In my blog post The best bias that money can buy I outlined how doing trials of their drugs in conditions like depression is the ultimate way companies hide bodies. That what is needed instead are studies of drugs in healthy volunteers.
Here’s a good example of what a healthy volunteer (phase 1) study can show, and how the story of antidepressants and suicide might have unfolded in an entirely different manner had this study been in the public domain.
How might the story of antidepressants and suicide have unfolded had this Zoloft study by Dr. Hindmarch been in the public domain?
In early 1983, almost a decade before it launched in the US, a study of Zoloft (sertraline) was run by Dr. Ian Hindmarch in Leeds, UK. There were 12 female volunteers aged between 34 and 40, drawn from the control panel in the Department of Psychology in Leeds University. The study was supposed to randomize half its subjects to sertraline and half to placebo for a week followed by a cross-over between drugs. It was abandoned before the first week was out.
The Pfizer medical report by Declan Doogan noted that the side effects reported in the study were all elicited independently, without communication between participants, that there was a clearcut difference in side effect reporting between placebo and sertraline, and that the volunteers on sertraline were experiencing marked discomfort. The study was accordingly terminated.
All of the sertraline subjects had problems, as had one of the placebo subjects. The placebo subject having problems, however, had sertraline levels in her blood, making the finding even more convincing. The side effects that seemed most clearly linked to sertraline were apprehension, insomnia, movement disorders, and tremors. There were wonderful descriptions of akathisia – the mechanism later linked to suicide induction on SSRIs.
The side effects that seemed most clearly linked to sertraline were apprehension, insomnia, movement disorders, and tremors.
The report to Pfizer noted that these side effects had been described previously by subjects on SSRIs (such as Zelmid, Luvox, and Celexa), that they were well known to be linked to SSRIs, and that as such these effects in this study were likely to be due to serotonin reuptake inhibition.
The volunteers kept diaries in which they reported clear behavioral effects consistent with the warnings that were put on sertraline and other SSRIs 21 years later (in 2004) for agitation and suicidality, as well as a range of other interesting effects such as aggression – see Volunteer.
The Hindmarch study was never published. I got to hear about it in 1998 from Ian Hindmarch himself when we were chatting about an article in the New Yorker by Andrew Solomon that compared the agitating effects of Zoloft to drinking 55 cups of black coffee. Hindmarch said he’d been involved in a study that mapped onto just what Solomon was describing.
Perhaps of considerable importance, despite the outcome of this study, Hindmarch later did another study of Zoloft in healthy volunteers in Leeds that was published in which the volunteers got a much lower single dose of Zoloft. If anyone tries to find a Hindmarch study of Zoloft in volunteers, they will find this one whose report seems completely innocuous.
If anyone tries to find a Hindmarch study of Zoloft in volunteers, they will find this one whose report seems completely innocuous.
Shortly after our conversation, I came upon Hindmarch’s first Leeds study when I was in Pfizer’s archives in New York acting as an expert witness in a case taken by the parents of Matt Miller.
Matt Miller was a 13-year-old boy who committed suicide a week after going on Zoloft. Quite extraordinarily, Pfizer argued that this was not suicide but auto-erotic asphyxiation gone wrong. Pfizer recruited Hindmarch as an expert witness in the case. In a pre-trial hearing, he said that nothing much had happened in his healthy volunteer study in Leeds – that the volunteers had been suggestible, as evidenced by the woman on placebo having side effects.
Hindmarch said that nothing much had happened in his healthy volunteer study in Leeds – that the volunteers had been suggestible, as evidenced by the woman on placebo having side effects.
I tried to get the MHRA (the British regulator) to review the study, but am confident to this day they have not seen what I had seen. The correspondence was published on Charles Medawar’s Social Audit website at one point. Journalists applied under the Freedom of Information Act for the study and four years later got a version stripped of its most interesting details.
There are a few points worth noting. Blinding and randomization perhaps make this study more powerful, but the effects were Evident – see False friends. A controlled trial was not needed to show SSRIs can cause suicide, homicide, sexual dysfunction, and other effects. Pfizer monitors didn’t think they needed to test these findings for statistical significance before deciding what was happening.
Here, many years before these drugs triggered tens of thousands of suicides and acts of violence, was a great deal of evidence outlining the nature of the problem. It still sits in Pfizer’s archives.
Here, many years before these drugs triggered tens of thousands of suicides and acts of violence, was a great deal of evidence outlining the nature of the problem and their understanding of it.
It still sits in Pfizer’s archives.
There were other healthy volunteer trials of Zoloft and other SSRIs in which every single volunteer dropped out – with FDA reviewers aware of this but explaining it away. In a study of another SSRI one of the most distinguished psychopharmacologists in the world at the time stated he had never seen effects like this after a psychotropic drug was given to volunteers and strongly recommended against the drug being developed further. Many of these studies have correspondence that should see the light of day. In a Cymbalta healthy volunteer study, Traci Johnson committed suicide. At least one other volunteer has committed suicide. Other volunteers have become aggressive. None of this has happened on placebo.
The seven women in Leeds who got Zoloft may not know to this day what they had or that they are at greater risk of comparable reactions from an SSRI than others. These women are likely to have many more experiences than they committed to their diaries. What did they notice when they got into bed at night? Have any gone on to commit suicide? It is quite possible that becoming agitated in this way has put each of these volunteers at greater risk of suicide.
Social media are reputed to all but bring people back from the dead. If alive, the women would be between 61 and 69. They may be living near Leeds still.
There are almost certainly others from other studies with stories worth hearing. But there is a bias that even social media cannot overcome – those who were most badly affected if exposed to a further SSRI are more likely to be dead now from suicide or another serious problem.
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Be interesting to see if the UK government intervene here – I doubt it though. Any interference by our government would see a backlash from Pharma. The threat of losing the UK’s biggest pharmaceutical company [GSK] overseas is enough to keep them from speaking out.
Any idea what the Leeds study was called? They are usually given names as I understand it – would the woman have known that Zoloft was the experimental drug or would it have been ‘Drug A’ Vs placebo?
I wonder if any of the women went on to have families and if their children were born healthy – be great if they did come forward.
[…] to save lives (and save psychiatry) 11 years earlier. Against the backdrop of the Miller case (see Mystery in Leeds), they approached the Millers and their lawyer, Andy Vickery. Vickery asked first if they would […]
The following story has just run in the Yorkshire Evening Post
It is my own personal conclusion based on my own use of sertraline for OCD that this particular SSRI may *cause* depression. I did not have depression concomitant with my OCD. Sertraline does help with OCD, but it is also a “flattening” drug and makes me want to do nothing but sleep. In essence, this is what I call an organic depression. I believe that anxiety disorders and depression are not the same thing and are rooted in different chemistries. I would like to opine that suicidality on these drugs is in fact due to increased bioavailable serotonin (what the drug is intended to do), but that depression itself is possibly do to HIGH baseline serotonin within the CNS, not low. I’ve noticed that going off of these drugs does lead to rebound anxiety but also an increase in energy and drive.
I have also used Saint John’s Wort for anxiety (mostly social anxiety) but decided to taper off after 3 months of daily usage because of reduced interest in life/drive, sleepiness, elimination of emotions (including towards my closest family members), and radical personality changes.
I am slowly getting back to my normal, old self (it’s taking time), but I would also opine that had I stayed longer on SSRIs I might have well become suicidal.
If the people in the study were having such dramatic effects in less than a week then they were obviously not cycling up gradually on the Zoloft. There is normally no noticeable effects within the first 2 weeks of cycling up in small steps. (For example, I noticed increased skin itching after 3 weeks but nothing else.)
In addition, my personal experience is that minor side effects subside after a few months of taking Zoloft. They return when my generic brand is switched, only to subside again.
Zoloft has really held me together. I think it’s a blessing for those who are compatible with it. I have been prescribed many other medications over the years but consistently come back to this one. I never feel like it’s doing anything. My life is just OK when I’m on it. I am more “level headed” when bad things happen.
You are lucky and probably unusual. For most takers of Zoloft, there are marked effects within days, sometimes hours of starting. DH
I have had the same experience with Zoloft. Unlike anything I tried in the past, I was surprised that it helped both my depression & anxiety, including compulsive behaviors. It immediately improved my ability to deal with stressful situations. It is a lifesaver for some of us. My doctor said she has been taking it for over 15 yrs & feels the same way.
Zoloft has singled handedly destroyed my life. The withdrawal has caused severe irreparable damage to my body and mind. During the withdrawal, a lot of doctors try and blame your “condition” as opposed to the actual withdrawal. Withdrawal doesn’t even get real until one month clean when the metabolites finally leave the system.
Some people think the drug is helping without realizing how out of their mind they are. It doesn’t help anxiety it alters your mind and makes you a completely different person. Therefore, you simply no longer care.
The highest does I ever took is 50 mg. I can only imagine how out of my mind I would be on the high doses everyone else is forced to take. Withdrawal includes hallucinations, seizures, blindness, low or high blood pressure, pseudo cushings, colitis, severe panic and depressio etc. If you order the new drug info directly from Pfizer they will admit this. Generics won’t tell you this.
People who go around and claim ssris are safer than benzodiazepines are severely misinformed. The damage from ssris is worse and withdrawal is no different only longer lasting with ssris. Common sense says, “If you have to take a drug daily for it to work, there is no possible way you won’t withdrawal from it.”
Psych meds are Neuro toxins and powerful ones at that. Serotonin resides not only in your brain, but your heart and gut. It is playing with fire. Zoloft was given to me when I was 16 years old when they had commercials about how it “isn’t addictive.” What’s worse is people take these years indefinitely when they FDA approval says one should only take them between 6 and 18 months.
I would do anything to go back in time to refuse that trash. I haven’t been able to leave my house in over 2 years since I went through the trauma of Zoloft withdrawal. I would do anything to get my life back, but I know this drug has caused so much damage that I will never be who I was before starting the drug.
If you want to know how serious akathisa is, look on YouTube. There is a man who has had it over 4 years with no cure. What the doctor won’t say even if they recognize it, is that it could likely be permanent. Same thing with the sexual dysfunction ssris cause.
I urge everyone who is currently able to function and has not been exposed to psych drugs to seek therapy. Once you turn down the psych med road you will never be the same again. When the drugs damage you, you will be hard pressed to find any doctor who will admit what is actually happening. I wish someone had warned me.
And unless you are a violent schizophrenic who is in an unstoppable state of psychosis, there is ZERO reason ever to be given an antipsychotic. And even then they aren’t meant to be taken long term. Any doctor who gives out drugs like seroquel for things like anxiety and depression in the absence of psychosis deserves prison imo.
Was just watching this free psychiatry webinar for GP trainees April 2020
“Sertraline if chronic health problem (lower risk of drug interaction)” Sertraline inhibits CYP450 2D6 and CYP450 3A4 so ‘lower risk of drug interaction’… really ?
So a whole new batch of GP’s will be causing more suicide and horror shows.
I started taking Prozac in 1990 and switched to Zoloft about 10 or so years later. I was mostly on a dose of 200mg. I firmly believed all the lies about SSRIs being a wonderful drug that had few side effects, did not put on weight and had none of the serious side effects or addictive properties of Benzos. I believed it was a wonder drug and persuaded my husband to switch to Zoloft too.
The first thing we noticed was that my husband could no longer achieve an orgasm and we both had a slow steady loss of interest in sex. During all the years prior to taking antidepressants I was never suicidal. During the years taking antidepressants I attempted suicide several times and lived with the worst depression, including persistent suicidal ideation that I have ever endured. Over those 30 years I lost a lot of myself often without even noticing. I tried many times to stop taking Zoloft with my doctor’s knowledge. He stated that Zoloft was not addictive and it was merely a return of my depression. He never mentioned possible withdrawal effects, or the need to taper. It took me over 10 years to see the connection between stopping Zolift cold turkey and the severe bouts of vertigo that followed.
Twice I was hospitalised because the dizziness and vomiting were so serious. It was only when I became aware of the dangers of SSRIs through discovering Dr David Healy, among others and set about some serious research that everything started to fall into place.
Then began my many attempts at tapering off Zoloft. Every time I failed because the vertigo was so awful once I got down to about 5mg. I also had other withdrawal effects such as intense restlessness and irritability but the vertigo was my Achilles heel.
Three years ago, my depression intensified, as did an almost overwhelming desire to kill myself that always accompanied it by then. I knew I could never use violent means so I developed a couple of safety measures to keep me alive. Slowly I realised that I had to get off Zoloft. I now had no choice if I ever wanted a meaningful and fulfilling life. So I tapered down and eventually the vertigo hit me at a low dose once again. This time I consumed tapering anyway and stopped completely about 4 months ago. I used an anti-vertigo drug to deal with the attacks which continued.
Reading back through Dr Healys articles I found one from 2011 which mentioned in passing that nortryptyline in a small dose may help so I decided to give it a go. It did help a great deal. About 2 weeks ago I stopped taking the nortryptyline as I had no intention of replacing one antidepressant with another. I took the nortryptyline soley to help with withdrawals. Since coming off all antidepressants I can actually feel my real self emerging. From what? I still can’t find the words to explain what I have lost during those long years. Sharpe edges are falling away and I feel some of that old joy returning. My husband tells me I am softer and more caring. Of course, I retain my furious anger at the injustices and evils perpetrated by human beings on one another, individually and en mass.
Since stopping the Zoloft, I have developed some strange and often painful heart symptoms. The ECG showed I had had some kind of cardiac incident but I refused further testing as I knew how traumatising that would be. I now have a new GP who understands that I cannot have any more invasive tests or treatment so I will just deal with it. I have no idea whether my very atypical heart condition has anything to do with the taking of or the stopping of Zoloft but felt it important to mention it.
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