52which is a prolonged exposure,
32:54trauma focused treatment for people
32:56with substance use disorders
32:57to relapse prevention.
32:59This was done in New York City with
33:02individuals who basically entered our trial.
33:05We're not receiving any other care.
33:07So pretty severe PTSD histories
33:10and substance use problems.
33:13And So what you see here just to
33:15Orient you to the slide is horizontal
33:17axis is the weeks of treatment,
33:19vertical is the PTSD symptoms severity.
33:23And we broke out the groups by how much use,
33:27how much they were using during
33:29the course of treatment.
33:30And this is just one example and
33:32I know it's media has also worked
33:35on using these clinical trials to
33:37do cross lagged analyses to try to
33:39look in real time as what's going
33:41on with the person's substance use
33:44while they're receiving treatment
33:46in relation to their PTSD symptoms
33:50as they are going through treatment
33:52and then over the course of time.
33:54And so here we see the end of treatment.
33:57So after 12 weeks of treatment,
33:59we see one month follow up,
34:01two months and three months in this
34:03in this trial And the Gray box are
34:07all those who end up through the
34:10course of treatment entering into the
34:13clinically significant change group.
34:16So like significant reductions in
34:18their PTSD to a level that we would,
34:21it's not just a change in severity
34:23but it's a clinically significant.
34:25So we see everybody's getting
34:27better over the course of time,
34:29but those that make it into the Gray box
34:32of what we want to see by the end of
34:35treatment and then over the course of time,
34:38the two curves to look at.
34:41So the blue are the people that received
34:44relapse prevention as the comparator
34:45and the orange and red are those that
34:48received the trauma focus treatment.
34:50And what we see is that for those who
34:53received relapse prevention who were
34:55the very frequent substance users,
34:57so they were using four times a week
35:00or more during the course of the
35:03trial their symptoms if they received
35:05the not you know the comparison
35:07treatment of relapse prevention,
35:09they don't get into the clinically
35:12significant change realm in
35:14terms of their PTSD.
35:15Those that were actively using.
35:17So the yellow bar that were actively
35:20using to a level of four times a
35:24week or more when they received the,
35:26the the prolonged exposure trauma
35:29focused treatment you see they make
35:31it into the clinically significant
35:33change box over the course of the
35:36study and their followup period.
35:37So what does that tell us?
35:39That tells us that that our patients
35:43are not as fragile as we would
35:45think that the people and that
35:47the people that are using the most
35:50actually benefit more from the trauma
35:53focused intervention than from a
35:56psychoeducational or or control treatment.
35:58So then moving along to the
36:04pharmacotherapy story,
36:05which we know a lot about,
36:08thanks to Doctor Petrakis and
36:12others who have really been working
36:15in this space in a way, you know,
36:19consistently over decades.
36:21There are a number of treatments,
36:22medications that we have to target
36:25both alcohol or substance use
36:28disorders alone with PTSD agents
36:32that target both And then agents
36:34that focus on craving aversive,
36:37you know,
36:38agents like disulforam and agents
36:41that target withdrawal.
36:43And So what we know thus far and I
36:46think I I did one trial that was a
36:50combined medication we use sertraline
36:52and and and seeking safety for
36:55individuals with alcohol use disorders.
36:57And I swore I'll never do another
37:01pharmacotherapy trial because of how
37:02hard it is to do, how long it takes,
37:05how how hard it is to engage patients,
37:08to keep them in treatment,
37:09all these things.
37:10And so I think these numbers
37:12are probably higher now,
37:13but some of the systematic
37:15reviews that have been done
37:17really show us not so much which
37:21interventions are superior,
37:22but rather the fact that we can
37:25see significant reductions in both
37:28PTSD and alcohol use disorders.
37:30There's no evidence against using
37:33medications in non comorbid populations
37:36and but yet we don't fully know
37:39what are the best practices yet for
37:43these kinds of medications that have
37:46been applied for both PTSD and a
37:49UD individually and then together.
37:53However, I do have more.
37:55So stay, you know,
37:57hold off the judgment because we we
37:59have more to say on that when I get
38:02to our our data science project.
38:04But largely, you know,
38:05we do know things that I can tell
38:08you happily that we can say okay.
38:10Now we we do have ideas about
38:13signals for how to treat PTST and
38:16Sud both with medications and also
38:19with behavioral interventions.
38:21But in fact doing this work for anyone
38:24who spent their time doing it's really hard.
38:27It takes forever.
38:28Our effect sizes are small.
38:31We see most impacts directly
38:33in the PTSD domain.
38:36We have high rates of attrition
38:39in our studies.
38:40Like I said before,
38:42we have spotty uptake of evidence
38:44based treatments and we are.
38:46It's very hard to examine to
38:48go beyond just like compare the
38:50treatment and the comparator.
38:51We don't get to say who does these,
38:53who do these treatments work best
38:55for and also how do they work?
38:57Like what are the mechanisms?
38:58Because our ends are just too small.
39:01So, you know,
39:03our latest solution to this problem
39:06has been to to use data science
39:08as a means to help us move the
39:11drive the field forward.
39:12And so I'm going to tell you
39:14spend a little bit of time talking
39:16about Project Harmony,
39:17which was mentioned earlier,
39:19which is an integrative data analysis
39:22where we managed to pool together.
39:25We acquired 42 studies agnostic
39:29to treatment type.
39:31And you'll see what I mean when
39:33I show you the the variety of
39:35treatments that we pooled in.
39:37But we we identified using a set
39:40of inclusion criteria any study in
39:42the world that we could get our
39:45hands on that attempt to a treat
39:48PTSD and substance use disorders
39:51in adults that had measures of
39:54both PTSD&amp;SUD outcomes and that
39:56had evidence that the treatments
39:58were being delivered in fidelity,
40:00with fidelity.
40:01And this was regardless of
40:04treatment type and also you know
40:09other other characteristics.
40:10And we we acquired a pool
40:13of over 4500 participants.
40:15This was a.
40:17And all hands on deck and I'm
40:19going to show you our team from,
40:21you know, City College,
40:23Columbia University,
40:24Rutgers University,
40:25Medical University of South Carolina,
40:28Yale University,
40:29University of South Wales,
40:32University of Washington,
40:35Stanford University and
40:37University of Toronto.
40:38These are our team members and our
40:41Scientific Advisory Board members
40:43who shared their data with us
40:46as well as and Antonio Morgan.
40:48Lopez was the MPI on this project.
40:51He's at RTI International with
40:53me and did all the elegant quant
40:57work on the project.
40:58This is just, I can't spend time on this,
41:01but these are our international
41:03consortium that we call our cast
41:06and all of these individuals
41:08shared their data sets with us.
41:10And when I say shared their data,
41:12I mean they gave us their data sets.
41:14So we were able to do things with the
41:17data and I'll just show you about that.
41:20But first we brought together the
41:22international group and one of the
41:24things we needed to do given that
41:26we were agnostic to treatment type
41:28was we had to categorize treatment.
41:31So we had the international group,
41:34they were involved with us.
41:35We had several meetings,
41:37consensus meetings and we did surveys
41:40but we we identified and categorized
41:44treatments into trauma focused like the
41:47ones you know the stage two treatments
41:49that we were talking about and non
41:51trauma focused which were treatments
41:53like a seeking safety treatment that
41:55didn't target the trauma but may have
42:00been an integrated treatment for traumatics,
42:04PTSD and Sud.
42:05And we also so we had
42:07behavioral interventions,
42:09we had integrated behavioral where
42:11they tried to address both PTSD and
42:14substance use in the same treatment we
42:16had combined so integrated plus meds,
42:18we had meds alone.
42:20So targeting either the alcohol
42:22or substance use outcome,
42:25the PTSD outcome or both.
42:29And then we also had a variety
42:31of controls because when you're
42:32doing comparative effectiveness,
42:34you need to be able to classify
42:36the treatment so that you're
42:38kind of reducing the number of,
42:40you know,
42:41kind of degrees of freedom or
42:45increasing the degrees of freedom,
42:47but you are also comparing it to
42:51the same comparator.
42:52So we classified the control
42:56groups as psychotherapy that was
42:58targeting a alcohol or drug use only,
43:02psychotherapy controls that were really
43:05treatment as usual and then placebo
43:09controls which was medication placebo.
43:13And so by doing that we end up with
43:15about with eight classes that were
43:18comparing to 1 comparator which would
43:21either be treatment as usual or placebo.
43:24And so you know one of the things
43:27that we did with Project Harmony
43:29was a traditional systematic review
43:31and we did a network meta analysis.
43:34And so that's taking, you know,
43:35a typical traditional meta analysis is
43:37when you go in to the published data
43:40and you look at what's out there and you,
43:44you know extract effect sizes from
43:47that data and then you examine
43:50the effects of the treatments
43:52and you and you come up with a,
43:53you know,
43:54some kind of an idea about what's
43:56what's going.
43:57And so we did the a traditional
44:00systematic review from the literature.
44:03This is not the pooled analysis yet,
44:05which I'll show you in a moment.
44:07But we then did a a network meta
44:10analysis to kind of characterize
44:13the state of science and to
44:15look at PTSD and a UOD outcomes.
44:18And out of you know 1000,
44:21you know hits that we got,
44:23we we sifted through 700 trials that
44:27met our criteria and in the end we
44:31identified 39 trials with two
44:34subnetworks of the this network I'm
44:38showing you above is the behavioral
44:40interventions compared to a psychotherapy
44:43control like a treatment as usual.
44:47And then there was another step
44:49network of the medication trials that
44:52were compared to placebo and what we
44:55found in this network meta analysis
44:57which is about to be published in
45:00psychological bulletin like today,
45:03tomorrow who knows it's it's coming
45:05out very shortly is that the for
45:10PTSD the integrated trauma focus.
45:13So again those trauma focused interventions
45:17did significantly better compared to
45:19the treatment as usual controls than
45:22any of the other other classifications.
45:25And for the medications,
45:28we saw that alcohol targeting
45:32medications with or without trauma
45:35focused treatment appeared to be
45:39superior to placebo interventions
45:41in this network meta analysis.
45:45So it's giving us an indication
45:48of yes trauma focused and yes,
45:51our alcohol targeting medications and
45:53that's a direct effect on alcohol outcome.
45:57So in this network meta and then to go
46:01into the Project Harmony piece where
46:04we did an integrative data analysis
46:07with the individual patient data that
46:10we got from all of these trials over
46:13the world that was recently published.
46:16And you can get more of the the
46:18fine finer details from the American
46:21Journal of Psychiatry and in February.
46:23But basically,
46:23and I don't have time to go into all of it,
46:26but we did a bunch of fancy analyses
46:29that kind of what I like to say is
46:32this virtual clinical trial basically
46:34does like on your iPhone where you
46:37have a photograph and then you go
46:39into edit on the photo and there's a
46:41little magic wand and you press the
46:43wand and the photo just looks better.
46:45It like makes it pop.
46:48That's what I think of as this,
46:50this type of analysis where we did
46:52a variety of things.
46:53We did propensity score weighting to
46:57sort of the equivalent of covariates in
47:00a single trial to address measurement
47:03inequalities and other issues
47:06with across all of these trials.
47:08Because remember,
47:09we're pooling all these trials,
47:12we have to harmonize the measures and
47:15do we did modified nonlinear factor
47:18analysis to create harmonization so
47:20we could look at the same outcomes.
47:22The outcomes were PTSD,
47:25alcohol use and substance drug use.
47:28So those were our outcome measures.
47:30We harmonize all across all studies.
47:33So in one study it might have
47:35used timeline follow back to look
47:36at substance use outcomes.
47:38In another study they might have
47:39used the ASI or some other metric
47:42and we you have to kind of harmonize
47:44it so you can compare across.
47:46We categorize like I told you
47:49before and we structured time.
47:50So we were looking at post treatment
47:53which is 3 months post treatment
47:55and 12 month which was estimated
47:57because of course some trials might
47:59have looked at six month outcomes,
48:01others might have looked at one
48:02week outcomes,
48:03others might have looked at
48:04one year outcomes.
48:05And so we did analysis to structure the time
48:09and what we ended up finding was very
48:12good news and the good news overall was
48:15that all of the intervention classes,
48:18patients got better.
48:19So we like to say there are no wrong doors.
48:22You can apply these variety of
48:25interventions and everyone got better,
48:28but some doors are better than others.
48:30So people got better with some
48:33of the trauma focused integrated,
48:37I'm sorry non trauma focused
48:40integrated models whoops,
48:41but but as you can see here it
48:47wasn't statistically significant.
48:48So, so the seeking safety model was a non
48:54was an integrated but non trauma focused.
48:57We don't see significant impacts
48:59compared to treatment as usual,
49:01whereas the big winner was drum roll
49:06trauma focused interventions with
49:08alcohol targeting medications and
49:10what you can see here are very large
49:13effect sizes for those interventions.
49:15So we might not have seen that in any
49:17of the individual clinical trials like
49:19all of the ones that this mini has been
49:22working on and working on where you
49:25might not have seen the impacts also
49:27because she was comparing to placebo Med,
49:31placebo Med also does pretty
49:34well on PTSD for example.
49:37And but what we're seeing is direct
49:40effects on the alcohol outcomes and
49:43then you know you know the it's so the
49:46winners are the trauma focused whether
49:48they're integrated or they're not
49:50integrated and alcohol targeting meds.
49:52So it's sort of expands on the lit review
49:55network meta analysis that I showed you.
49:58So we're but we're taking
49:59this data and we're we're,
50:02we're sort of able to examine it.
50:04And so this just gives you a
50:06taste of what we're finding.
50:08And then we are also doing moderator
50:11mediator analysis as we speak.
50:13The one thing that you see you might take a
50:16note of is that in terms of drug outcomes,
50:18we're not seeing a lot of direct impacts
50:21on drug from either any of the kinds
50:23of interventions on drug directly.
50:25And what we do expect to be able
50:28to talk about more is that that
50:31indirect effect of if you target the
50:34trauma you will see impacts like
50:36downstream on the drug effects.
50:40And why it is that we are able to
50:42see the impact on alcohol more
50:44directly for the first time here
50:47with this analysis at Versus Drugs.
50:49I'll leave it to,
50:50you know maybe we can talk about
50:52that during the Q&amp;A.
50:53But so that that sort of gets us to,
50:56I'm going to spend the last few
50:58moments before we have time for
51:01chat to talk about as clinicians
51:03okay what's the take away.
51:04So I mean the take away from
51:06the treat my science,
51:08you know the science of our
51:10interventions is good news.
51:11We have a lot of things that we can
51:14do and now we have to try to start,
51:17you know,
51:18doing them more more systematically
51:20and enabling places that may not have
51:23access to care to do these interventions.
51:26So I was in Australia giving a
51:28talk to a
51:29bunch of, you know, addiction medicine
51:33professionals recently and you know,
51:36they were like our system is so
51:39separated that how do we bring these
51:42interventions to to our, our population.
51:46And so I encourage them to get
51:49creative because not, you know,
51:51and and because we know the answer,
51:53we know that these
51:54interventions actually work.
51:55So now we have to start
51:57really pushing them out.
51:59So how do we apply an integrated framework?
52:02Well, these are some of the questions from
52:04a clinician perspective that we need to
52:06start thinking about and trying to answer.
52:09What does success look like?
52:10Like, Is it really abstinence or is
52:14it really diminishment of symptoms?
52:16Probably not.
52:17If you're thinking about your client,
52:19you want quality of life.
52:20You want to think about other
52:23types of outcomes.
52:24What if the person still using do?
52:26Can we call it a win if someone goes
52:29shifts from being a daily opioid
52:32user to a nightly cannabis smoker?
52:36Is that a good thing?
52:39You know, how do we make those judgments?
52:41How do you match for your client
52:44the right kind of therapy for them?
52:47And what do you do if your
52:49patient starts getting worse?
52:50How do you handle that and how
52:53do we understand differences by,
52:56you know,
52:58social determinants and other
53:00individual characteristics?
53:01How do we incorporate cultural variations
53:04and how we deliver our treatments?
53:07So what we basically advocate for
53:09is what I call an integrative
53:11treatment framework where we you
53:13know it's it's it's good treatment.
53:15So this is nothing new to anyone
53:17who's a provider is like we want
53:19a comprehensive assessment so
53:20we know what we're dealing with.
53:22Obviously we want to use
53:26those destigmatizing,
53:27motivational interviewing and harm
53:29reduction techniques to understand
53:31that not you know what might be
53:33abstinence model might be great
53:35for one patient and really and not
53:37a good model for another patient.
53:39So really matching and having
53:42kindness and care and a sense
53:45of positivity for our clients.
53:48Harm reduction therapy is one
53:50example that we can use,
53:52but there are many other approaches
53:54motivational interviewing we
53:56want to think about engaging our
53:58clients and therapeutic alliance.
54:00So you know,
54:02understanding that patients may not
54:04seek treatment or stay in treatment
54:06or use treatment in the same way and
54:08that doesn't mean that they should
54:10be denied treatments of these ideas
54:11that like 3 strikes and you're out
54:14because our clients don't attend
54:16sessions for lots of different
54:19reasons due to those emotional
54:21dysregulation and other factors.
54:23But you know,
54:24there's a lot of things that
54:25we need to do and that we can
54:27help support our clients.
54:29So a lot of these treatments if
54:31even if you don't have trauma
54:33focused training at your agency yet,
54:36there's a lot of treatments for
54:39dysregulation that can be used to
54:41help address traumatic stress in our
54:44clients and help with treatment processing.
54:47So again,
54:48treatment planning,
54:50coordinated care,
54:51working together across disciplines
54:54and promoting stability,
54:56these are all just like really good
54:58principles of treatment planning that we
54:59should apply in working with our clients.
55:01So to sum it up, people with PTSD stutter,
55:07highly comorbid and undertreated
55:12integrated care is safe and efficacious.
55:15I feel confident in saying that
55:18and optical optimal care should be
55:21individualized and you know as I just
55:24said involves having a client centered
55:27approach and and incorporating A harm
55:30reduction model doing comprehensive
55:32assessment that's collaborative and
55:35then using evidence based particularly
55:39combined treatments will lead our
55:43clients down a very positive path.
55:46Before I end, I just want to express
55:49appreciation to all of my colleagues
55:51that over 101,000 participants in
55:53the clinical trials that have helped
55:56us gain the knowledge that we have.
55:59You know my institutions,
56:01Rutgers, Columbia University,
56:02City College of New York,
56:05and you for being such good listeners and
56:09hopefully engaging with me in conversation.
56:12And then I'm going to end with some words.
56:15I like to end with the words of one of
56:19our clients who was is a woman from
56:23a disadvantaged background who was a,
56:26you know,
56:27receiving treatment in one of our
56:29treatment programs here in New York City,
56:31The Women's Health Project at
56:33Saint Luke's Roosevelt.
56:34Now it's Mount Sinai.
56:35I
56:37forget what the full name is but hospital
56:41and she was someone who had a very
56:46challenging background multiple you know
56:49cocaine and opioid use disorder disorder.
56:54You know profile sexual abuse ongoing
56:58victimization and this was her poem.
57:02Multi trauma survivor heals
57:04to find wedded bliss.
57:06Healing universe applauds.
57:09You are next. I'm a new house.
57:12I've come out of thick,
57:14tough hide swearing by the rock I
57:17rubbed against to be tender again.
57:20To able to receive and give love for
57:23my most vulnerable, healed self.
57:26Appreciating freshly discovered
57:28beauty from its fearless depths.
57:31Of honesty.
57:32Feeling peace out of the gratitude
57:34of being accepted as is by the
57:38universe myself and the reflection
57:40in the eyes that behold me.
57:43I believed it for me.
57:46Believe it for you.
57:49Thank you.