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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 18 to 42 of 49. Go back in thread:
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?
Posted by linkadge on April 27, 2010, at 19:35:24
In reply to Re: Multiple drug exposures and treatment resistence » conundrum, posted by SLS on April 26, 2010, at 7:55:05
>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.
Not necessarily. One factor that people sometimes fail to account for is life circumstances. Looking back, when celexa worked, most other things in my life were in check. When I retried it, it didn't work, but my life was in a much more uncontrollable state.
>We know that exposure to these drugs leads to >changes in receptor sensitivities. Perhaps such >changes in dynamics persist after drug >discontinuation.
Sure, certain receptors become less senstive after drug exposure, but during drug withdrawl, the receptors are not going to become any *less* sensitive.
>I guess it is also possible that this treatment >resistance would have occurred anyway as a >result of the natural course of the illness.
Some studies show progressive loss of grey matter and hippocampal volume in depression. Actually some studies link SSRI exposure to acellerated grey matter loss, but thats a different thread.
>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.
Well, the other possibility too is that the drug may have stoped working *anyway*.
Linkadge
Posted by SLS on April 27, 2010, at 19:43:51
In reply to Re: Multiple drug exposures and treatment resistence, posted by linkadge on April 27, 2010, at 19:35:24
> >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.
>
> Not necessarily. One factor that people sometimes fail to account for is life circumstances. Looking back, when celexa worked, most other things in my life were in check. When I retried it, it didn't work, but my life was in a much more uncontrollable state.
>
> >We know that exposure to these drugs leads to >changes in receptor sensitivities. Perhaps such >changes in dynamics persist after drug >discontinuation.
>
> Sure, certain receptors become less senstive after drug exposure, but during drug withdrawl, the receptors are not going to become any *less* sensitive.
>
> >I guess it is also possible that this treatment >resistance would have occurred anyway as a >result of the natural course of the illness.
>
> Some studies show progressive loss of grey matter and hippocampal volume in depression. Actually some studies link SSRI exposure to acellerated grey matter loss, but thats a different thread.
>
> >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.
>
> Well, the other possibility too is that the drug may have stoped working *anyway*.
Sure.
- Scott
Posted by linkadge on April 27, 2010, at 19:50:59
In reply to placebo, posted by desolationrower on April 27, 2010, at 0:23:37
>I mean that as the number of trials increases, >the placebo effect asymptotically approaches >zero.
Yes yes! This is a very good point.
There is something very powerful about the "unknown". I think the whole novelty of trying a "new" drug activates discreet brain regions involved in the placebo effect.
Just like you will never get the same rush from trying a roller coaster for the 2nd time. Quite simply because your brain knows it has experienced this before, and therfore seeks to process the experience with other circuitry.
Linkadge
Posted by Bob on April 27, 2010, at 23:55:38
In reply to Re: placebo » desolationrower, posted by linkadge on April 27, 2010, at 19:50:59
> >I mean that as the number of trials increases, >the placebo effect asymptotically approaches >zero.
>
> Yes yes! This is a very good point.
>
> There is something very powerful about the "unknown". I think the whole novelty of trying a "new" drug activates discreet brain regions involved in the placebo effect.
>
> Just like you will never get the same rush from trying a roller coaster for the 2nd time. Quite simply because your brain knows it has experienced this before, and therfore seeks to process the experience with other circuitry.
>
>
> Linkadge
Yes, that makes a lot of sense to me.
Posted by Bob on April 28, 2010, at 0:03:04
In reply to Re: Multiple drug exposures and treatment resistence » Bob, posted by conundrum on April 27, 2010, at 19:16:41
> Has the nortriptyline helped? Are you still on Celexa because you are having trouble getting off of it?
I guess the Nortriptyline has helped. It seems to enable me to at least get a decent amount of sleep at night as I take it before I go to bed. Then again, I've never had much trouble sleeping too much. Still depressed and anxious as hell in the mornings though.As for the citalopram... I don't really know why I take it. It seems to provide that little bit that keeps me out of the deepest depths of the black hole, but any doses considered truly therapeutic prove to be intolerable. So I'd say that having no SSRI is worse than a little, and a lot is just not doable for me these days. Quite a quandry to be in.
Posted by Katgirl on April 28, 2010, at 9:57:49
In reply to Re: Multiple drug exposures and treatment resistence, posted by Bob on April 26, 2010, at 20:44:19
I'm coming in very late to the conversation, but I too am treatment resistant and/or treatment intolerant. I can't take any of the SSRI's anymore. I definitely had a great response to SSRI's at first (felt great/normal on Paxil, it was like a wonder drug at first).
After having improvement with rTMS I decided not to do further drug trials because they just seemed to make the situation worse and worse.
I definitely know that my brain chemistry has been permanently changed, whether from taking Paxil or from going through withdrawal to paxil, I don't know. And its not just psych drugs. When I would get the stomach flu, the only thing that could stop me throwing up was compazine. Besides making me stop throwing up, it always made me feel relaxed and "dreamy". I haven't taken compazine in years (since the withdrawal etc) until this fall in the hospital after surgery. Every time they gave me a dose of compazine, I would get shaky and my muscles would feel "too tight" (hard to explain, it was a really weird feeling--I would start clenching my jaw). I also react differently to my inhaled steroid nasal spray and a host of other medications. Sigh.
I was hoping that the rTMS would "reset" my brain in terms of medications, but the fact that I still react to these other drugs differently leads me to believe it didn't.
I will not be trying any medications until something new comes out that is not an SSRI. But that is a luxury I have, because I have some stability/functionality due to the rTMS. Before I found rTMS, I kept trying the drugs and trying the drugs, because as Scott said earlier, what other choice do you have?? I was suicidal and non-functional. I SO wish I had known about rTMS before I did all those drug trials that made me worse and worse and worse. I can't help but wonder how differnt my life would be if I had gotten rTMS right away after the paxil withdrawal and subsequent lapse into a severe, suicidal, agitated clinical depression.
Posted by SLS on April 28, 2010, at 13:01:51
In reply to placebo, posted by desolationrower on April 27, 2010, at 0:23:37
> I mean that as the number of trials increases, the placebo effect asymptotically approaches zero.
I am still pretty clueless as to what you are describing here. Is this something you found in the article or is it a commonly observed phenomenon?
- Scottt
Posted by SLS on April 28, 2010, at 14:38:03
In reply to placebo, posted by desolationrower on April 27, 2010, at 0:23:37
> 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.
I don't know what you are describing here. If it was my use of the word "sensitization" in a prior post, I was not referring to allergy. Sensitization to cocaine might make a good example of the analogy I was trying to draw.
Sorry for the confusion.
- Scott
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