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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 18 of 18. This is the beginning of the thread.
Posted by Meagan on October 9, 2007, at 10:05:21
I know there is a lot of history on this site about a selegiline/prozac combo, but I don't think I've had the answer I'm looking for.
I'm taking 40 mg prozac, and my pdoc has pushed me up to 15 mg of selegiline, which seems to be helping, but I'm not out of the woods yet. I'd like to push my selegiline dose up even higher to prevent depression relapse.
Of course, at higher doses than 10 mg, I've read that selegiline may act on the same MAO (A?) that prozac does; my question is: despite the risk of serotonin syndrome, isn't it possible that having both drugs work on the same MAO will be helpful in my fight against depression?
Along with the selegiline I'm also taking 1500 mg tryptophan (which my pdoc prescribed); the idea being to push up my serotonin levels since the prozac "pooped out" on me.
I'd be grateful for a response from anybody who has any theories on this question.
Posted by Phillipa on October 9, 2007, at 12:47:05
In reply to Please help w new ? about selegiline prozac combo, posted by Meagan on October 9, 2007, at 10:05:21
So if prozac pooped out doesn't he want to try another or just a boost what about lamictal? Phillipa
Posted by d0pamine on October 9, 2007, at 19:51:12
In reply to Please help w new ? about selegiline prozac combo, posted by Meagan on October 9, 2007, at 10:05:21
I'd be VERY careful about combining selegiline and prozac. High serotonin levels are hard on all of your organs, but particularly your heart. It is entirely possible to use this combo to increase serotonin levels to the point that they don't cause the dreaded serotonin syndrome, but are still slowly and silently damaging your heart valves. Once you inhibit both of the body's mechanisms of reducing serotonin levels, you're truly taking things into your own hands, which I feel is a risky place to be. There is a reason that there are redundant mechanisms for handling excess serotonin. See the old phen-fen story for the outcome of sub-serotonin syndrome hyper-serotonin levels. Be safe.
Posted by amigan on October 10, 2007, at 8:34:29
In reply to Re: Please help w new ? about selegiline prozac co, posted by d0pamine on October 9, 2007, at 19:51:12
I agree with what d0pamine said.
selegiline+fluoxetine+tryptophan = A dangerous combination.
Posted by Jimmyboy on October 10, 2007, at 9:41:41
In reply to Re: Please help w new ? about selegiline prozac co, posted by amigan on October 10, 2007, at 8:34:29
I don't understand why prozac and low dose selegiline would be so dangerous, because the selegiline is mainly just raising dopamine by inhibiting MAO-B at that dosage, its not really affecting seratonin...
JB
Posted by Meagan on October 10, 2007, at 11:39:46
In reply to Re: Please help w new ? about selegiline prozac co, posted by Jimmyboy on October 10, 2007, at 9:41:41
Jimmyboy, That's what I thought too, and I don't think that D0pomine necessarily implied that the combo was dangerous at low levels (right D0pamine?), just that when it was taken at a higher dose, it would be acting on the same MAO as prozac, and that would be bad for heart valves.
> I don't understand why prozac and low dose selegiline would be so dangerous, because the selegiline is mainly just raising dopamine by inhibiting MAO-B at that dosage, its not really affecting seratonin...
>
> JB
Posted by Meagan on October 10, 2007, at 11:40:01
In reply to Re: Please help w new ? about selegiline prozac co, posted by Jimmyboy on October 10, 2007, at 9:41:41
Jimmyboy, That's what I thought too, and I don't think that D0pomine necessarily implied that the combo was dangerous at low levels (right D0pamine?), just that when it was taken at a higher dose, it would be acting on the same MAO as prozac, and that would be bad for heart valves.
> I don't understand why prozac and low dose selegiline would be so dangerous, because the selegiline is mainly just raising dopamine by inhibiting MAO-B at that dosage, its not really affecting seratonin...
>
> JB
Posted by Meagan on October 10, 2007, at 11:46:46
In reply to Re: Please help w new ? about selegiline prozac co, posted by d0pamine on October 9, 2007, at 19:51:12
Thank you very much Dopamine. I see my pdoc this Saturday and will speak with him about it. You are very knowledgeable; are you a pharmacologist?
Presently I'm taking 15 mg (slowly raising dose from 5, 10 to 15 selegiline), 40 mgs prozac, and 1500 mgs tryptophan - this combo has been very effective and has lifted me out of my treatment resistant depression, but I sure do not want heart damage. The risk/benefit of all these drugs is a constant challenge.
Meagan
> I'd be VERY careful about combining selegiline and prozac. High serotonin levels are hard on all of your organs, but particularly your heart. It is entirely possible to use this combo to increase serotonin levels to the point that they don't cause the dreaded serotonin syndrome, but are still slowly and silently damaging your heart valves. Once you inhibit both of the body's mechanisms of reducing serotonin levels, you're truly taking things into your own hands, which I feel is a risky place to be. There is a reason that there are redundant mechanisms for handling excess serotonin. See the old phen-fen story for the outcome of sub-serotonin syndrome hyper-serotonin levels. Be safe.
Posted by Meagan on October 10, 2007, at 11:53:40
In reply to Re: Please help w new ? about selegiline prozac co, posted by amigan on October 10, 2007, at 8:34:29
Amigan,
Why do you agree? Have you had personal experience, or are you well-versed in the subject area? Do you think the combo is dangerous at any level? 15 mg of the selegiline seemed to boost me out of the depression - what drug do you suggest I drop, if you feel the combo is dangerous?
> I agree with what d0pamine said.
> selegiline+fluoxetine+tryptophan = A dangerous combination.
>
Posted by amigan on October 11, 2007, at 16:06:58
In reply to Re: Please help w new ? about selegiline prozac co, posted by Meagan on October 10, 2007, at 11:53:40
Ok, if you're trying to say that i shouldn't speak without having personal experience or being well versed, you have a point.
I have only tried fluoxetine and tryptophan.
I do know though that:
- The combination of SSRI+MAOI is considered a no-no by some doctors.
- Selegiline at more than 10mg, starts to lose its selectivity and thus becomes potentionally dangerous.
- 40mg of fluoxetine is double the usual, suggested dosage.Since you asked, i would reduce selegiline at 10mg or less, daily.
Bottom line: If it works well for you, it works well! Who am i to argue.
Posted by Larry Hoover on October 11, 2007, at 20:27:04
In reply to Please help w new ? about selegiline prozac combo, posted by Meagan on October 9, 2007, at 10:05:21
> Of course, at higher doses than 10 mg, I've read that selegiline may act on the same MAO (A?) that prozac does; my question is: despite the risk of serotonin syndrome, isn't it possible that having both drugs work on the same MAO will be helpful in my fight against depression?
I'm confused by this comment. Fluoxetine has no MAOI activity that I ever recall hearing about. As you increase the dose of selegeline, there is more inhibition of serotonin breakdown. Maybe that's what you're thinking of, as fluoxetine is a serotonin-reuptake inhibitor.
In my opinion, you've pushed the envelope much further than I ever would consider. On a risk-benefit analyis, your lack of response so far does not justify the increased risk you would take by increasing selegeline dose. I'm glad you're under medical supervision, but I also suggest that you learn all you can about the symptoms of serotonin syndrome. Just because you haven't had it yet doesn't mean you won't develop it, even without increasing anything further.
Lar
Posted by Meagan on October 12, 2007, at 13:18:34
In reply to Re: Please help w new ? about selegiline prozac co, posted by amigan on October 11, 2007, at 16:06:58
Posted by Meagan on October 12, 2007, at 13:30:27
In reply to Re: Please help w new ? about selegiline prozac co, posted by amigan on October 11, 2007, at 16:06:58
Sorry, previous message didn't get through. I am grateful you responded, and I in no way meant to imply (nor did I think) "experience" was a prequalifier to responding.
Your response, and those of others on this board, are invaluable to me; you pose questions that I need to raise with my doctor, (especially since he is not so forthcoming about the risks). I certainly don't want to worry about a "sub" serotonin syndrome with the combo I'm on, where I could potentially suffer heart valve damage without knowing about it! Ultimately, it is the patient who needs to make a determination of the risk/benefit ratio to them, based on full and accurate information.
BTW, I was on prozac and tryptophan too, unfortunately didn't work for me.
Meagan
Posted by Meagan on October 12, 2007, at 14:24:00
In reply to Re: Please help w new ? about selegiline prozac combo » Meagan, posted by Larry Hoover on October 11, 2007, at 20:27:04
Thank you Lar, I did indeed mean that selegiline at higher doses would inhibit serotonin breakdown, similar to prozac.
BTW, did you read Dopamine's comments about "sub" serotonin syndrome and possible "silent" heart valve disease with the combo I'm taking? What do you think? I have read the articles on Phen-Fen, but is it too simplistic to equate what happened to patients on Phen-Fen with the combo I am presently taking?
I'm seeing my pdoc in NYC tomorrow and the risk/benefit issue you bring up is precisely what I attend to bring up with him. Thanks
Meagan
>
> I'm confused by this comment. Fluoxetine has no MAOI activity that I ever recall hearing about. As you increase the dose of selegeline, there is more inhibition of serotonin breakdown. Maybe that's what you're thinking of, as fluoxetine is a serotonin-reuptake inhibitor.
>
> In my opinion, you've pushed the envelope much further than I ever would consider. On a risk-benefit analyis, your lack of response so far does not justify the increased risk you would take by increasing selegeline dose. I'm glad you're under medical supervision, but I also suggest that you learn all you can about the symptoms of serotonin syndrome. Just because you haven't had it yet doesn't mean you won't develop it, even without increasing anything further.
>
> Lar
>
Posted by Pitviper on October 16, 2007, at 3:05:27
In reply to Re: Please help w new ? about selegiline prozac combo » Larry Hoover, posted by Meagan on October 12, 2007, at 14:24:00
Hi Meagan. I'm assuming you're using the pill form of selegiline, and not the patch (since the patch is in 6 mg increments).
> Thank you Lar, I did indeed mean that selegiline at higher doses would inhibit serotonin breakdown, similar to prozac.
Selegiline and Prozac don't have the same mechanism of action at any dose.
Monoamine oxidase (MAO) is an enzyme that catalyzes the breakdown, as you say, of serotonin and other monoamines (norepinephrine, dopamine). So MAO inhibitors will prevent these monoamines from being broken down, increasing the concentration of extracellular monoamines.
*Reuptake* inhibition is entirely different. A serotonin reuptake inhibitor, like Prozac, prevents stray serotonin molecules from being sucked back into cells, again increasing the amount available extracellularly.
It's the combination of the two different mechanisms that leads to the serotonin syndrome when MAOIs are combined with SRIs (not just the SSRIs, but drugs like Effexor and Cymbalta, certain tricyclics (clomipramine, imipramine, amitriptyline, and doxepin are contraindicated with MAOIs, while desipramine, nortriptyline, and amoxapine present minimal risk, if any). You are right that selegiline is a selective inhibitor of MAO-B at low doses but loses its selectivity at higher doses. 20 mg (orally) is a bit on the low side for depression, actually. For Parkinson's the recommended dose
I tried selegiline a while ago, at 40 mg/day, without success (had better luck with Parnate). However, even this dose may actually have been too low.
Fenfluramine is neither a MAOI nor an SRI. The way it works is analogous to amphetamine, only fenfluramine causes serotonin to be released rather than dopamine. This leads to subsequent depletion of serotonin (also not an issue with Prozac). Another drug that works this way is MDMA, the street drug Ecstasy.
(Phentermine, incidentally, is a mild stimulant, akin to amphetamine, but considered to have less abuse potential. "Fen/phen" (or should it be "phen/fen?") was a protocol using phentermine and fenfluramine in combination for weight loss, usually with phentermine taken in the morning and fenfluramine at bedtime. Fenfluramine, not phentermine, was the cause of the heart valve defects and PPH, which caused it to be taken off the market. Phentermine is still available in the U.S.)
I do not think that heart valve damage is a realistic concern with your combination. Prozac does not cause the type of problems that you get with fenfluramine, and neither do MAOIs.
The serotonin syndrome is what you have to watch out for. You should familiarize yourself with the symptoms so you can be on the lookout for them. There have been at least a couple of reports of serotonin syndrome when nonselective MAOIs were combined with L-tryptophan.
But actually, I think your doctor's idea of taking you off the Prozac makes sense. It seems to me, from what you've said, that the Prozac isn't making much of a contribution. Eliminating the Prozac would make it safer to try higher, nonselective doses of selegiline. I doubt that you will have a problem with 20 mg but of course you should keep your eyes open, of course.
If selegiline by itself should prove inadequate, there are antidepressants that you can take safely in combination with MAOIs.
However, I think your doc's claim about chronically depressed people having "too much MAO" is mistaken. I'm not sure where he would get this idea. He may be oversimplifying, as many doctors do, believing they are doing their patients a favor; you did mention he hasn't been very informative. There are no known consistent lab findings in depressed individuals, and while some may have elevated MAO, it's certainly not universal.
> is it too simplistic to equate what happened to patients on Phen-Fen with the combo I am presently taking?
Exactly right.
Good luck to you.
Pitviper
Posted by Pitviper on October 16, 2007, at 5:14:46
In reply to Re: Please help w new ? about selegiline prozac co, posted by amigan on October 11, 2007, at 16:06:58
> - The combination of SSRI+MAOI is considered a no-no by some doctors.
This is true of the traditional nonselective MAOIs -- Nardil, Parnate, Marplan, etc. I can't imagine any situation that would justify the very serious danger of prescribing these with Prozac or another SSRI. Selegiline, in the low dose Meagan is taking, is another story.
> - Selegiline at more than 10mg, starts to lose its selectivity and thus becomes potentionally dangerous.
The key word is "starts," and I'm not even certain that's true, although 10 mg is the typical dose used in Parkinson's disease. The doses of oral selegiline typically required to treat depression effectively are quite a bit higher. I doubt Meagan will have a problem in the 15-20 mg range, particularly if she tapers the Prozac, although careful monitoring is of course essential.
> - 40mg of fluoxetine is double the usual, suggested dosage.
No...the usual recommended *starting* dose is 20 mg (although a lot of people may need to start lower because of side effects such as agitation and increased anxiety, especially those with panic disorder). The recommended *maximum* dose is 80 mg.
And of course, we're all individuals with different needs. Some people might do great on 20 mg, or even 10, while others might need 80. But anyway, there is no such thing as "one size fits all" when it comes to the human brain. (Although there is no established therapeutic serum level for fluoxetine, it is possible that differences in metabolism also contribute to variation in dose requirements.) When deciding what is the right dose for an individual, it's more important to look at what works for that person than to rely on claims based on statistics.
I know of at least one drug monograph in the PDR (Ambien) that actually does essentially claim there is only one "right" dose for adult patients (it allows for a half dose for elderly patients). This betrays a misunderstanding of what statistics do and don't tell us. I've known several people who did not benefit from the standard 10 mg of Ambien but did well on 15-20 mg.
> Since you asked, i would reduce selegiline at 10mg or less, daily.
I think ditching the Prozac and going all-out with the selegiline (or perhaps switching to the transdermal patch) sounds like a better idea. It doesn't sound like she's getting much out of the Prozac.
Pitviper
Posted by Meagan on October 16, 2007, at 9:13:14
In reply to Re: Please help w new ? about selegiline prozac co » Meagan, posted by Pitviper on October 16, 2007, at 3:05:27
Thank you Pitviper for your very enlightened and informative discussion of the distinctions that can be made between other meds and the particular combo I am on. And yes, I'm glad my pdoc is lowering my dose of prozac.
The one interesting development is that when I tried to renew my prescription for Selegiline in this part of NY most pharmacies are out of it and their suppliers can't get it because the manufacturer has not made enough.
Meagan
> Hi Meagan. I'm assuming you're using the pill form of selegiline, and not the patch (since the patch is in 6 mg increments).
>
> > Thank you Lar, I did indeed mean that selegiline at higher doses would inhibit serotonin breakdown, similar to prozac.
>
> Selegiline and Prozac don't have the same mechanism of action at any dose.
>
> Monoamine oxidase (MAO) is an enzyme that catalyzes the breakdown, as you say, of serotonin and other monoamines (norepinephrine, dopamine). So MAO inhibitors will prevent these monoamines from being broken down, increasing the concentration of extracellular monoamines.
>
> *Reuptake* inhibition is entirely different. A serotonin reuptake inhibitor, like Prozac, prevents stray serotonin molecules from being sucked back into cells, again increasing the amount available extracellularly.
>
> It's the combination of the two different mechanisms that leads to the serotonin syndrome when MAOIs are combined with SRIs (not just the SSRIs, but drugs like Effexor and Cymbalta, certain tricyclics (clomipramine, imipramine, amitriptyline, and doxepin are contraindicated with MAOIs, while desipramine, nortriptyline, and amoxapine present minimal risk, if any). You are right that selegiline is a selective inhibitor of MAO-B at low doses but loses its selectivity at higher doses. 20 mg (orally) is a bit on the low side for depression, actually. For Parkinson's the recommended dose
>
> I tried selegiline a while ago, at 40 mg/day, without success (had better luck with Parnate). However, even this dose may actually have been too low.
>
> Fenfluramine is neither a MAOI nor an SRI. The way it works is analogous to amphetamine, only fenfluramine causes serotonin to be released rather than dopamine. This leads to subsequent depletion of serotonin (also not an issue with Prozac). Another drug that works this way is MDMA, the street drug Ecstasy.
>
> (Phentermine, incidentally, is a mild stimulant, akin to amphetamine, but considered to have less abuse potential. "Fen/phen" (or should it be "phen/fen?") was a protocol using phentermine and fenfluramine in combination for weight loss, usually with phentermine taken in the morning and fenfluramine at bedtime. Fenfluramine, not phentermine, was the cause of the heart valve defects and PPH, which caused it to be taken off the market. Phentermine is still available in the U.S.)
>
> I do not think that heart valve damage is a realistic concern with your combination. Prozac does not cause the type of problems that you get with fenfluramine, and neither do MAOIs.
>
> The serotonin syndrome is what you have to watch out for. You should familiarize yourself with the symptoms so you can be on the lookout for them. There have been at least a couple of reports of serotonin syndrome when nonselective MAOIs were combined with L-tryptophan.
>
> But actually, I think your doctor's idea of taking you off the Prozac makes sense. It seems to me, from what you've said, that the Prozac isn't making much of a contribution. Eliminating the Prozac would make it safer to try higher, nonselective doses of selegiline. I doubt that you will have a problem with 20 mg but of course you should keep your eyes open, of course.
>
> If selegiline by itself should prove inadequate, there are antidepressants that you can take safely in combination with MAOIs.
>
> However, I think your doc's claim about chronically depressed people having "too much MAO" is mistaken. I'm not sure where he would get this idea. He may be oversimplifying, as many doctors do, believing they are doing their patients a favor; you did mention he hasn't been very informative. There are no known consistent lab findings in depressed individuals, and while some may have elevated MAO, it's certainly not universal.
>
> > is it too simplistic to equate what happened to patients on Phen-Fen with the combo I am presently taking?
>
> Exactly right.
>
> Good luck to you.
>
> Pitviper
Posted by Meagan on October 16, 2007, at 9:21:07
In reply to Re: Please help w new ? about selegiline prozac co » Meagan, posted by Pitviper on October 16, 2007, at 3:05:27
Pitviper,
You seem so knowledgeable in this area; so naturally I'm curious about your background, if you care to share.
Meagan
This is the end of the thread.
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