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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 25 of 26. This is the beginning of the thread.
Posted by banga on March 2, 2005, at 8:11:17
Can anyone clarify/affirm this? Sort of an obvious question, but the med interaction descriptions on rxlist.com and drugs.com in my mind were not completely clear in their wording:
IN the literature, it SEEMS that Luvox inhibits a particular enzyme, and increases the levels of Abilify; my guess is that they are assuming it does although they have no direct proof and that is why it is stated in an unclear manner?
And it is also inclear to me whether levels of Luvox are also then elevated in parallel to the Abilify (is there competition for this enzyme, or does Luvox simply and directly inhibit the enzyme? (CYP450?? Maybe it's my braing fog, but just could not understand the relationship between these drugs and enzymes)
And a related q. 2?: the lit also does say clearer that Luvox will raise desipramine levels; do then blood levels of Luvox also go up when taking desipramine?
Anyone have the patience to understand my question ? The short version is: what are the effects of taking desipramine, Luvox and Abilify together?
Posted by Bill LL on March 2, 2005, at 11:37:09
In reply to Drug interactions q., posted by banga on March 2, 2005, at 8:11:17
Sounds like this new guy is really on the ball. Good luck!
Posted by Larry Hoover on March 2, 2005, at 14:42:49
In reply to Drug interactions q., posted by banga on March 2, 2005, at 8:11:17
> Can anyone clarify/affirm this? Sort of an obvious question, but the med interaction descriptions on rxlist.com and drugs.com in my mind were not completely clear in their wording:
>
> IN the literature, it SEEMS that Luvox inhibits a particular enzyme, and increases the levels of Abilify; my guess is that they are assuming it does although they have no direct proof and that is why it is stated in an unclear manner?
>
> And it is also inclear to me whether levels of Luvox are also then elevated in parallel to the Abilify (is there competition for this enzyme, or does Luvox simply and directly inhibit the enzyme? (CYP450?? Maybe it's my braing fog, but just could not understand the relationship between these drugs and enzymes)
>
> And a related q. 2?: the lit also does say clearer that Luvox will raise desipramine levels; do then blood levels of Luvox also go up when taking desipramine?
>
> Anyone have the patience to understand my question ? The short version is: what are the effects of taking desipramine, Luvox and Abilify together?Sure. Lots of patience. All of the enzymes (number/letter/number) are members of the class of enzymes known as cytochrome P450 (CYP450) enzymes.
Fluvoxamine (Luvox) has three routes of metabolism (elimination), via enzymes 1A2, 2C9, and 2D6.
Desipramine uses 1A2 and 2D6.
Aripiprazozole (Abilify) uses 2D6 and 3A4.
You can see that all three are substrates for the 2D6 enzyme, so there will be direct competitive effects. Each will slow the other down in its use of 2D6, just like a line-up at a ticket window. You will also note, however, that each has alternate pathways to elimination, so the dependency on 2D6 is a little bit reduced. 2D6 also has an incredible broad range of functionality, based on genetic factors, so losing some 2D6 activity can be a big deal, or it could be trivial.
The other way drugs interact is by inhibition or induction. Fluvoxamine inhibits five different enzymes (1A2, 2C9, 2C19, 2D6, and 3A4), and desipramine inhibits 2D6. Abilify doesn't appear to inhibit or induce other enzymes.
It's safe to assume that all three drugs would have some mutual inhibition on their individual clearance rates, leading to higher than normal blood levels, for increased periods of time (i.e. lengthened half-lives). That is compensated for by titrating to lower therapeutic dose levels. Adding e.g. Abilify to an existing desipramine/fluvoxamine regimen might require slight dose reductions in the latter two, to avoid side effects (as an example). It's all about titrating to tolerable levels which are still efficacious. Taking maximum doses of any of them would not be a good idea, generally.
Lar
Posted by banga on March 2, 2005, at 15:35:37
In reply to Re: Drug interactions q. » banga, posted by Larry Hoover on March 2, 2005, at 14:42:49
Thank you Larry for laying it out so clearly!
I recently added 100 mg of Luvox to :
75 mg desipramine
5mg Abilify
30mg AdderallAnd within a day noticed orthostatic hypotension--knew the Luvox may be upping the desipramine; BUT also the next day felt very spacey and my tongue felt odd--sensations that I had had when I had once tried a higher Abilify dosage. So I suspected there must be an interaction RE Luvox and Abilify too. Thanks for the confirmation.
SO I am now going to try 2.5mg Abilify and 75mg desipramine and only 50mg Luvox--all three then will have lengthened half-lives. Figures the three drugs that seem logical for me should interact...
I wasnt sure if I can assume the Luvox itself will be raised in my system too...50mg is a pretty small dose, didn't know if I could even hope for benefit.Good news is that other than spaciness the combo seems to be doing good things!
Posted by Phillipa on March 2, 2005, at 16:51:05
In reply to Re: Drug interactions q. » Larry Hoover, posted by banga on March 2, 2005, at 15:35:37
Glad to hear that you're doing well. Luvox also raises the levels of xanax. Maybe the fact that luvox raises levels of so many other drugs is one of the reasons that Solvay stopped manufacturing it and it's so hard to get a pdoc to rx it. Fondly, Phillipa
Posted by ed_uk on March 4, 2005, at 7:57:53
In reply to Re: Drug interactions q. » Larry Hoover, posted by banga on March 2, 2005, at 15:35:37
Hi,
>SO I am now going to try 2.5mg Abilify and 75mg desipramine and only 50mg Luvox
Sounds like a good idea. Perhaps 50mg fluvoxamine will be enough.
Ed.
Posted by banga on March 4, 2005, at 8:53:20
In reply to Re: Drug interactions q. » banga, posted by ed_uk on March 4, 2005, at 7:57:53
Hi Ed!
It truly seems that the 50mg is just plenty. It was well worth it, it has helped with anxiety quite a bit. Possibly will even try and eliminate Abilify. With the long half-life, it quickly builds up in my system. If I feel a turn for the worse in dropping the Abilify, I will try 2.5mg every other day.I am sorry to hear you have not felt good. I hope your health is returning. .
Posted by ed_uk on March 4, 2005, at 9:12:37
In reply to Re: Drug interactions q., posted by banga on March 4, 2005, at 8:53:20
Hi banga!
Has the dizziness etc reduced?
>It truly seems that the 50mg is just plenty.
Low doses of SSRIs sometimes seem to work really well- with the advantage of milder side effects.
>Possibly will even try and eliminate Abilify.
Yes, I think that's a good idea. You could try taking it on alternate days for a couple of weeks and then quit altogether.
After you've been stabilised on fluvoxamine for a few weeks, perhaps you could consider increasing the desipramine and decreasing the Adderall. Just a suggestion, it might be more effective in the long run.
Ed.
Posted by Larry Hoover on March 4, 2005, at 10:21:40
In reply to Re: Drug interactions q. » Larry Hoover, posted by banga on March 2, 2005, at 15:35:37
> Thank you Larry for laying it out so clearly!
You're very welcome.
> I recently added 100 mg of Luvox to :
> 75 mg desipramine
> 5mg Abilify
> 30mg Adderall
>
> And within a day noticed orthostatic hypotension--knew the Luvox may be upping the desipramine; BUT also the next day felt very spacey and my tongue felt odd--sensations that I had had when I had once tried a higher Abilify dosage. So I suspected there must be an interaction RE Luvox and Abilify too. Thanks for the confirmation.
>
> SO I am now going to try 2.5mg Abilify and 75mg desipramine and only 50mg Luvox--all three then will have lengthened half-lives. Figures the three drugs that seem logical for me should interact...
> I wasnt sure if I can assume the Luvox itself will be raised in my system too...50mg is a pretty small dose, didn't know if I could even hope for benefit.
>
> Good news is that other than spaciness the combo seems to be doing good things!Now that you're feeling comfortable, I'm going to raise another factor that I purposely did not discuss before. One bit at a time.....
One of the other possible issues with respect to interactions at liver enzymes involves active metabolites. The way I described things up until now, I was only speaking in terms of the parent drug, which was assumed to be responsible for all effects. That is often not the case.
When a monotherapy comes to equilibrium in the body (generally after the passage of five half-life periods at a set dose), there is a balance of active parent to metabolite concentrations. If one (or more) of those metabolites exerts its own effects, then the ratio of active parent:active metabolite concentrations is part of the total drug effect.
Whenever a new substance/drug is introduced to a monotherapy system, and that substance affects enzyme activity, then the ratios of parent:metabolite are shifted as well. That can change the "balance" of effects, often increasing side-effects from the parent drug, or inhibiting beneficial effects of active metabolites (that would be the result of competition, or enzyme inhibition). Those relative effects are inverted if an enzyme is *induced* (up-regulated) by the new substance.
I just throw these ideas in for a more complete understanding of what may happen with combinations of drugs. In the end, it's only fair to say that an individual will likely have to experiment with doseages, to find the most comfortable new balance point.
Lar
Posted by banga on March 4, 2005, at 11:57:02
In reply to Re: Drug interactions q. » banga, posted by Larry Hoover on March 4, 2005, at 10:21:40
That is interesting....I of course also considered the effects on the liver (toxicity) in the long run. I do take various supplements and herbs, including milk thistle, and push myself to drink more water.
Posted by banga on March 4, 2005, at 12:04:23
In reply to Re: Drug interactions q. » banga, posted by ed_uk on March 4, 2005, at 9:12:37
The dizziness is better, as is the general spaciness I had yesterday. For the first time in who knows how long I felt almost giddy--but the spaciness made it feel a little like buzzed-giddy which I did not like. I skipped Abilify last night, I feel better physically today. I only have a bit of the (hypotension) dizziness when I first get up in the morning.
the Adderall I feel will need to at least be decreased--energy swings are not pleasant. But as I am out the door on a trip overseas, to work, this is not the time (and also having just changed other meds...)If someone was hoping for a good effect from Cymbalta but it did not work, I think a combination of desipramine and Luvox is an option.
Posted by ed_uk on March 4, 2005, at 15:02:52
In reply to Re: Drug interactions q. » ed_uk, posted by banga on March 4, 2005, at 12:04:23
Hi,
>I skipped Abilify last night, I feel better physically today.
Will you continue to take it on alternate days?
>But as I am out the door on a trip overseas, to work, this is not the time.
Legally, will it be ok for you to take Adderall abroad? As far as I know, amphetamines are prohibited in some countries, and are not available on prescription.
Ed.
Posted by banga on March 6, 2005, at 1:56:26
In reply to Re: Drug interactions q. » banga, posted by ed_uk on March 4, 2005, at 15:02:52
I am actually going to try it without Abilify for a bit. I already feel a difference in level of physical agitation. I just can feel that all the medxc interactions are making blood levels unpredicatble, if possuble I would happily increase the desipramine and Luvox instead.
Adderall and a problem with traveling? Oh well too late now!
This is so strange, I still have to remind myself to reflect and note how different I feel, so much less anxiety and less of the impulsive self-harm visions.
Posted by ed_uk on March 6, 2005, at 9:23:54
In reply to Re: Drug interactions q. » ed_uk, posted by banga on March 6, 2005, at 1:56:26
Hi B,
>I am actually going to try it without Abilify for a bit.
Best of luck, I don't think you really need it though because I think you'll be fine!
>I already feel a difference in level of physical agitation.
So you think the fluvoxamine is helping?
>I still have to remind myself to reflect and note how different I feel, so much less anxiety and less of the impulsive self-harm visions.
Perhaps you should keep a diary of your symptoms, and what meds (and doses) you are on.
>Adderall and a problem with traveling? Oh well too late now!
LOL, you're not in America anymore? What dose of Adderall are you on? Do you take the XR?
Ed.
Posted by banga on March 6, 2005, at 9:52:20
In reply to Re: Drug interactions q. » banga, posted by ed_uk on March 6, 2005, at 9:23:54
I am on 30mg Adderall...but I am trying to go down lower . I am not sure whether the Abilify was previously suppressing its action or what, but for the past two days I have felt jittery and I think my blood pressure may be up (feel my jugulars aching, hands shake, headache) could be also withdrawal from Abiify I suppose. So emotionally doing well, but probably the 30mg Adderall is suddenly way too much stimulation.
Posted by ed_uk on March 6, 2005, at 10:16:33
In reply to Re: Drug interactions q. » ed_uk, posted by banga on March 6, 2005, at 9:52:20
Hi B,
>30mg Adderall
Can you lower the dose? It depends what tablet strengths you have.
Low dose is good! It's cheaper and easier to get hold of. Hmmm.... Although with your current pdoc everything seems to be easy to get hold of!
Ed.
Posted by banga on March 6, 2005, at 10:23:16
In reply to Re: Drug interactions q. » banga, posted by ed_uk on March 6, 2005, at 10:16:33
LOL actually my pdoc was not able to get approval for the 2x day dosing of Adderall in time before I left anyway.
They are capsules, so I just have to start pouring some off daily.
What's a quick way to lower blood pressure? Would Benadryl do anything at all?
Posted by ed_uk on March 6, 2005, at 10:47:14
In reply to Re: Drug interactions q. » ed_uk, posted by banga on March 6, 2005, at 10:23:16
Hi B,
>What's a quick way to lower blood pressure? Would Benadryl do anything at all?
I honestly doubt that your BP is elevated very much. Hypertension is almost always asymptomatic unless the rise in BP is extremely fast and dramatic eg. MAOI-hypertensive crisis. It is extremely unlikely that your BP has risen this much. Small short-term rises in BP are not dangerous unless a person has severe underlying cardiovascular or cerebrovascular disease.
Your symptoms should improve quickly after reducing the dose of Adderall, if not, you could always take a dose of Abilify once every two days for the next few days. If you are worried, you could take a dose of Abilify right now!
I don't think Benadryl would do anything. Your current symptoms are probably just side effects of Adderall that were being 'masked' by Abilify. Alternatively, as you said, they could be withdrawal symptoms. If you are very worried you could go to see a doctor, I think you will be absolutely fine though so I don't think you need to.
>What's a quick way to lower blood pressure?
Probably to relax in a darkened room and listen to some soothing music :-?
Are you very worried?
Ed.
Posted by ed_uk on March 6, 2005, at 10:48:25
In reply to Re: Drug interactions q. » ed_uk, posted by banga on March 6, 2005, at 9:52:20
>hands shake, headache
These symptoms are common with Adderall even if your BP is fine.
Ed.
Posted by banga on March 6, 2005, at 10:59:17
In reply to Re: Drug interactions q., posted by ed_uk on March 6, 2005, at 10:48:25
HI Ed,
Thanks, I am not overly worried that my head will fall off or something, it is just uncomfortable and slight chest pains and aches by the jugular and wrists; pressure and ringing in ears (all of this mild, mind you). I dont feel panicky or anything of that nature, just feel my body is not happy and signals all is not well. To be perfectly honest I am visiting with my brother and sister-in-law and want to leave an impression that I feel on top of the world. Instead my hands shake and I worry they may think I am drinking again or something, and can't concentrate on my work. (which is why I am checking psychobabble every five minutes!!--cant work ) So actually technically I AM worried but not for fear of hypertensive crisis.
Posted by banga on March 6, 2005, at 11:15:52
In reply to Re: Drug interactions q. » ed_uk, posted by banga on March 6, 2005, at 10:59:17
And yes, I do know this is unreasonably neurotic of me to focus on what others think. Self-diagnosis and interpretation is my specialty. Actually CHANGING my cognitions and altering unhealthy attitudes is another story. I almost have it going with the meds, I will now be able to start changing how I think.....
Posted by ed_uk on March 6, 2005, at 11:21:55
In reply to Re: Drug interactions q. » ed_uk, posted by banga on March 6, 2005, at 10:59:17
Hi,
>it is just uncomfortable and slight chest pains and aches by the jugular and wrists; pressure and ringing in ears (all of this mild, mind you).
Hmm, maybe your BP is up. I think it would be best if you took an Abilify now and reduced your dose of Adderall tomorrow. Will you try that?
Ed.
Posted by banga on March 6, 2005, at 11:27:50
In reply to Re: Drug interactions q. » banga, posted by ed_uk on March 6, 2005, at 11:21:55
The thing is is that I felt fine when I first woke up, this developed about an hour after I took Adderall--so I actually doubt it is the Abilify. And it is better than say an hour ago. If it were getting worse and worse, then I would start worrying.
Posted by ed_uk on March 6, 2005, at 11:43:11
In reply to Re: Drug interactions q., posted by banga on March 6, 2005, at 11:27:50
Hi B,
>I actually doubt it is the Abilify.
I just thought that the Abilify might have been reducing the sympathomimetic side effects of the Adderall. I though it might be best to reduce them once again (by taking an Abilify) until you can reduce the Adderall tomorrow. I don't think you're having withdrawal symtoms. Dexedrine appears to be less sympathomimetic than Adderall so it is probably safer for your cardiovascualar system.
>And it is better than say an hour ago. If it were getting worse and worse, then I would start worrying.
Chances are, you'll be absolutely fine. If symptoms get worse, you know where to go- I sincerely doubt that it will come to that though. If your symptoms are getting better the Adderall is probably wearing off already. Don't take too much Adderall tomorrow.
OMG, it's 5.40 and I haven't even done ANY work today! I'm so lazy and I'm an internet junkie! I just burnt my cheese on toast because I left it cooking and forgot about it- so typical of me. I'm a disaster in practicals at university. At school, I once left some oil boiling in cookery and accidently set a wall display on fire.
Ed.
Posted by Phillipa on March 6, 2005, at 16:17:21
In reply to Re: Drug interactions q., posted by ed_uk on March 6, 2005, at 11:43:11
Hi Ed! You're not lazy, you're just doing what you like to do helping others. You'll get around to your studies. Fondly, Phillipa O
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