Everything You Need to Know About Trintellix (Vortioxetine)

Summary

In 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

• 👨‍⚕️ Dr. Rossi discusses Trintellix (vortioxetine), a newer antidepressant medication, providing an overview of its uses and effects.
• 🔍 Trintellix is approved in the U.S. for major depressive disorder, with off-label uses having limited evidence, such as generalized anxiety disorder.
• 🌐 The medication's name was changed to Trintellix in the U.S. to avoid confusion with another medication, Brelanta, used for cardiovascular disease.
• 💊 Trintellix is considered a serotonin modulator and stimulator, working through various mechanisms including serotonin reuptake inhibition and receptor modulation.
• 🧠 It shows potential in improving cognitive dysfunction associated with depression, particularly in geriatric patients, but not in dementia or neurocognitive disorders.
• 🛑 The drug manufacturer discontinued trials for ADHD after failing to show adequate benefit.
• 💡 The most robust actions of Trintellix are serotonin reuptake inhibition and 5HT3 receptor antagonism, which are key to its mechanism of action.
• ⏱ Trintellix has a half-life of 66 hours, allowing for once-daily dosing, with common doses ranging from 5 to 20 milligrams per day.
• 📉 No specific lab tests are required before starting the medication, but basic labs are generally recommended for all patients.
• 🤢 Common side effects include nausea, vomiting, constipation, sexual dysfunction, and potentially weight gain, with nausea being the most prevalent.
• ⚠️ Rare but serious side effects to watch for include seizure induction, mania, and suicidal thoughts, especially in patients under 24 years old.
• 💰 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

00:00

💊 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.

05:02

🧠 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.

10:03

📊 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.

🚫 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.

Keywords

💡Vortioxetine

Vortioxetine is the generic name for the antidepressant medication discussed in the video, sold under the brand name Trintellix. It is primarily used to treat major depressive disorder (MDD) and is noted for its ability to modulate multiple serotonin receptors. The video explains its mechanisms, potential benefits, and limitations, particularly emphasizing that it performs similarly to other antidepressants.

💡Serotonin Modulator and Stimulator

This term refers to the class of medications that Vortioxetine belongs to. Serotonin modulators and stimulators work by influencing serotonin levels in the brain through multiple mechanisms, including inhibiting serotonin reuptake and interacting with various serotonin receptors. The video highlights this as the key way Vortioxetine works, which is essential for its antidepressant effects.

💡Major Depressive Disorder (MDD)

MDD is the primary condition for which Vortioxetine is prescribed. The video discusses how Vortioxetine is approved for treating MDD in the U.S., focusing on its potential to alleviate symptoms such as cognitive dysfunction in depressed patients. MDD is characterized by persistent sadness and a lack of interest in daily activities.

💡Cognitive Dysfunction

Cognitive dysfunction refers to impairments in memory, focus, and concentration that can occur in patients with depression. The video discusses how Vortioxetine may help improve cognitive dysfunction, particularly in patients with geriatric depression, making it a potential choice when cognitive issues are prominent in depressive symptoms.

💡Serotonin Reuptake Inhibition

This is one of the primary mechanisms through which Vortioxetine works. By inhibiting the reuptake of serotonin, the medication increases the amount of serotonin available in the brain, which can help improve mood and reduce symptoms of depression. The video emphasizes that this is a well-established mechanism found in many antidepressants.

💡5-HT Receptors

5-HT receptors are a group of receptors in the brain that interact with serotonin. The video specifically mentions 5-HT1A, 5-HT3, and 5-HT7 receptors, discussing how Vortioxetine modulates these receptors to exert its effects. For example, 5-HT3 antagonism is associated with improved cognition and reduced nausea, which are key points in the video.

💡Sexual Dysfunction

Sexual dysfunction is a common side effect of many antidepressants, including Vortioxetine. The video discusses how Vortioxetine may cause sexual dysfunction, despite some initial hopes that it might reduce this side effect due to its 5-HT1A agonism. This side effect is important for patients to consider when choosing an antidepressant.

💡CYP450 Enzymes

CYP450 enzymes, particularly CYP2D6, are involved in the metabolism of Vortioxetine. The video explains that Vortioxetine is metabolized by several CYP450 enzymes, which can influence how it interacts with other medications. This is crucial for understanding potential drug interactions and dosing considerations.

💡Generalized Anxiety Disorder (GAD)

GAD is another condition that Vortioxetine has been studied for, although the video notes that the evidence for its effectiveness in treating GAD is poor. The video contrasts its limited use in GAD with its primary indication for MDD, emphasizing the need for careful consideration of its use outside of its main approved use.

💡Serotonin Syndrome

Serotonin syndrome is a potentially life-threatening condition caused by excessive serotonin activity in the brain. The video warns against combining Vortioxetine with certain other medications, such as MAOIs, because of the risk of serotonin syndrome. This highlights the importance of monitoring drug interactions when prescribing Vortioxetine.

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