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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 10 to 34 of 49. Go back in thread:
Posted by ed_uk2010 on April 25, 2010, at 7:48:25
In reply to Re: Multiple drug exposures and treatment resistence » bulldog2, posted by Phillipa on April 24, 2010, at 20:25:06
> What about if you have an autoimmune disease? The body attacks itself and resistance is down? Phillipa
Hi Phillipa,
I don't think Scott has an autoimmune disease. I've not heard him mention any major medical problems apart from bipolar depression.
xx
Posted by Zyprexa on April 25, 2010, at 16:47:44
In reply to Multiple drug exposures and treatment resistence, posted by SLS on April 24, 2010, at 11:53:56
This is why I think that a med trial sould usualy be short.
Posted by linkadge on April 25, 2010, at 19:24:14
In reply to Re: Multiple drug exposures and treatment resistence, posted by Zyprexa on April 25, 2010, at 16:47:44
Perhaps I am missing something but people havn't mentined the obvious question:
Does multiple drug exposures lead to treatment resistance or does treatment resistance lead to multiple drug exposures?
Linkadge
Posted by SLS on April 25, 2010, at 19:39:48
In reply to Re: Chicken or the egg here folks?, posted by linkadge on April 25, 2010, at 19:24:14
Which would you place your bet on?
- Scott
Posted by SLS on April 25, 2010, at 19:59:05
In reply to Re: Chicken or the egg here folks?, posted by linkadge on April 25, 2010, at 19:24:14
> Perhaps I am missing something but people havn't mentined the obvious question:
>
> Does multiple drug exposures lead to treatment resistance or does treatment resistance lead to multiple drug exposures?
I'm betting that both scenarios occur with great frequency.
- Scott
Posted by Phillipa on April 25, 2010, at 20:26:22
In reply to Re: Multiple drug exposures and treatment resistence » Phillipa, posted by ed_uk2010 on April 25, 2010, at 7:48:25
Ed sorry wasn't referring to Scott. I guess I hyjacked sorry about that. Love PJxx
Posted by linkadge on April 25, 2010, at 20:53:31
In reply to Re: Multiple drug exposures and treatment resistence » ed_uk2010, posted by Phillipa on April 25, 2010, at 20:26:22
I dunno.
Which scenario is easier to prove?
The forward direction is easy to see:
Logically, a patient who has inherently treatment resistant depression (to start with) will fail many antidepressant trials.
Proving the converse, that infact multiple antidepressant exposure *produces* treatment resistance requires comprehesive analysis. The study only notes a correlation.
In order to prove this assertion you would need to find a group of patients who:
a) had sucessful initial trials with tidepressants
b) didn't come off this antidepressant because of poop out
c) retried other antidepressants in a similar fashon
d) only later became treatment resistant
Failing any of these, you introduce other possibilities. For instance, if the patient comes off the antidepressant because its not working anymore, then logically they are starting to show signs of resistance even before a subsequent agent is introduced.
Of course it has been a theory that those who keep coming on and off antidepressants fair more poorly, but I would argue the other way around. That people come off the drugs because they're not doing a heck of a lot of good for them.
Linkadge
Posted by linkadge on April 25, 2010, at 20:57:26
In reply to Re: Multiple drug exposures and treatment resistence » ed_uk2010, posted by Phillipa on April 25, 2010, at 20:26:22
Basically you're damned if you do and damned if you don't. Take the drugs, they don't work, come off them...and the doctors have something to blame your treatment resistance on.
In the end, I think it just gives doctors a more positive way to frame things i.e. its patient noncompliance that causes treatment resistance not the fact that the drugs suck.
Linkadge
Posted by SLS on April 25, 2010, at 21:32:51
In reply to Re: Multiple drug exposures and treatment resistence, posted by linkadge on April 25, 2010, at 20:53:31
These are some pretty smart folks. It is probably important to ascertain what is meant by "gradual and stepwise tachyphylaxis" in order to get an idea as to what they were recording and measuring. They were not counting only previous drug failures, but previous successes as well.
- Scott
Posted by SLS on April 25, 2010, at 21:51:02
In reply to Re: Multiple drug exposures and treatment resistence, posted by SLS on April 25, 2010, at 21:32:51
> They were not counting only previous drug failures, but previous successes as well.
I am wrong. They restricted their measurements of previous drug exposure to the current depressive episode.
- Scott
Posted by SLS on April 25, 2010, at 22:13:41
In reply to Re: Multiple drug exposures and treatment resistence, posted by SLS on April 25, 2010, at 21:51:02
"Logistic regression analysis found that an increasing number of prior antidepressant drug exposures was significantly associated with a poorer response to initial sertraline therapy, with a 19.9% lower likelihood of response with each prior antidepressant exposure (odds ratio = 0.81, p = 0.0035)."
The interpretation of these results requires a bit of thought and an understanding of statistics that I sorely lack. The logic here might be counterintuitive.
- Scott
Posted by conundrum on April 26, 2010, at 7:13:21
In reply to Re: Multiple drug exposures and treatment resistence, posted by linkadge on April 25, 2010, at 20:53:31
> a) had sucessful initial trials with tidepressants
>
> b) didn't come off this antidepressant because of poop out
>
> c) retried other antidepressants in a similar fashon
>
> d) only later became treatment resistant
>
Guess thats me, the real reason I stopped prozac was that I didn't bother to get my script refilled and thought maybe I didn't need it anymore. Now I seem to be treatment resistant although I don't know how many drugs you have to fail to be declared treatment resistant.
Posted by SLS on April 26, 2010, at 7:55:05
In reply to Re: Multiple drug exposures and treatment resistence » linkadge, posted by conundrum on April 26, 2010, at 7:13:21
> Guess thats me, the real reason I stopped prozac was that I didn't bother to get my script refilled and thought maybe I didn't need it anymore. Now I seem to be treatment resistant although I don't know how many drugs you have to fail to be declared treatment resistant.
That you have become resistant to the drug that you responded to previously gives evidence that something in the brain has changed since your initial exposure. It may be that physiological adaptations to the drug have occurred as a result of your exposure to it. We know that exposure to these drugs leads to changes in receptor sensitivities. Perhaps such changes in dynamics persist after drug discontinuation. I guess it is also possible that this treatment resistance would have occurred anyway as a result of the natural course of the illness. However, my own experience leads me to believe that drug exposure can indeed produce changes in therapeutic responsitivity. I became unresponsive to Nardil within two weeks of its being discontinued and subsequently restarted. Pulsing of antidepressants is probably a bad idea for some people.
- Scott
Posted by conundrum on April 26, 2010, at 11:16:14
In reply to Re: Multiple drug exposures and treatment resistence » conundrum, posted by SLS on April 26, 2010, at 7:55:05
Great...
Posted by bulldog2 on April 26, 2010, at 12:37:26
In reply to Multiple drug exposures and treatment resistence, posted by SLS on April 24, 2010, at 11:53:56
> Yeah. No kidding...
>
> If you are severely ill, what choice do you have?
>
> I had a doctor tell me that I should remain as clean as possible between trials of newly available medications. He was right. The brain must surely change in response to drug exposure. If it didn't, there would be no such thing as an antidepressant response or the phenomenon of poop-out. Why am I no longer responsive to the same treatment I had success with previously? Something must be different.
>
>
> - Scott
>
>
> -------------------------------------------------
>
>
> Neuropsychobiology. 2009;59(4):227-33. Epub 2009 Jul 2.
>
> Tachyphylaxis after repeated antidepressant drug exposure in patients with recurrent major depressive disorder.
>
> Amsterdam JD, Williams D, Michelson D, Adler LA, Dunner DL, Nierenberg AA, Reimherr FW, Schatzberg AF.
>
> Depression Research Unit, Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-3309, USA. jamsterd@mail.med.upenn.edu
> Abstract
>
> OBJECTIVE: The aim of this post hoc analysis was to examine whether tachyphylaxis occurs after repeated courses of antidepressant drug therapy. METHOD: 276 patients with major depressive disorder (MDD) were treated with sertraline (150-200 mg daily) for 8 weeks. Patients with persistent MDD after sertraline therapy were randomized to continuation therapy with either sertraline plus atomoxetine (n = 72) or sertraline plus placebo (n = 74) for 8 additional weeks. Logistic regression was used to test the hypothesis that an increase in prior antidepressant drug exposure is associated with a reduced responsiveness to sertraline therapy. RESULTS: The number of prior antidepressant drug exposures was negatively associated with response to initial sertraline therapy (odds ratio = 0.81, p = 0.0035). The odds ratio indicates a 19.9% reduced likelihood of response with each prior antidepressant treatment trial. In contrast, the number of prior antidepressant treatment trials was not associated with response to continuation sertraline plus atomoxetine or sertraline plus placebo therapy. CONCLUSION: This observation supports the hypothesis that tachyphylaxis may develop after repeated antidepressant drug trials. Copyright 2009 S. Karger AG, Basel.
>
> PMID: 19571597 [PubMed - indexed for MEDLINE]I wonder if you would do the best going back in time to the oldest medication that worked for you. For instance if imipramine was the first ad that worked for you give it another whirl. So work it from oldest to newest if you do retrys. Just a thought.
Posted by conundrum on April 26, 2010, at 14:15:59
In reply to Re: Multiple drug exposures and treatment resistence, posted by bulldog2 on April 26, 2010, at 12:37:26
Hmm, I don't know. I recently found that 2.5 mg prozac gave me some motivation. However it did also give me headaches and diarrhea that I didnt' get the first time. I increased to 5 mg and felt even more blunted. I doubt that going back to the original 20mg.
Also, I don't think the response at 2.5 was adaquate on its own.
Even when it was working I was getting weird pressure headaches in the front of my head, like a sinus headache. My liver functions were also all elevated.
I think overtime the drugs also have greater effects than at their primary receptors and when you go back on the drug that doesn't happen right away. Like prozac has some NRI potency, but I bet after 4 years its a way more potent NRI than after a couple months, especially since the drug inhibits liver enzymes that break it down so it builds up in your blood.
Posted by SLS on April 26, 2010, at 14:46:46
In reply to Re: Multiple drug exposures and treatment resistence » bulldog2, posted by conundrum on April 26, 2010, at 14:15:59
> Hmm, I don't know. I recently found that 2.5 mg prozac gave me some motivation. However it did also give me headaches and diarrhea that I didnt' get the first time. I increased to 5 mg and felt even more blunted. I doubt that going back to the original 20mg.
>
> Also, I don't think the response at 2.5 was adaquate on its own.
>
> Even when it was working I was getting weird pressure headaches in the front of my head, like a sinus headache. My liver functions were also all elevated.
>
> I think overtime the drugs also have greater effects than at their primary receptors and when you go back on the drug that doesn't happen right away. Like prozac has some NRI potency, but I bet after 4 years its a way more potent NRI than after a couple months, especially since the drug inhibits liver enzymes that break it down so it builds up in your blood.
Maybe there is a sensitization process occurring.
- Scott
Posted by Phillipa on April 26, 2010, at 20:28:42
In reply to Re: Multiple drug exposures and treatment resistence, posted by SLS on April 26, 2010, at 14:46:46
Is it really any different from alchohol tolerance, or motrin won't relieve headaches anymore, coffee more and then withdrawal. I feel the aging process changes most if not all of us as homones change. Or bones change, organs age, the heart ages, the brain ages. Phillipa
Posted by conundrum on April 26, 2010, at 20:41:36
In reply to Re: Multiple drug exposures and treatment resistence, posted by Phillipa on April 26, 2010, at 20:28:42
I think most of those tolerances disappear over time. I still can't tolerate SSRIs, its almost more like a negative reaction to them, not just that they don't work.
I also think that having a drug in your body 24hrs a day, everyday, for years produces changes in your body that drugs like motrin, caffeine, and alcohol can't produce since they clear out when you stop using them.
Posted by Bob on April 26, 2010, at 20:44:19
In reply to Re: Multiple drug exposures and treatment resistence » Phillipa, posted by conundrum on April 26, 2010, at 20:41:36
> I think most of those tolerances disappear over time. I still can't tolerate SSRIs, its almost more like a negative reaction to them, not just that they don't work.
>
> I also think that having a drug in your body 24hrs a day, everyday, for years produces changes in your body that drugs like motrin, caffeine, and alcohol can't produce since they clear out when you stop using them.My experience with SSRIs is similar in that I can hardly tolerate them any longer.
Posted by conundrum on April 26, 2010, at 20:51:03
In reply to Re: Multiple drug exposures and treatment resistence, posted by Bob on April 26, 2010, at 20:44:19
From a somewhat neutral standpoint. Not moping and feeling sorry for myself, but I think its amazing that the brain can do that. Its obviously rejecting the drug or at least it feels that way. Perhaps the body learns to decrease the effects of the drug over time but when its reintroduced it doesn't know how and for some reason the brain gets overwhelmed. I say all us SSRI users here donate our organs to science to find out what changes occurred from SSRI use after we die.
Bob have you found other drugs that were tolerable and helpful?
Posted by Phillipa on April 26, 2010, at 21:35:00
In reply to Re: Multiple drug exposures and treatment resistence » Bob, posted by conundrum on April 26, 2010, at 20:51:03
That reminds me of the autoimmune system. Rejects foreign invaders. Phillipa
Posted by desolationrower on April 27, 2010, at 0:23:37
In reply to Re: Multiple drug exposures and treatment resistence, posted by Bob on April 26, 2010, at 20:44:19
I don't know how to write math symbols on this board.
I mean that as the number of trials increases, the placebo effect asymptotically approaches zero.
also, separate issue, I think there is just a distribution of p eople.
on the lucky end, people resonsive to just about anything.
some resond to anything serotonerigic.
some only resond to a certain class, like sris.
some need 5ht plus NE
some don't respond to anyting in current aresnal.
i don't think the immune system could even become sensitized to most drug molecules, i think it has to be a larger protein for an antibody to work, though i'm not sure.
-d/r
Posted by Bob on April 27, 2010, at 15:53:23
In reply to Re: Multiple drug exposures and treatment resistence » Bob, posted by conundrum on April 26, 2010, at 20:51:03
> From a somewhat neutral standpoint. Not moping and feeling sorry for myself, but I think its amazing that the brain can do that. Its obviously rejecting the drug or at least it feels that way. Perhaps the body learns to decrease the effects of the drug over time but when its reintroduced it doesn't know how and for some reason the brain gets overwhelmed. I say all us SSRI users here donate our organs to science to find out what changes occurred from SSRI use after we die.
>
> Bob have you found other drugs that were tolerable and helpful?
>
>
No, not really. I have mangaged to get on 60mg of Nortriptyline but am still on 10mg of Celexa. It's a very tenuous position. I don't do well at all off of drugs, but the SSRIs are very problematic for me. I'm not sure what I can tolerate any longer. It's so, so difficult.
Posted by conundrum on April 27, 2010, at 19:16:41
In reply to Re: Multiple drug exposures and treatment resistence » conundrum, posted by Bob on April 27, 2010, at 15:53:23
Has the nortriptyline helped? Are you still on Celexa because you are having trouble getting off of it?
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