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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 15 of 15. This is the beginning of the thread.
Posted by Prefect on April 24, 2018, at 20:20:49
It's a med option I'm considering as an alternative to Zoloft which isn't doing much for me. I was wondering if anyone's tried it and what their experience was?
Posted by SLS on April 25, 2018, at 5:53:33
In reply to Any experience with Trintellix?, posted by Prefect on April 24, 2018, at 20:20:49
> It's a med option I'm considering as an alternative to Zoloft which isn't doing much for me. I was wondering if anyone's tried it and what their experience was?
Trintellix is the next drug that I will be trying. I can't start taking it for another month, though. I have some personal matters to attend to. I then have to allow for a 10-14 day washout period after discontinuing Parnate (MAO-inhibitor).
From what I understand, Trintellix is particularly good at promoting clear thinking. I don't know about apathy and sexual dysfunction.
I guess you get to be a guinea pig.
:-)
- Scott
Posted by Prefect on April 26, 2018, at 8:40:05
In reply to Re: Any experience with Trintellix? » Prefect, posted by SLS on April 25, 2018, at 5:53:33
Clear thinking? wow that would be good. Much of my anxiety goes hand in hand with derealization and cognitive deficit, so if clear thinking is promoted by this drug now I'll definitely be pursuing it.
Posted by Prefect on April 26, 2018, at 8:44:59
In reply to Re: Any experience with Trintellix? » Prefect, posted by SLS on April 25, 2018, at 5:53:33
I should add one big reason I'm considering this drug is my cousin has had a good outcome from it. I'm of the belief (though have no proof) that people who are related and share a close genetic makeup respond similarly to psyche drugs. We both had a pretty good run on Luvox for 20 years, so there might be something to my theory. He says it didn't cause apathy but a bit of libido loss.
Posted by linkadge on April 27, 2018, at 8:50:43
In reply to Re: Any experience with Trintellix? » Prefect, posted by SLS on April 25, 2018, at 5:53:33
Is parnate no longer working for you?
Linkadge
Posted by SLS on April 27, 2018, at 11:07:30
In reply to Re: Any experience with Trintellix? » SLS, posted by linkadge on April 27, 2018, at 8:50:43
Hi Linkadge.
> Is parnate no longer working for you?
Parnate gives me a partial improvement that is inadequate for me to be able to get out of the house and become part of mainstream society. It gives me some mental energy and improves cognition and memory to a degree. Anhedonia persists, though. I am definitely better on it than off of it. However, a huge problem emerges when I take Parnate. Beyond what are already features of my baseline depression, Parnate causes a loss of interest and motivation to engage in activities. It is a sort of numbing feeling. It took me a little while to identify Parnate as the culprit. I tried tweaking the other drugs I take. It made no difference except that I relapsed upon lowering the dosage of any one of them. Then I remembered having this same problem whenever I would raise the dosage of Parnate to 60 mg/days. I was in my 20s.
I'll be okay.
My immediate plans are to switch from Parnate to Trintellix while leaving everything else in place. If this is a dead end, then I will switch from Trintellix to Effexor at a dosage of 300 mg/day or higher. My doctor is reluctant to have me on Trintellix and Effexor at the same time. Serotonin syndrome is a concern. I didn't think Trintellix was that potent as a serotonin reuptake inhibitor. I don't know. Trintellix does improve cognitive and memory function to a significant degree, even for people who do not have major depressive disorder. Since these things are among the most prominent symptoms for me, this is a welcome benefit. If neither Trintellix nor Effexor yield adequate results, it will be back to Nardil. I have not taken Nardil while on lithium and prazosin. I could probably live with a 50% improvement over baseline. I haven't had this since 1987.
I could use more alternatives. If you can think of anything for me, I could use some help. The only standard drugs I can think of that I have not tried are Luvox and Celexa. Of course, there might be combinations that I haven't tried yet.
- Scott
Posted by linkadge on April 27, 2018, at 13:52:18
In reply to Re: Any experience with Trintellix? » linkadge, posted by SLS on April 27, 2018, at 11:07:30
Luvox and celexa are ok, but probably not likely to break TRD on their own. Luvox may be worth a shot, as it's mechanism is slightly different from SSRIs.
I found luvox was ok for sleep and anxiety, but not so much for depression. The sigma agonism of fluvoxamine could be useful if OCD or psychotic features were present (but it doesn't sound like this is the case).
I don't think that trintillex is super potent as an SSRI (at least in therapeutic doses), the idea being that it's action at other sites seems to provide a theraputic effect with less potent action as an SSRI.
I found escitalopram a better antidepresant than citalopram (marginally). It could be good to combine with something like bupropion. The norepinephrine active drugs supposedly are more effective if high inflamation is present.
I don't suppose your doctor is able to test for markers of inflammation (not standard practice, but perhaps informative)?How is your blood glucose? Any prediabetes? Some studies show that drugs like piogitazone can augment standard antidepressants, even if glucose is marginally dysregulated. Pioglitazone is also a mild / moderate MAO-b inhibitor.
What about selegiline? I'm not sure how comfortable your doctor is, but supposedly it can be combined with SSRIs, at least in lower doses.
Have you ever used dextromethorphan? (you didn't respond well to ketamine, if I recall..). Dextromethorphan, combined with bupropion or quinidine, may be useful.
Celebrex may augment some antidepresants, again, if inflamation is high.I still swear by pure cocoa powder and an anti-anhedonic strategy. Cocoa nibs are also useful. Also, as you know I've been trying medical marijuanna with relative sucess (more research is emerging on the use of cannabanoids for depression / anxiety). The cannabinoids THC and CBD are as potent at ppar-gamma receptors (action of pioglitazone) as they are at cb1 receptors.
Effexor and remeron do work very well together (apparently more effective than parnate for TRD) but the initial remeron sedation can be strong.I did well with effexor, remeron and a bit of the herb "fo-ti" (mao-b inhibitor). I stopped taking the fo-ti for liver concerns, but it was very effective for reducing taking the edge off anhedonia.
Have you tried dopamine agonists (mirtapex is suppsedly effective for TR bipolar depression).
Mirapex might work well with trintillex (for a more broad spectrum receptor agonism profile).There's some ideas, let me know if you want more.
Linkadge
Posted by SLS on April 28, 2018, at 8:18:01
In reply to Re: Any experience with Trintellix?, posted by linkadge on April 27, 2018, at 13:52:18
Hi, Linkage.
> I found luvox was ok for sleep and anxiety, but not so much for depression. The sigma agonism of fluvoxamine could be useful if OCD or psychotic features were present (but it doesn't sound like this is the case).
What are the functions and locations of sigma receptors? I don't know anything about them. All I know is that agonists like Luvox reduce akathisia while antagonists like Zoloft can make akathisia worse.
> I don't think that trintillex is super potent as an SSRI (at least in therapeutic doses), the idea being that it's action at other sites seems to provide a theraputic effect with less potent action as an SSRI.
What do you think about combining Trintellix with Effexor? Are there any times where combining two SRIs is safe? If Trintellix helps with cognition and memory and Effexor is a stronger antidepressant, I may petition my doctor to combine them if Effexor is insufficient.
> I found escitalopram a better antidepresant than citalopram (marginally). It could be good to combine with something like bupropion.
You are likely right. I have seen people report that Wellbutrin combined with Zoloft or Effexor work well. A friend of mine achieved remission with Pristiq + Wellbutrin. She described Wellbutrin as giving her more energy while Pristiq gave her "the wanna dos". I take this as meaning improvements in interest and motivation, and perhaps anhedonia.
> The norepinephrine active drugs supposedly are more effective if high inflamation is present.
It would be interesting to have my CRP tested. Imipramine, desipramine, amitriptyline, and nortriptyline help me while protriptyline (high NRI) and reboxetine made me very, very much worse. Straterra was neutral.
> I don't suppose your doctor is able to test for markers of inflammation (not standard practice, but perhaps informative)?
He would do it. I just don't know if insurance will cover it.
> How is your blood glucose? Any prediabetes? Some studies show that drugs like piogitazone can augment standard antidepressants, even if glucose is marginally dysregulated. Pioglitazone is also a mild / moderate MAO-b inhibitor.
It doesn't surprise me that you should come up with such interesting ideas. I wish I had your memory. Glucose is fine, but my triglycerides are very high. My primary care provider thinks the Abilify is the culprit. I may ask to try metformin to tackle this.
> What about selegiline?
I tried it at 12 mg/24hr. It was neutral.
> I'm not sure how comfortable your doctor is, but supposedly it can be combined with SSRIs, at least in lower doses.
I would feel uncomfortable doing this. Even at 6mg/24hr, there is quite a bit of MAO-A inhibition. This is acknowledged in the manufacturer's label. In my estimation, MAO-A inhition results in most of the antidepressant effects of MAOIs. I don't know what to make of pargyline. Moclobemide is a reversable MAO-A inhibitor (RIMA). It makes for a potent antidepressant, but only for a few days to a few weeks - even at 1200 mg/day. The most potent antidepressant I ever took as monotherapy was clorgyline, an irreversible and specific inhibitor of MAO-A. I was with it at the US National Institutes of Health. Unfortunately, I wasn't allowed to add anything to it other than lithium. Ultimately, I stopped taking it because we couldn't get a stable mood state with it. I swung between euthymia and depression over the course of days. Clorgyline was discontinued for human consumption because of reports of cardiac sequalae. It is still used in the laboratory as a marker of MAO-A activity.
> Have you ever used dextromethorphan? (you didn't respond well to ketamine, if I recall..). Dextromethorphan, combined with bupropion or quinidine, may be useful.
Once I discontinue Parnate, I can try DXM. Ketamine was completely inert. I interpret this as my probably having the met66met genotype for the synthesis of BDNF. This is the worst genotype to have. It's always something with me.
> Celebrex may augment some antidepresants, again, if inflamation is high.
I might try naproxen. Celebrex gives me diarrhea.
> I still swear by pure cocoa powder and an anti-anhedonic strategy. Cocoa nibs are also useful. Also, as you know I've been trying medical marijuanna with relative sucess (more research is emerging on the use of cannabanoids for depression / anxiety). The cannabinoids THC and CBD are as potent at ppar-gamma receptors (action of pioglitazone) as they are at cb1 receptors.
I'm not familiar with ppar-gamma receptors. Interesting.
> Effexor and remeron do work very well together (apparently more effective than parnate for TRD) but the initial remeron sedation can be strong.
I'm afraid of Remeron. Another NE alpha2 antagonist made me feel horrendous. I began taking Remeron, but aborted it after only 2 days because I thought I was feeling a worse.
> Have you tried dopamine agonists (mirtapex is suppsedly effective for TR bipolar depression).
I haven't tried Mirapex. I just don't see anyone getting a consistent antidepressant effect from it. I do profit from Abilify, though. So maybe DA agonism is a good thing.
> There's some ideas, let me know if you want more.
I really do appreciate it.
- Scott
Posted by linkadge on April 28, 2018, at 9:07:31
In reply to Re: Any experience with Trintellix? » linkadge, posted by SLS on April 28, 2018, at 8:18:01
>What are the functions and locations of sigma receptors? I don't know anything about them.
They appear to have neuroprotective and neurotrophic effects. The brain growth factor NGF acts via sigma receptors (just as BDNF acts at trk-b receptors). Sigma agonists appear to have pro-cognitive effects, and can counteract the psychotomimetic effects of NMDA antagonists (or other schizophrenogenic agents). The sigma receptors interact with ion channels (calcium) and also modulate neurotransmitter release. Supposedly combo 5-ht1a + sigma agonists have synergistic effects on cognition.
>What do you think about combining Trintellix >
>with Effexor? Are there any times where
>combining two SRIs is safe? If Trintellix helps >with cognition and memory and Effexor is a
>stronger antidepressant, I may petition my doctor to combine them if Effexor is insufficient.I'm not sure. I haven't taken trintillex, so I don't have a feel for it. There could certainly be synergy (especially at higher doses of Effexor - which may impact norepinephrine more). Because both bind at the serotonin transporter site, it's possible that the SERT transporter becomes saturated at lower doses of each. If this occurred, each drug would begin to have greater binding at its alternative sites (i.e norepinephrine for Effexor, and 5-ht receptors for trintillex).
>It would be interesting to have my CRP tested.
>Imipramine, desipramine, amitriptyline, and >nortriptyline help me while protriptyline (high >NRI) and reboxetine made me very, very much >worse. Straterra was neutral.It could be that there are secondary binding sites for the TCAs which exert the anti-inflammatory effects. Wellbutrin supposedly has a strong effect on inflammation - not sure if this is through norepinephrine.
>I would feel uncomfortable doing this. Even at
>6mg/24hr, there is quite a bit of MAO-A
>inhibition. This is acknowledged in the
>manufacturer's label.I was thinking more oral selegiline. When used in anti-Parkinson doses, it primarily affects MAO-b and can be taken orally. Supposedly, using oral selegiline and SSRIs is not uncommon in parkinsons with depression.
Inhibiting MAO-b (even mildly) can exert a neuroprotective / neurotrophic effect. Also, MAO-b selective doses may have an effect on motivation / anhedonia. MAO-A inhibitors likely do have the stronger effect on traditional depression, however MAO-b inhibitors can still exert a punch on certain depressive symptoms.
>Once I discontinue Parnate, I can try DXM.
>Ketamine was completely inert. I interpret this
>as my probably having the met66met genotype for
>the synthesis of BDNF. This is the worst >
>genotype to have. It's always something with me.Have you had this tested? If for some reason you do have a bad BDNF gene, there may be hope via direct TRK-b agonists. TRK-b agonists directly activate the 'bdnf' receptors (no BDNF required). Amitriptyline is a trk-b agonist, as are some emerging investigational drugs. The problem with amitriptyline (as you know) is the secondary binding sites. However, there may be more selective trk-b agonists on the way. Sigma receptors also interact with BDNF (although it's a bit too complex for me to understand), however, they can potentiate the action of BDNF at trk-b receptors.
>I began taking Remeron, but aborted it after
>only 2 days because I thought I was feeling a
>worse.Yeah, I can only tolerate in the 1-2mg range for mirtazapine. The initial antihistamine effects are strong. It may also act as a kappa opioid receptor agonist (which, in the short term, could cause dysphoria).
>I just don't see anyone getting a consistent
>antidepressant effect from it. I do profit from
>Abilify, though. So maybe DA agonism is a good
>thing.One things BDNF does is sensitize the d3 recpetors in reward regions of the brain. If (for some reason) your BDNF level was low, you could (very theoretically) have recduced dopamine activity at d3 receptors. Mirapex is fairly selective towards d3 (and d2), however it also has some action at 5-ht1a receptors. Another plus is that it exerts neurotrophic / neuroprotective effects. It could be worth a shot (low probability for interaction with other drugs).
Linkadge
Posted by linkadge on April 28, 2018, at 9:09:44
In reply to Re: Any experience with Trintellix? » linkadge, posted by SLS on April 28, 2018, at 8:18:01
Another thing to consider is that sometimes (for strange, unexpected reasons) one drug can cancel out the effect of another.
For example, I noticed that the effect of medical marijuana is much stronger when I'm off Effexor.
It's possible that the effect of a drug like ketamine works better when a patient is on fewer other drugs.
For example, abilify might actually block (or neutralize) the AD effect of ketamine.
Linkadge
Posted by PeterMartin on April 28, 2018, at 15:01:41
In reply to Re: Any experience with Trintellix? » linkadge, posted by SLS on April 27, 2018, at 11:07:30
.
>
> I could use more alternatives. If you can think of anything for me, I could use some help. The only standard drugs I can think of that I have not tried are Luvox and Celexa. Of course, there might be combinations that I haven't tried yet.
>
>
> - Scott
>
Have you taken the Gavis version of Nardil?Metformin has prevented major weight gain so far btw (only up 2lbs at 3months and just up to the full 2000 so hoping to maybe lose).
Posted by SLS on April 28, 2018, at 15:13:02
In reply to Re: Any experience with Trintellix?, posted by PeterMartin on April 28, 2018, at 15:01:41
> > I could use more alternatives. If you can think of anything for me, I could use some help. The only standard drugs I can think of that I have not tried are Luvox and Celexa. Of course, there might be combinations that I haven't tried yet.
> Have you taken the Gavis version of Nardil?I don't know what version of Nardil I used last. Where would I get Gavis?
> Metformin has prevented major weight gain so far btw (only up 2lbs at 3months and just up to the full 2000 so hoping to maybe lose).
That's very good news. Do you get any GI side effects?
Thanks.
- Scott
Posted by B2chica on April 28, 2018, at 16:36:59
In reply to Any experience with Trintellix?, posted by Prefect on April 24, 2018, at 20:20:49
Hello Prefect
I was on Trintellix last fall For a short while. It ended up not working.
But
I would like to note that it is pretty well established that I do Routinely BAD on any SSRI. But we were hoping it would be a simple augment.Otherwise, it was pretty smooth med, no real side effects (No weight gain!). I think I initially reacted well, then my mood dropped and kept on going. Become depressed with agitation and suicidal thinking.
Id say worth a shot, just keep notice of yourself a nd keep in contact with Pdoc.
Best wishes
b2c.
Posted by PeterMartin on April 29, 2018, at 1:46:18
In reply to Re: Any experience with Trintellix? » PeterMartin, posted by SLS on April 28, 2018, at 15:13:02
> > Have you taken the Gavis version of Nardil?
>
> I don't know what version of Nardil I used last. Where would I get Gavis?
>Just call the pharmacy ahead of time and ask which generic manufacturer they carry for Nardil (if they even have it in stock). Then say you need the Lupin version (sorry I should have mentioned Gavis was just bought by Lupin so it'll eventually be in called Lupin in their system if not already but same thing). From what I've read on the http://www.socialanxietysupport.com/forum/f30/ forum Gavis intended to make the coating like the original when they started making the generic. Greenstone is exactly the same as Pfizers. While people who took the original pre-2004 version of Nardil still don't think Gavis(Lupin) is as good almost all say it's stronger than Greenstone. It's finally kicked in for me after 3months (6wks on 60 and 6wks on 75).
I've never personally taken the Greenstone but I regardless of bioavailability I respond very differently to different generics. Topamx/Lamictal/Seroquel.....different brands do cause different side effects or feel stronger. In some cases (Lamictal) some generics flat out don't work for me. Greenstone seemed to be more popular originally but I think Gavis/Lupin is just as common now. Since there was a decent chance in the past you took the Pfizer/Greenstone brand if you do go back on Nardil at least keep track of the generic brand you try. If you hit a wall w/ it switch. That might be enough to give you better results.
> > Metformin has prevented major weight gain so far btw (only up 2lbs at 3months and just up to the full 2000 so hoping to maybe lose).
>
> That's very good news. Do you get any GI side effects?
>I BM more with it which honestly is a great thing. I did seem to get pretty tired after each dose increase for a a few days to a week. It's a little difficult to gauge since I started Nardil at the same time. I've only been on 2000 for a few days now and this is the real test. If I start _losing_ weight than I'll ecstatic. Keeping Nardil wt. neutral is my main goal though.
If the met starts to fail I think my only real option is Zonegran which seems to be either great or terrible. Similar cognitive effects like Topamax but the wt loss is supposed to be great. I've also heard Topamax doesn't tend to work for wt loss if you've taken it before (which I have). I'm optimistic Metformin will help though - I'll continue to update.
Posted by SLS on April 29, 2018, at 7:41:49
In reply to Re: Any experience with Trintellix?, posted by PeterMartin on April 29, 2018, at 1:46:18
Thanks for all of the information.
I'm so glad that you are responding well to Nardil!
Will you be able to recognize when you reach full remission? Are you there right now?
Regarding Zonegran, I experienced no cognitive or memory impairments with it. I don't remember the dosage, though :-). Hopefully, you will experience the same thing. Everyone is different, of course. I found that Zonegran suppressed my appetite.
Get well and stay well!
- Scott
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