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Dr. Bob is Robert Hsiung, MD,
[email protected]Shown: posts 1 to 7 of 7. This is the beginning of the thread.
Posted by deniseuk190466 on January 10, 2024, at 10:53:27
If it were me, I would be dead or I would want to be dead and I definitely wouldn't have been able to:-
Do the jobs that I do
Buy a lovely flat
Buy and connect with a lovely little dog
Wouldn't have all the good memories
Been on some lovely holidaysI owe my life to Antidepressants and relaxants so it frightens me when there are studies that try to claim they don't work.
Tried so much therapy over the years and none of that helped!
Just felt like saying that.Denise
Posted by SLS on January 11, 2024, at 11:42:54
In reply to Where would you be without my meds, posted by deniseuk190466 on January 10, 2024, at 10:53:27
Hi, Denise.
It is nice to see you. It is especially nice to see that you feel better.
Thank you for bringing up an old issue with old arguments. I hope it helps give hope to people with TRD.
> If it were me, I would be dead or I would want to be dead and I definitely wouldn't have been able to:-
>
> Do the jobs that I do
> Buy a lovely flat
> Buy and connect with a lovely little dog
> Wouldn't have all the good memories
> Been on some lovely holidays
>
> I owe my life to Antidepressants and relaxants so it frightens me when there are studies that try to claim they don't work.
>
> Tried so much therapy over the years and none of that helped!
>
>
> Just felt like saying that.
I'm glad you haven't lost faith in science. Unfortunately, today's clinical trials are no longer the purview of pure science. They rely on businesses that act as a proxies to perform the logistics of a trials as a proxy for the drug company trying to get their drug approved. The clinical trial facility gets paid by the drug company according to how many subjects they recruit. The greater the number of recruits, the more lucrative the business becomes.How does one higher more recruits in the 2020s than they did in the 1970s? Advertising? Educating the public? I think that has a great deal to do with it. However, in order to increase the percentage of applicants accepted for a trial, the inclusion criteria have become broader in scope and allows for the acceptance of less severe presentations, many of which are actually symptoms of another diathesis (underlying cause) entirely. Should people with dysthymia be included in the study? What about an abnormally long bereavement period? All they need is to say, "I'm depressed". These subjects don't have the illness being studied. Therefore, the drug being investigated might actually be more effective than the trial facility reported. When people who don't have MDD fail to respond to the antidepressant being studied, the success rate will be greatly reduced.
What about the rate of placebo response? Why is it so much higher now than it was 35 years ago? First of all, "placebo" does not equal "no treatment". A subject usually gets supportive care in addition to the test drug. The U.S. National Institutes of Health found that most of their patients with depression report feeling better for about two weeks upon entering the clinical center building as an inpatient. However, the same principle operates with outpatients. The patient has gained hope that they will soon be relieved of their pain soon because they are being treated by professionals - perhaps for the first time. A patient's outlook is one of the most critical factors that determine a person's overall depressive condition. Having a brighter outlook early in the drug trial at the beginning of treatment is often accompanied with relief from feelings of doom. However, this is considered to be a placebo response if the test drug had not been administered.
1. 1960s / 1970s / 1980s
- Response Rate = 65-69%
- Placebo Rate = 15-25%2. Today
- Response Rate = 46%
- Placebo Rate = 35-40%
"We identified 252 placebo-controlled trials (26 324 patients on placebo) done between 1978 and 2015. *THERE WAS A STRUCTURAL BREAK IN 1991, and since then, the average placebo response rates in antidepressant trials have remained constant in the range between 35% and 40%"https://www.thelancet.com/journals/lanpsy/article/PIIS2215-0366(16)30307-8/fulltext
The reported statistics presented here are facts. The hypothesis for why they changed is mine. You can go back to 2001 and read my thoughts on this subject. They were the same then as they are now. Finally, scientists acknowledge the differences in the historical response / placebo rates over the course of decades.I recommend that you not give credence to people citing statistics gathered after 1990.
As I have so often argued with others here in the past, these drugs work. The disappointment is that no one person will respond to every drug sold. The nay-sayers of 2001 are now the ones taking standard antidepressants in 2024. Why?
I hope you understand why your story and conclusions are so important for others to read. You are right. These drugs work. These drugs save lives.
One thing to pay attention to is that biological psychiatry is now studying clinical and pharmacological properties of "non-standard" antidepressants. This includes psilocybin ("magic mushrooms") and ketamine. These substances are bound to have clinical profiles that are different enough from standard antidepressants to have different response rates. In my case, if I were to relapse or get diminishing returns from my currently effective treatment regime, I am looking at adding micro-dose psilocybin to my other medications.
Take care, Denise.
* I didn't have time to proofread this.
- Scott
Posted by deniseuk190466 on January 19, 2024, at 10:29:39
In reply to Re: Where would you be without my meds » deniseuk190466, posted by SLS on January 11, 2024, at 11:42:54
Hi Scott,
Sorry but I am really struggling to concentrate lately. My mind just keeps wondering all the time to death and suicide and why am I like I am and why can't I just be normal etc and just general anxiety and inability to sit still and focus!!!
Thanks for all of the information, it's quite heavy reading.
I'm not sure what point you are making and maybe it is me not being able to concentrate very well.
I am interested in your paragraph about the placebo response. Why do you think that it is so much higher since the 1990s?
Denise
Posted by SLS on January 22, 2024, at 22:27:49
In reply to Re: Where would you be without my meds, posted by deniseuk190466 on January 19, 2024, at 10:29:39
> Hi Scott,
>
> Sorry but I am really struggling to concentrate lately. My mind just keeps wondering all the time to death and suicide and why am I like I am and why can't I just be normal etc and just general anxiety and inability to sit still and focus!!!
Damn it. I'm sorry, Denise. I really am. I misunderstood your words, and thought that you were doing well. You are truly heroic in your fight to stay alive.> Thanks for all of the information, it's quite heavy reading.
> I am interested in your paragraph about the placebo response. Why do you think that it is so much higher since the 1990s?
Too many subjects chosen for clinical trials simply don't have the disease being studied. Without going into too much detail, the proof of this is that those subjects who have the severest of depressions respond more often than the rest of the population in a study. Severe depression is much more likely to be a presentation of Major Depressive Disorder than subjects admitted to the study with milder presentations. These often have other causes, including purely psychological ones. For example, true dysthymia, sometimes called minor depression, responds poorly to antidepressants. Yet, they are depressed enough to meet the study inclusion criteria.In my estimation, MONEY is the explanation for poor response rates and exaggerated placebo rates. Business owners of clinical trial centers don't give a damn how accurate their screening process is. Pharmaceutical companies pay them according to how many subjects they recruit. The rest is easy to figure out.
Disgusting.
Again -
1. 1960s / 1970s / 1980s:
- Response Rate = 65-69%
- Placebo Rate = 15-25%2. Today
- Response Rate = 46%
- Placebo Rate = 35-40%
This is a dangerous farce. Good drugs fail to get approved.
- Scott
Posted by deniseuk190466 on January 29, 2024, at 6:03:24
In reply to Re: Where would you be without my meds » deniseuk190466, posted by SLS on January 22, 2024, at 22:27:49
Hi Scott,
I was doing well but then I asked to be switched from Seroxat to Prozac and then the extreme anxiety started again. Luckily the Zyprexa does help with that. Back on the Seroxat now and feeling better.
Are you saying that people with the most severe depression are more likely to have a placebo response or less likely? I don't know what is wrong with me any more but I know for a fact that I've never had a placebo response to anything related to my mood. You could say "well how would you know? if your response is placebo or not?" but I have tried so many other things over the years, Ketamine, ECT, TMS, health supplements, homeopathy and I Zilch, nothing, I could not detect any improvement in mood. Whereas with Seroxat and Zyprexa, Lyrica, Klonopin, I KNOW they help with my mood and it is nothing to do with placebo. I don't think my depression is severe in the sense that when I am at my worst I am able to get out of bed and function to a certain degree.
It is awful though if the placebo affect is skewing the data. To be honest I am not sure how a person with depression could have a placebo response. Afterall, when you are depressed your thinking is totally negative so you don't expect to feel better. Thats the whole point. To get a placebo response there has to be a certain degree of positive thinking involved. I know having people pay you attention and take an interest can be helpful but I would expect the patient would still know whether it is the actual treatment that is helping or just the situation itself is helping.
I'm going to look up why placebo response is higher these days than it used to be as it is interesting.
I am really glad to see that you are doing well and it's lovely that you are still on this board, helping people. I know that your struggle with biopolar has been far greater than mine.
I have been very fortunate with meds. Although I have never understood why my reaction to SSRIs was totally different in my late 30s to how it was in my 20s, I still was fortunate enough so that by the time I got really bad, they knew about Zyprexa and how that helps with anxiety.
Denise
Posted by SLS on January 29, 2024, at 21:43:20
In reply to Re: Where would you be without my meds - Scott, posted by deniseuk190466 on January 29, 2024, at 6:03:24
> Hi Scott,
>
> I was doing well but then I asked to be switched from Seroxat to Prozac and then the extreme anxiety started again. Luckily the Zyprexa does help with that. Back on the Seroxat now and feeling better.Man, you just made my day.
> Are you saying that people with the most severe depression are more likely to have a placebo response or less likely?
In any one modern clinical trial, people who are severely depressed are the most likely to achieve remisssion.
> I don't know what is wrong with me any more but I know for a fact that I've never had a placebo response to anything related to my mood.You are a perfect example of my criticism of modern clinical trials for antidepressants. Today's placebo response rate is much higher than that seen in the 1960s, 1970s, and early 1980s. The reason? Today's clinical trials are all paid for by drug companies rather than being projects funded and conducted by university research departments. They were very strict as to who they chose as subjects. Today, drug companies pay clinical trial centers, which are in business. Businesses act to make as much money as possible. They get paid for each person they recruit. They are NOT strict with who they allow in to the study. Severe depression turns out to be the smallest study group. The rest are presentations of dysthymia (minor depression), psychologically depressive thinking, childhood adversity leading to complex post-traumatic stress disorder (CPTSD).
People who do *not* have MDD are accepted into a clinical trial because there is more money to be made by taking in people who don't have MDD, but complain of depression. These subjects are much more apt to report feeling better when they are given hope with the new support system they have received at the clinical center. People who are psychologically depressed with no biological contribution are certainly more apt to respond to placebo. You can research the placebo response by researching the work performed by Frederick Quitkin, MHRIP.
Clinical trial screener: "Are you depressed?".
Prospective subject: "Yes".
Clinical trial screener. "Okay, we can sign you up right now."
> You could say "well how would you know? if your response is placebo or not?"
You wouldn't until the trial is over and the investigators perform a "blind-breaking" with you and tell you what you were given. If you were given sugar pills, only then will you be told.
Gotta go...
Get well and stay well...
- Scott
Posted by deniseuk190466 on February 18, 2024, at 13:48:41
In reply to Re: Where would you be without my meds - Scott » deniseuk190466, posted by SLS on January 29, 2024, at 21:43:20
Hi Scott,
That's worrying and disturbing.
I think we need more qualititative research as well as quantitative.
Thanks for explaining it to me and thanks for the links.
Denise
This is the end of the thread.
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Dr. Bob is Robert Hsiung, MD,
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