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Trintellix Side effects


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I have been on antidepressants for 20 years. I started on Prozac at the age of 26. Along the years I have switched meds for one reason or another, sometimes to take a safer one during pregnancy and other times just because I felt I needed a change. I do not currently see a psychologist but I have in the past and have had my gynecologist and now internal medicine doctor prescribe my medications.

I have recently switched from Effexor which was successful for a few years but I decided I needed a change.

I weaned off the Effexor which was a nightmare--very glad that part is over. But I don't feel I am getting the results with the Trintellix that I "think" I should be getting. 

In the past, whenever I have switched, I could tell an improvement within a few weeks. But not with the Trintellix. 

I had severe itching hands and feet only when I first started the Trintellix. Benadryl and Xzyzal helped. I also need zofran almost daily to help with the nausea, which is helping beautifully. 

I am looking for advice to see if it is worth continuing for the full 6-8 weeks.

I started on 20 mg of Trintellix but the nurse in me decided to half the dose to see if dropping to 10 mg would ease the side effects.

I had no more itching, but still need the zofran for nausea. I used to take my antidepressants in the morning, but I decided to take the Trintellix at night to help with the side effects. But the itching has returned after a week on the 10 mg. The itching is now waking me up at night.

My diagnosis is depression w/anxiety. So I have xanax to take mostly in the evenings to quiet my mind and help me sleep.

So bottom line, I would like to hear from anyone that has experience taking Trintellix. Is it worth it to continue a full 6 weeks or should I just try a different medication? And if a different medication is a suggestion, what would be a good one? I didn't care for Zoloft, cymbalta, or Lexapro. I didn't have any side effects with these, but just didn't feel I was getting much benefit.

I would greatly appreciate any feedback.

Thank you for taking the time to read my post and offer any suggestions.

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Trintellix is a 5HT3 antagonist like Zofran. I was just saying in another thread how perplexing it is that Trintellix causes nausea when one of its strongest pharmacological actions happens to be the same as Zofran. So weird. However, what most people don't know is that antagonism of 5HT3 can lead to histamine release, and this can lead to itchy skin. For some people, the itchiness does go away after a week or two.

I'm amazed that your pdoc started you right at 20mg. That's insane based on my own experience with it. I started at 5mg and increased by 5mg every few weeks until I hit 20mg. And it did start making a difference about 2 weeks after I hit 20mg. However, I've read a lot of people's accounts of taking this medication, it seems that a third of people it doesn't do anything and just feels like placebo; another third have some combination of either nausea, itchiness, headaches, or anxiety that are just intolerable; and for the remaining third it's a miracle drug. Count me in the last group. This has been the best antidepressant that I've taken but I didn't always feel that way. I felt like I wanted to ditch it until I had been on 15mg for a week or two but 20mg really made a difference. Started taking this around September of last year.

Fast forward to the present and I've learned to taper back Trintellix and increase Rexulti in the spring/summer and then reverse it for fall/winter and that cadence seems to be doing pretty well for me (bipolar 2, FYI). I actually really like the Trintellix+Rexulti combination and they jive really well with Vyvanse and Depakote to keep me going but keep me mellow too.

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Thank you so much for the information. It is very helpful.

I have decided to stop the trintellix and I plan to start back on prozac tomorrow actually.

I wish I would have known about starting at a lower dose first. I think it would have made a difference. I have been pretty miserable for the past month. This is unlike anything I have experienced before when trying a new medication. I had success many years ago with the prozac so that's why I decided to try it again. 

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Yeah Trintellix definitely needs to be taken carefully. Even the manufacturer dosing recommendations say to start at 10mg for a week and go right to 20mg. I even find that I bit crazy. I found Trintellix to be very activating when I started it. I was a bit irritable, I actually felt restless the way antipsychotics make me feel when I'm on too high a dose. It didn't really do much for my mood at all until 15mg. And I went from 5mg to 15mg over the course of 2-3 months. But I luckily didn't get itchy skin or nausea. Would just feel really hyper and a bit snappy after dose increases. Other than that it was totally tolerable. And not to mention I was stimulated during the day but my sleep actually improved too.

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I am one of those you mentioned - Trintellix was a sugar pill to me, even at 20.

People taking Trintellix shall know that it is also a 5HT1A agonist, which means that on lower doses it will hit presynaptic autoreceptors of Serotonin, leading to a decrease in its release. If that happens while its SSRI effect is not yet strong enough - you have a recipe for depression.

This effect is compensated for with higher doses that hit postsynaptic 5HT1A receptors like Serotonin does.

In a way, Trintellix is like a combination of SSRI with Buspar.

Edited by HydroCat
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11 hours ago, HydroCat said:

I am one of those you mentioned - Trintellix was a sugar pill to me, even at 20.

People taking Trintellix shall know that it is also a 5HT1A agonist, which means that on lower doses it will hit presynaptic autoreceptors of Serotonin, leading to a decrease in its release. If that happens while its SSRI effect is not yet strong enough - you have a recipe for depression.

This effect is compensated for with higher doses that hit postsynaptic 5HT1A receptors like Serotonin does.

In a way, Trintellix is like a combination of SSRI with Buspar.

You would think this would be the case, but there are other things to consider as well. Trintellix has an affinity for the serotonin transporter of 1.6nM and an IC50 (half-maximal inhibitory concentration) of 5.4nM, which is fairly similar to Lexapro which has an affinity for SERT of 1.8nM. At 5mg, Trintellix has a SERT occupancy of ~45%, which in the context of SSRIs isn't significant enough to produce an antidepressant effect in most people (unless they have multiple repeats for the short allele on the SERT gene like myself, in which case it takes far less SERT inhibition to attain therapeutic serotonin levels). However, Trintellix is also a strong 5HT3 antagonist like Zofran. So specifically, 5mg of Trintellix is like 5mg of Lexapro combined with an average daily dose of Zofran.

5HT3 receptors are very different from other receptors like 5HT1A, which are G-protein coupled receptors. 5HT3 receptors on the other hand are ion channel receptors and function to regulate several other systems. These receptors are inhibitory auto-receptors to an extent and blocking them does increase serotonin release. However, they do function more as inhibitory heteroreceptors for dopamine, acetylcholine, glutamate, histamine, and acetylcholine. So one could think of 5mg of Trintellix as an "indirect agonist" of the 5HT1A receptor. You are correct though, @HydroCat, that this does actually slow down serotonin outflow while the receptors are being desensitized. However, once the receptors reach saturation, desensitization of the receptors then invalidates this inhibitory effect and the serotonin pump will begin to increase again.

However, Trintellix only has an affinity for the 5HT1A receptors itself of about 15nM, which is much higher than its effect on SERT and 5HT3 and likely wouldn't be reached until 10mg or 15mg. Additionally, it has an intrinsic activity at 5HT1A of about 96%, which means, like you said, further breaks would be put on serotonin release as you increased, but in this case still the SERT inhibition of 55% occupancy at 10mg combined with stronger 5HT3 antagonism should functionally override this feedback loop to an extent. Additionally, at 10mg and 15mg, you're starting to employ 5HT7 antagonism (19nM, but an IC50 of only 450nM) which is also an inhibitory autoreceptor and would lend towards more serotonin release.

Really, the reason they want you to start on 10mg of Trintellix and go right to 20mg after a week is because all of the other effects at 5HT3, 5HT7, 5HT1D, 5HT1B dramatically reduce the time to desensitize the 5HT1A receptors, potentially allowing Trintellix to kick in faster than even Viibryd in some patients. The only problem is that Trintellix's activation period is so intense for some people that any advantage this may give it over other antidepressants is invalidated because nobody can titrate up the dose fast enough to take advantage of that "feature".

EDIT: Wanted to make another point from the last paragraph. I will still point out that despite the fact that the Trintellix activation period is why most people switch to something else, Trintellix statistically over several different trials and independent research studies is still technically considered more tolerable than most other antidepressants. This is potentially why some people think it feels like a sugar pill.

Edited by browri
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