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Domestic Violence and Abuse

Psychiatric Sequelae of Traumatic Brain Injury with Dr. Jesse Fann


JESSE FANN: Right. Hi. My name’s Jesse Fann. I’m a professor in psychiatry
and behavioral sciences at University of Washington
and have adjunct appointments in rehab medicine
and epidemiology. And today, we’ll talk
about psychiatric sequelae of traumatic brain injury. Here are our
objectives for today. And it’s a large topic
to cover in 30 minutes. So I’ll be going
relatively quickly. But basically, we’ll
talk about the prevalence of psychiatric conditions
after brain injury and talk about the
impact and risk factors and then talk about
assessment and treatment. I’ve been working with this
population for about 25 years. And certainly, there’s
a lot of information that’s been accumulated
during that time. But still quite a bit of
work to be done, particularly in the realm of treatment. So these are the areas that
I’d like to touch on today. And again, it’s a lot to
cover, but hopefully we’ll be able to cover that
in some meaningful way. So before we start,
I want to encourage people to not just think
about TBI as not just a neurobiological injury but
also a traumatic event that may have some significant
impact on a person’s emotions, cognitions, and behaviors. And also, the impact of TBI as
a chronic medical condition that can lead to a number of chronic
conditions going forward. Why do we really care
about psychiatric problems after traumatic brain injury? Well, we know that
traumatic brain injury has a number of
mechanisms on the brain, including diffuse
axonal injury and impact on a number of important
neurotransmitters that are involved with
the behavior, emotion, and cognition of a person
following a traumatic brain injury. So we know, for example
that diffuse axonal injury disrupts the serotonin
system in the brain. And serotonin, as most
of you probably know, has a significant impact on
mood following traumatic brain injury in people with depression
and anxiety et cetera. So just a very quick review. And I won’t go through
all these in detail. But it’s important
to, when possible, think about any specific
lesions in the brain associated with the traumatic brain injury. And if there are
specific lesions that can be identified, for example
in neuroimaging, for example, then you can
potentially anticipate some of the problems
that might arise. So for example, in
orbitofrontal injuries, you might anticipate some
problems with impulsivity, disinhibition, et cetera. And similarly, with lesions
and injuries in temporal lobe, you can find a really
wide array of problems in terms of certainly
cognition but also emotion and other behavioral issues. This is just an
example of a study that was able to find a correlation
between the severity of a person’s
depression symptoms following a traumatic brain
injury and functional MRI findings showing a correlation
in the left frontal lobe with the severity of
depressive symptoms. Similarly, one can
look at the areas of the brain that are associated
with traumatic brain injury, as well as areas
of the brain that have been associated with
post-traumatic stress disorder. And you see that
in the blue color, you see an overlap with areas
vulnerable to TBI as well as PTSD, for example the
orbitofrontal and hippocampal areas of the brain. So again, thinking
about the neurobiology, there’s clearly a
biological mechanism that can lead to
psychiatric symptoms. So I want to turn
now to assessment and encourage people
to think again about the biopsychosocial
approach to assessment and evaluation and follow up
after a traumatic brain injury. And I just want to
highlight a few things here. For example, in
terms of etiologies of neuropsychiatric
problems, it’s very important to get
a very good history of prior neuropsychiatric
or behavioral problems, because many of the studies
that I’ll talk about have shown that people with a
history of psychiatric problems are actually much more
prone to problems following a traumatic brain injury. And also thinking about a
history of substance abuse. So those things are
very important in terms of doing a good evaluation. And this is just an
example that illustrates that in a large
population based study that we did at Group
Health Cooperative here in Seattle in
the Puget Sound area. We found that among people
with traumatic brain injury, they had a much higher rate
of psychiatric problems prior to their injury compared
to a control of people who did not have TBI. When we’re thinking
about workup, again, the
biopsychosocial approach, but also very important would
be to get a good history from collateral informants,
such as family and friends. And the reason for this
is that patients often will focus on their physical
and cognitive complaints, while family members and
others who know the patient may pick up on
more the behavioral or emotional problems. So very important to get
that collateral information. And then at follow up,
again, really, really emphasize the importance
of using outcome measures that have been validated. We still have some
work to do in terms of validating many of the
measures in this population. But also, very close
follow up in terms of tolerability and response
to pharmacologic and behavioral interventions. So there’s been a
group of investigators who have been really
interested in looking at TBI as a chronic condition,
because as I mentioned, we know that TBI
can be associated with not just
acute or post-acute but chronic
conditions, including a lot of neuro, behavioral,
and psychiatric problems. So this is a table really
based on expert opinion and available evidence
from the literature that proposes some recommendations
for how to monitor and screen for problems
following a TBI. And I’ll just point to,
for example, depression, and anxiety. We recommended that
people use the PHD4, which is a very, very brief
and easy thing to use at every visit for the first
couple of years post-TBI and then as needed afterwards. And if they have a history
of depression or anxiety or an otherwise high risk, then
to continue to use the PHD4, which literally takes one minute
to two minutes to complete. And you can see some of
these other recommendations as well for cognition,
sleep, et cetera. So turning towards treatment,
what are some basic treatment principles? Well, the first thing
I want to emphasize is that when somebody has
a traumatic brain injury, or for that matter, any
sort of neurologic injury, like a stroke, for example,
the nomenclature that we’re typically used to
based on the Diagnostic and Statistical Manual
for Mental Disorders typically does not apply
very exactly to the symptoms that patient may present with. So I recommend people
to know the DSM criteria but not to get too stuck on
whether or not the patient fits the DSM criteria. If they’re missing
one or two symptoms, but the symptoms
are still leading to significant
functional impairment, it’s very important
to consider treatment. It’s also important
to, again, assess what was going on
prior to the injury and to really assess
their are coping skills prior to their
injury, because what was going on before may actually
be accentuated following the injury. And again, to really
define your treatment goals and to be realistic with
those treatment goals and to monitor them
very, very closely with validated instruments. So the basic principles
really, again, focus on functioning
and improving functioning following TBI. And when we’re thinking
about pharmacology, we want to really think
about starting low because of their propensity
for adverse effects of many of the psychotropic medications
that I’ll talk about but also to titrate
slowly but to not stop too soon, because many
patients will still need the usual or even sometimes
higher than usual doses to get a therapeutic effect. And the effect may be latent. So it’s very, very tempting
to give up on a treatment too soon, where
we know that many of the medications,
for example, and even the behavioral interventions may
have a delayed onset of effect. I’m going to skip this. But this is just to
show you the trajectory of psychiatric problems
in the group health study that we conducted,
showing that people with a prior
psychiatric problem had a much higher rate of
psychiatric problems following their TBI. And the association
between the severity of the TBI and the
psychiatric problems were not the clear
dose-response relationship. This is another study, a
large population-based study in Sweden showing that
children and adolescents with traumatic
brain injury, when followed for 15 years
following their injury, had a much higher rate
of disability, welfare involvement, and also
psychiatric visits and hospitalizations compared
to people without a TBI. So as I move towards
pharmacology, I want to start by talking
about polypharmacy. And the reason is
because we know that there’s a high
rate of co-morbidity among the various
neuropsychiatric problems listed here, for example. And as a result, many
patients over time, because of often, unfortunately,
the fragmentation of our health care system, get put on a
number of different medications by, sometimes,
different providers and at different time points. And that can lead
to big problems, including accumulation
of adverse effects, but also accidental overdose,
especially among those with cognitive problems,
drug dependence, confusion, falls, further
accidents, et cetera. And so I encourage people to
think about the opportunity to be efficient with
medications in terms of looking at the
co-morbidities of the symptoms and finding medications that
may hit as many of the symptoms as possible. For example, if you look at
these symptoms across the top, you see that antidepressants
have a potential for benefiting all of these, not
that everybody should be put on an antidepressant. But this is just to illustrate
that there is an opportunity to be efficient with a lot of
these medications trying to hit a lot of the symptoms at once. So turning now to the
specific conditions, depression is the
most common problem following traumatic
brain injury in terms of a neuropsychiatric problem. And the prevalence I’ll
show you is quite high. But it should be
differentiated from apathy, which is more of a disinterest
or amotivation, which can certainly overlap
with depression. But apathy can also present
by itself without depression. And it’s often the
caregivers that complain about the
patient who’s apathetic. And oftentimes the
patient is not aware of or is not as distressed about
the apathy as caregivers. And that can be true
for depression as well. You see that across a
number of large studies, in terms of the prevalence,
both point prevalence and period prevalence, there’s
a wide array of rates because of the differences
in study methodology. But if you look at
the first two years, for example, a very consistent
finding that at any point in time over the first
one to two years, you can expect that
about 1/4 of patients will have significant
clinical depression going on. And then even going out decades
following the brain injury, the rate of depression
is still higher than the general population. Now, it’s interesting
that most of these studies were done in civilians. And then if you look at the
military population, also very high rates of depression. And there does seem to be a dose
response relationship between whether or not there was
loss of consciousness versus no loss of consciousness. And this is somewhat different
from the civilian population, where the rates of
depression are not directly correlated to
severity of the TBI. So this is a study that
Dr. Bombardier and I and other colleagues here at
the University of Washington conducted at Harborview Medical
Center, our level one trauma center, showing that
among over 500 patients followed for a year
following their TBI that over time, about
1/2 of the patients eventually developed
probable major depression. And the rates were highest
within the first three to six months. In terms of risk factors, there
been a lot of risk factors thrown out in the literature
as probably risk factors. But I’ve highlighted
here the ones that seem to have held
up the best in terms of multivariate analyses. And you see that
these are probably not a big surprise to you when
you look at these risk factors highlighted in red. This is just a look at what the
patient health questionnaire depression scale looks like. It’s been validated
in TBI populations. And the difference in
the way it’s usually used in, for
example, primary care is that a score of several
days versus more than half the days seems to
be enough to qualify for a significant symptom. So if somebody has
five or more symptoms of several days or
more with at least one of the first two symptoms, which
we call the cardinal symptoms, then they very likely have
what we call a major depressive disorder. So probably preaching
to the choir here, but depression has
very significant associations with a number of
adverse outcomes following traumatic
brain injury, including cognition,
post-concussive symptoms, and of course, higher
rates of suicide in people with traumatic
brain injury in general. And depression is a significant
risk factor for suicide. And when we think about
post-concussive of symptoms and particularly persistent
post-concussive symptoms, this is just to
illustrate that depression has quite an overlap in
terms of the symptoms with post-concussive symptoms. And so it’s an opportunity
to, number one, detect people with depression, and number
two, treat depression, which is a treatable condition. And that may actually
significantly improve the array of post-concussive
symptoms that patients have. And this is a review
that we conducted looking at the risk factors for
persistent or prolonged post concussive symptoms. And I’ve circled
the, really, many behavioral and
psychiatric risk factors, both pre-injury and post-injury,
things like depression, PTSD, learning
disorders, history of psychiatric
problems, anxiety. These are all significant
risk factors for prolonged post-concussive symptoms. And much of what
I’ve said has been found to be true in
the military population as well for those of you who
work, for example, in the VA system. Unfortunately, from a
public health standpoint, we know that the minority
of patients with depression actually get treatment for it. And from our Harborview study,
we found that less than 1/2 of our patients
who were identified as having major
depression actually were receiving any treatment
during that first year of follow up. And most of the people
who did get some treatment were getting antidepressants. We don’t know from
this study if they were getting adequate
doses of antidepressants. But we know that from
many, many other studies in other populations
that less than 1/2 of patients who
are depressed tend to get adequate treatment,
either pharmacologic or psychotherapeutic. And the literature for treatment
of psychiatric problems is quite minimal following
TBI, unfortunately. The two level one level
evidence randomized controlled trials
showed that people with more the chronic
phase may actually benefit from SSRIs, whereas
our study showed that in the acute and
post-acute phase, people, when given an SSRI
versus placebo, they did not differentiate
from placebo. So I think the
take-home message here is that antidepressants
may help, but they alone are or
are likely not enough, particularly in the
post-acute phase when people are really
adjusting to the consequences of the brain injury. And so clearly, more
and more studies are needed to look at that
the place of antidepressants in the treatment of depression. But the studies that we
do have, and many of them are non-randomized, showed
that SSRIs, and sertraline and citalopram are the ones
that have been studied the most, seem to be relatively
well-tolerated and are likely worth a
try for many patients but also in conjunction
with behavioral treatments, which I’ll talk about. There are a number
of antidepressants now that we have
available to us. And many of these have
not had adequate trials. But for example, SSRIs
may have an advantage to help with things
like neuropathic pain. Bupropion is a good
antidepressant, particularly for people
who are very fatigued. But for people who have
a history of seizures, it would not be a good
choice because of its ability to lower the seizure threshold. And then for apathy,
again, very few trials, but the dopaminergic
agents seem to be, potentially, the most effective. In terms of anxiety
and related disorders, I’ll just mention generalized
anxiety disorder, panic, and phobias as the
most common anxiety disorders following TBI. And then obsessive
compulsive disorders no longer considered anxiety
disorders in the DSM V. And then post-traumatic
stress disorder also not consider an anxiety
disorder anymore. But I’ll clump
them together here. I want to emphasize with PTSD,
what people typically think about is things like
nightmares and flashbacks, hyper-vigilance, which are all
potentially important symptoms. But people often don’t
consider the importance of avoidance behaviors in PTSD. And in many people,
the avoidance is what leads to the greatest
level of functional impairment, because they’re not
leaving their home. They’re not participating
in the community. They’re not going back to work. They’re not engaging in their
family roles, for example. Again, a wide mishmash of
rates among different studies based on different methodologies
of assessing anxiety in different populations. But in general, you see a higher
rate across these disorders compared to the
general population, which is in the
parentheses in the top row. And a large study among the
TBI model system population, a national cohort, shows that
one year, 20% to 25% of people have significant anxiety, and
similarly with depression. But over 2/3 of patients
with depression or anxiety also have co-morbid
anxiety or depression. So this is just to
illustrate the importance of looking for both when you
suspect one or the other. And this is just to show
you that GAD-7, the anxiety screener that we
proposed that people try to use as a general
screener for anxiety. So again, PTSD, more
common in people with more severe injuries
in the military population. But actually,
people with mild TBI have about twice
the rate of PTSD compared to people with
moderate to severe TBI in the civilian population,
likely because of the often lack of recall of
the actual injury. But in the military,
of course, they’re in a much different setting. And as I’ll show you
in a couple of slides, the risk factors for
PTSD do correlate with the setting of the trauma. So this is just to show
you, similar to depression that overlap with PTSD and
post-concussive symptoms is quite great. And so again, I think of it as
certainly a diagnostic dilemma but also an opportunity
to treat something like PTSD, which
can be treatable, to help with post-concussive
symptoms that may be persisting. This is a slide showing
some of the risk factors that have been found
for PTSD following TBI. And you see that the setting
and severity of the trauma certainly impacts the
prevalence of PTSD but also the level
of co-morbidity with other things
like pain, depression, other medical
co-morbidities I do have an impact on the
prevalence of PTSD. So what are the pharmacologic
approaches to anxiety? Well, for acute
anxiety, if one wants to think about a
medication, benzodiazepines are still the most quick-acting. But there are a lot of potential
problems with people with TBI, particularly those with
cognitive impairment. And so if one is to
use a benzodiazepine, I encourage people to start with
a much lower dose, about 50% the usual starting dose,
and to really think about a very time-limited
and closely monitored trial. For many anxiety disorders,
most anxiety disorders, antidepressants are
quite effective. And I encourage,
for people who need more chronic treatment, SSRIs,
SNRIs, and tricyclics can be very effective. For things like
anticipatory anxiety, beta blockers can be helpful. And a number of
other medications can be useful as
adjuncts but typically not as primary
treatments for anxiety. Similarly, for PTSD,
benzodiazepines are not the treatment
of choice for PTSD. They may have a role
in short-term treatment for acute symptoms, for example. But again, the antidepressants,
particularly SSRIs, SNRIs, and sometimes tricyclics,
which unfortunately have more potential for
adverse effects, but still are very effective
medications and should be considered, particularly if a
patient’s not tolerating or not responding to an SSRI or SNRI. And then you’ll see here,
other alternative medications that can be used typically
more as adjuncts. And prazosin, for
example, has been shown in a number of studies
to be helpful for things like nightmares and flashbacks. So again, I encourage
people to really think about what
other things are going on in terms
of co-morbidities and trying to find the
combination of medications that really treat
as many symptoms as possible at the same time. Very important,
of course, and I’m not able to give adequate
time to discuss this. But non-pharmacologic
treatments are very important. Again, we need more
randomized controlled trials. But cognitive behavioral
therapy approaches seem to be the most promising
approach for anxiety disorders. But depending on the symptoms
and the stressors that are involved, a number
of other approaches may be beneficial to consider. Although, again, more randomized
controlled trials are needed. Similarly, with PTSD, a number
of evidence-based treatments have been shown, at
least in small studies, to have efficacy and
tolerability in people with TBI, for example, prolonged
exposure, cognitive processing therapy, and
behavioral activation. And then again, other
adjunctive approaches like motivational
interviewing may be very important and
effective for behavior change and substance use et cetera. EMDR has also been
shown to be effective and is an evidence-based
treatment for PTSD. Very briefly, mania is
not nearly as prevalent as depression and
anxiety but is more prevalent after
traumatic brain injury than in the general population. And what we typically
think of bipolar disorder, particularly the kind of
more euphoric presentation is actually not very common. And one might actually
much more commonly find irritability and kind
of emotional lability or incontinence as a
presentation of quote, unquote, manic type or bipolar
type presentations. It’s important to look for
epileptiform activity on EEG, because that can present
as mood lability. And there may be some
genetic loading as well and some correlation
with right-sided lesions with bipolar disorder. But again, more data
would need to be present to really confirm that. And then in terms
of treatment, there are really no randomized
controlled trials in TBI. So we really draw from
other populations. But knowing that
things like lithium, which are very effective
for other populations may not be the best
choice for somebody with a TBI because of the
potential neurotoxicity and the narrow therapeutic
range for people who may have cognitive
problems and trouble keeping track of their medications. But again, this is just a review
of some of the acute and then more chronic approaches. And very important,
again, to think about, if somebody has a
lot of irritability or maybe use seizures,
then anticonvulsants may be the first-line treatment
for a person presenting with mania after a TBI. Pseudobulbar affect can
present with lability. But it’s basically
uncontrolled crying or laughing and can occur
after a TBI as well as other neurologic conditions. And there is an FDA approved
medication, dextromethorphan, that has been found to be
effective for pseudobulbar affect. Psychosis, again, not
the most common following TBI but still more common than
in the general population. And studies have shown
that people with TBI are at high risk for
schizophrenic-like symptoms. And then when you interview
people with schizophrenia, they seem to have a
higher history of TBI. And again, trying to minimize
the doses of antipsychotics, because there have been
some studies, mostly in the animal literature,
suggesting that it may impair neural recovery. And so because of the
propensity for adverse effects, particularly extrapyramidal
and sedating effects, the third generation
antipsychotics tend to be recommended. But again, really a
lack of randomized controlled trials with treating
psychosis following TBI. Very important to rule
out, of course, delirium, particularly in the acute
and post-acute phases, because delirium can present
with psychotic symptoms. Cognitive impairment is, of
course, a big issue for people, particularly with
moderate to severe TBI. And it can present with a number
of different presentations. Oftentimes,
particularly for people who were working
prior to their injury, the effect on
executive functioning can be quite problematic
in terms of multitasking and problem solving et cetera. And studies have now
shown that TBI is likely associated with the
prevalence of dementia, particularly people
with more severe TBIs and people with
more than one TBI. There seems to be a
dose-response relationship. And the effect of the
TBI on the relative risk seems to be higher when people
have had their TBI at a younger age. And again, it’s very
important to look at other conditions that
might be contributing to the cognitive
impairment, because we know that people with
significant depression, anxiety, PTSD can also present
with cognitive problems. And those are potentially
modifiable and treatable. This is just to show you the
dose-response relationship in the study that we did in
the Danish National Registry, showing that as the
number of TBIs increased, the risk of dementia increases. And we found that the
risk was also increased for Alzheimer’s disease. In terms of
treatment, we’re still looking for a good
pharmacological treatment, both for prevention
and treatment for cognitive impairment. And I just
highlighted a few that have been suggested
as potentially beneficial for some patients. And so again, if there’s a
need to use, for example, a stimulant to
help with fatigue, it may also help with
things like attention and concentration. But we’re clearly still
looking for the best approach. And there’s no
one-size-fits-all, unfortunately. There’s certainly a place
for cognitive rehabilitation, compensatory
strategies for people with cognitive impairment. That’s very important
to consider as well. In terms of medications that
impair cognitive impairment, there have been a number. This is just a sampling of
mostly case reports or case series. And one can think
about medications that either decrease dopamine,
decrease acetylcholine, or increase GABA
as likely culprits for impairing cognition
following a traumatic brain injury. And finally, looking at anger,
irritability, aggression, agitation. I clump these together, mostly
because the literature is not very precise in defining these. And clearly, these
are not all the same. But they do tend to
be clumped together. And the rates of these
problems is quite high. And the presentation
can be quite variable. But a common
presentation would be somebody who’s tends to be much
more reactive to things that come up in their environment. The behavior tends to
be non-reflective and non-purposeful and can be
quite explosive at times. It can be periodic in terms
of being very infrequent and then and then
popping up unexpectedly. And is often dystonic. People often tend to feel
very guilty after having these behavioral outbursts. And again, very
important to think about the other contributors
to these symptoms. For example, people
who are depressed have been shown in
multiple studies now to have much
higher rates of anger and irritability and aggressive
behavior, and similarly with bipolar and
PTSD co-morbidity. And of course,
behavioral strategies are very important in
terms of treatment, particularly
psychoeducational strategies have been shown now
in a number of studies to be promising approaches. In terms of pharmacology,
again, very few randomized controlled trials. The randomized controlled
trials that have been done tend to show that beta
blockers can be very effective, sometimes needing
relatively high doses. And amantadine as well
has shown promise, although the literature
is somewhat mixed. And methylphenidate might
seem a little paradoxical. But people, particularly
with significant cognitive impairment that may be
contributing to their behavior, methylphenidate may improve
attention, concentration and in turn improve behavior. But thinking about kind
of splitting up acute versus chronic approaches. Acutely, the antipsychotics
and benzodiazepines certainly act the quickest when
you need a very quick response. But they may not
be, particularly the benzodiazepines, the best
approach in a chronic setting. And again, this is where
finding the best approach that hits as many chronic
co-morbidities as possible is really important,
because it’s, in many cases, kind of an n of 1
experiment based on lack of randomized controlled data. And then just finishing
up very quickly, hypopituitarism is very
important to consider. More data is coming
out now suggesting that this may be
associated with a number of behavioral conditions. And then just kind of wrapping
up with a summary slide, showing that the
severity of TBI is not directly correlated with
neuropsychiatric and post-concussive symptoms. It is correlated with
cognitive impairment. And people with a history
of psychiatric vulnerability are at much higher risk for
neuropsychiatric problems following a TBI. And all of these things
funnel into impacting functioning, quality of life,
and health care utilization. So that’s it. I want to thank many
of my collaborators here and elsewhere that
really helped develop many of the studies and
contributed to the findings that we’ve had. So thank you very much. LECTURER 2: OK. So we have a
question in the chat. So the chart showing
what benefits each class of medication
could provide is very helpful. Is there a similar chart
showing what side effects those classes of meds can cause
to compare benefits and harms? JESSE FANN: Yeah. I’m sorry I didn’t have a
slide comparing side effects. But there are charts like that. Some of the chapters that
we’ve written kind of tried to summarize
many of the pros and cons of the medications. So I would say that rather
than going through all of them, if you have an interest
in that, send me an email. And I’d be happy to
send you what we have. LECTURER 2: Are
there differences in treatment plans
for depression after a TBI versus depression
in non-TBI patients? JESSE FANN: Yeah. So that’s a great question. And I don’t know that we
have the absolute right answer to that. I think what we can
glean from the literature and with what has been shown in
randomized controlled trials is that antidepressants, by
themselves, are typically not enough. And that can be true for not
just TBI but other populations as well. But that psychotherapy
counseling strategies can be quite effective,
and particularly with some, oftentimes
just very mild, accommodations for people
with cognitive impairment. Things like cognitive
behavioral therapy can be very well-tolerated
and feasible and effective. But you do need to think about,
particularly if the patient does have some
cognitive impairment to try to make some
adjustments for particularly the more cognitively demanding
therapeutic approaches. And I think really in
this complex population, it’s often the
combination of a number of approaches that will end
up being the most effective. But again, we need more
studies to confirm that. LECTURER 2: OK. And that wraps up our time. Thank you very much. JESSE FANN: Thank you.

Cesar Sullivan

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