Thanks for your feedback. 🙏🏼

That's good to know.

Excellent ! to hear that this combo is working for you 👍 May I ask what is your current dose of Trintellix ?

You are welcome

Glad it was helpful!

Thank you for your feedback.

How did it go?

@@jrman413 I stopped taking it within two-three weeks and started meditating seriously every day instead (to improve impulse control and concentration) and taking my therapy more seriously. Why did I stop taking it so early? I sensed emotional numbness/flatness and sexual dysfunction after 3-4 days and got flashbacks from how I experienced flouxetine/prozac. However, this medication might work for others and the eventual flatness effect might be a good place to be for a while for some.

Please see this video - Clinical Symptoms and Treatment of Severe Depression - Melancholic and Psychotic Depression kzfaq.info/get/bejne/lbKWnZqevd65lWQ.html . We also have the video on the descent into despair that provides another perspective.

It doesn't work for anxiety predominant conditions because it's action on the SERT is 50% lower than SSRIs. SSRIs reduce anxiety because of their action at the GABA receptor on 5HT2A receptor. Vortioxetine effect is much lower in increasing serotonin in the cleft to do this. Further vortioxetine is more activating - greater increase of NA, DA / which helps in treating the mod to severe forms of depression but can increase anxiety in some

Helped my anxiety which I use it for🤷🏽‍♂️

@@alexanderfernandez2863- Do you find that it help with increasing your Dopamine levels making you fell happier?

@@PsychiatrySimplifiedHi Doc, Thank you for clarifying this! I have severe anxiety & depression & I was considering taking this medication but I’m confused because I’ve come across some articles online that say that it helps with anxiety & you are saying that doesn’t help with anxiety.. but I would go with your information since you’ve explained it why!!

@@intermilan6202 i was prescribed vortioxetine a few days back , my anxiety is at an all time high and my resting heart rate goes above 130 most of the times, my heart rate has not crossed above 120 in the last 3 days of starting it... will have to give it time to know how it affects you.. go for it,, you miss all the shots you dont take.. best of luck

Not contraindicated but not as effective for GAD predominant. It can be effective if depression plus secondary anxiety. Anxiety can be treated by addressing the amygdala end of the equation - SSRIs , BZDs , Pregabalin etc OR by enhancing PFC inhibition of amygdala ‘firing’ e.g Agomelatine , SNRIs

@@PsychiatrySimplified thanks, I am trying to develop a strategy for treatment of GAD without the SSRI sexual dysfunction and blunting issues.

I cover the algorithm and evidence based treatments - psychscenehub.com/psychinsights/generalised-anxiety-disorder-diagnosis-and-management-2/

​@@PsychiatrySimplifiedHi, I read your article in the link about GAD and it looks like cymbalta was the top antidepressant for GAD. I have always stayed away from Snri's because I was under the impression that the noradrenaline would make my anxiety worse. Maybe I am mistaken. Could you please clear up my confusion in regards to Snri's and GAD. Thank you.

1. It can improve cognition so in mild cases benefits may be seen 2. Stimulate is a vague word ? So not sure what that means. It has activating effects if that’s what you mean 3. Usually 30 mins after food in the evening to prevent nausea but not too late at night as can affect sleep / some individuals prefer taking it in the morning.

What are your doubts or questions ?

Many have reported Trintellix being helpful for their anxiety. It’s always a wonder why certain antidepressants work for some for some things but for other quite the opposite. I’m going on week 2 at 10 mg and I was prescribed to me off label for anxiety. Hope I am one of the ones it helps

@@NorthCountry84I wouldn’t say many. Meta analysis shows Trintellix to be lower than pretty much all other psychotropic in effect size for anxiety, including buspirone which has largely not been used anymore due to better drugs for anxiety. That says a lot. Especially since the drug trials were done by the people making it, so they had a vested interest in getting it approved for anxiety but that didn’t work. It doesn’t mean it can’t help, and it may show reduction in severe anxiety, but most people unfortunately would probably benefit from something else for anxiety which sucks since Trintellix otherwise has a great side effect profile and less sexual dysfunction.

Exactly! hence why Ketamine infusions have had decent success and a large advancement towards treating depression since 2000. It suppresses excessive glutamate via NMDA antagonism and other downstream effects

Wish you well

how re u on agomelatine i was so blunted on agomelatine like on ssri and no sexual function i started off label Valproate and i hope it will stabilize me

@@danielkanka495 I was blunted for the first 3 weeks or so, then it went away.

I’ll be doing a video on SSRI and REM sleep rebound . But essentially some reduction / suppression is good ( via Serotonergic inhibition of amygdala noradrenergic neurons ) - but too much is not good. REM is essential in synaptic plasticity. So in PtSD where NA activity is significant - it may help but in normal REM sleep this may not be helpful. Hope this helps

I guess deep is important for memory and meaning of REM sleep is not well known. But my knowledge might be outdated since havent read this stuff for quite some time. Vortioxetine sounds so good that even healthy people might want to take it and elder people without depression, just for cognitive benefits and better sleep, which are probably connected to each other.

@@bogse here is a the article on neuropsychiatry of sleep. REM sleep is needed for establishing synaptic plasticity and for ensuring adequate emotional tone the following day. It is also responsible for creativity. Non rem sleep is essential for glymphatic system to work - the system removes the toxins r.g amyloid and is 85% active in N3 phase of deep sleep. psychscenehub.com/psychinsights/neurobiology-sleep/

en.wikipedia.org/wiki/Vortioxetine 5-HT3 antagonism appears to have a better effect on REM sleep compared to SSRI's. However what concerns me is that SSRIs and 5-HT1A receptor agonists often produce nausea as a side effect, whereas 5-HT3 receptor antagonists like ondansetron are antiemetics and have been found to be effective in treating SSRI-induced nausea. It was thought that the 5-HT3 receptor antagonism of vortioxetine would reduce the incidence of nausea relative to SSRIs. However, clinical trials found significant and dose-dependent rates of nausea with vortioxetine that appeared to be comparable to those found with the SNRI duloxetine 😒

We have a couple of videos on Agomelatine. Different mechanism - ‘ Milder ‘ in a way Agomelatine is and won’t be able to address moderate to severe depression on its own - Vortioxetine at 15-20 mg becomes broad spectrum which Agomelatine doesn’t. Thanks for feedback

Thanks for your feedback 🙏🏼

Thanks for the feedback 🙏🏼

Depends on what is being targeted. If it’s depression, cognition then yes it can help.

@@PsychiatrySimplified that's exactly what i would use it for...just went out and bought it at 10mg. thank you

Please seek medical advice and consider supervision. Especially as side effects of nausea can occur . Usually this is prevented by starting at a low dose of 5 mg half hr after food in early evening and then increasing the dose. If persists there are other options. Ps not medical advice Wish you well .

I can't specifically advise but in general. 1. Sertraline half life approx 26-32 hrs - lets say 30 hrs •30*5 = 150 hrs 95% is washed out = around 7 days almost all of sertraline will be out. Margin of safety say 10 days. 2. Vortioxetine does not have significant SERT blockade ( 50% less than SSRI) so risk of serotonin syndrome with combination is low. 3. Withdrawal syndromes are most prominent when lower doses are reduced e.g 25 mg to 0 - but if vortioxetine is present it will reduce this ( due to mild SERT blockade) Based on the above principles one can formulate a plan with their doctor. Switch should always be done under medical supervision. Wish you well.

Sorry to hear

It can but doses need to be higher around 20 mg. Having said that its important to ensure that stress repsonse is addressed i.e sleep, anxiety as stress induced hyperalgesia plays an important role. In such cases augmentation may be needed or duloxetine is an option. Ofcoourse agents like pregabalin, memantine also present - Ps not advice

You're welcome!

It isnt as effective for anxiety on its own ; there is evidence for depression with anxiety. It's mechanism moves away from SSRI - hence does not have the amygdala suppressing action as an SSRI - therefore not equivalent benefits in anxiety - but this same property reduces emotional blunting which vortioxetine does not do ( or reduced risk) . Vortioxetine is more activating as a mechanism

@@PsychiatrySimplified Still, it has some SERT and 5HT1A activity, so should offer some relief. Right?

@@Slazerable yes it should and in some it can. At lower doses 5-10 mg. Not medical advice

Sorry to hear. I can't answer those questions because it requires an assessment. Would recommend consider a psychologist as this can help with strategies to combat the health anxiety. And it's important to address the insomnia if present. Wish you well.

Was this predominantly for anxiety?

@@PsychiatrySimplified my problem was mainly related to anxiety and a bit of ocd symptoms. Vortioxetine didn't worked but paroxetine worked quite well on 25 mg cr dose. The only problem is that when I try to taper it my anxiety returns and I am forced to go back to my usual dose . Don't know how to tackle it .

While we can't provide specific advice - “Our study suggests that chronic (8-week) l-theanine administration is safe and has multiple beneficial effects on depressive symptoms, anxiety, sleep disturbance and cognitive impairments in patients with MDD. However, since this is an open-label study, placebo-controlled studies are required to consolidate the effects.” it is, however, best to ask the prescriber and pharmacist as they will individualise the advice. Ps not advice

Histamine promotes wakefulness . Histamine does not only modulate the immune response and inflammation, but also acts as a neurotransmitter in the mammalian brain. The histaminergic system plays a significant role in the maintenance of wakefulness, appetite regulation, cognition and arousal.

@@PsychiatrySimplified Thanks! So if we're not encountering an antigen/allergen, but the response is activated, how does that affect the immune system?

The immune system is involved in response to any ‘stress’ pain, infection, allergen, physical injury , psychological stress ( including positive stress )

The 5HT1A receptor is a feedback (negative ) so it regulates the release of serotonin 5HT from the presynaptic neuron depending on the amount of extracellular synaptic serotonin. Too much and it will act as a brake ; too little and it will act to release. It depends on endogenous serotonin. We covered this more in SSRI mechanism video on this channel. Here when the 5HT1A receptor is desensitized (i.e not antagonised ) then the break is released.

Thank you 🙏🏼

I think as with all agents its the targeted use that is most beneficial I.e linking the diagnostic formulation to psychopharmacology. It has lower SERT so not as good as SSRI in anxiety but also does not lead to emotional bunting as a result. It is more ‘activating’ hence better for mod - severe ends of depression than SSRI. It has a good tolerability profile. Also specifically can be used for cognition. In practice in the presence of mixed features or severe depression often a single agent doesn't help. Here an agent might be prescribed but the mixed features or other factors ( sleep apnea) aren't addressed. The medication needs help - in this case the medication is still working but there are other factors preventing it from working. Maximising that gives a better outcome. In summary it is a good agent ; milder compared to TCA, but stronger than agomelatine & SSRI. Hope this helps

I use to be on vortioxetine for a while and it didn’t work for me. It made me feel anxious and depressed it was very poor although it was easy enough to stop, withdrawals weren’t evident. It makes me suspicious that all those other effects at 5ht receptors even play much role in depression. As an example mirtazapine also hits various 5ht receptors and this didn’t help my depression either. So I am dubious that blocking these 5ht receptors does what it’s cracked up to do

All references here 👉psychscenehub.com/psychinsights/vortioxetine-mechanism-of-action-2/

@@PsychiatrySimplified so 8 week trials. Are there any long term trials of a year or more with follow-ups?

@@SuperCody888 www.tandfonline.com/doi/full/10.1080/03007995.2023.2178082#:~:text=In%20the%20long%2Dterm%2C%20maintenance,61%25%20at%20one%20year20

@@SuperCody888 pubmed.ncbi.nlm.nih.gov/28693903/

GI issues is the main side effect. Usually low doses can do that but activating effects come in at higher doses. To combat nausea - administer in evening, after food. For some the first two weeks or so may need anti nausea agent or antacid cover. If still an issue probably not the best tolerability profile for you. Ps not advice

Thanks for your comment. Vortioxetine increases BDNF - also, most antidepressants bind to the TRKB receptor with the downstream effect of increasing BDNF. This agent actually does not act via increasing serotonin predominantly. BDNF is one aspect - there are multiple other aspects that play a part. also 5HT receptors are part of the G protein receptor superfamily that allows the receptor to modulate the activity of different effector systems, such as ion channels, phospholipase C and adenylyl cyclase. 5HT3 is a ligand-gated channel. .

It can be if there is underlying significant activation already - GABA inhibition is needed to increase dopamine for example - this is why some antidepressants activate. It all depends on baseline tone

Just saw the whole video and I understand why.I am already on elvanse and both drugs probably raise my NA levels too high.Do you think I should change vortioxetine with escitalopram or reduce my vyvanse dosage?I really dont want to drop vortioxetine because it works so good for depression

In general - half hr after food in the evening ( not too late ) several hrs before bed time . 2. If not resolving short term ondansetron 4-8 mg for two weeks . 3. Antihistamine short term for two weeks also can help. Ps not medical advice

@@PsychiatrySimplified thanks a lot sir. Sir I'm having too much side effects.... ( Nausea, stomach issues, urinary issues and fever from last 4, 5 days, Can't sleep at night even after taking lithium 400mg and Clonazepam 1.5mg at night and Seroquel xr 50 in the morning with trintellix. But my psychiatrist wants me to continue it. I meet him 2 days ago and again gonna see him next week.

Yes please follow the psychiatrist advice and carry out lithium level. But this could also be unrelated to medication - perhaps a viral infection etc - but it’s important to discuss with your doctor which you have done. Ps not advice

Don’t drink milk 🥛

Please discuss this with your doctor however the dose is low. Usually doses range between 10-20 mg. Wish you well.

Here you go 👉kzfaq.info/get/bejne/aZplmqh835zPfIU.html

Good question, I’d like to know too

I’ve also got OCD and have been on vortioxetine in the past. It didn’t benefit me and there was no benefit for anything. Maybe that’s why it doesn’t seem to be used as often as many other antidepressants. Of course, my experience is also that OCD is very difficult to treat and SSRI’s don’t offer much benefit either, it’s a tricky condition to treat

@@cultfiction3865 Have your tried fluvoxamine (Luvox) for OCD?

Yes

@PsychiatrySimplified 1 second ago Thanks for your feedback 🙏🏼

Please discuss this with your doctor. In the context of postpartum depression it would be inappropriate for me to provide any comments - your doctor would have individualised your treatment and any side effects should be discussed with your doctor. Wish you and your family well.

Information as in summary? Here. Still available in Australia & US as of now psychscenehub.com/psychinsights/bupropion-mechanism-of-action-psychopharmacology-clinical-application/

@@PsychiatrySimplified Thank you, that's a good summary. What I can't find out is how long the investigation into *nitrosamine impurities* (either from manufacture or storage) is going to take. Very importantly, why Bupropion is still available in the US and Australia. How is that possible if a drug is suspected of carcinogenic properties in another territory? Either it is or it isn't. GSK just send out cut & paste responses. Any ideas how I can find out something? It's the only antidepressant I can tolerate. Literally tried everything else. Really struggling without it. Thanks.

It is not indicated for depression. It does not have significant evidence for OCD but may be able to address it if part of a depressive syndrome . If antipsychotic is present for psychosis then it is unlikely to worsen the psychosis

Thank you sir❤

Half hr after food usually early evening ( not too close to bed time) to avoid nausea but this can vary . . It should not affect sleep.

It can treat SSRI indices sexual dysfunction but PSSD there is no significant evidence. Bupropion has benefits mentioned in PSSD

Buspar is available only under special access: it’s good that Vortioxetine is helping. There are several existing medications in Australia that can address Sx without need for Buspar. If sertraline did that - likely mixed state may be present (arousal plus or minus agitation). Consider ruling out mixed state with your doctor. See video on this on channel.

I could not walk down the street it was terrible with the sert the. They added lithium cause I was feeling very low. They have ruled out mixed states I have health anxiety which is muscle tension in neck and shoulder and i can’t relax ? Will you help if I were to contact your office and organise a referral.

GABA is an inhibitory neurotransmitter and widely present on other neurons ( serotonin, dopamine , noradrenaline) . While gaba is good in terms of arousal reduction an optimal balance occurs with adequate excitation and inhibition. So e.g NA & DA release is under a GABA control - if this was inhibited too much that results in cogntive and motor slowing. GABA inhibition at 5HT3 improves neurotransmitters in the PFC improving cognition . Hope this helps

Ok thanks, so PFC is prefrontal cortex I assume. I was just wondering that if Vortioxetine enhances sleep but at the same time inhibits GABA it sounds, weird, since I associate GABA for relaxation and sleep but I guess this is not so simple.@@PsychiatrySimplified

Very unlikely. Best to discuss this with the endocrinologist / doctor though. Were the thyroid tests significantly better pre trintellix ?

Thanks for quick respond. My tsh was in June 2022 around 2,4(0,5-4) and after a year when diagnosed 7,04. Latest test showed 4,1. The next renewed depression was last November. Levothyroxine dose lift helped. Mild latent depression still rears its head from time to time. Can you tell how Lamictal affects thyroid function? It is considered as the next option.

Lamotrigine had no significant effect on thyroid hormone levels. The TSH may be independent of medications. But your doctors are in the best position to opine.

Sorry to hear. While I can’t comment specifically for you : vortioxetine is less activating that duloxetine at higher doses. In general loss of medication effect or activation can indicate an underlying arousal state - poor sleep, racing thoughts, irritability etc - mixed features should be ruled out as if arousal is present treating that helps improve the overall picture. Ps not medical advice. Please see video on mixed features and melancholic depression. Ultimately it depends on the clinical symptoms for which the meds are prescribed. Wish you well

@@PsychiatrySimplified thanks for the reply sir. I live abroad and in 6 september will see my home town psych. I didn't have a hypomania and mania before but when doctor raised my cymbalta to 90mg and remeron to 45mg, my depression went worse. Very suicidal and depressed as hell, melancholic, anxiety to roof. Same thing happened when tried MAOI. Now after 4 years remission on CBT + remeron 30mg + cymbalta 60mg, They added for me trintillix, after week on 5mg, melamcholic depression went away, i became just anxious and mild moderate depression, once i upped it for 10mg in the last 3 days, I am depressed again severely, suicidal thoughts, anxiety, cant eat or do any small activity like eat. I returned back now to 5mg..do you think patients who get worse on high avtivating antidepressants may have hidden bipolarity?

Vortioxetine has a lower risk. SSRIs and SNRIs reduce platelet aggregation and hence can be associated with this risk which is more common in the elderly and if on anticoagulants etc . Vortioxetine has a lower SERT affinity so theoretically a lower risk. But as in all cases if risk factors present it’s helpful to monitor

Quicker in action than traditional SSRIs - within two weeks usually effects are noted at appropriate dose. Sometimes in the first week. However dose titration should be slow if nausea is an issue or covered with anti nausea treatment. Ps not advice

Thanks so much

There is no single formula. This is best done under medical supervision and advice. It's not necessarily challenging. Generally it is a cross taper. Stopping desvenlafaxine too quickly can result in significant withdrawals for some

@@PsychiatrySimplified i'm under medical supervision.. but my doctor is too optimistic and i'm the one who suffer...

Sorry to hear. Best to follow advice and inform if any side effects . Wish you well

@@PsychiatrySimplified thanks...i'm a walking side effect..

Vortioxetine reduces REM sleep and promotes NREM sleep which is a good thing. If sleep or anxiety worsens it’s important to let the doctor know as usually it means a mixed state should be ruled out - e.g vivid dreams , nightmares, racing thoughts etc. Vortioxetine is an effective antidepressant. We have a done a video on mixed state.

Hi, I came by to watch a video to better understand this medication. Like you, I was on Lexapro and HATED it, I fell into a horrible depression, all I wanted to do was eat and sleep. I gained weight which I hate, because I have worked so hard on losing weight to gain it back so easily. I was told to start Trintellix but after my experience with Lexapro I am so scared! How have you been feeling with this medication and how is your sleep?

@@PsychiatrySimplified thanks so much Doctor for your useful and considered opinion. I really appreciate it. 🌻🌻

@@mimiii444 Hi Mimi oh l know that feeling oh so well of being nervous over a new medication. I would say try Trintellix. Give it a chance. First impressions for me are somewhat positive as l feel a bit less anxiety. Start slow on 5mg and then like me now go up to 10mg. That is the therapeutic dose l have been told by my doctor. My sleep is a bit better and am less anxious on waking compared to last week say. Am quietly hoping and praying for the best with this medication. Hoping for no weight gain as l am just like you Mimi and want to keep weight off. Keep me posted if you like. Sending 🌻🌻

It has evidence for it 👉pubmed.ncbi.nlm.nih.gov/34497709/

It doesn't have a significant effect either way - though does not mean either can't happen.

There is some evidence of vortioxetine being beneficial in improving cognition. However in the context of ADHD - evidence based treatments are recommended. There is a proof of concept study and there is a trial ongoing to evaluate this. We have just released a video on other agents that may be beneficial if stimulants are not indicated. Clonidine and guanfacine - kzfaq.info/get/bejne/f92CfdiY07msg5c.html

This is a medication that does not mediate its action through reuptake inhibition. The SERT inhibition is up to 50% less than SSRIs - it’s action is mediated by many other neurotransmitters - and that’s seen in clinical practice in terms of addresing melancholic depression , cognition etc.

Recommendations are not to due to risk of serotonin syndrome. There is a study of Vortioxetine add on to SSRI - Vortioxetine has 50% lower SERT affinity which means there is a reduced risk but such combinations should be done under expert care

Best done under supervision . Activation is the main side effect so one should monitor closely

Limited efficacy for anxiety.

Thanks for sharing. Yes I can see that can be a possibility

Sorry but it's important that one discusses the issues with the prescriber or get a second opinion from another provider. Any advice here can be detrimental and not appropriate for the individual. It is general in nature

@@PsychiatrySimplified sir my psychiatrist turned out to have misdiagnosed me this whole time, and i have already taken this stelazine due to misdiagnosis , ending up i have tardive dystonia and tardive dyskinesia because of misdiagnosis. They misdiagnosed me with schizophrenia paranoid, my actual illness is social phobia

Isn't it crazy?

Lower incidence

Before I'm taking sertraline it's good for my panic disorder but I notice it's ruins to my sexlife it's so hard get orgasm, So I'm went back to my Pysch tell about that, he gave me a prescription Brintellix , every I take I feel Nausea that is normal it will gone?

Nausea is a very common side effect - it should reduce in 2 weeks . Taking it in the evening half hr after food usually keeps nausea away. This however varies.

Thanks for sharing.

Why?

why?

@@jocs8824 It disrupts the brain's 6 receptors and cuts people off from life.

Why? Please explain! It's important!

@@langueundlife3667 Antidepressants disrupt two receptors in the brain. Brintellix causes insomnia by disrupting 6 receptors in the brain. And it causes many diseases.

It’s not useless. It is a very effective medication when used for the right targets. It doesn’t have much evidence for anxiety

@@PsychiatrySimplified Can give you Glaucoma

You mean it does nothing for YOU.

I’ve always felt like all this medication does is give me insomnia

@@latisha334 rule out mixed states. See the video. The medication should be matched to patient symptom profile.

In AUS - 60 AUD / Month