HOW TO MONITOR AND MANAGE THEM
Two out of the 10 biggest sellers in the Unites States
Pharmacopeia last year were anti-psychotic medications. What do we need to
know about these meds, should non-psychiatrists be prescribing them routinely.
You're listening to ReachMD XM 157, The Channel for
Medical Professionals. Welcome to the Clinician's Roundtable.
I am Dr. Leslie Lundt, your host, and with me today is
Dr. Stephen Stahl. Dr. Stahl is the Adjunct Professor of Psychiatry at the
University of California in San Diego. He is an internationally recognized
clinician, researcher, and teacher in psychopharmacology and the author of more
than 350 articles and chapters. His latest book is the third edition of
Stahl's Essential Psychopharmacology.
Welcome to ReachMD, Dr. Stahl.
Hi, Dr. Lundt, how are you doing?
Not bad! There is a lot about antipsychotics in the news
today, Dr. Stahl, and my first question is should non-psychiatrists even be
prescribing these medicines as liberally as they seemed to be?
This is a topic of great controversy today. I believe that
any well informed prescriber can give these medications, but the secret is not
necessarily being primary care physician so much is being well informed. They
are expensive drugs and there are drugs with risks. If they are given out in a
cavalier way, and particularly if they are given off label, then it's probably
not such a good thing; however, they can be used prudently and we certainly can
leverage the psychiatry community by having non-psychiatrists prescribe them.
Let's back up and talk about some of the basic pharmacology
of these drugs, we talk about the conventional antipsychotics like Haldol and
Thorazine and then the atypical antipsychotics like olanzapine and several
others. What makes an atypical antipsychotic atypical?
Well, that's very good question. Some people would say it's
their pharmacology, some would say it's their price, as they are very
expensive. The definition of atypical comes from the idea that you could have
antipsychotic actions without having extrapyramidal side effects. That is
really what atypical means and it turns out that when you have a blocker of the
D2 receptor for dopamine, the dopamine D2 receptor, you have at least a
conventional antipsychotic because that will help psychosis. However, if you
add a serotonin to an antagonist to the atypical, you can get 'hey, may be have
your cake and eat it too.' What I mean by that is the D2 properties will allow
you to have antipsychotic action just like in a conventional antipsychotic, but
for pharmacological reasons the serotonin 2A antagonist properties take away or
at least mitigate the extrapyramidal side effects, so there is your atypical,
something that causes antipsychotic action without extrapyramidal side effects.
But doesn’t having your cake translate into significant
Wow! That was a good one, Leslie, wow! You know, in the old
days, I am an old guy, you know, and I was at Stanford in the 70s, and I had a
Tardive Dyskinesia Clinic. Now, people are walking around with no tardive
dyskinesia from EPS or extrapyramidal symptoms, but they are walking around 300
pounds, what's happened? Well, the world, of course, has changed and for a
while we thought that's all that's happened, there are too many McDonald's and
bad diets and certainly patients who take antipsychotics that live in North
America have the same problems that we all have with our weight, and if you are
a schizophrenic, it turns out that the chances of getting diabetes and gaining
weight is even higher just because you are schizophrenic, but that's a
smokescreen that kept us from recognizing as fast as we probably should have
recognized that these drugs can cause problems with weight that have nothing to
do with eating too much McDonald's or having the gene for schizophrenia. They
have only to do with the fact that certain drugs cause changes in metabolics.
Some of that is pure weight gain because <_____> and your appetite goes
up, but it turns out it is even more complicated than that and has a lot more
to do with things like insulin resistance, which can change with these drugs.
So is that what you mean when you talk about the metabolic
highway in your book?
Actually, the metabolic highway, the first on ramp is weight
gain and weight gain, of course, leads eventually to obesity and then obesity
on this highway leads to insulin resistance, which leads to stress on your
pancreatic beta cells, which then can lead to prediabetes, which then can lead
to diabetes, which then, of course, is a risk for having heart attacks and
death. So the metabolic highway starts with obesity and ends with death. What
we thought was that you got on this highway only at the obesity on ramp and
that the drugs gave you the <_____> ate too much, it got too
heavy, and then you propelled yourself down the highway, but what is very
interesting is that these drugs can have you enter the highway at the level of
changing triglycerides. In other words, you can have dyslipidemia without any
weight gain. If you gain weight, you are going to have dyslipidemia. If you
lose weight, you'll actually improve that, there is no question about that, but
there are people that have changes in lipids very much faster than their weight
changes. It's as though these drugs, in some people, with some drugs, can
immediately change insulin, such that you have insulin resistance shortly after
taking them, and if insulin resistance persists, this will lead to diabetes and
Can we do anything to stop all this?
There are a few things, one is monitoring. Even though some
of the drugs, clozapine and olanzapine might be examples, cause dyslipidemia
and obesity more than the others, they don’t always cause it. I have patients
in my practice; I think two of them on clozapine that are as thin as a rail.
They are lucky. May be pharmacogenomics some day will likely tell us who they
are, but trial and errors is all that we have today. So it doesn't mean that
you have to avoid all patients taking drugs that have high risk of this. It
just means you have to monitor and what is monitoring, it's not just taking
your weight. It's getting triglycerides, fasting triglycerides. You know, one
of the things that happen is that it takes weeks, may be even months, to be
sure you're getting weight gain. If someone comes in with a 4-pound weight
gain, I am not sure I can tell it, you know, somebody can see this in my
clothes, it's my menstrual period or whatever, but by the time you gain 40
pounds, boy, I can even tell with my eyes, too late. However, if you get
fasting triglycerides you can see that changing before your weight changes and
it can go up, you know, in 10, 20, to even 40 points and you can do that within
days to weeks after starting a medicine that is going to do that. Well, if
somebody is taking olanzapine and their triglycerides go up, party is over. If
somebody takes olanzapine and the triglycerides don’t go up, may be they are
one of those lucky ones. So you have to monitor, and there is also low-risk
drugs and drugs in the middle. The lowest risk drugs are aripiprazole and the <_____>
with the drugs like risperidone and clothiapine in the middle, it doesn’t
really matter. The thing is that this all came up with the atypicals including
your conversation that as a psychopharmacologist the listener should be
thinking about doing this to any psychotropic drugs. Have you ever seen the
patient gaining weight on Depakote, valproic acid, on lithium, on certain
antidepressants? The idea is that one should be monitoring weight, body mass
index, which is just, you know, how tall the person is and there is charts that
will help you convert it, and at least fasting triglycerides. If someone is
already a diabetic, of course, you have to measure glucose and you have to make
sure they are not a diabetic by measuring the fasting glucose at least once,
but long before somebody has a fasting glucose problem and long before they
have gained 40 pounds and become obese, we want to know whether they are going
to get dyslipidemia and eventually become a diabetic and so forth. Almost make
a joke out of this, I think that one of the psychiatric vital signs is fasting
triglycerides, no matter what drug you are on.
If you're new to our channel, you're listening to the
Clinician's Roundtable on ReachMD XM 157, The Channel for Medical
Professionals. I am Dr. Leslie Lundt, your host, and with me today is Dr.
Stephen Stahl. We are discussing antipsychotics and how to monitor and manage
Dr. Stahl how soon after starting one of these medications
should we get a fasting triglyceride?
Realistically, I would say every month. I think you need a
fasting triglyceride before you start, but I see most patients monthly, and I
think that when you're adding a drug, subtracting a drug or changing the dose
of the drug, you should be getting these monthly. Now if somebody is unstable
and you know that they have or haven't changed their triglycerides and of
course you're measuring weight as if this is a long time along with it, you
know, once you're stable, may be you only have to do it once a year, but I
think the idea is when you start a high-risk drug, monitor weight, BMI, and
Now, back to anything we can do to prevent the antipsychotic
induced weight gain, so monitoring clearly, what if they are gaining weight,
you just have to stop the drug or can reduce something else?
Theoretically, you could change lifestyle. You really think
you're going to get patients to stop smoking and start exercising and restrict
calories enough to lose 40 or 100 pounds, it's not impossible, it's just
unlikely. You can't change your grandmother. May be some of us would like to
change a few of our parents, but you know, we've got the genes that we've got.
You can't change your risk factors. So what you really can do, I think, is one
thing for sure and the second thing possibly; the sure thing is you can switch
to another drug and the class, particularly a low risk one. The other thing
you can do is possibly some experimental ideas of new diabetes drugs added on,
metformin, but even some things like pramlintide, which is an injectable
peptide, these drugs, which have been out on the market for treatment of
diabetes can also mitigation of the dyslipidemia and weight gain in patients on
antipsychotics. Now, I am saying this is again widely off label because it's
still in investigation. So, it's not ready for prime-time and can't be
endorsed, but this is where the field is moving. Some people try, you know, the
usual appetite suppressants. Topiramate can do that and some people Topamax.
There is a zonisamide, which is Zonegran; it's another anticonvulsant that can
make some people lose weight. These are not highly effective. There is an old
fashioned appetite suppressants. They have their own problems, side effects
and efficacy. I think that the actual thing is to switch drugs is probably the
most potent and if you can't do that, I believe, you can try to get people to
have lifestyle changes, but I've had a couple of people in my practice, I've
actually tried some of the diabetes drugs on.
And what kind of results?
Pretty good actually. I've got a specific lady who
basically is a bipolar who tried essentially everything that was out there and
she consistently got better on olanzapine and nothing else and consistently
gained 40 pounds and so we put her on pramlintide, which is an injectable
peptide. It's actually something that changes your appetites and your sense of
satiety and she either had a choice of being bipolar or obese, couldn't have
been not bipolar and not obese, so, so far it's early days, it's hard to tell.
I have tried metformin a few times with moderate results. Usually, it's hard
to make olanzapine or clozapine have that kind of weight gain mitigated, but
drugs with a little more moderate signal such as risperidone or clothiapine
might be better to use. There is some techniques on, but that's just my own
anecdote and it's early days.
And certainly groups such as the Mood Disorders Group in
Toronto, Dr. Roger McIntyre, they are looking closely at these sorts of
Yes, there is a big push to try to find a solution for
this. You know, I believe that it is probable that these antipsychotic drugs
find some yet unknown receptor probably and skeletal muscle or fat or liver to
change insulin resistance almost immediately and if we knew what that was, and
I don't think that that will be a secret forever, we can then engineer the new
antipsychotics to not have that binding property, but until then it's going to
be pretty hit and miss.
Well, thank you for educating us on this today, Dr. Stahl.
We've been speaking with psychopharmacology expert, Dr.
Stephen Stahl, about what's new in antipsychotics and the importance of
monitoring the patients closely.
I am Dr. Leslie Lundt, you've been listening to the
Clinician's Roundtable on ReachMD XM 157, The Channel for Medical
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