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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 19 of 19. This is the beginning of the thread.
Posted by linkadge on November 16, 2022, at 14:20:43
I saw my psychiatrist today. We're going to go with venlafaxine 37.5mg + bupropion 150mg (also taking lithium 300mg and mirtazapine 7.5mg).
Fingers crossed.
Linkadge
Posted by SLS on November 17, 2022, at 11:22:40
In reply to Going with Venlafainxe + Bupropion, posted by linkadge on November 16, 2022, at 14:20:43
> I saw my psychiatrist today. We're going to go with venlafaxine 37.5mg + bupropion 150mg (also taking lithium 300mg and mirtazapine 7.5mg).
>
> Fingers crossed.
>
> Linkadge
Hi, Linkadge.I like your choice - a lot.
I think you will come close to receiving an acceptable improvement that you can build on.
So that you not be spooked by side effects and flinch as a knee-jerk reactions to them when they first appear, I think you should make addressing potential side effects a crucial and necessary part of your trial protocol.
A few thoughts.
1. A *very* gradual titration of Effexor. It might be appropriate to allow 6 weeks to reach a therapeutic dosage. Start at one half of a 37.5 mg capsule. If you reach a dosage that produces side effects, decrease the dosage for two weeks and try increasing again.
2. I don't think it is in your best interest to stop at 37.5 mg/day. I doubt anyone improves robustly at dosages lower than 75 mg/day. I didn't reach my optimal response to Effexor until I reached a dosage of 300 mg/day. 225 mg/day didn't cut it. I had side effects early in treatment, but I eventually was able to establish a dosage of 300 mg/day without side effects.
3. You must begin thinking that you are going to try each treatment only ONCE. Be thorough, and try not to abort the trial unless side effects, including psychiatric side effects, are intolerable. By this time, you will already have in place a strategy to treat side effects. Be creative when developing strategies. Benzodiaepine? Beta-blocker? Buspar? Anti-psychotic? I am absolutely sure that you are more competent than me in designing palliative treatments for the side effects that you expect.
4. If you find the psychiatric side effects (anxiety, etc.) of Effexor (venlafaxine) to be intolerable and refractory to mitigation, I implore you to try Pristiq (desvenlafaxine) afterwards, regardless of expense. Drug company financial aid? Regardless, this should be considered am imperative in order to perhaps give you the motivation and functionality to work and pay for the Pristiq. Employee benefits?
Good luck. No more circles.
- Scott
Posted by SLS on November 17, 2022, at 14:52:44
In reply to Re: Going with Venlafainxe + Bupropion, posted by SLS on November 17, 2022, at 11:22:40
I forgot to mention guanfacine.
It has anxiolytic and anti-ADHD properties.
- Scott
Posted by linkadge on November 17, 2022, at 15:16:23
In reply to Re: Going with Venlafainxe + Bupropion, posted by SLS on November 17, 2022, at 14:52:44
Thanks for the tips. I'll let you know how it goes.
I am literally starting with spheroids of a 37.5mg cap of venlafaxine. I was hoping that I could manage on just lithium + wellbutrin. The problem is that it was kind of mindless energy without insight. Effexor has been better at helping introspection. I.e. ability to look at the pieces and actions of my life that contribute to me staying on track.
Linkadge
Posted by SLS on November 18, 2022, at 6:39:28
In reply to Re: Going with Venlafainxe + Bupropion, posted by linkadge on November 17, 2022, at 15:16:23
> Thanks for the tips. I'll let you know how it goes.
>
> I am literally starting with spheroids of a 37.5mg cap of venlafaxine. I was hoping that I could manage on just lithium + wellbutrin. The problem is that it was kind of mindless energy without insight. Effexor has been better at helping introspection. I.e. ability to look at the pieces and actions of my life that contribute to me staying on track.
>
> LinkadgePerhaps that is the result of mental *clarity*, which I find to be an effect essential to a global antidepressant response.
Stay on the lithium. I may or not be helping. However, like me, it might be required to respond robustly to everything else. For *me* low-dosage lithium 300 mg/day has a significant antidepressant effect. 450 mg/day and higher actually reverses the improvement, and I relapse. My research into this phenomenon is supported by a few articles appearing on Medline / PubMed.
"Bimodal effect of lithium plasma levels on hippocampal glutamate concentrations in bipolar II depression: a pilot study"
https://pubmed.ncbi.nlm.nih.gov/25522399/
I find that the bimodal effect of lithium on my depression can be explained by this article and its finding that lithium has a bimodal effect on glutamate release.
This might be an overgeneralization, but I have seen literature that depicts:
-----------------------------------------------------
1. Low dosages of lithium: Improves depression only.
2. Low levels of glutamate are associated with depression.
-----------------------------------------------------
1. High dosages of lithium: Used traditionally for bi1. polar disorder. High dosages are necessary as an acute treatment for an ongoing episode of a mania or for its prophylaxis.
2. High levels of glutamate are associated with mania.
------------------------------------------------------
Please do not neglect these associations. If your depression reacts to lithium like mine, 300-450 mg/day should work better than higher dosages. If 300 mg/day of lithium is a better antidepressant for you, it won't take more than a week to see an improvement. If you already tried this without success, consider that higher dosages are necessary for you. A nice secondary benefit to taking extremely dosages of lithium is that it prevents Alzheimer's Disease and probably other neurodegenerative diseases.
In my way of thinking, lithium is aspirin for the brain, and probably neurons in general. It prevents apoptosis and lengthens telomeres. The telomere thing is astonishing.
- Scott
Posted by undopaminergic on November 18, 2022, at 9:38:29
In reply to Re: Going with Venlafainxe + Bupropion, posted by SLS on November 17, 2022, at 14:52:44
> I forgot to mention guanfacine.
>
> It has anxiolytic and anti-ADHD properties.
>And it lowers pulse and blood pressure. It was first marketed for these problems, under the names Tenex and Estulic.
These effects are particularly handy when ADHD-drugs like methylphenidate, amphetamine, and atomoxetine do the opposite.
-undopaminergic
Posted by undopaminergic on November 18, 2022, at 9:47:48
In reply to Re: Going with Venlafainxe + Bupropion » linkadge, posted by SLS on November 18, 2022, at 6:39:28
>
> -----------------------------------------------------
>
> 1. Low dosages of lithium: Improves depression only.
>
> 2. Low levels of glutamate are associated with depression.
>
> -----------------------------------------------------
>
> 1. High dosages of lithium: Used traditionally for bi1. polar disorder. High dosages are necessary as an acute treatment for an ongoing episode of a mania or for its prophylaxis.
>
> 2. High levels of glutamate are associated with mania.
>
> ------------------------------------------------------
>The evidence seems to be conflicting. Ketamine, a NMDA-glutamatergic antagonist, improves depression. Memantine, another NMDA-glutamatergic antagonist, can induce mania.
There must be an explanation of course. Perhaps antagonising the NMDA-subtype receptors triggers an increase in glutamatergic tone at other receptor subtypes.
-undopaminergic
Posted by linkadge on November 18, 2022, at 13:54:36
In reply to Re: Going with Venlafainxe + Bupropion, posted by undopaminergic on November 18, 2022, at 9:47:48
I do hold quite tightly onto the lithium 300mg. It has helped reduce the intensity of episodes. I find that lower dose zinc and magnesium supplementation also help.
It's funny. On lithium alone, I seem to do "ok" for say a month. Then I start to sink (usually brought on by some sort of external stressor). It can happen quite quickly and result in severe symptoms. Usually then, I start a low dose antidepressant, which usually helps after 1-2 weeks. The problem is that if I continue taking the antidepressant, I start to feel ongoing impairment. So, I usually stop the antidepressant after I start to feel better. I continue taking the lithium, and usually I can continue to feel "normal" for a few weeks or months.
I understand that I should continue taking the antidepressant. But, my strategy has seemed to work in terms of keeping me most functional.
Linkadge
Posted by SLS on November 18, 2022, at 18:22:19
In reply to Re: Going with Venlafainxe + Bupropion, posted by linkadge on November 18, 2022, at 13:54:36
> I do hold quite tightly onto the lithium 300mg. It has helped reduce the intensity of episodes. I find that lower dose zinc and magnesium supplementation also help.
>
> It's funny. On lithium alone, I seem to do "ok" for say a month. Then I start to sink (usually brought on by some sort of external stressor). It can happen quite quickly and result in severe symptoms. Usually then, I start a low dose antidepressant, which usually helps after 1-2 weeks. The problem is that if I continue taking the antidepressant, I start to feel ongoing impairment.What kind of impairments? Are they exactly the same regardless the antidepressant you take?
> So, I usually stop the antidepressant after I start to feel better. I continue taking the lithium, and usually I can continue to feel "normal" for a few weeks or months.I am extremely optimistic for you because of how easily low-dosage lithium moves you, despite the brevity of the improvement.
> I understand that I should continue taking the antidepressant. But, my strategy has seemed to work in terms of keeping me most functional.Yes. I forgot to address that. During your Wellbutrin + SNRI trial, use all of your other strategies / tricks to keep your head above water. Really, really, really try to make Effexor / Pristiq + Wellbutrin work for you. If side effects remain intolerable with Effexor, despiite using an extremely slow titration, I don't think that switching to Pristiq should be overlooked. If the side effects you experience with Effexor involve an uncomfortable "wired" or stimulant effect, along with brain-fog, my guess is that this is being produced by the parent molecule, venlafaxine. Most of the venlafaxine is metabolized in the body to desvenlafaxine.
What if desvenlafaxine (Pristiq) can produce an improvement in the absence of venlafaxine?
What if it is only venlafaxine that causes you side effects?
Just some thoughts.
This is advice that I hope you find helpful:
"Keep your eyes on the prize."
The prize is NOT mild palliative relief or an unstable improvement. If you need time to recover after a challenging drug trial, rest. Use your strategies to mitigate the severity of your depression without attempting another drug trial. Rest and wait until you are ready for resuming treatment experiments.
Before moving away from Effexor / Pristiq + Wellbutrin, consider adding nortriptyline while you remain on the low-dosage lithium. As you know, nortriptyline is a tricky drug to find an optimal dosage for.
Too low = no response
Just right = full remission
Too high = relapseNortriptyline is the mildest TCA with respect to side-effects, and isn't very much less effective than its parent molecule, amitriptyline. You should experience much reduced anticholinergic side-effects, and less tachycardia and palpitations compared to desipramine. I find nortriptyline to be more anti-anhedonic and more of a "mood-brightener" than desipramine.
Same rules for you: Start very low and titrate very gradually. I think you will find nortriptyline very tolerable. I don't know I'm taking it - even at 150 mg/day.
My impression of nortriptyline is that people respond to either 25-75 mg/day or 125-150 mg/day. Nothing in between. Not until you have concluded that there is no way the low dosage range is ineffective should you then try the higher range - again, titrated very gradually.
If you ultimately need only 2 of the 3 drugs to achieve remission, taking all three at the same time will dramatically reduce the time it takes to:
1. Determine whether or not you can achieve remission while taking all 3 drugs, regardless of the number of drugs necessary treatment success.
2. After an extended period of a stable remission with all 3 drugs, you can then try removing each drug until you find the drug that is not contributing at all to your success.
I hope to suggest the most logical treatment strategy as a protocol to establish the best response with the fewest drugs.That's the prize. It might be frustratingly slow and challenging to titrate so gradually, but right now, given your sensitivity to side effects, I don't think you have a better choice. I could be wrong, but I don't think you should act under the premise that your brain responds only to sub-therapeutic dosages of antidepressants. Perhaps you are mistaking the appearance of side effects to be an indicator of your dosage limit. What if you need the same dosages that are observed to work for the vast majority of people? If Effexor can produce side effects in me when I first arrived at 75 mg/day, yet eventually responded to 300 mg/day without side effects, maybe your experience will be the same given careful titration.
Perhaps you have already concluded unequivocally that you are indeed a low-dosage responder - or at least incapable of establishing higher dosages. It's all empirical.
- Scott
Posted by SLS on November 18, 2022, at 20:40:04
In reply to Re: Going with Venlafainxe + Bupropion » linkadge, posted by SLS on November 18, 2022, at 18:22:19
My proofreading sucks.
- Scott
Posted by jay2112 on November 19, 2022, at 14:38:39
In reply to Re: Going with Venlafainxe + Bupropion, posted by undopaminergic on November 18, 2022, at 9:47:48
> >
> > -----------------------------------------------------
> >
> > 1. Low dosages of lithium: Improves depression only.
> >
> > 2. Low levels of glutamate are associated with depression.
> >
> > -----------------------------------------------------
> >
> > 1. High dosages of lithium: Used traditionally for bi1. polar disorder. High dosages are necessary as an acute treatment for an ongoing episode of a mania or for its prophylaxis.
> >
> > 2. High levels of glutamate are associated with mania.
> >
> > ------------------------------------------------------
> >
>
> The evidence seems to be conflicting. Ketamine, a NMDA-glutamatergic antagonist, improves depression. Memantine, another NMDA-glutamatergic antagonist, can induce mania.
>
> There must be an explanation of course. Perhaps antagonising the NMDA-subtype receptors triggers an increase in glutamatergic tone at other receptor subtypes.
>
> -undopaminergic
>Like SSRI's, glutamatergic drugs often start out as agonists, then down-regulate and antagonize. Low dose lithium = pro-glutamatergic...high dose down-regulates. Perhaps a higher dose of Memantine would down-regulate, and depress?
I dunno...just a guess.
Jay
Posted by undopaminergic on November 20, 2022, at 7:47:56
In reply to Re: Going with Venlafainxe + Bupropion » undopaminergic, posted by jay2112 on November 19, 2022, at 14:38:39
>
> Like SSRI's, glutamatergic drugs often start out as agonists, then down-regulate and antagonize. Low dose lithium = pro-glutamatergic...high dose down-regulates. Perhaps a higher dose of Memantine would down-regulate, and depress?
>
> I dunno...just a guess.
>
> JayWell, I don't think so, because I took a massive overdose (several grams) of memantine. I recall very little of what happened afterwards, except that I was lying catatonic on the floor performing repeated purposeless movements, and I couldn't muster any will to stop, it just felt pointless. Judging from what I was told by others about what happened, I was more manic than depressed. After I started to remember again, I was still manic, trying to smash the window of my room at the hospital. Then I got gradually more depressed, probably because the memantine was finally wearing off.
So, it appears that memantine can "depress" certain functions, such as memory, but not cause depression, except possibly a mixed state of both depressive and manic symptoms. They did tell me I tried to hang myself in the shower hose.
-undopaminergic
Posted by SLS on November 20, 2022, at 10:51:52
In reply to Re: Going with Venlafainxe + Bupropion » jay2112, posted by undopaminergic on November 20, 2022, at 7:47:56
> >
> > Like SSRI's, glutamatergic drugs often start out as agonists, then down-regulate and antagonize. Low dose lithium = pro-glutamatergic...high dose down-regulates. Perhaps a higher dose of Memantine would down-regulate, and depress?
> >
> > I dunno...just a guess.
> >
> > Jay
>
>
> Well, I don't think so, because I took a massive overdose (several grams) of memantine. I recall very little of what happened afterwards, except that I was lying catatonic on the floor performing repeated purposeless movements,
Do you think that what you experienced was a sort of stereotypy?
- Scott
Posted by undopaminergic on November 22, 2022, at 12:25:37
In reply to Re: Going with Venlafainxe + Bupropion » undopaminergic, posted by SLS on November 20, 2022, at 10:51:52
> > >
> > > Like SSRI's, glutamatergic drugs often start out as agonists, then down-regulate and antagonize. Low dose lithium = pro-glutamatergic...high dose down-regulates. Perhaps a higher dose of Memantine would down-regulate, and depress?
> > >
> > > I dunno...just a guess.
> > >
> > > Jay
> >
> >
> > Well, I don't think so, because I took a massive overdose (several grams) of memantine. I recall very little of what happened afterwards, except that I was lying catatonic on the floor performing repeated purposeless movements,
>
>
> Do you think that what you experienced was a sort of stereotypy?
>
>
> - ScottI think that is possible, but I'd have to know more about how memantine affects others, especially at higher doses, which may be very hard because it is usually not used clinically at doses higher than 20 mg/day.
I do know, however, that stimulants can produce stereotypy. Given that the manic effects of memantine resemble a stimulant response (dopaminergic-like), it's not unlikely it can do the same.
-undopaminergic
Posted by linkadge on November 22, 2022, at 15:02:08
In reply to Re: Going with Venlafainxe + Bupropion » linkadge, posted by SLS on November 18, 2022, at 18:22:19
>What kind of impairments? Are they exactly the >same regardless the antidepressant you take?
Basically, I always feel that I am on drugs. It feels like something is controlling my thinking and that I am being blocked off from myself.
For example, I don't get this on ritalin, but I do on bupropion. Even bupropion feels like its compartmentalizing my brain. It's like it is setting up these mental walls and I am only able to live within a certain portion of my brain.
My thoughts are automatically made positive. I am not able to 'see' or analyze a problem properly because it's like the circuitry involved in thinking about anything negative is being blocked off.
I tolerate lithium because it doesn't do this. I can still think deeply about an issue it's just that the intensity of the emotional reaction to a particular thought is lessened. Antidepressants don't reduce the intensity of the negative thoughts, they just prevent me from feeling them at all.
Linkadge
Posted by jay2112 on November 22, 2022, at 21:24:36
In reply to Re: Going with Venlafainxe + Bupropion » SLS, posted by linkadge on November 22, 2022, at 15:02:08
> >What kind of impairments? Are they exactly the >same regardless the antidepressant you take?
>
> Basically, I always feel that I am on drugs. It feels like something is controlling my thinking and that I am being blocked off from myself.
>
> For example, I don't get this on ritalin, but I do on bupropion. Even bupropion feels like its compartmentalizing my brain. It's like it is setting up these mental walls and I am only able to live within a certain portion of my brain.
>
> My thoughts are automatically made positive. I am not able to 'see' or analyze a problem properly because it's like the circuitry involved in thinking about anything negative is being blocked off.
>
> I tolerate lithium because it doesn't do this. I can still think deeply about an issue it's just that the intensity of the emotional reaction to a particular thought is lessened. Antidepressants don't reduce the intensity of the negative thoughts, they just prevent me from feeling them at all.
>
> Linkadge
>I think that, shall we say, 'numbness' is the norepinephrine down-regulation. In my studies in addiction, that is much of what seems to prevent relapse. In case studies, people describe very much of what you are feeling and thinking. It could also be dopamine down-regulation. I have found this feeling, in particular, with the SNRI's, and NDRI's, myself. It's most certainly *NOT* a feeling of 'relief', and that is why there is so much relapse.
Linkadge, there is that new a.d. out that combines bupropion and dextromethorphan. I *have* tried extended release dextromethorphan and low dose Cymbalta, with some quite robust results. Have you thought of combining the Wellbutrin with the dex?
Jay
Posted by linkadge on November 23, 2022, at 16:03:11
In reply to Re: Going with Venlafainxe + Bupropion » linkadge, posted by jay2112 on November 22, 2022, at 21:24:36
Where did you get extended released dextromethorphan?
Linkadge
Posted by NKP on December 16, 2022, at 2:17:52
In reply to Re: Going with Venlafainxe + Bupropion, posted by linkadge on November 23, 2022, at 16:03:11
My doctor decided to add 150 mg/day bupropion to the 225 mg/day venlafaxine, and 200 mg/day lamotrigine, that I am already taking. So far, it seems to be working well.
Posted by creepy on December 21, 2022, at 19:23:22
In reply to Going with Venlafainxe + Bupropion, posted by linkadge on November 16, 2022, at 14:20:43
I know everyone is different, but against all advice I tried venlafaxine and it was as awful as people said. I have never been so suicidal in my life, and have never had such a horrible time D/C'ing any medication. I literally had to count pellets out of the capsules to cease it without nausea and zaps.
I hope you do better on it than I did.
This is the end of the thread.
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