Everything You Need to Know About Trintellix (Vortioxetine)
Summary
TLDRIn this informative video, Dr. Rossi, a board-certified psychiatrist, discusses Trintellix (vortioxetine), a newer antidepressant medication. He explains that while it's approved for major depressive disorder and may improve cognitive dysfunction associated with depression, there's no strong evidence supporting its use in treatment-resistant depression or other conditions. Rossi also highlights the medication's mechanism of action, dosing, side effects, and potential drug interactions, emphasizing its moderate effect size compared to other antidepressants.
Takeaways
- π¨ββοΈ Dr. Rossi discusses Trintellix (vortioxetine), a newer antidepressant medication, providing an overview of its uses and effects.
- π Trintellix is approved in the U.S. for major depressive disorder, with off-label uses having limited evidence, such as generalized anxiety disorder.
- π The medication's name was changed to Trintellix in the U.S. to avoid confusion with another medication, Brelanta, used for cardiovascular disease.
- π Trintellix is considered a serotonin modulator and stimulator, working through various mechanisms including serotonin reuptake inhibition and receptor modulation.
- π§ It shows potential in improving cognitive dysfunction associated with depression, particularly in geriatric patients, but not in dementia or neurocognitive disorders.
- π The drug manufacturer discontinued trials for ADHD after failing to show adequate benefit.
- π‘ The most robust actions of Trintellix are serotonin reuptake inhibition and 5HT3 receptor antagonism, which are key to its mechanism of action.
- β± Trintellix has a half-life of 66 hours, allowing for once-daily dosing, with common doses ranging from 5 to 20 milligrams per day.
- π No specific lab tests are required before starting the medication, but basic labs are generally recommended for all patients.
- π€’ Common side effects include nausea, vomiting, constipation, sexual dysfunction, and potentially weight gain, with nausea being the most prevalent.
- β οΈ Rare but serious side effects to watch for include seizure induction, mania, and suicidal thoughts, especially in patients under 24 years old.
- π° Trintellix is more expensive than some other antidepressants and may not offer a significantly better side effect profile, such as with duloxetine.
Q & A
What is Trintellix or Vortioxetine?
-Trintellix, also known as Vortioxetine, is a newer type of antidepressant medication approved in the U.S. for major depressive disorder. It has been studied for other conditions such as generalized anxiety disorder, but its primary indication remains major depressive disorder.
Why was the name changed to Trintellix in the U.S.?
-The name was changed to Trintellix in the U.S. to avoid confusion with another medication called Brelanta, which is used for cardiovascular disease and has a similar name.
What is the role of Vortioxetine in treating Generalized Anxiety Disorder (GAD)?
-While Vortioxetine has been studied for GAD, the quality of evidence is poor, and it does not appear to significantly improve symptoms or quality of life in patients with GAD.
How does Vortioxetine compare to other antidepressants in terms of effectiveness?
-According to the research literature, Vortioxetine does not perform better than other antidepressants overall. However, individual responses may vary, and some patients might respond better to this medication than others.
What is unique about Vortioxetine's potential for cognitive enhancement?
-Vortioxetine may improve cognitive dysfunction associated with depression, which includes poor concentration, focus, and memory. It also appears to improve cognitive function in geriatric depression, but it has not shown benefits in cognitive function for patients with Alzheimer's disease or in ADHD.
How does Vortioxetine work as a serotonin modulator and stimulator?
-Vortioxetine works by several mechanisms, including serotonin reuptake inhibition, partial agonism at 5HT1A and 5HT1B receptors, antagonism at 5HT3 receptors, and antagonism at 5HT7 receptors. These actions contribute to its antidepressant and potential cognitive-enhancing effects.
Which cytochrome P450 enzymes are involved in the metabolism of Vortioxetine?
-Vortioxetine is metabolized by multiple cytochrome P450 enzymes, with the most significant being CYP2D6, followed by 3A4, 2C19, 2C9, 2A6, and others.
What is the half-life of Vortioxetine, and how does it affect dosing?
-The half-life of Vortioxetine is 66 hours, which allows for once-daily dosing. The typical doses range from 5 to 20 milligrams per day, with the initial dose for depression being 10 milligrams per day.
Are there any specific lab tests required before starting Vortioxetine?
-There are no specific lab tests required before starting Vortioxetine for healthy individuals. However, it is generally a good practice to obtain basic labs before starting any new medication.
What are the common side effects associated with Vortioxetine?
-Common side effects of Vortioxetine include nausea, vomiting, constipation, sexual dysfunction, and possibly weight gain. Sexual dysfunction was noted to occur even in the placebo group during clinical trials.
What are the rare but serious side effects that should be considered with Vortioxetine?
-Rare but serious side effects of Vortioxetine include the potential to induce seizures, mania, or suicidal thoughts, especially in patients under the age of 24. It should not be combined with MAOIs due to the risk of serotonin syndrome.
Outlines
π Introduction to Trintellix (Vortioxetine)
Dr. Rossi introduces the topic of Trintellix, also known as Vortioxetine, a newer type of antidepressant medication. He discusses its approval for major depressive disorder in the U.S. and its off-label uses, including generalized anxiety disorder, though with limited evidence. The video aims to provide a comprehensive understanding of the medication, its mechanisms of action, and its effectiveness compared to other antidepressants. Dr. Rossi clarifies that while the medication may perform as well as others overall, individual responses may vary.
π§ Cognitive Enhancement and Mechanisms of Trintellix
This section delves into Trintellix's potential for cognitive enhancement in patients with depression and geriatric patients, though it does not benefit cognitive function in Alzheimer's disease or ADHD. The medication's classification as a serotonin modulator and stimulator is explained, along with its various mechanisms of action, including serotonin reuptake inhibition, receptor agonism and antagonism, and its effects on cognitive function and antidepressant properties. The importance of the medication's metabolism via cytochrome p450s, particularly 2D6, and its half-life of 66 hours, allowing for once-daily dosing, is also highlighted.
π Dosage, Side Effects, and Contraindications of Trintellix
The paragraph outlines the dosing guidelines for Trintellix, ranging from 5 to 20 milligrams per day, with the initial dose for depression being 10 milligrams, adjustable up to 20 milligrams. The medication can be taken without regard to food. Dr. Rossi discusses the common side effects such as nausea, vomiting, constipation, sexual dysfunction, and the rare but serious risks including seizures, mania, and suicidal thoughts. Contraindications are also mentioned, such as its use with tramadol or MAOIs, and the current recommendation against its use in pregnancy due to lack of evidence for safety.
π« Conclusion on Trintellix's Indications and Considerations
Dr. Rossi concludes by summarizing that while Trintellix may be beneficial for some individuals, particularly those with significant cognitive dysfunction due to depression, there is no evidence to support its use in treatment-resistant depression or other disorders outside its primary indication for major depressive disorder. He emphasizes the importance of considering cost, as Trintellix is more expensive than some alternative medications, and notes that its side effect profile, including nausea and sexual dysfunction, is not significantly different from other antidepressants.
Mindmap
Keywords
π‘Vortioxetine
π‘Serotonin Modulator and Stimulator
π‘Major Depressive Disorder (MDD)
π‘Cognitive Dysfunction
π‘Serotonin Reuptake Inhibition
π‘5-HT Receptors
π‘Sexual Dysfunction
π‘CYP450 Enzymes
π‘Generalized Anxiety Disorder (GAD)
π‘Serotonin Syndrome
Highlights
Dr. Rossi discusses Trintellix (vortioxetine), a newer type of antidepressant medication.
Trintellix is approved in the U.S for major depressive disorder and has been used off-label for other indications.
The name was changed to Trintellix in the U.S to avoid confusion with the cardiovascular medication Brelanta.
Trintellix has been studied for generalized anxiety disorder at lower doses but evidence is poor.
Effect size of Trintellix is moderate and does not outperform other antidepressants.
Trintellix may stand out in cognitive enhancement for patients with depression.
Improvement in cognitive function is observed in geriatric depression with Trintellix.
Trintellix failed to show benefits in cognitive function for Alzheimer's disease or ADHD.
Trintellix is a serotonin modulator and stimulator with multiple mechanisms of action.
The most robust actions of Trintellix are serotonin reuptake inhibition and 5HT3 antagonism.
Trintellix is metabolized by multiple cytochrome P450s, primarily CYP2D6.
The half-life of Trintellix is 66 hours, allowing for once-daily dosing.
Dosing for Trintellix ranges from 5 to 20 milligrams per day.
Trintellix can be taken with or without food, with no significant difference in absorption.
Technically, Trintellix can be stopped without a taper due to its long half-life.
No specific lab values are required before starting Trintellix.
Common side effects of Trintellix include nausea, vomiting, constipation, sexual dysfunction, and possibly weight gain.
Rare but serious side effects of Trintellix include seizure induction, mania, and suicidal thoughts.
Trintellix is not recommended for patients who are pregnant or trying to conceive.
Trintellix may be beneficial for patients with significant cognitive dysfunction due to depression.
The main side effects of Trintellix are nausea and sexual dysfunction, common in antidepressants.
Cost consideration should be made as Trintellix is more expensive than some other antidepressants.
Transcripts
what's up everybody dr rossi shrinks and
sneakers i'm a board-certified
psychiatrist making mental health
content here on youtube and if you're
new to the channel i would love you to
subscribe to the channel really helps me
to know that this material is helpful
and if you're a returning viewer thank
you so much for your support so today we
are going to talk about a topic that's
been requested before and it's called
everything you need to know about
trintillix or vortioxetine this is a
newer type of antidepressant medication
that people have asked me to cover in
the past so we're going to go ahead and
get right into this and i'm going to
tell you what you need to know about
this medication so as i've already
alluded to for you guys here
bordeoxyteen is sold under the brand
name trintillix or bryntillix
and it's approved in the u.s for major
depressive disorder only although it's
been used off label for other
indications and we will talk about them
here
now interestingly enough in the united
states the name was actually changed to
traintylics because in the u.s there's
another medication that has a really
similar name that's an antiplatelet
medication used in cardiovascular
disease called brelanta
and so they didn't want people to get
confused with the naming
it was also studied like i said for
other indications one of those being
generalized anxiety disorder mostly at
lower doses but the quality of evidence
is poor and it does not appear to
improve symptoms or quality of life in
patients with gad
now i want to take a quick moment to
make a point here before going into more
details about the medication when i say
to you guys on one of these videos that
the effect size is moderate and when you
look at the research on 4d oxetene it
does not perform any better than other
antidepressants
i'm not saying that in an individual
case by case basis it's not possible
that one person may respond really well
to this medication or even several
people right in the population could
respond to this medication better than
other antidepressants but when we're
looking at the research literature as a
whole we're looking at remember large
sample sizes and we're saying in general
it does not perform as
it performs rather as well as other
antidepressants doesn't perform any
better so i want to kind of make that
point for you guys here
so it very well might be the case that
an individual does better on this than
somebody else but it on the whole it is
about the same and based on all the
literature i reviewed to bring you this
presentation i do not believe this
medication is effective for treatment
resistant depression although people
sometimes say that it is
the one place
i do think this medication stands out a
little bit and again this is sort of
questionable too
is in cognitive enhancement or the
enhancement of cognitive function now i
want to point out that we're not talking
about cognitive enhancement in the sense
of like taking amphetamines to improve
your score on your test in college we're
talking here about cognitive dysfunction
associated with depression so for a
patient that's depressed their cognitive
function is sometimes poor not everybody
is that way but they have poor
concentration poor ability to focus poor
ability to remember things they just
can't really seem to get the energy to
try so this medication actually does
seem to improve cognitive dysfunction
associated with depression it also
appears to improve cognitive function in
geriatric depression so that's a good
thing for geriatric patients and you
might be saying to me dr rossi well what
about dementia or neurocognitive
disorders unfortunately this medication
failed to show any benefit in cognitive
function for patients with say
alzheimer's disease it has also been
looked at in adhd but the trials failed
to show any adequate benefit and the
drug company that manufactures
vortioxetine decided to not go through
with their plan to continue looking into
approval for adhd so this medication
falls into a class of medications that
is now known as the serotonin modulators
and stimulators so this medication is
considered a serotonin modulator and
stimulator
and it's really thought to work by
several different mechanisms the first
one is an oldie but a goodie and that is
serotonin reuptake inhibition so we know
that this is going to block the cert
transporter and it's going to prevent
the reuptake of serotonin meaning more
will be available in the synaptic cleft
to bind to receptors
the next logical thing to be thinking
about is well what receptors are we
talking about here
so the other receptors that are
modulated by this medication
r5ht1a and here it works as an agonist
and that may be why this there's a small
well i shouldn't say that this is
entirely true because people still get
sexual dysfunction on this medication
but this may diminish
the sexual side effects associated with
this medication
so again 5ht1a agonism
of 5ht 1b
partial agonist and then there's a
myriad of other ones there's 5ht 1d and
5ht3 and the 5 ht3 antagonism is thought
to enhance neuroadrenergic as well as
cholinergic activity and there's some
thought that this is what's responsible
for the improved cognition and reduced
nausea associated with
trintillics
now 5ht 7 antagonism is also a pro
cognitive and antidepressant an
antidepressant receptor so this blockade
of 5hta7 is going to also improve
cognitive function and enhance the
antidepressant effects of this
medication i do want to point out and
you can check out the link to my website
where i will have a full chart on the
targets for this medication as well as
the affinity for the receptors and what
it does at each receptor
but the most robust action is actually
on serotonin reuptake no surprise there
right it's an oldie buddy goodie and
5ht3 antagonism so the two most
important mechanisms of action when
we're talking about this medication is
going to be blocking the cert
um blocking cert and then also blocking
five ht3 receptors so there are other
receptors at play here like i talked
about but those are the two main ones
important things to know about the
metabolism of trantelic is it's actually
metabolized by many of the cytochrome
p450s but the most important one as
usual with most antidepressants is going
to be cytochrome p452d6
2d as in dog 6. it's also metabolized by
3a4 and 5 2c19 2c9 2a6
c8 2 b6
and
that's about it but it's a lot so the
point is whenever something is
metabolized by multiple cytochrome p450s
inhibition or
inhibition of one of them is not
necessarily going to
make that big of a difference although
the 2d6 does seem to be the main route
of metabolism and the one that you have
to watch out for with drug interactions
so
the half-life of this medication is 66
hours so obviously with a 66 hour
half-life you can dose this once a day
you don't have to take it more than once
a day and you may need to reduce the
dose if a patient's taking a strong 2d6
inhibitor say something like bupropion
let's talk a little bit about the dosing
it's actually quite simple like i said
it's just once a day and the doses are
anywhere between five and 20 milligrams
per day the tablets come as either fives
tens or twenty milligram tablets and the
initial dose for depression has been 10
milligrams per day which can be
increased as needed to a
a target dose of 20 milligrams daily now
for generalized anxiety disorder i said
people looked at slightly lower doses
and in those cases they looked at 5 to
10 milligrams per day not the 10 to 20
seen in depression
it can be taken with or without food so
there's no enhanced bioavailability or
absorption with food there's nothing
that changes if you eat or don't eat
when you take the medication the other
interesting thing about this medication
is given its half-life you can
technically stop it without a taper so
that may or may not be something that
you would want to do but technically you
could stop this without tapering it so
before starting this medication there
are no specific lab values that need to
be done for healthy individuals it might
always be a good idea to get basic labs
on anybody before you start one of these
medications but still there's no
specific indication for a laboratory
examination
the common side effects are the ones
that are seen with many other
antidepressant medications and those
include nausea vomiting constipation
sexual dysfunction
and possibly weight gain although this
is unusual it's still possible the most
common of the side effects of course was
nausea even though i said that that 5
ht3 antagonism or blockade could
potentially help with nausea it doesn't
seem to alleviate all of the nausea from
the clinical trials so this is over ten
percent the rest of the side effects i
listed are reported in less than ten
percent of cases but it is important to
note that sexual dysfunction was seen
not only in the treatment arm of these
clinical trials but also the placebo arm
so it was very interesting to see that
there was a pretty high rate of sexual
dysfunction people who were taking a
placebo when they did some of these
clinical trials
now
the rare life-threatening side effects
to be aware of are seizure induction of
mania or suicidal thoughts those are
again there's always a black box warning
about suicidal thoughts in patients
under the age of 24 for all
antidepressants and the induction in
mania of course taking an antidepressant
without a mood stabilizer is like
throwing gasoline on a dumpster fire
so you want to also avoid using this
medication in a couple of cases if
someone is using the medication tramadol
for pain it can increase the risk of
seizure and you're not going to want to
combine this medication with an maoi so
a monoamine oxidase inhibitor because it
can cause serotonin syndrome as of right
now this medication is not recommended
for patients who are or are trying to
get pregnant so i'm going to wrap the
video here it's a bit of a long one but
there's some pieces i want to just tie
up so while this medication may be
helpful for some individuals there's no
evidence to support it to use in
treatment resistant depression or other
disorders outside of the primary
indication for major depressive
disorders so i think it's important to
note that this medication is really for
patients with major depressive disorder
and if you're treatment resistant you're
likely going to want to look elsewhere
there does seem to be a benefit for
patients who have significant cognitive
dysfunction because of their depression
and maybe that's where this medication
really fits into the treatment algorithm
for me is if i have somebody with severe
cognitive dysfunction that i believe is
completely related to their depression
this may be a good choice of medication
the main side effect of course is nausea
and sexual dysfunction and this is
common in all antidepressants so to be
honest you really don't get a better
side effect profile with these serotonin
modulators
you must also contin consider the cost
here because this medication is going to
be significantly higher cost than say a
comparison medication like duloxetine
which actually outperformed vordioxatine
in some of the clinical trials
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