One of the main arguments for continuing drug treatment for depression, psychosis and bipolar disorder is that you will get worse from stopping the drugs, especially if they are stopped abruptly. These are findings from mainstream psychiatry. However, if we combine this information with the methodology of the randomized controlled trial, we may see that these drug trials do not show efficacy of drugs, and may not be usable to show safety. The positive side to this is that the trials may actually demonstrate the healing power of our own minds.
When drugs are tested, patients are given a placebo for 4 to 14 days in order to wash out the drug that they have been taking before the trial. Patients do not know that they are getting a placebo, and many of them may think that they are lucky and have been given the new wonder drug.
During this washout period, many individuals react very well, so well that they do not have enough psychological problems to enter the real drug trial. These are so-called placebo responders. They are removed from the trial, since they are not depressed or psychotic enough to take part in the research project.
This seems like it is going to give the drug and unfair advantage. However, if the drug group and the placebo group are of the same size, this does not actually provide an advantage for the drug. But something much more significant is happening.
The placebo washout period is used to ensure that all participants have brains free from the previous drug they were taking before they start treatment with the new drug.
That means that at the end of the placebo washout period, all the patients are in acute withdrawal. One would reasonably expect these patients to do quite poorly, to be quite disturbed. Some of them are , but many who had a problem when they were on the drug, actually get well from stopping the drug cold turkey.
However, those who react badly to the cold turkey withdrawal get to continue. Half of them then get a drug very similar to the one they had abruptly stopped, and the rest, the placebo group, get to continue on cold turkey withdrawal.
So this is what we are testing: Difference between continuing cold turkey withdrawal and getting back a drug very similar to the one you were dependent on.
So the classic RCT is not at all testing the difference between drug and no-drug.
This may actually explain some strange effects seen in drug trials:
- The positive effects of the SSRIs start immediately, even if doctors tell their patients that the drugs have to be taken from 4 to 8 weeks to feel better
- Patients in the placebo group get a lot of negative effects such as sleeplessness, and inner turmoil (akathisia). One would not expect such negative placebo effects (nocebo) from a pill that patients think will actually relieve their problems.
- Effect only in the severely depressed. Many doctors seem to accept that SSRIs don’t have an impressive effect on the moderately depressed, but justify their use on the severely depressed because of a larger difference between placebo and drug for this group. We know that patients in this severely depressed group must have taken larger doses of their previous drug for longer times. It is then quite obvious there will be more severe withdrawal reactions in the placebo group. The group getting back a similar drug will be even more relieved, since they were very addicted to the previous drug.
- Drugs not working in children and adolescents. This may be the only case where participants have not been on a similar drug before they start the trial, and here we don’t see a difference between drug and placebo.
So what is being tested in an RCT is not at all the difference between a drug and an inactive pill, we are testing how good it feels to get back something very similar to the drug you were dependent on, compared to going cold turkey! Anybody who has had a serious hangover and then “repaired” by taking a few drinks knows this difference. The relieving drug doesn’t have to be the same: Acute alcohol delirium can be cured with benzodiazepines since they are similar to alcohol in effect on the nervous system.
So the first conclusion may then be that none of these RCTs prove that the drugs work.
The second conclusion may even be more startling: We cannot say anything about the safety when we compare a drug to abrupt withdrawal.
One of the reasons drug companies give for not leaving depression untreated, is the the untreated patient may die from suicide. One could then think that taking the drug away from a patient would increase the risk for suicide. So according to drug company logic, a patient who has abruptly stopped the life-saving drug, would have a higher risk for suicide than the medicated patient.
This is confirmed in a very large study reported in Journal of Clinical Psychiatry in 2009. The abstract states:
“Antidepressant discontinuation showed a significant risk for suicide attempt as did the period of an abbreviated trial, that is, stopping before a therapeutic regimen of 56 days had been reached. The highest risk was associated with initiation, a finding consistent with other studies, closely followed by periods of dosing changes and discontinuation.”
Slowly increasing the dose (titration up) increased the risk to 262% of normal risk. Decreasing dose gradually lead to a 219% increased risk according to the article.1
This means that patients on placebo have at least a doubled suicide risk after 2 weeks in withdrawal. The 219% risk was on gradual withdrawal, not abrupt, which would possibly be much worse.
RCTs compare suicidal ideation on the drug to placebo. Many studies find a doubled risk. One study found a 6-fold risk for Paxil2. Since the risk in the placebo group is already doubled, the increased risk from the drug may be 4 to 12 times the risk of unmedicated depression. The conclusion is difficult to avoid: antidepressants are extremely hazardous to our health.
However, the flipside of this problem is quite positive: avoiding medication for depression is associated with much less suicide!
And now we come to the truly amazing power of hope in the form of a placebo. Let us take a typical antidepressant trial with some simple numbers: 100 participants in the placebo group and 100 in the drug group. Let us be optimistic for the drug and assume that 60% get well. 50% typically get well on the placebo. This means that 100 out of 200 patients actually would get well from the placebo, since 50 patients in the drug group also are expected to get well from just popping a pill whether it is sugar or drug. This means that only 10% got anything out of the drug. The rest get well on a placebo. The results are thus that placebo is 5 times more effective than the drug.
If we combine this with our first observation that placebo treatment is actually abrupt withdrawal, it becomes really amazing. Going cold turkey off the previous medication makes 50% of patients well, often instantly in the case of those who respond in the washout phase. This is very bad advertising for the makers of the previous drugs. And the new drug is only one fifth as effective as cold turkey.
There are so many other things wrong with RCTs, such as publishing only the positive trials, that we cannot even be sure of this 10% drug effect.
In addition to this, even the very pro-drug Dr. Gibbons’ meta-analysis of industry-sponsored trials showed that the placebo reached the exact same level as the drug just four days later. All this shows that we can trust our own minds to heal themselves as long as we don’t add chemicals.
To conclude: From this analysis it becomes clear that we don’t have ANY research showing the effects or safety of SSRIs since we are testing cold turkey withdrawal against getting back a me-too drug. The research shows the opposite of what the drug makers hoped to find: placebo is extremely effective and has no side effects. Hope is curing us.
* * * * * *
- Valuck RJ, Orton HD, Libby AM. Antidepressant discontinuation and risk of suicide attempt: a retrospective, nested case-control study. J Clin Psychiatry. 2009 Aug;70(8): 1069-77. doi: 10.4088/JCP.08m04943.
Kjetil: When I was first incarcerated, I did the RP McMurphy trick and did not swallow the medication. The psychiatrist, remarked, “Mr. Reed, You are doing so much better.
That’s the most important thing – placebo effect working on the psychiatrist.
this is one of the most important articles I’ve read on this site.
You have completely reversed the conclusions of the drug company funded trials.
This throws just about every psyche drug trial into question.
Thank you John. I would encourage everyone to be devil’s advocate when it comes to this article. Even though I am sure that my reasoning is correct, the scientifically correct procedure would be to try to disprove it. I would also warn anybody against going cold turkey of medication even if these short-term trials seem to prove that this is okay for many people. A very gradual withdrawal is however recommended even by mainstream psychiatry for patients who have been symptom-free from six months to one year. I would suggest a maximum of 1% per day if anybody is going to withdraw. This can be done in many creative ways, for instance by using a nail file. Approximately three strokes with the nail file will give 1%.
I gave a friend a pill cutter. He managed to cut the pills into eight. He reduced every two weeks. Onlytwo days of withdrawal effects till the last eighth when he was sleepless. Am doing some further research for him. However he is much healthier and much less tranquilised on this much lower dose.
People’s withdrawal reactions are individual and vary from drug to drug.
There are hardly any psyche drug withdrawal clinics. Most people find what works by trial and error.
So I’d say the nail file methoed is one method that people will find useful and there are others.
John: I am whittling on the Zyprexa. This a difficult drug to titrate from. Thanks to MIA,and no thanks to the psychiatrist, I became aware that the difficulty of this is high.
I’m keeping fingers crossed for you. I only took Zyprexa for a short time and occasionally as a sedative – half of the lowest dose (I believe lowest was like 2.5mg) and had terrible side effects anyway (my “doctors” were telling me I’m exaggerating when I had narcolepsy-like symptoms, binge eating and disabling tiredness). Plus after stopping (even after taking one dose) I had withdrawal effects for 2 or more weeks. I don’t know what sadist has developed this drug.
Please go really slowly and if you become very emotionally unstable – it’s likely a withdrawal. Just be patient with yourself then.
Maybe the nail file method is helpful to get off the last very low dose?
“I would encourage everyone to be devil’s advocate when it comes to this article.”
Okay Kjetil. Let me explain what I’m struggling with here.
If I get a burn on my arm from a cigarette then my body (physiology) does certain things and the damage heals. If I practice meditation (with my mind) then the damage may heal quicker. But I can not demonstrate this, it is an act of faith. Faith healing. I have no trouble accepting that this is the case, but it is a problem that can not be resolved through scientific methodology.
If so, isn’t what you are discussing in your article that it is the act of faith that results in the healing of the mind? And further, that all the experimenters are doing is causing physiological changes in the brain that result in the need for an act of faith to heal the body (brain)?
Probably sounds like a question that means I require an examination by a psychiatrist, but I get where I’m coming from lol.
Boans, I will have a go at this for you:
You have a cigarette burn, and you now know that given the right circumstances and a little time, your body will heal itself – protect it, keep the wound clean, maybe put some antiseptic cream on it, maybe put a plaster on it. You now know that sticking a penknife in it, burning it some more, or pouring caustic soda on it is not going to help. Before you learned this, your mum probably did the first aid for you, maybe explained why, told you not to mess with it, and reassured you that it would be ok. Because it was your mum (I’m making this presumption) you believed her, you trusted her, and by not messing with it you allowed your body to heal itself. It healed like she said, and although not scientifically proven in any way, sufficiently proven for you to now believe this to be the correct course of action. The only faith involved was that your mum would be proved correct, which she obtained by reassurance.
Clearly a psychological burn is more complicated, but is the principle not the same? Give your mind the correct circumstances and it will heal itself. The placebo seems to me to be the equivalent of a trusted source (your doctor, how ironic) reassuring you it will be ok, whilst at the same time not messing with the wound. Sadly, the reason the same benefit might not be had from your doctor simply reassuring you the wound will get better on its own if you don’t mess with it is due to the general success of pharma’s marketing behemoth in convincing us we should take ‘something’ rather than nothing.
So if you practice meditation, your faith is in the self-healing power of your mind. Meditation is no more the cure than keeping the cigarette burn clean; it is a circumstance that allows the mind to heal itself. Placebo is not faith healing per se because it is not the faith that does the healing, but faith in the placebo and therefore not messing with the wound that allows healing to occur. The physiological change caused by the placebo is reassurance.
This was a very good explanation of the placebo effect- not messing with the wound. Mechanisms for placebo effect may vary, but just leaving things alone is certainly one of the factors. That was the experience of researchers in the 70s: leave depression alone and it clears up.
I’m getting a ‘three men in a restaurant’ feeling here.
Three men go into a restaurant and have a meal. The waiter comes with the bill and it’s $30. Each man puts in $10 and the waiter goes to the cash register. He rings up the bill and it’s only $25, so he takes five $1 bills from the register, puts two in his pocket and gives $1 back to each man at the table. Therefore each man has paid $9 for his meal.
3 X $9 is $27, and the waiter has $2 in his pocket. $27 + $2 = $29.
Where’s the missing dollar?
What would be a good way of demonstrating the efficacy of a drug in a trial?
It would appear the scenario as you describe it is the one the drugs companies befuddle us with each time they publish results of their trials.
What Kjetil has done is show you that the till has had $25 and the waiter has had $2 and there is therefore no missing dollar. (25+2=27)
If there was a missing dollar I’m pretty sure the drug companies would have had it anyway.
Oh yes AngryDad 🙂
I will note that it was a cheap lunch and the diners paid from their own pockets, so we can assume it wasn’t three doctors having lunch on the drug companies money.
As long as people remain confused about these trials though, the more emboldened Big Pharma will get.
I think it’s a good question and if you explain how exactly placebo works on a biological level Nobel price is coming ;).
You look for a devil’s advocate so I have so potentially critical questions:
– do the studies reveal how many participants were on a drug previous to enrollment? You’re making an assumption that most if not all of them are in withdrawal but maybe some trials actually involve medication naive participants? If so how do these trials compare?
– how do you even distinguish what are symptoms of withdrawal and what is the original problem (ok, this one is actually problematic for psychiatry’s interpretation as well)?
Thank you for this. So effing obvious when the maths are spelled out; the massive elephant in the maths room.
What a tragedy that going to a psychiatrist or GP and requesting to be given a placebo to aid your difficulty would be delusional.
Or would it ?
Doctors could actually prescribed quite good placebos without deceiving the patients. Placebos work better if they’re given by the trusted medical professional. They also work better if they are big, colorful and have to be taken several times a day. Omega-3 tablets and several vitamin tablets could fulfill this need quite well and also have research showing that they are better than totally inactive placebo’s. The power of placebo can actually be harnessed by many different things, including exercise. Exercise actually has a good effect this set in itself compared to antidepressants, but they also lead to strong placebo effect. To stop smoking is also an advice that can be given but has a real effect but that would also have placebo effect.
So combining a very slow taper with all these real/placebo interventions could have a very strong effect. And this would be so scientifically correct that any doctor could prescribe it with good conscience.
Yes, but where can I find a doctor who will do this?
“Doctors could actually prescribed quite good placebos without deceiving the patients. Placebos work better if they’re given by the trusted medical professional.”
You could look at the MIA directory. There are a lot of good and sensible doctors there.
Homeopathy is one good example. Doctors, even those who know it’s expensive water, use it as an acceptable way to prescribe placebos and it sometimes works even when the patient does not believe in it. Magic ;).
I would suggest that the number of people who did alright going cold turkey might be a lot smaller than it may seem, since there is often a period of feeling better in many ways before one gets slammed with the symptoms of acute withdrawal. I’ve gleaned this from the accounts of others and it was my experience as well. In my case I had a period of one or two months after going off the drugs (after 13 years) in which I felt better than I had in over a decade. Then the acute withdrawal started; I developed akathisia, couldn’t sleep, couldn’t eat, etc. Nocebo effect was not a factor, because I had no idea what I was doing.
Just to be clear, the withdrawal effects I am referring to here were from Paxil (and also possibly from Remeron).
What has happened to you since? Did you successfully get off the drugs?
Thanks for asking. I’d say the acute withdrawal lasted about six months. As I said, I couldn’t eat, so I lost fifty pounds in about three of those months (80 lbs over the year). Lack of sleep was the worst, though. I was scared of being hospitalized, so I started taking low doses of benzos to help with the akathisia and insomnia. They did help a little, so I did that for about a year, and then I took another year tapering off them. (I’m not recommending prolonged benzo use, however. It may have been a horrible mistake for me to have taken them for that long.)
Now I’m drug free, but I’m still healing. I developed new withdrawal symptoms coming off Klonopin, such as extreme depersonalization, derealization, and tinnitus, but at this point my appetite is almost normal and my sleep is probably at least 80% back to normal. I haven’t had akathisia in a long time now, though I do have chronic fatigue. But all of the symptoms I had ON psychiatric drugs, like metabolic disorder, daily panic attacks, sexual dysfunction, and constant suicidal impulses, are all completely gone. I still have notable anhedonia, but it seems to be improving very slowly over time along with my ability to sleep. (The mentions of symptoms at each stage are just highlights; there were many more.)
So, all together, I was on different combinations of psych drugs for 15 years, and getting off them has been hell, but I still feel like it’s the best thing I have ever done for myself.
Oops – meant to say “metabolic syndrome” (abdominal obesity, elevated blood pressure, elevated fasting plasma glucose, high serum triglycerides, and low HDL levels), not “metabolic disorder.”
Thank you so much for telling your story! People seem to be very different when it comes to both reactions to medication and to withdrawal. Some cannot be without their Paxil for a day without withdrawal symptoms. Getting a delayed withdrawal seems to happen to some, but there is a danger to expecting it also: it is easy to get a nocebo effect, a negative expectancy effect. I know this was not the case for you, but it could happen to others.
Very gradual withdrawal with small breaks if necessary, even increasing for a while of necessary, seems to be the absolutely best way.
I am bipolar and have been put on numerous medication, if i don’t like them my doctor gets upset or insist on upping the dosage I do take vyvance but if i refuse to take the others he will not give them to me. When i am depressed like right now due to the season change he says my vyvance is causing it but i cannot function with out it and I just started a job last week I cannot go without it, well if i want to sleep 20 hours a day i could I am also ADHD.
Although my depression gets really bad i saw no improvement with the medication other than i felt like i was drugged or drunk, unable to wake up or function at all. I use what i need the other med i am on is for my blood pressure. I am a moderator on a bipolar board and the people on there are so screwed up and are on 5-10 meds a day so…, one girl is young she takes 3 10mg Valiums a day i think 50mg of remrod 300 mg of seroquel in the morning and 100 at night along with a mood stabilizer and antidepressant she thinks she is fine. How could anyone handle all of this they are over taxing our kidneys and liver on top of our minds we are mere guinea pigs in their game they read it and it must work they have absolutely no idea what we feel like or what this is doing to people makes me sick.
They also say if you are treated as a child it will help cure you otherwise it will be worse in adulthood Really?? Maybe this might explain all of the shootings in the schools these kids do not need to be so medicated, My God!
I believe talk therapy works wonders another is 5HTP an amino acid magnesium they have found it attaches in the brain much like lithium exercise is good too which i am going to start soon.
I was first diagnosed with bipolar 1 when I was thirteen. I’m now 37. Maybe it’s get better is some people, but it certainly hasn’t helped me. I have always struggled with fall and winter. My husband used to have multiple watch movies set up during the late fall because he was afraid that I could pose a significant threat to myself. This all ended last year, and I’m going to tell you what I did, and you’re going to laugh at me… I would get where everything was so overwhelming. It was almost like a physical force suffocating me, and I was so deep under the depressn … anyway, at some point I realized I was either going to have to end my life Or I had to find a safe harbor for myself. The first time I did this I felt really stupid. I made tea, but not just tea. I turned on music, Tom down the China that you always get got your wedding but you’re never allowed to eat off of, I lit candles, I even got dressed.. and by that time, I had been living in pajamas for going on three months. I made a spread of disturbing treats and’s when I was surrounded by simple but moment things, I have myself fifteen minutes. I can control fifteen minutes. Fifteen minutes to enjoy how little things make me happy. I didn’t even begrudge have to wash all the China by hand. Tea is my thing, but find that simple thing that makes you happy and give yourself fifteen minutes. I honestly think the trick to surviving bipolar disorder is to choose to wallow in the depression (it’s easier) or decide to make steps to make your life better. Last fall was the best one I’ve ever had.
This reminds me of a very useful evidence based technique that I use with almost all my patients:
Write down, every day at least 3 good things that have happened this day. It can be as simple as drinking good tea from expensive china. If you are not sure you have enough to write one day, do some positive things so you have something to write. Many of my patients say this is the technique that really got them out of their problems.
It is important to write them down, preferably in a nice diary so that you can look at them later. Couples can do this together and quickly feel a closer connection.
This technique was found in research by Martin Seligman to be one of the most effective techniques for raising anybody’s mood.
Didn’t work for those dogs in Seligman’s learned helplessness experiments lol.
Great point about polypharma not being evidence based medicine Kjetil. I will be explaining this to some people I know on cocktails.
Taking many drugs at the same time is pr definition not evidence based. All the drugs have been tested seperately in only short term trials, and very few have been tested in combination. So neither long term treatment nor poly pharmacy are based on research. Doctors who prescribe several drugs at the same time are not giving evidence based treatment.
“I do take vyvance but if i refuse to take the others he will not give them to me. ”
Change a doctor or if it’s not possible lie. Tell him you take all of his crap and take only the ones you really need. You’re in charge of your help not some arrogant a****ole.
I am quite interested in the placebo effect. Recently the NY Times ran this intriguing article on aging being a state of mind. http://www.nytimes.com/2014/10/26/magazine/what-if-age-is-nothing-but-a-mind-set.html
I would like to help my son better as he tapers off his current medication. The last three times he has tried have not worked well, and he gets a delayed reaction, which invariably means he goes back on a medication. I sincerely doubt his therapist will go along with administering him sugar pills. So, what can he or I do to create the placebo effect, other than saying that this is just a normal reaction and it won’t last more than a day or a week?
Placebo treatment doesn’t have to include any kind of deceit. Like I have mentioned, using the best nutritional supplements such as massive doses of omega 3 and certain vitamins gives a realistic hope for change. By the way, to get a dose corresponding to 20 capsules of omega3, it is sufficient to eat one box of canned mackerel or a good serving of smoked salmon.
Reading your latest post reminded me of this. You may have seen it. The phenomenon of taking a placebo and knowing it is a placebo showing some beneficial effect.