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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 25 of 51. This is the beginning of the thread.
Posted by law663 on November 25, 2005, at 12:30:13
Does anyone know of *any* studies that have examined the effect of prolonged use (more than 1 year) of SSRIs? Since 5HT projections go to many parts of the brain, including the pituitary, that chronic elevation of 5HT may have some effect outside of AD effect. I did a MEDLINE search, but not much out there. Too bad that no one seems to be doing these studies.
Posted by Chairman_MAO on November 25, 2005, at 12:45:28
In reply to Studies on long term use of SSRI's, posted by law663 on November 25, 2005, at 12:30:13
Taking a D2 agonist (think: pituitary) initially completely reversed my sexual dysfunction from buprenorphine+phenelzine. The effect went away, and it has never worked again, even at doses used by end-stage Parkinson's patients. I always like to mention that even at 8mg/day cabergoline had no detectable side effects in me.
Taking testosterone propionate ~250mg/wk has eliminated any trace of drug-induced sexual dysfunction. This suggests that buprenorphine+phenelzine together many have a testosterone-lowering effect and/or some other deletrious hormonal effect. One study in buprenorphine maintained healthy, young male heroin addicts showed no lowering of T at 16mg/day, but in combination with phenelzine this may not be the case ...
Given that many people on buprenorphine also take serotonergic psych meds, this warrants further investigation.
Posted by law663 on November 25, 2005, at 15:25:26
In reply to Re: Studies on long term use of SSRI's, posted by Chairman_MAO on November 25, 2005, at 12:45:28
That's interesting becasue I take 5G of androgel for a pituitary adenoma and while it as helped sexual funtioning somewhat (even with cialis) it's main effect has been improvment in mood. I take Cymbalta 30 mgs (once a day even days, bid odd days -- i find i don't need the full 60 mgs all the time). Additionally, I take 18 mgs of Concerta and noticed slight improvement in sexual functioning (it has some D2 agonist properties) but overall I still struugle with the full spectrum of sexual progams assocaited with SSRI's (but need the anti-anxiety effects of them).
> Taking a D2 agonist (think: pituitary) initially completely reversed my sexual dysfunction from buprenorphine+phenelzine. The effect went away, and it has never worked again, even at doses used by end-stage Parkinson's patients. I always like to mention that even at 8mg/day cabergoline had no detectable side effects in me.
>
> Taking testosterone propionate ~250mg/wk has eliminated any trace of drug-induced sexual dysfunction. This suggests that buprenorphine+phenelzine together many have a testosterone-lowering effect and/or some other deletrious hormonal effect. One study in buprenorphine maintained healthy, young male heroin addicts showed no lowering of T at 16mg/day, but in combination with phenelzine this may not be the case ...
>
>
> Given that many people on buprenorphine also take serotonergic psych meds, this warrants further investigation.
Posted by linkadge on November 25, 2005, at 16:21:06
In reply to Re: Studies on long term use of SSRI's, posted by law663 on November 25, 2005, at 15:25:26
I have suffered many problems related to long term use to SSRI's. I don't think long term use of SSRI's has been sufficiantly studied.
Linkadge
Posted by med_empowered on November 25, 2005, at 17:18:23
In reply to Re: Studies on long term use of SSRI's, posted by linkadge on November 25, 2005, at 16:21:06
its strange, really; the manufacturer studies for SSRIs and other antidepressant usually ran about 8 weeks. Shrinks were then using this data (in which the pills didn't come up much better than Placebo, btw) to recommend taking antidepressants for several months...now, the recommendation seems to be *keep taking it* indefinitely to avoid risking "relapse" (or withdrawal symptoms, I think). Its pretty scary. On the plus side...patient compliance with this kind of medication tends to be pretty low, especially over the long haul, so...since people quit taking them so much, there may not be as many long-term side effects popping up as with, say, the old neuroleptics, when people started to pay attention to those side effects around the 70s (I imagine forced drugging and depot injections made discontinuing those meds nearly impossible for a lot of people).
Posted by law663 on November 25, 2005, at 17:25:22
In reply to Re: Studies on long term use of SSRI's, posted by med_empowered on November 25, 2005, at 17:18:23
I have one bone to pick with this: I know that Healy and others have claimed that AD's haven't shown much superiority to placebo. This is simply factly incorrect. They don't present the data honestly. AD's have shown superiority to placebo -- they work -- that's why people take them. The issue, in my mind, is that no one is doing long-term studies b/c the drug companies will not fund these studies and NIH seems unwilling to as well.
> its strange, really; the manufacturer studies for SSRIs and other antidepressant usually ran about 8 weeks. Shrinks were then using this data (in which the pills didn't come up much better than Placebo, btw) to recommend taking antidepressants for several months...now, the recommendation seems to be *keep taking it* indefinitely to avoid risking "relapse" (or withdrawal symptoms, I think). Its pretty scary. On the plus side...patient compliance with this kind of medication tends to be pretty low, especially over the long haul, so...since people quit taking them so much, there may not be as many long-term side effects popping up as with, say, the old neuroleptics, when people started to pay attention to those side effects around the 70s (I imagine forced drugging and depot injections made discontinuing those meds nearly impossible for a lot of people).
Posted by med_empowered on November 25, 2005, at 17:56:47
In reply to Re: Studies on long term use of SSRI's, posted by law663 on November 25, 2005, at 17:25:22
The data used to show that antidepressants are no better than placebo has often come from *drug company data* that simply wasn't reported, since federal law does not currently require that the outcome of each and ever clinical trial be presented to the FDA at the time the medication comes up for approval. The fact that "people take them" does *not* mean they are in fact any better than placebos, or that they are superior to other (drug or non-drug treatments). People take them b/c the current paradigm in mental health is the biopsychiatric model. People take them b/c they are prescription drugs that generate billions of dollars for the companies that make them. People take them because sales reps (ex: Merck's "Merckettes") push them...HARD. These drugs have been pushed hard and prescribed like candy--much to the glee of drug companies and well-paid consultants and psychiatrists, much to the disservice of patients and their families, and society at large.
Interesting fact: in studies where ADs come up about as good as placebo, an inactive placebo was used. Imagine the results using an "active" placebo--one that could cause some minor side effects, but nothing too major (and no major psychiatric effects, either). The results, I imagine, would be astounding.
Posted by linkadge on November 25, 2005, at 19:05:59
In reply to Re: Studies on long term use of SSRI's, posted by med_empowered on November 25, 2005, at 17:56:47
I agree with med empowered. There isn't really sufficant data to show they are better than placebo. Sometimes the drug companies have to test the drug many many times even to show it is better than the placebo.
One of the largest studies designed to dismiss the antidepressant effects of St. Johns wort failed to show that the comparitor drug zoloft actually performed worse than SJW !
The best that antidepressant could do was to make me numb to my problems. They never made me any happier.Of course there are different interpretations, and different takes on the available data.
Linkadge
Posted by Phillipa on November 25, 2005, at 19:50:48
In reply to Re: Studies on long term use of SSRI's, posted by linkadge on November 25, 2005, at 19:05:59
Well said Med and Link. They never made my anxiety better and never did a darn thing for me. Fondly, Phillipa
Posted by law663 on November 25, 2005, at 19:56:45
In reply to Re: Studies on long term use of SSRI's, posted by med_empowered on November 25, 2005, at 17:56:47
Sorry, but I have to disagree. Most of the drug company studies are sponsored by academic medical centers and they publish their results. Are you really saying that the only reasons that people take AD's is that their doctors push them to take them? So, all of the people who claim that AD's have helped them -- they're all brainwashed? The BILLIONS of dollars that people spend are spent on drugs that have no effect? That all of the brain imaging studies, the studies on BDNF, those are all false?
My point is thus: I agree that there are porblems with Phamra sposorsed studies and the lack of long term studies. I also think that psychiatry has ignored the fact that 5HT elevations can have profound endocrine effects that are not fully understood. But, let's not through the baby out with the bathwater. Prozac et al have helped numerous people and these agents have true thereputic, biological effects. To claim otherwise, I think, borders on perposterous.
> The data used to show that antidepressants are no better than placebo has often come from *drug company data* that simply wasn't reported, since federal law does not currently require that the outcome of each and ever clinical trial be presented to the FDA at the time the medication comes up for approval. The fact that "people take them" does *not* mean they are in fact any better than placebos, or that they are superior to other (drug or non-drug treatments). People take them b/c the current paradigm in mental health is the biopsychiatric model. People take them b/c they are prescription drugs that generate billions of dollars for the companies that make them. People take them because sales reps (ex: Merck's "Merckettes") push them...HARD. These drugs have been pushed hard and prescribed like candy--much to the glee of drug companies and well-paid consultants and psychiatrists, much to the disservice of patients and their families, and society at large.
>
> Interesting fact: in studies where ADs come up about as good as placebo, an inactive placebo was used. Imagine the results using an "active" placebo--one that could cause some minor side effects, but nothing too major (and no major psychiatric effects, either). The results, I imagine, would be astounding.
Posted by Jakeman on November 25, 2005, at 20:39:51
In reply to Studies on long term use of SSRI's, posted by law663 on November 25, 2005, at 12:30:13
What has always been curious to me is the wild variations of efficacy that people report.
Recently I was perusing the website
askapatient.comhttp://www.askapatient.com/classreport.asp?class=ANTIDEPRESSANTS
Prozac for example.. 224 people rated their experience. Several commented that it had saved their lives and had used it for years. Others said that the drug was worthless and/or dangerous. About as many people rated it 5 as rated it 1. The reviews are similarly mixed on other AD's.
Maybe SSRI's are efficacious, but only for about a third of us.
warm regards ~Jake
Posted by Phillipa on November 25, 2005, at 21:45:11
In reply to Re: Studies on long term use of SSRI's, posted by Jakeman on November 25, 2005, at 20:39:51
Jake, sounds about right with the largest response indicating around a 70-80% satisfaction for lowering depression not eliminating it. Fondly, Phillipa BTW even the inserts say they do not work for everyone even shortterm.
Posted by law663 on November 25, 2005, at 22:30:52
In reply to Re: Studies on long term use of SSRI's, posted by Jakeman on November 25, 2005, at 20:39:51
Yes, but for most psychiatric drugs that is the case. I think we must remember that before the SSRI's came out we only had the typicals which were "effective" but only with HUGE side-effects which prevented most from having any semblence of a routine life. So, Prozac et al was a "life saver" but not perfect. What troubles me is that we have no idea if long term use of SSRI's is associated with alterations in brain morphology. Epidem people will say that there is no assocaition with SSRI's and cancer, heart disease, etc -- but that speaks nothing to things like pituitary disease, diabetes, or subtle disease.
> What has always been curious to me is the wild variations of efficacy that people report.
> Recently I was perusing the website
> askapatient.com
>
> http://www.askapatient.com/classreport.asp?class=ANTIDEPRESSANTS
>
> Prozac for example.. 224 people rated their experience. Several commented that it had saved their lives and had used it for years. Others said that the drug was worthless and/or dangerous. About as many people rated it 5 as rated it 1. The reviews are similarly mixed on other AD's.
>
> Maybe SSRI's are efficacious, but only for about a third of us.
>
> warm regards ~Jake
Posted by fuchsia on November 26, 2005, at 1:55:43
In reply to Re: Studies on long term use of SSRI's, posted by linkadge on November 25, 2005, at 19:05:59
> The best that antidepressant could do was to make me numb to my problems. They never made me any happier.
They made me so happy I was dancing and singing. And I've been bipolar ever since.
Maybe that's a long term effect.
Posted by flmm on November 26, 2005, at 9:38:44
In reply to Re: Studies on long term use of SSRI's » linkadge, posted by fuchsia on November 26, 2005, at 1:55:43
They are not supposed to make you "happy"! They are intended to reduce depression, and for many people, me included, they do just that! They make people with severe panic and depression, "functional". Once you acheive that you must find happiness the same way everyone alse does! They are not "happy pills". does not work that way people. Once you realize that, you can start doing the positive things in your life needed to bring contentement and satisfaction into your life.
Posted by linkadge on November 26, 2005, at 10:47:51
In reply to Re: Studies on long term use of SSRI's, posted by law663 on November 25, 2005, at 19:56:45
Some doctors consider them "placebo's with a buzz", since the placebo margin can be increasingly reduced when active placebos are used. I don't admit they do something, but as far as saying they effectively treat the condition of depression is hard for some to accept.
Like I said in previous posts, I think they initially help because they cause a profound reduction in rem sleep. This improves depression in its own right. But the brain fights back, desparately wanting rem sleep. The result? You become what so many psychiatric patients complain about being "a zombie". Rem sleep is critical for the brain to create the most insighful ideas into its current state of being. So yes I think they have initial "effects", but I don't think they actually are very effective long term at all.
Neuroimiaging is another thing. It was shown that the people who respond to SSRI's have frontal cortex activation. But that doesn't say anything, because the patients who didn't respond didn't have that activation. Therapy was also shown to activate the frontal cortex. So I don't think it is necesarily the drug, as much as recovery, or placebo effect.
THe BDNF issue too has not been too conclusive. I was reading a nice little page on how prozac increased BDNF in mice. But then the article went on to say that BDNF was increased to a similar extent in any mouse that had been "handled".
Some of the BDNF increases are phasic, showing elevations for a number of hours and then going back to baseline.Not all studies show that SSRI's reliably increase BDNF.
Another thing to consider is this. Scientists have been trying to find a bad serotonin gene. One of the latest studies has found a significant predisposition to depression if you cary a Short-Short varient of the serotonin transporter gene. Ie. The people with this varient showed significantly more lifetime depressive episodes, than people with the long-long or other varients.
But the problem is this. The short-short varient codes for a slower reuptake of serotonin than do other varients.So essentially, researchers have found that the people who are the most depressed already have a slower serotonin uptake than people without the gene. These findings are the exact opposite to what researchers were expecting to find.
This is a case for Tianeptine, a clincally effective antidepressant that is a serotonin reuptake acellerator.
There is a lot of reasearch being done to discover their hazards too. I know that there is research being done into the propensity of antidepressants to induce rapid cycling and manic, and suicidal behaviors. This kind of research does not become accepted overnight. Just like how valium was not declared overnight to be addicting.
Then their is poop out and withdrawl. I talked to a lady who said she had taken prozac for 5 years and it took her five years to fully get over withdrawl. I said to myself, "thats about right".
Untreated depression rarely lasts longer than a year, but we have people on these drugs for many many years.
Meds are like Shawshank prison. At first you can't stand them, then you grow to tollerate them. Soon enough you can't live without them.
Linkadge
Posted by linkadge on November 26, 2005, at 10:52:26
In reply to Re: Studies on long term use of SSRI's, posted by flmm on November 26, 2005, at 9:38:44
In the angle that depression is accompanied by a severe deficit in happiness, they never made me happy. In the sence that they never tackled severe deificits in happiness, they never treated the depression.
Linkadge
Posted by linkadge on November 26, 2005, at 10:54:30
In reply to Re: Studies on long term use of SSRI's, posted by law663 on November 25, 2005, at 22:30:52
Yes, I would think that if you avereraged every clinical trial, you might get an effect in about a third of people.
Linkadge
Posted by flmm on November 26, 2005, at 11:24:03
In reply to Re: Studies on long term use of SSRI's, posted by linkadge on November 26, 2005, at 10:54:30
I think overanylisis is part of everyones problem. Depression is self obsession. Get off the couch, stop worrying about what drug is doing what, go help someone else and you might just stop obssessing about yourself so much!You will never find the perfect drug,deal with it!
Posted by law663 on November 26, 2005, at 11:26:19
In reply to Re: Studies on long term use of SSRI's, posted by linkadge on November 26, 2005, at 10:52:26
Well put linkage. Do you happen to have the cite for the short-short paper? I'm aware of the tiapine paradoxical effect. I still say that AD's are effective. The BNDF is more than just transient I believe, but I think the jury is still out for the final verdict.
Posted by linkadge on November 26, 2005, at 12:34:50
In reply to Re: Studies on long term use of SSRI's (linkadge), posted by law663 on November 26, 2005, at 11:26:19
Here is one.
It starts by talking about the effect of the transporter on drinking, and then goes on to discuss its relationship to depression.
http://www.futurepundit.com/archives/001611.html
But the story goes much deeper. One can do engine searches with key words short-short, SERT, depression, etc. There is lots of work being done, but most of the data seems to show that the short-short varient confers susceptability to depression and alcoholism.
Linkadge
Posted by Tomatheus on November 26, 2005, at 13:04:32
In reply to Re: Studies on long term use of SSRI's, posted by flmm on November 26, 2005, at 11:24:03
> Depression is self obsession.
What makes you say this? Do you speak from experience? Or is this part of a theory that's been written about in the scientific literature? If this theory is scientific, I am not familiar with it. Could you please cite an article from the literature discussing this theory of self obsession? I'd be interested in learning more about it.
> go help someone else and you might just stop obssessing about yourself so much!
It seems to me that helping others is what this meds board is all about. It's been helpful to me, and I'd like to hope that some of my posts have been helpful to others.
> You will never find the perfect drug,deal with it!
I don't think that any of us seeking drug therapy for depression are looking for perfection. I can't speak for others, but when my depression is at its most severe, all I'm looking for is the ability to lead some semblance of a normal life - to be able to feel alive and to be able to enjoy all of the things that I know I should be enjoying but cannot due to my condition.
Tomatheus
Posted by ed_uk on November 26, 2005, at 14:24:11
In reply to Re: Studies on long term use of SSRI's, posted by Tomatheus on November 26, 2005, at 13:04:32
Hi
>I'd like to hope that some of my posts have been helpful to others.
They have. You have many excellent posts to your name :-)
Ed
Posted by Tomatheus on November 26, 2005, at 14:44:40
In reply to Re: Studies on long term use of SSRI's » Tomatheus, posted by ed_uk on November 26, 2005, at 14:24:11
Thanks, Ed. I'm glad to hear that you've enjoyed my posts, even though I really haven't written very *many* of them yet. I've certainly learned a lot from the many (and I do mean many) insightful posts you've made (since I've joined and from before, when I was in lurking).
Tomatheus
> Hi
>
> >I'd like to hope that some of my posts have been helpful to others.
>
> They have. You have many excellent posts to your name :-)
>
> Ed
Posted by flmm on November 26, 2005, at 14:44:42
In reply to Re: Studies on long term use of SSRI's » Tomatheus, posted by ed_uk on November 26, 2005, at 14:24:11
All I am saying is dealing with depression will always be more than taking a pill. They help, but only about 50% of the way. The rest is up to you. Spending time looking on this board for the perfect drug is counterproductive and helps to increase the thought process of your own illness. Spend a couple weeks away from the board, if you can,and see if you do not feel a little better not looking for that "perfect" drug. There is a lot more to it than just drugs!In the end they all pretty much do the same thing!
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