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Adding a SSRI To Partial-Response Brintellix NOT Overkill?: A Theory Based On A Study

Geaux Tigers!

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I just read "Electrophysiological Investigations on the Role of Selected Serotonin Receptors and the Serotonin Transporter on Serotonin Transmission in the Rat Brain" which is a study by Maurice Lecours who works at the University of Ottawa, Institute of Mental Health Research.

I found his research to be fascinating. I am actually on Day 41 of my Brintellix (vortioxetine) prescription; however, for the past 12 days, I have been administering 20mg. vortioxetine 1TPOQAMCF in place of my prior 10mg. trial. I have only had a partial remission of my symptoms with this medication. I'm not so sure if I'd follow the suggestion of my own thread title, but I was wondering what everybody thought about the following excerpts paralleled to patients like myself that have not responded adequately to vortioxetine monotherapy for MDD?:

"These findings indicate that either the co-administration of an SSRI in addition to a 5-HT3 receptor antagonist or a multimodal agent that acts as a SSRI and 5-HT3 receptor, such as vortioxetine, could enhance 5-HT neurotransmission to produce AD and antiemesis effects, similar to that of litoxetine, after long-term administration."

Lecours seems to suggest that augmentation of a classical SSRI to vortioxetine may be a good idea because you have to keep this in mind (also excerpted from the study):

"selective 5-HT agents alone, such as escitalopram, and multimodal agents, such as vortioxetine, alter 5-HT neurotransmission through different receptors and exert different actions, via transporter and/or receptor activity, on the serotonergic system in the hippocampus consistent with other antidepressant strategies and with a unique pharmacological profile."

Supplementary, compared to other SSRIs, this study revealed: "vortioxetine has a low occupancy for the 5-HTT, escitalopram was used at a dose of 5 mg/kg in order to better mimic the effects of low occupancy alone."

I'm suggesting, based upon these excerpts that I've provided from Lecours' study, that augmentation of a traditional SSRI would perhaps enhance vortioxetine's unique pharmacological effects for patients that are diagnosed with MDD? Perhaps aggrandizing Brintellix with a typical SSRI could theoretically provide a more potent antidepressant/anxiolytic response for patients prescribed Brintellix that are not responsive or were not able to achieve full remission of their symptomatic depression?

Just a theory. What do y'all think about it?
 
Well it's certainly a reasonable hypothesis. In general SSRI's need around 70-80% SERT occupancy to achieve therapeutic effects (see http://www.ncbi.nlm.nih.gov/pubmed/22261982 for a review), so increasing occupancy could have an additive effect.

It's also possible that vortioxetine's unique mechanism of action lowers the occupancy requirement so that increased SERT blockage won't give any more benefit, just more side effects. With a drug as new as vortioxetine you're going to have a very hard time finding a conclusive answer one way or another.
 
May I ask why you're even on such a new drug? You're willingly participating (and paying to be) in a "phase iv" clinical trial. IMO, Lexapro(20mg max) + a sodium channel inhibitor (lamictal xr, trileptal) is one of the most potent "cure alls" for treatment resistant depression, with or without comorbid anxiety, but WITHOUT psychoses. Add a 50-100mg trazodone at night for insomnia and enhanced 5HT response if necessary.


All three of these drugs cost less than $10\month, which is probably less even once combined than Brintellix, and Lamictal XR 250mg + Lexapro 20mg + Trazodone 50mg can all be taken in one handful at night.
 
I take Brintellix concomitant on Lamictal XR, Topamax XR, both 200mg. with Latuda 80mg. relevant. I'm also prescribed Dexedrine IR, Provigil and Xanax XR.

SSRI/SNRI wise exclusively, I have failed on Effexor XR, Pristiq and Zoloft.

You can ask, yes.

Vortioxetine, due to your reasoning, should be prescribed for treatment-resistant MDD, in my opinion, only after trialling an antipsychotic and failing two antidepressants from two different classes.

Check my analysis of trazodone compared to Abilify: Trazadone ER after failing Abilify because of similarity?

My choice formula of trazodone is the extended-release formulation, Oleptro XR, that should have a lower prevalence of sedation than the IR medication due to its time-release mechanism. This stratagem may deliver the preeminent opportunity to aggrandize trazadone intake. It should adequately be a potent antidepressant, providing acceptable reliability in terms of low perverseness of daytime sedation and other side effects linked to the trazodone IR formulation. Oleptro XR should deliver satisfactory and perpetual blood plasma levels of trazodone for antidepressant response, yet be notionally no more anesthetizing than a lower dosage of the IR medication. The continual blood plasma levels generated by Oleptro XR, since it is a time-release medication, is idyllic for triggering tolerance to torpor.

Mood stabilizers like sodium channel inhibitors are the first-line treatments for the resistant depression of bipolar patients (who must be stabilized before proceeding to second-line medicaments). Also highly suggested for MDD patients.

Cool post, Warning!
 
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i'm so skeptical of Vortioxetine, it's pharmacology looks incredible on paper but after reading the seemingly few reports available I've yet to see more than 10% of people respond positively.
 
Fyasko, I have responded well to vortioxetine.

To elucidate, I rank Brintellix among the ADs I've been on. I put wayy too much thought into this, by the way. :D

Zoloft: 8.1/10
Wellbutrin XL 450mg. (as Aplenzin 522mg.): 6.0/10
Effexor 75mg. (as Pristiq 50mg.): 6.7/10
Brintellix: 8.9/10

Verdict: Not sedating, not activating unless you want to count relief which translates to more activity. A good AD, but I suggest:

I suggest that patients trial Brintellix only after they have failed a proven SSRI and two other antidepressants from two different classes. If an AD is tolerated, then that AD should be augmented with an atypical antipsychotic before trying vortioxetine.
 
Just out of curiosity have you tried selegiline or any other MAOI?
 
Want to share with your my case of mixing vortioxetine and vanlafaxine (SNRIs). Here is my case report:

My current dosage is : Vortioxetine 20mg + Venlafaxine 112.5mg + Desvenlafaxine 50mg + Imipramine 10mg + melatonin 3mg (This dosage was reached on 2017 May 6, and today is 2017 June 7)
Male, age 39 now. Yellow skin person (asian). Weight stable at around 64kg. Still in the same job (improvement is not a result of environment change).
Heart rate and blood presure no change (at a normal level). No serotonin syndrome. Have constipation due to this drug combination.

Single administration of Vortioxetine was only partially useful for me. Not satisfactory. I would rate it 50 out of 100. Could keep my office job, but my hypersomnia with excessive daytime sleepiness and non-24 hours sleep wake problem still disturbing and “painful”, made me want to quit the job and rest at home.
However later on, venlafaxine was added (and then desvenlafaxine also). The situation became significantly better and at the current dosage I would rate this vortioxetine+venlafaxine combination 75 to 80, out of 100.
My drug history in vortioxetine:
I was on vortioxetine 15mg (and melatonin 3mg) for 1 year, from 2015 September to 2016 August, but only partially responsive. Tried mixing bupropion over the course, but no use.
Then a doctor started to add venlafaxine (and later on desvenlafaxine) and Imipramine 10mg, starting from 2016 August. There was signifcant and noticable improvement as dosage increase. My current dosage is : Vortioxetine 20mg + Venlafaxine 112.5mg + Desvenlafaxine 50mg + Imipramine 10mg + melatonin 3mg (This dosage was reached on 2017 May 6, and today is 2017 June 7)
Heart rate and blood presure no change (at a normal level). No serotonin syndrome. Have constipation due to this drug combination.
Male, age 39 now. Yellow skin person (asian). Weight stable at around 64kg. Still in the same job (improvement is not a result of environment change).
Remark 1: I take these drugs not directly because of depression, but because of certain serious residual symptom of depression: “Hypersomnia with excessive daytime sleepiness” and “non-24 hours sleep wake problem”. I have had this serious residual symptom of depression for like 20 year. In these 20 years I only had 2 major depressive epidsode which lasted for 4 months and 2 months only. The rest of the time was very stable and severe “Hypersomnia with excessive daytime sleepiness” and “non-24 hours sleep wake problem”. Never have any mania or psychosis.
Remark 2: the Imipramine 10mg + melatonin 3mg is for my “non-24 hours sleep wake problem”. In the past melatonin 3mg was useless when I was taking other anti-depressant. Now Imipramine 10mg + melatonin 3mg works effectively in the current drug combination.
 
I'm wondering how on Earth a prescribing psychiatrist arrives at such a combination:

Vortioxetine 20mg + Venlafaxine 112.5mg + Desvenlafaxine 50mg + Imipramine 10mg
 
I'm wondering how on Earth a prescribing psychiatrist arrives at such a combination:
Vortioxetine 20mg + Venlafaxine 112.5mg + Desvenlafaxine 50mg + Imipramine 10mg

He seems to suffer from shopping addiction or at least wants to induce shopping addiction in his patient ;)

wikipedia said:
Shopping addiction is defined as the deficiency of impulse control which appears as the eagerness for constantly making new purchases of unnecessary or superfluous things
 
Hes giving you effexor and the metabolite of effexor? Why.

Thats like giving someone hydroxyzine and certizine
 
Even though the psychiatrist is stupid, I'm just glad he isn't stupid enough for something like this:

Vortioxetine 20mg + Venlafaxine 112.5mg + Desvenlafaxine 50mg + Imipramine 10mg + 60mg Tranylcypromine ;)

Be glad that your psychiatrist's incompetence is still within limits ;)
 
Venlafaxine and desvenlafaxine were prescribed together because, at the beginning, I was having vortioxetine 15mg + desvenlafaxine 50mg and the effect was insufficient. Wanted to increase the dosage of desvenlafaxine, but its minimum dosage was 50mg only (equivalent to about 75~100mg of venlafaxine). He probably wanted to avoid to risk of adding too quickly. So added 37.5mg venlafaxine first. And then increased to 75mg. And then increased to 112.5mg. Then, we were lazy. Just keep things intact at the current point.
Drinking coffee makes my mouth dry, and may provoke stomach upset. But I had no choice during these years. Now I haven’t drunk coffee for 3 months. No need.
 
The psychiatrist is not stupid. I luckily had him willing to try something different when almost all the conventional drug combinations were not useful / not decent enough. (I think the only thing I have still haven't tried so far was MAOI)
He is not incompetence. In simple, my current status is the best among these 20 years. (having hypersomnia for more than 20 years.)
 
Prescribing multiple SSRI/SNRIs together is absolutely pointless, unless you have a resistant case of OCD.
For maximum response you want to add a more potent NRI with 5ht antagonist properties to an SSRI, since SNRIs aren't potent enough at doing that on their own.
 
Makes sense to try a SSRI beside something with multiple 5ht receptor antagonism. People have been augmenting with atypical antipsychotics, TCAs and meds like nefazodone for awhile.
 
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