FDA to review “missing” drug company documents
BMJ 2004; 330 doi: https://doi.org/10.1136/bmj.330.7481.7 (Published 30 December 2004) Cite this as: BMJ 2004;330:7All rapid responses
Rapid responses are electronic comments to the editor. They enable our users to debate issues raised in articles published on bmj.com. A rapid response is first posted online. If you need the URL (web address) of an individual response, simply click on the response headline and copy the URL from the browser window. A proportion of responses will, after editing, be published online and in the print journal as letters, which are indexed in PubMed. Rapid responses are not indexed in PubMed and they are not journal articles. The BMJ reserves the right to remove responses which are being wilfully misrepresented as published articles or when it is brought to our attention that a response spreads misinformation.
From March 2022, the word limit for rapid responses will be 600 words not including references and author details. We will no longer post responses that exceed this limit.
The word limit for letters selected from posted responses remains 300 words.
It is a sad day when the almighty dollar means more than human life. Eli Lilly knew what Prozac was doing to people, nevertheless they saw its income potential and ran with it. I really hope that the justice system will finally admit that Prozac can cause people to commit violent acts. Many people who are taking this medication commit crimes or acts of violence and if they had not been on this deadly medication the thought would have never crossed their minds.
Maybe now the justice system will swallow their pride and give leniency to those poor people sitting in jail because they trusted Prozac to help them.
Competing interests: None declared
Competing interests: No competing interests
Dear Editor, May I thank you for the publication of Jeanne Lenzer's article which contributes greatly to issues of drug regulation and the priority assigned to drug safety by industry. It is stated that Lilly said that " .....[Prozac] has been prescribed for more than 50 million people worldwide ...."
Epidemiological studies and clinical trials show that those treated with SSRIs demonstrate more suicidal behaviour than those who are not treated, and now Lilly's own hitherto undisclosed 1988 trial data confirms that Lilly may have known this 15 years ago but failed to tell the MCA in the application for approval of Prozac.
As reported by M/s Lenzer, Lilly found that suicidal symptoms were doubled in prozac patients versus untreated patients and amazingly Lilly "had excluded 76 of 97 cases of reported suicidality". i.e. 78% of adverse results !.
Lilly's figure of 50 million patients worldwide is interesting and is supported by other independent estimates. 50 million patients can be expressed as 500 x 100,000 patients. Very many clinical and epidemiological studies show that the rate for excess suicides under SSRI treatment could lie somewhere in the rate range of 20 to 180 suicides/100K patients (these are in excess of any background suicides that may occur in those who are not treated).
So this would suggest, worldwide, a potential range of (500x20) = 10,000 to (500x180) = 90,000 excess suicides since 1988.
Whatever the excess suicide rate, it is definitely not zero, if it is only 1 excess suicide per 100K patients then 500 people have died, if it is 5 then 2500 people have died, if it is 10 then 5000 people have died, etc etc. And there are more than 8 other SSRIs used in similar volumes throughout the world.
I agree with Simon Sebo, SSRIs should not be "handed out like candy " for normal life problems by GPs who do not have specific knowledge of the drug and the patient so as to be able to evaluate daily all the effects that signal inappropriate therapy for this patient and onset of agitation and covert suicidality.
Many doctors and patients believe that these drugs are effective, many other doctors and patients know that these drugs produce dangerous symptoms that compound and exaggerate the original mood condition. Lilly's results from 1988, if true, will only confirm yet again that these drugs should never have been so extensively used in primary care and their use should have been restricted to certain serious depression indications which may carry significant risks of suicide if not treated.
Lilly's assertion of more than 50M prozac users worldwide has, perhaps quite unintentionally, confirmed an estimate of the possible extent and scale of this avoidable manmade international tragedy that Lilly will find difficult to deny. 10,000 to 90,000 (or more) potential suicides must now challenge those who would justify and equate lethal harm for some patients with uncertain benefit for others and claim that they were "striking the right balance !"
Graham Aldred
Competing interests: None declared
Competing interests: No competing interests
I'm from Montreal Canada and read the article concerning the contreversy of Prozac in a French newspaper.
I have to admit that I was really concern since I've been using Prozac (the generic Novo-Fluoxetine)for the last 10 years.
I use to suffer of severe depression, anxiety attacks, panick attacks and more. Doctors prescribed me Xanax with therapy. Xanax really didn't do me good. I was willing to do more stuff but the medication sucked out all of my energy.
I went to my familly doctor and told him about the Xanax. He then prescribed the Prozac and told me that if that drug suited me, I was a really lucky person and that life will be better for me.
He explained that I suffer from chemical imbalance in my brain (a gland that secretes that chemical isn't working good) so I have to take the Prozac to maintain a balance.
Good news, I started with 40 mg a day and things were great. Went down to 30 mg and things are still great. I am a good candidate for Prozac and when I read that article, it really made me think that if these sad things really happened with users of the medication, I blame their doctors for not keeping a close look at them.
My doctor clearly told me that not all people are good candidate and followed me on a bi-monthly basis. After ten years, he still follows me but every three months.
Prozac was a life saver for me so please, don't point at the medication but at the person that prescribed it wrong. I can't take Tylenol because it hurts my stomach but some other people can, so same thing for Prozac and all medications.
Thank you
Competing interests: None declared
Competing interests: No competing interests
Bypassing peer review and not adequately reviewing or researching information is not acceptable... unless one wants to boost readership using proven British tabloid tactics. Perhaps a bit more discretion next time...?
Competing interests: None declared
Competing interests: No competing interests
Equally many people do report harmful side effects, not just of Prozac but many other drugs too. Too often they have then been positioned as neurotic, 'anti-medication', uneducated or misinformed, They have been manipulated against their better judgement into carrying on with them and even now many are not properly informed, including of potential adverse effects. In the UK it is not uncommon for psychiatrists and other health workers to evade responding to questions about medication honestly, (rather than being misinformed about them themselves, re previous anonymous rapid response from a GP), by fobbing off questions with statements such as, 'they are not addictive, they cannot possibly harm you, they will make you feel better, think of yoursef as having diabetes, you will probably need to take medication for the rest of your life'. The issue of informed consent comes way down the list compared with 'getting them on medication'. We are not even talking about people labelled as potentially dangerous, it is across the board. It is often very powerful and potentially harmful medication with huge implications for quality of life.
When side effects become so serious they cannot be ignored there is no guarantee the episode will be reported accurately if at all on the Yellow Card Scheme for fear of disclosing mistakes or careless treatment. It is not easy to register with another doctor so cover ups of adverse effects are an unknown quantity. In the field of mental health but other areas as well feedback about adverse effects has been so underreported/unreported that members organisations such as MIND set up their own Yellow Card Scheme. This needs to be formally extended so that people are either given evidence that an accurate report of their experience has been made or they have the means to report the adverse or unusual effects themselves.
Competing interests: None declared
Competing interests: No competing interests
As a father of two (and another on the way), I would like to first thank you for making this information public. For too long we have remained in the dark while the world's children have become targets of greedy pharmaceutical companies like Lilly. We have, what, 8+ million _children_ on Schedule II (prone to cause addiction) drugs like Ritalin and 35 million people have taken Prozac.
And now we see that the 1988 documents Lilly withheld showed 3.7% on the drug actually attempted suicide, more than 12 times that of any other anti-depressant. They didn't just consider suicide--they DID it (and hopefully failed).
That means that Lilly has the distinction of potentially causing 129,500 suicides if the 35 million above continue to take the drug. But hey, how can you argue with outrageous profits, right? How long are we doing to stand by and wait for more bad news--student's opening fire at school, or another Wesbecker whipping out an AK-47 and taking lives?
And what are the responses from Lilly and their psychiatrist flunkies when that happens? We just need to get them some "help" and here's a prescription for more psychotropic, mind-altering drugs--maybe a whole cocktail this time. Anyone see a pattern here? And now here in the US, we have the TeenScreen program drilling their way deep into our school systems to get access to our kids' personal information so they can identify who is "suicidal". Using a subjective, unscientific "survey" they ask questions that, on a bad day, any kid could flunk and therefore be labeled.
What, might one ask, is the next step for our poor adolescent targets? Ask Lilly. They funded the Tennessee TeenScreen program and probably are behind the others for all we uninformed parents know. Thanks to the efforts people behind BMJ and other concerned netizens, we need not be in the dark any longer. http://www.psychsearch.net/teenscreen.html
My family and I thank all of you again for what you are doing to expose this unscientific madness in the name of profits.
Hans Eisenman
Competing interests: None declared
Competing interests: No competing interests
Editor - Jeanne Lenzer reported that documents reporting an activation rate of 38% with fluoxetine (prozac) was suppressed by Lilly and has only come to light from an anonymous source last month.1 I am outraged! Had I been aware of this data, I would never have taken fluoxetine myself or prescribed this drug so frequently to my patients as a GP.
On 6 September I was offered fluoxetine by my own GP to deal with an episode of depression secondary to multiple life stressors. I was of the belief, as many GPs are, that it is an FDA- approved, safe and effective first-line SSRI and that the benefit is a shorter depressive episode instead of enduring depression for 6-9 months without medication. On 23 September I found myself taking one painkiller after another. I was at a loss to understand my actions. I sought help from my partner to keep an eye on me and cancelled all my clinical sessions. I could not understand why I was both obsessing about suicide and acting upon these thoughts 2.5 weeks after commencing fluoxetine. I had no prior history of suicidal thoughts, depression or mental illness. I decided to keep a diary. I found myself attempting an almost fatal overdose on the 6th of October. I stopped momentarily after taking 13 tablets of coproxamol thinking I might actually die. What am I doing? My partner rushed me to Casualty. I felt as though I was literally under the control of a mind-altering drug, like LSD; although I have never taken illicit drugs. I had constant visual obtrusive thoughts and imagery of seeing myself commit suicide.
Even after discharge, the imagery persisted, changing to a scene of me jumping out of a window. I could not stop shaking; I was agitated and manic and thought I need mood-stabilising drugs! I have been fortunate that between the rapid access psychiatric team and me, we reasoned that it must be the effects of prozac, and this was stopped. It took 2 weeks to clear from my system during which time I experienced my last suicide attempt on 19 October; I found myself walking backwards on an underground train platform onto the white line prepared to jump in the path of a train! Fortunately my partner never left my side and I did not die. I am fine now and have no further episodes of agitation, mania or thoughts of suicide. Now with the passage of time alone and no magic pills, the stressors in my life have resolved and my mood has lifted. I decided to enquire among colleagues about fluoxetine and was saddened to hear that the elderly Catholic aunt of my best friend from medical school was not so fortunate. She jumped out of a 23-storey window in NYC 3 weeks after taking prozac last year. Her aunt had sought help from her priest the day prior, as she was also aware that something was wrong. Prozac is no longer a first-line drug for my patients! Prozac kills and the medical community needs to be informed!
Competing interests: None declared
Competing interests: No competing interests
A member of my family was nearly suicidal this past weekend and has been on Prozac for several years. In this case the prescription was stopped for six weeks (too "busy" to refill the prescription), then started again for a week, then stopped again when on a family vacation for the weekend (forgot it at home). The second day into being off of it again, resulted in a trip to the emergency room for safety due to thoughts of suicide.
Cleary the on again, off again nature has more to do with this, medicinally, than anything else, but to what extent does the effects of Prozac have? That's what I am attempting to uncover now. How appropriate that this issue was again brought to the public eye at this time?
Further, my son is ADHD is on low doses of Adderall. I have been fighting with his mom (my ex-wife) to maintain a regimen of therapy and behavior modification, with the Adderall as an aid only.
My hope is to eventually ween him off the Adderall as he learns how to deal with his issues. This is not to say, however, that I feel that he shouldn't take the medicine. I just don't feel that it is the be all and end all of his treatment.
I took it upon myself to research all available alternatives. This research included, but was not limited to, interviewing several doctors that are reputable in this field in order to form a qualified opinion to the best of my ability.
The bottom line message that one must take from the Prozac, and similar, stories, and from Dr. Sobo's reply and articles is one of reasonability, the forest from the trees, as it were.
Too often we, as humans, get caught up in extremes. I have found, dealing with the public daily, that there are generally THREE sides to every story...not two. "My" side, "your" side and what is actually the case.
The pharmaceutical industry is not "evil", nor is it the answer to all our ailments. Too often we see profits outweighing sound medical decisions while the original intent is to cure.
The fact is that we are all responsible for what I would call "due diligence". Question why a drug or treatment is being prescribed. What can one expect? What are the potential side effects? Is this the right treatment for me? Get a second, third, fourth, etc., opinion if you are not satisfied.
We hear these words time and again but rarely heed them. It is far too easy to sit back and wait for something to go wrong, blame someone else, and say we didn't know. This is similar to suing McDonalds for burning yourself on a hot cup of coffee.
Doctors should be looked up to for their knowledge as well as their ability to help and heal. However, they are also human and can make mistakes. We carry a responsibilty to learn all we can to augment treatment.
Of course, all the so-called "due diligence" in the world is worthless if the information one seeks is being deliberately withheld. Therein lies the true story here.
Competing interests: None declared
Competing interests: No competing interests
I would like to first of all mention that I am a bi-polar II sufferer who was only diagnosed correctly in 1998 when I turned 40. This led me into a lot research into what this specific "illness" "imbalance" is and what types of medication is curently on the market to help people like us.
I have suffered from mood swings from my early teens and I have always felt that I was often "mad" and why couldn't I cope with life like "normal" people. Since the age of 22 I have been put through the mill, sleep therapy, ECT, librium, rohypnol, and many others (etamine, I think was one which almost made me catatonic!). I have changed pyschiatrists until I finally met my current psychiatrist who diagnosed me with a mood disorder. I remember asking her if I was a manic depressive (ignoramus?) and she would always reply "something like that", although she did not tell the whole story. Eventually during her CBT with me, we found a medication that would not make me feel as though I was living in a cloud, but let me feel NORMAL. We tried many and eventually found the right combination, and in South Africa this medication needs to declared a chronic condition with the medical aid, so she submitted a report which stated my diagnosis. Well, that is how I discovered the name to me disorder, so know thine enemy - that's where my investigations started.
Since then I have taken a very deep interest in psychiatry and I have found, my to my horror, that anti-depressants are being handed out willy nilly, but by non-specialists like the family doctor. In my opinion this is a very specialised field and can have dire consequences on any patient, and family of the patient. With medication must come counselling, acceptance and knowledge. Since being on Lilly Fluoxetine (a generic of Prozac), I have not had one suicide attempt, nor have I had violent outbursts which occured quite frequently during my hypomanic episodes. What I am trying to state is that in my personal experience yes, Prozac (fluoxetine), does help, but it MUST be administered by a specialist not a general practitioner. A specialist should then monitor side affects, as my psychiatrist did until I was well balanced again.
If I look back at my life, I have had more suicide attempts THAN I CAN COUNT but none since correct medication has been administered, and maybe, my life could have been a lot, lot HAPPIER than it has been... life only started for me at 40, so what is right, and what is wrong?
Competing interests: None declared
Competing interests: No competing interests
SSRIs, suicide and violent behavior: is there a need for a better definition of depression?
To what extent do SSRIs increase the risk of suicide or violent behaviour? A recent meta-analysis on both published and unpublished data (Whittington et al., 2004) indicates that some SSRIs lack a favourable 'risk–benefit' profile for treating childhood and adolescent depression.
This study underscored the need for improved transparency in clinical studies, and led to a statement by the International Committee of Medical Journal Editors (ICMJE) requiring open registration of such studies (Abbasi, 2004). In addition, the BMJ recently reported (Lenzer, 2005) that documents could cast doubt on conclusions that fluoxetine treatment was not associated with violence observed. This controversy raises other critical issues of SSRI use that merit our consideration.
First, it questions the external validity of clinical trials in which ‘depressed’ patients at high suicide risk are excluded, and therefore potentially different from those treated by SSRIs in primary care settings.
Second, SSRI treatment can trigger mood changes in undiagnosed bipolar patients (Henry and Demotes-Mainard, 2003) resulting in agitation and disinhibition, and such effects may lead to suicide and violence.
Finally, although all these subjects can be viewed as suffering from depression, far less is known concerning the nature of their depression.
The defining criteria for DSM-IV (APA, 1994) major depression remain in fact very similar to those employed during 19th century, where pharmacotherapy was absent and descriptions of depression phenomenology were typically restricted to profoundly depressed patients. Currently, a large number of patients are diagnosed as depressed because they complain about sadness, however it is not clear if they should be considered as depressed. They may certainly have severe depressed mood that merits attention, but do they necessarily exhibit the same illness needing the same medication? An increasing amount of data now shows that some types of depression recover under antidepressants, whereas some other forms are worsened under the same treatment (Henry et al., 2003; Benazzi et al., 2004). These studies demonstrate that patients may fulfil all DSM-IV criteria for major depressive episode, but they show highly divergent clinical patterns: responders to antidepressants appear to correspond to the former ‘endogeneous depression’ description (characterised by psychomotor retardation, affective anaesthesia, and inhibition) whereas patients worsened by antidepressants have a mixture of depressive symptoms and agitation (restlessness, racing thoughts, emotional lability and hyper -reactivity). As we now have access to efficient drug treatment, it is important to reconsider diagnostic categories in the light of patient response to treatment (as is the case for other medical fields). Perhaps differential response to antidepressants could lead practitioners to better define depression, and its subtypes.
Chantal Henry and Jacques Demotes-Mainard
chenry@perrens.aquisante.fr
Hôpital Charles Perrens, 121 rue de la Béchade, 33076 Bordeaux cedex. France
Whittington CJ., Kendall T., Fonagy P., et al. SSRIs in childhood depression: systematic review of published versus unpublished data. The Lancet, vol 363: 1341-1345
Abbasi K. Compulsory registration of clinical trials. BMJ, 2004, vol 329, 637-638
Lenzer J. FDA to review ‘missing’ drug company documents. BMJ 2005, 330:7
Henry C., Demotes-Mainard J. Avoiding drug-induced switching in patients with bipolar depression. Drug Safety 2003, 26:337-351.
American Psychiatric Association. Diagnostic and statistical Manual of Mental Disorders (DSM-IV), 1994.
Henry C., Van den Bulke, Demazeau N., Demotes-Mainard J. Why are some depressions worsened by antidepressant? Bipolar Disorders 2003: 5(1): 24.
Benazzi F., Koukopoulos A., Akiskal HS. Toward a validation of a new definition of agitated depression as a bipolar mixed state (mixed depression). Eur Psychiatry. 2004, 19(2): 85-90.
Competing interests: None declared
Competing interests: No competing interests