May 15, 2009Was Suicidality Covered-Up In STAR*D Depression Study?Yesterday, I was contacted by a source with vast experience in mental health systems and research, bringing to my attention patent applications filed in May 2008 in the name of the Department of Health and Human Services (meaning NIH in this case) and the University of Texas and several underlying inventors, one of them being John Rush, formerly a psychiatrist at the University of Texas who's now at the Duke University Medical School in Singapore. More on Rush and the University of Texas in a moment. The patents applications were for a genetic screening test--an assay as they are known--that would determine if a patient would (or could) develop suicidal ideation as a result of taking an anti-depressant. Suicidal ideation (much less suicide itself) is one of the biggest problems attached to anti-depressant use, one long denied by the medical establishment and many patient advocates and some in the media. (Here's the US patent application and the worldwide one.) These particular patent applications claimed that they had isolated certain polymorphisms (variations in specific genes) that accounted for suicidal ideation due to research conducted around the STAR*D trial of anti-depressants and psychotherapy. Rush was one of the leaders of STAR*D, which was underwritten by the National Institute of Mental Health. He also was formerly a director of the controversial Texas Medication Algorithm Project. The trial was a long-term trial of the efficacy of depression treatments and basically the takeaway message was that the best anti-depressant (Celexa in the STAR*D trial) relieved depression about 30 percent of the time with decreasing degrees of relief for each other anti-depressant tried. But suicidality? I'm pretty up to speed on STAR*D and was very surprised by the claim I read in the patent applications (using Google Viewer, see pages 3 and 4 of this US patent application): that 120 patients in the initial Celexa arm of the trial experienced suicidal ideation while 1,742 did not. So out of 1,862 patients, 6.4 percent of them experienced suicidal ideation within three months of commencing treatment with Celexa yet hadn't experienced suicidal ideation before entering the trial. Given that STAR*D is considered a gold standard, long term trial, that finding out to shut up those in the mental health industry who claim that anti-depressants aren't linked to suicidality (yeah, there are loads of FDA black box deniers out there). I was stunned. The press has never picked up on the matter of suicidality within the STAR*D trial, likely because it was never flagged for them by NIMH's press office or by the researchers later interviewed by the media, who tried to paint STAR*D as "proof" that depression treatment worked 67 percent of the time (a story of spin run amok for another day). I was stunned further because I had never run across any reports of anything but stray suicidality in any of the STAR*D papers (and there have been many STAR*D papers), so I wondered if the researchers had somehow covered up this finding, despite its obvious public health implications. In this first STAR*D paper from January 2006, only six people out of a total of 2,876 who took Celexa in the first arm of the trial were mentioned as experiencing suicidal ideation. And in the two STAR*D papers that garnered much media attention in March 2006, I don't recall any mentions of suicidality. So was there a cover up? Or perhaps an obscuring of the finding that showed up in the HHS/Texas patent applications? As it turns out, Rush and other STAR*D researchers reported what is essentially the same finding in this June 2007 STAR*D paper in the Archives of General Psychiatry (which used a slightly different subset of STAR*D patients). "Of 1447 participants, 124 (8.6%) subsequently reported suicidality on at least 1 visit." Suicidality at 8.4 percent is very high. In fact, it's twice the 4 percent rate among kids and young adults that were the basis for the 2004 and 2006 black box warnings demanded by the FDA. And guess what? STAR*D was a study of adults aged 18 to 75. So it's even more striking, because the claim is abroad in the medical world that anti-depressant suicidality doesn't affect adults older than 24 years of age. So much for that claim. So why didn't the press pick up on this? Well, the Archives paper is entitled "Association Between Treatment-Emergent Suicidal Ideation With Citalopram and Polymorphisms Near Cyclic Adenosine Monophosphate Response Element Binding Protein in the STAR*D Study." It's pretty easy to understand why it got missed by myself and others in the media. As for why the NIMH and others involved in STAR*D didn't alert the media to this startling finding, I have no idea. I don't even want to guess at their motives. But someone in that loop had to know about the level of suicidality in the STAR*D trial yet they remained silent. Look folks, in STAR*D the researchers clearly designed the protocol to at least try to capture whatever suicidality might crop up around anti-depressant use. This wasn't an approved-by-pharma study, the kind that seek to avoid suicidality detection--and thence possible public reporting--at all costs. But keep in mind that the protocol for STAR*D was designed in the early years of this decade, well ahead of the black box warnings on anti-depressants. At the time, researchers and many clinicians were still largely in denial about an anti-depressant/suicidality link, so the fact that the STAR*D crew even went looking for any signals of that is amazing. The fact that they detected a demonstrable amount of suicidality is astonishing. But what really blows my little mind is that none of them then went out of their way to raise their voices above a peep about what they had found. That's amazing, astonishing and disappointing. Your tax dollars at work. That said, I hope the gene assay described in the patent applications turns into a real winner. It could probably help save some lives, if its methodology proves out. The listed inventors are: Francis J. McMahon, NIMH; Gonzalo E. Laje, NIMH; Silvia Paddock, Karolinska Institute, Sweden; Husseini K. Manji, NIMH; and, John Rush, then at the University of Texas. We'll see where the assay winds up. But in the meantime, I do have some very serious questions as to why the suicidality in the STAR*D trials never got any public attention, because it obviously deserves attention. Posted by Philip Dawdy at May 15, 2009 12:03 AM
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I'm amazed that they have the courage to claim that suicide ideation can be predicted by genetic tests. "In 1995 Michael Adams-Conroy, a nine years old boy, died due to Prozac overdose. His parents were accused of giving him a premeditate overdose but it was discovered that the boy had a "CYP 2D6 gene defect" - lacked the enzyme that metabolizes the drug." I would love to make this test because I had drug-induced suicide ideation and would like to see what is wrong with my genes. Humans must have their genes changed in order to metabolize synthetic drugs. First of all, it's hard to interpret the Celexa monotherapy part of STAR*D, because there was not placebo control arm, making the results basically uninterpretable. That means that it is impossible to know how much of the 30% remission rate of Celexa was due to the medication, placebo, and natural course of illness (amongst others). That also means that it is impossible to know the degree to which the 8% rates of suicidal ideation are due to the medication, the illness itself, or other factors. Secondly, in the first STAR*D paper, 17.9% of the 2,876 patients enrolled had a prior suicide attempt. In other words, almost one in five subjects had tried to kill themselves in the past. It stands to reason that they would be at increased risk of suicidal ideation returning. Again, without a control arm, it's impossible to know. Thirdly, I can't access the patent application, but I'm already confused by what you wrote. Where are the 1,862 subjects coming from? The Celexa part had over 2,800 subjects. Could you link to the PDF file directly? Thanks! Posted by: dguller at May 15, 2009 05:05 AMHoly smokes. I had just come to this decision a month ago, and had started noting bits of evidence that some ppl genetically respond to SSRI with this aggression. My ballpark estimate is 4%-5% of the population. I was just discussing this idea with a colleague a week ago - and sadly noting that if only Lilly had monitored suicidality back in the 1980s as Prozac was developed, they would have detected this isolated effect for this modest portion of ppl. From that time, the genetics could have been pinpointed much more quickly than 20 years. Tragic. PLus, a warnign could have been placed on the label from day 1: "note: for approximately 4% of the population, SSRI medications lead to impulsive aggressive urges, including homicide or suicide. If you begin to feel aggressive toward yourself or others, or have unusual thoughts of harming yourself or others, discontinue this medication and inform your doctor." STAR*D: you could hide anything in that study. The design sounds OK on first blush: some patient preference decision points combined with some randomization to approach the scientific benefits of the randomized trial. But if you actually try to sketch out the entire design, and patient flow, like I tried, you will at least need several articles, plus you will give up long before you are sure who went where in the design, and for what reason. Posted by: MedsVsTherapy at May 15, 2009 06:10 AMI definitely agree with Ana that the way they are framing this problem is highly suspect. They are looking for a gene that's about how you process the drug, not that makes you prone to suicidal ideation. The point is if you don't process (e.g. metabolize) the drug just so you will become suicidal. Anyone will become suicidal if they aren't processing the drug in exactly the right way with exactly the right dose for them. This has nothing to do with whether a person is "naturally" suicidal or not. It's infuriating. These drugs make people suicidal unless they are taking exactly the right dose at exactly the right time with the right interval between doses etc. etc. The drugs are dangerous, not the people. Posted by: Sara at May 15, 2009 07:44 AMI think it's utter crap. There are well know variations in P450, 5HT, and others, but it is a major stretch to think one can draw a causal relation between genetics and thought pattern and actions. It's one thing to say genetic variability can make one more susceptible to AEs, and that these AEs in particular are associated with a higher risk of suicidality (akathisia anyone?). If a polymorphism is functional, and present to a sufficient proportion in the population, then it may be worthwhile pre-screening before administering said drug. The only value I see is in possibly reducing the number of unnecessary AEs, not in identifying patients at risk for suicide (drug induced or otherwise). The "genetic" problem is with the drugs, not the people consuming them. Posted by: Paul at May 15, 2009 07:59 AMHardly a youngster, and can confirm in at least my case my suicide ideation was overwhelming while on Paxil (arrested and hospitalized briefly). It was not until withdrawal that I fully realized how powerful and pernicious was the effect of Paxil Posted by: richard coughlin at May 15, 2009 08:08 AMAwesome reporting! It's not a shock to see Manji's name listed there, being he is affiliated with CABF bpkids dot org. Back in the early part of the last decade, when I wrote in their parent forum my daughter's direct link to suicidal thinking and Zoloft use, I was banned from that parent message board for saying that. The more I read here, the more it makes me sit back and wonder just what drug is free and clear on the market as a result of non-tainted studies and of course the efficacy is always questionable. Posted by: Stephany at May 15, 2009 10:15 AMActually, people have been studying antidepressant suicides since 1990 when Dr. Martin Teicher published his article on Prozac & suicide. Here is a Journal Article from SSRI Stories that explains about the genes and suicides on antidepressants. It states that 8.8% of those patients in clinical trials [who were non-suicidal when the trial started] developed suicidal thoughts and behaviors on the depression meds. It was published in June of 2007. http://www.ssristories.com/show.php?item=1826 Paragraphs 2 & 3 read: "Investigators studied more than 1,400 people taking part in a large clinical trial on depression treatments, looking for specific genetic mutations linked to antidepressant effects and suicide." "None of the people at the beginning of the study reported having suicidal thoughts or behaviors. After up to 12 weeks of treatment with an antidepressant, 123 reported such thoughts, including 54 men." http://www.ivanhoe.com/channels/p_channelstory.cfm?storyid=16362 Reported June 5, 2007 Genes Hold Clue to Antidepressant-Related Suicidal Thoughts ----------------------------------------------------------------------------------------------------
Paragraph 18 reads [in part]: "The patent for the new Prozac or R-fluoxetine (US Patent no. 5,708,035), which Lilly will market after the existing patent expires in 2001, contains a wealth of information about the original Prozac. According to the patent, the new Prozac will decrease side effects of the existing Prozac such as headaches, nervousness, anxiety, and insomnia, as well as "inner restlessness (akathisia), suicidal thoughts and self-mutilation" - the same effect Lilly has contended has not occurred in any substantial way in some 200 lawsuits against it over the past decade. Most of the suits were settled out of court and the terms kept confidential." SSRI Stories note: The new Prozac was never marketed. Just as the 14-year patent on Prozac is about to expire and the drug's maker, Eli Lilly and Co., is preparing to launch a new version, a body of evidence has come to light revealing the antidepressant's dark side. The company's internal documents, some dating to the mid-1980s, as well as government applications and patents, indicate that the pharmaceutical giant has known for years that its best-selling drug could cause suicidal reactions in a small but significant number of patients. The reports could become critical as Lilly seeks government approval for its new Prozac. Also, Thomas Moore wrote an article in the Washingtonian in about 1995 where he gave the statistics for Effexor & Serzone's clinical trials. Compared to placebo, more completed suicides were committed on the two antidepressants. It was something like 1 on placebo and 9 on the drugs. Thomas Moore used to have this article posted on his Website but it is no longer there. I suppose there was a lawsuit. And just yesterday there was an article on CBS News that the soldier who killed five fellow soldiers at the counseling clinic in Baghdad was denied medical treatment at the clinic. So these lies go on and on but we must not feel hopeless about this. Many people are being warned of the dangers of these drugs through the works of activists and advocates. Only the physicians are clueless. Here is the article from CBS. Paragraph four reads: "Russell had been relieved of his weapon a week earlier, after making some "inappropriate remarks," his fellow soldier said, and he'd been referred to the stress clinic for counseling. But each day, the counselors "sent him back to his base," where Russell complained the doctors were refusing to take his symptoms seriously or give him the medication he thought he needed." SSRI Stories note: Was John Russell in withdrawal or was his medication switched? http://www.cbsnews.com/stories/2009/05/14/national/main5014301.shtml (CBS) A soldier in accused shooter Army Sgt. John Russell's unit says Russell was angry because he thought he was suffering from combat stress. Posted by: Rosie at May 15, 2009 10:59 AM"Given that STAR*D is considered a gold standard, long term trial, that finding out to shut up those in the mental health industry who claim that anti-depressants aren't linked to suicidality" Except that it wasn't a controlled trial so we don't know if they would have developed suicidality on placebo pills, or with no treatment at all. Meaning that STAR*D isn't likely to shut up anyone, whatever they believe about antidepressants, pro- or anti-. Should it have been conducted, then? Good question... Philip Dawdy responds: good point, but real life doesn't include placebos either. Posted by: Neuroskeptic at May 15, 2009 12:33 PMHi Meds Vs Therapy, I am glad you are beginning to see the light on the aggression caused by SSRIs & SNRIs. What led you to this conclusion. Also you state: " SSRIs are actually helping some ppl, while the simple matter of getting attention helps some, and so the suicidality rate is decreasing in the general crowd entering treatment." While it is true that the suicide rate decreased from 11 per 100,000 to 10 per 100,000 during the 1990's and early part of the 21st century, this was only in the general population. It is UNKNOWN as to whether this happened among people who were "treated". Remember that the 1990's and the early part of the 21st century were years of low unemployment and high economic growth - all indicators of a low suicide rate. Even at that, the 1990's & early part of the 21st century did not match the mid 1950's where there was also a low unemployment rate and good economic times. The rate for the mid 1950's was 8 per 100,000 in regard to suicide. Posted by: Rosie at May 15, 2009 01:01 PM I have almost killed myself while tapering Effexor. I'm asking because i just did a post on "polypharmacy". Why the spell checker is not accepting Polypharmacy? "Drug-cocktail" accepted. This is the post I wrote on my suicide attempt: I still didn't write about the second time. I don't think I ever will. See also Laje et al: Genetic Markers of Suicidal Ideation Emerging During Citalopram Treatment of Major Depression. American Journal of Psychiatry 2007; 164:1530–1538. http://focus.psychiatryonline.org/cgi/reprint/6/1/69 About 6 percent of the participants developed treatment-emergent suicidal ideation (see chart on page 72). The authors state that “...the average incidence is 4% for antidepressants and 2% for placebo.” Posted by: Anonymous at May 15, 2009 10:54 PMI have, actually, sat on several seminars given by various people in the field (both basic res, and from pharma) who talked at great length about suicidal ideation. Numbers were thrown around that indicated that there is an increase in suicidal ideation, but a decrease in actual suicides while on SSRIs (this was, if I recall correctly, about Prozac). I have no references for this, but it is a point worth checking out. Posted by: M. at May 16, 2009 10:56 AMM. One of the great myths that psychiatry and big pharma try to perpetrate is that you can have an increase in suicidal ideation but a decrease in suicides. This simply defies common sense but academics still stand up on panels and say it with a straight face. Posted by: Sara at May 16, 2009 12:19 PMSome people, no matter what evidence you present them with, still choose to remain clueless and dissregard that evidence. Doctors have a reason to do so due to thier careers but when individuals do it I just do not get it. My mother in law is trying to get my just turned 18 sister in law to take Paxil, again. Now I told her this is the utmost WORST antidepressant any doctor could ever offer for an adolescent to take, or a young adult for that matter and that in the UK it is STRONGLY recomended (and maybe even prohibited?) that doctors do NOT rx paxil to children and adolescents....and that is why? because it makes kids violent, suicidal and leads them to self harm more than any other antidepressant - What a clueless doctor that he keeps suggesting that she get back on this med, which BTW didn't work well enough the 1st time around for her to stay on it. I also tell her that if my sister in law does have a true and tried mental illness then it is more likely than not it's Bipolar (judging by the Up and down swings in her mood and previalence in the family) and that antidepressants are very likely to induce rapid cycling and mixed episodes and just make things worse for her. I tell her all of this and she still keeps asking me why, again and again, I don't want my sister in law to be put on this medication. Luckily my sister in law believes me when I tell her I have spent a great deal of time over the past four years now, studying the safety of all types of psych meds and that I can say for certain, especialy for a girl who has the type of moodswings she's got going on now, an ssri would most likely only make it worse. It's taken a YEAR of myself and the rest of the family argueing, convincing, and reminding my mother in law to FINALY get her to set up an appointment with a THERAPIST and just at least TRY something that is not a pill. Unfortunately she's waited long enough that my poor sister in law is really all over the place now ...probably in part due to being put on Paxil for a week or two befor I convinced her mom and her herself to get off the drug befor she wound up completely bonkers and hooked on the med with the whole other problem of having to get off it again. Befor she started the Paxil she was depressed, but for good reason, her mother is pulling a munchousens by proxy with this kid, not like she's feeding her arsenic or anything, but giving her all sorts of meds that a kid her age really does not need, every sniffle is Mono, every ache is rheumatoid arthritis, every moodswing (in a couped up in the house inactive teenager) is a mental illness. And so now my sis in law has become a hypochodriac and ANY little ache or pain or heatburn etc., has become a reason that she doesn't need to go to school - mom encourages that behavior and has for YEARS-, and she's mostly home schooled with meetings a teacher a few times a month, and she misses even those. She has NO friends, she NEVER goes outside unless it is with mom, stays in a dark house all day every day, no exercise, no sun, has no social interactions IRL - they are few and faaaar between , She can't handle anyone teasing her at all, even gentle family nudging her to get out and get a life, she throws temper tantrums over stupid stuff and has ZERO social skills and ZERO real self confidence due to the lack of social interactions and relationships, and due to a lack in any real activities or hobbies, and she wonders WHY she feels like such crap all the time. Mom in law thinks she needs meds for her problems, everyone else KNOWS she needs to get out and have a life and that alone will most likely get rid of 80-90% of those problems, over time as she LEARNS to deal with life. The problem is that she's now 18, never had a boyfriend, has no friends, isn't going to graduate and is going to have to transfer to an adult school and is completely overwhelmed by the thought of becoming and adult, having to have a job, HAVING to do anything. Mom's never made her HAVE to do things despite her feeling even the slightest bit unwell or anxious etc. Every little bit of heartburn she may experience she can go ahead and make herself puke and then use it as an excuse to not have to leave the house, not have to push herself, go to school, do anything that is a challenge and would require her to become a stronger individual instead of ALWAYS giving into her weaknesses and NOT doing things she finds the slightest bit uncomfortable. It's excaberated her conditon and blown her problems out of proportion because she doesn't grasp the concept of not always giving in the the voice of "I can't do that" and thus proving to herself that she can do things, anything really, she's not stupid she's just over-protected to the point of making her incapable of handling real life. And the WORST thing about all this is that this poor girl was put on SSRIs when she was 12 years old, on and off since then... No wonder she has no drive or motivation, no wonder she can't deal with her emotions and the little every day "slights" (teasing, sh*t talking etc.). She's been taught that if a pill can't take care of the problem then there is nothing that can be done and so it's fine to just stay at home and not try. She can't deal with the normal annoyances of social interaction that one has to learn to shrug off if they're ever to have normal relationships or have a job, go to school etc. Mer mom, and her dad for that matter NEVER thought to get her therapy depsite her having such "huge" problems since being a pre-teen. FINALY now they are going to begrudgingly do it because she listened to me and has REFUSED to take anymore meds until she first gets to see a therapist for awhile and see if the therapist thinks she actually needs meds or if her problems are things that should be dealt with by, well, learning to deal with life. At least she now realizes that this "meds can fix everything" and are the only solution crap is crap. She see's it's gotten her nowhere. She "punched" the dresser the other day four times (open handed) because she had been reading her journal and realized that she has the exact same problems now, at 18, that she had when she was 16, and she feels like she's accomplished nothing with her life. Mom thinks that is something that requires meds (I mean really??? ARG! And of course she's got my sis in law wearing a wrist brace due to essentaily slapping the dresser and so my sis in law "can't" do anything right now cause she's oh so seriously injured. NOT. I mean it's this sort of coddling over anything, even a stubbed toe, that's lead to the problem in the first place) I know this is something that requires therapy., I've talked with my sis in law about her problems and what is bothering her so much and it is essentialy the fact that she has no life and no social skills and is soooo very thin skinned. Maybe if after a few months of therapy the therapist says, "okay, I know you well enough now to say that your moodswings and problems require medication" THEN meds are in order, but not until then. Her mom kept pushing and pushing to take her to a psychiatrist, and I kept telling her ALL they are going to do is push pills on her. It's taken almost six months now of my sister in law refusing to see a psychiatrist and insisting she see an actual therapist who has no reason or ability to resort to medications right off the bat without evaluating wether her problems are just issues of not having enough life experience and experience in social situations to LEARN the inter and intra-personal skills a person needs to have to keep themselves in a state of mental and emotional wellbeing. ... six months of this refusal and asking to see a therapist for her mom to set up an appointment and give up on trying to push the Paxil on her. In a few weeks she will have her first visit with a therapist, EVER in her entire life of having all these emotional issues, and I am worried that she's not even going to be able to handle therapy. She is so used to having every little complaint she has bought into, and not having to deal with or do anything that she doesn't want to that I worry she'll give up on therapy the first time the therapist points out to her that she has to make an effort to make changes in her life. I've got to call and talk to her about what to expect and WHY she needs to stick with it even if she doesn't like it. OTHERWISE it's going to be one or two appointments with the therapist, her having an emotional reaction to the therapy (which, I am sorry but that is PART of the process), and then it will be back to the meds and the "easy" solutions, and nothing will ever change for the better for this girl, She'll give into the "I can't do anything" state of mind, make no changes in her life, make no efforts, and she's never going to get better until she AT LEAST starts getting out into the sunshine for at least an hour a day and going for at least a walk every day if nothing else. I could hand my mother in law every study showing all the many bad things that can come from psyc meds, I could show her every study proving that therapy is just as effective as medications AND that the benefits one gains from therapy far outlast those from medications, I could have a doctor do the same thing and she'd still choose to disregard it. Some people only want one solution, take a pill that helps you ignore all the other things you could and should be doing, and be damned the risks. Now my mother in law has elevated liver enzymes, which is no suprise when you consider just how many meds she takes, usually at least 6 different ones a day, and more anytime she has a sniffle, then she needs antibiotics. I don't know what posses people to have so much faith in modern medicine and drugs to deal with every little problem they have, all I know is that it doesn't matter how many studies proving the dangers of any medication come out, there's still going to be people, and enough of them to make the drug comps enough money that they can spare the few hundred million or couple billion dollars they pay out in lawsuites to those of us who NOTICE that a medication is having bad effects upon us, that there's no reason for drug companies to come up with safer medications. WHY? why should they bother when there's a significant portion of the population that will even change thier doctor if the doctor recomends against taking a med they have thier mind set on taking (thanks DTC adverstising) in order to get a doctor who will just give them whatever medication they ask for, even if there is NO real reason for them to be jumping the gun and getting on that med. Like antibiotics for viral infections, and antidepressants for emotional issues caused by actual life problems that could be dealt with but that the person just doesn't want to take the effort to deal with. It's just sad. It's like there's a whole population of junkies out thier that are addicted to taking medications that don't even have any addictive qualities other than the whole placebo effect that helps these people think that they are somehow helping themselves by putting a pill in thier mouth and swallowing. Yeah if you're actually ill and the med actually works for that illness, then for all means take it if that is going to help more than it hurts, but I see people ALL THE TIME, taking meds they don't need for conditions they don't really have. They just want the medication, and they want the diagnosis because it gives them a card to pull "Oh I "can't" do this or that because I have X or Y condition"... You do? Really?... "Yeah I even take 4 medications for it, so you know it's gotta be real bad if the doctor will give me all these meds for it." We're being turned into hypochodriacs. I wonder if there are any studies on the incidence of hypochondria now versus, let's say 1950, 60 etc. I bet it's increasing at an insane pace since the whole DTC adverstising thing has started. They will warn medical students to not start freaking out and thinking they have some of the illnesses they learn about in med school because just knowing the condition exists and the symptoms carries a risk of leading a person to falsely believe they have that condition. I really think DTC adds are designed to have this effect, and all the articles written or promoted by big phrma posted on "health" websites that are sponsored by Phrma, if you're at all susceptable to being a worry wort about your health and the power of suggestion you're bound to end up being convinced you have one or two conditions that you don't really have at some point in your life, and if you're doctor is an idiot, then you're going to get the diagnosis and the rx to go with this psychosomatic condition. I really really REALLY wish the mainstream media could find it in thier hearts to get more reporters on thier payrolls like Philip here. More articles pointing out the complications, corruption and risks that come with all sorts of meds, not just psych meds. Maybe if people saw these sorts of articles next to the DTC adds they'd put a little more thought into wether or not it's really worth the risks of treatment to entertain the idea that they may have a non-serious condition that "requires" medication. Maybe they'd think twice about making an appointment to get an rx and insisting on that rx once they're in the doctors office for a condtion that, if they really evaluated their "symptoms", they upon second thought, may not really have. Because once you've got the rx and the daignosis/label, it's hard to go back if there is any sort of expressed sympathy or special accomidations that make your life easier that accompany that diagnosis. I think we all have the tendancy to be sympathy whores at some point or another and what better way to get sympathy than to be ill in one way or another. - I'm not suggesting that most peoples illnesses are some sort of psychosomatic thing, but I've known enough people who have more problems than they really have, if you know what I mean. If there was more info out there to discourage at least equally as much as there is info to encourage people to "evaluate thier symptoms and talk to thier doctors/visit x or y website for a free screening", and to not take every little slight ache, pain, sneeze etc so seriously, I think we'd all be a lot healthier. I mean seriously, people go out and ask for things like Zyrtect and all these new anti-allergy meds that have such wonderful side effects as viral infection, bloody nose, etc, (not to mention the really bad side effects, like cataracts for the nasal sprays, they don't mention in the adds cause they're "rare") when there is Claritin and benadryl, right there at the drug store available to anyone... I just don't get it. I'm glad that we have Philip and FS available to get the real info on the real risks, but unfortunately it's pretty damn hard to get people who are overconfident in moder medicines ability to treat things that really don't require any treatment, and who are happy to have things available to treat the most minor of symptoms, that they just will NOT come and visit and blog like FS and take the time to read the articles here because they are ADDICTED to being able to get rx's for anything and everything, the comfort that for some wierd reason taking those meds gives them, and don't want to have to second guess themselves and think about the very REAL risks they are taking everytime time they put a new chemical in thier body for no real good reason. In the 2006 paper, the one you describe as having only 6 reported patients with suicidal ideation, please reread the cited table (#3.) The 6 patients are in the category of suicidal ideation without hospitalization. The line immediately below it lists another 57 total "psychiatric serious adverse" events, which includes hospitalization for, among other things, suicidal ideation, worsening depression, substance abuse, etc. It's listed in item d of the footnotes to that table. Therefore, there could have been -up to- 63 people with suicidal ideation in that first 2006 paper - a rate of just over 2%. But even if ALL "severe adverse" events were suicidal ideation, the rate would have been 2% in that group. In a depressed population with the characteristics described, I guess I just don't see 2%as a stop-the-presses rate - maybe I've been too depressed in various episodes - I see it as a stop-the-treatment for that specific patient rate, a monitor everyone closely rate, and an "I'm glad they're looking at the polymorphism" kind of rate. There wer no other listed cases of suicidal ideation in that particular paper. Posted by: Ella at May 16, 2009 09:03 PMRe: Genetic Markers of Suicidal Ideation Emerging During Citalopram Treatment of Major Depression (Laje et al.) The authors appear to be reductionists with tunnel vision and retinal dollar signs. Even if genetic tests were available to predict the development of treatment-resistant suicidal ideation, there are many factors involved. The authors concluded, “In summary, we identified markers in two genes within the glutamate signaling pathway that may shed light on the biological basis of treatment-emergent suicidal ideation and have the potential to help identify patients at high risk of having suicidal ideation emerge during citalopram treatment. Such patients may benefit from closer monitoring, alternative treatments, or specialty care.” Here’s my counter response: All patients taking psychotropic drugs need closer monitoring, alternative treatments, and specialty care. If any of the authors are reading, consider this: “The ‘McDonaldization’ of Psychiatry: Psychiatric Knowledge is Not the Equivalent of ‘Fast Food.” You can read more here: http://psychiatrictimes.blogspot.com/2009/05/mcdonaldization-of-psychiatry.html Posted by: Anonymous at May 16, 2009 10:43 PM(dguller wrote at May 15, 2009 05:05 AM) NO it's not "impossible to know". In the actual Journal article it also says that 102 (82%) of the 124 who experienced suicidality on Celexa had NO prior history of suicide attempt. So it didn't work this time to blame the patients - they had no history of suicidality that could return. (dguller wrote at May 15, 2009 05:05 AM) NO it's not "impossible to know". In the actual Journal article it also says that 102 (82%) of the 124 who experienced suicidality on Celexa had NO prior history of suicide attempt. So it didn't work this time to blame the patients - they had no history of suicidality that could return. I believe that "drug-induced suicidal ideation" should always be described as "drug-induced...". "But what really blows my little mind is that none of them then went out of their way to raise their voices above a peep about what they had found. That's amazing, astonishing and disappointing."
"There wer no other listed cases of suicidal ideation in that particular paper." There weren't other -specifically broken out- cases. They're mentioned in that table footnote. Again, I agree, they should have been broken-out. At this point, given the other information you've reported, it seems appropriate to contact the authors and ask them to specify the breakdown of the 57 patients in that line for "psychiatric serious adverse events" - how many were hospitalized for suicidal ideation, how many were experiencing worsening depression, etc.
Re: 1) Genetic Markers of Suicidal Ideation Emerging During Citalopram Treatment of Major Depression. (AJP, October 2007) Gonzalo Laje, M.D., Silvia Paddock, Ph.D., Husseini Manji, M.D., A. John Rush, M.D., Alexander F. Wilson, Ph.D., Dennis Charney, M.D., and Francis J. McMahon, M.D. 2) Association Between Treatment-Emergent Suicidal Ideation With Citalopram and Polymorphisms Near Cyclic Adenosine Monophosphate Response Element Binding Protein in the STAR*D Study. (Arch Gen Psychiatry, June 2007) Roy H. Perlis, MD; Shaun Purcell, PhD; Maurizio Fava, MD; Jesen Fagerness, BS; A. John Rush, MD; Madhukar H. Trivedi, MD; Jordan W. Smoller, MD, ScD A. John Rush is the only author listed on both papers, and he is listed as one of the inventors on the patent, "Methods to identify patients at risk of developing adverse events during treatment with antidepressant medication," which was filed on October 26, 2007. According to the patent application, a provisional application was filed on October 27, 2006. In a commentary in Psychiatric News, October 19, 2007, Jun Yan wrote, "The genetic markers discovered in this study [Laje et al.] have been licensed to Neuromark, a private company that plans to market the genetic test. AJP editors learned of the arrangement after the study was printed and will publish an addendum in an upcoming issue to disclose the additional information." Click on Anonymous to read more. UT Southwestern has been unable to explain certain discrepancies between Dr. Rush's financial disclosures and the income paid to him as reported by pharmaceutical companies while he was employed by the university (Letter dated March 9, 2009, from Barry Burgdorf, General Counsel, The University of Texas System, to The Honorable Charles E. Grassley, United States Senate. The letter is posted on The Wall Street Journal Health Blog). As before, "...none of them then went out of their way to raise their voices above a peep..." (Philip Dawdy, May 15, 2009) Posted by: Anonymous at May 17, 2009 04:57 PM CYP 2D6 may be the new smallpox blankets. In a letter to the editor concerning the Laje et al. study [Am J Psychiatry. 2007 Oct;164(10):1530-8.], Douglas Levinson, M.D., stated, "It would be premature to assume that treatment-emergent suicidal ideation is common and well established or that attempting to prevent it through genetic tests would be possible or useful at this time. (The article by Dr. Laje et al. mentions the reported incidence in children and adolescents, but data for adults are controversial and often show no treatment effect...) In this regard, one might question the appropriateness of the decision (made by the National Institutes of Health [NIH] Office of Technology Transfer [http://www.ott.nih.gov/db/abstract.asp?RefNo=1670] and not by NIH investigators) to allow the genetic test to be commercialized at this stage." Dr. Levinson reported no competing interests. Read more here: http://ajp.psychiatryonline.org/cgi/content/full/165/3/395 Source: Am J Psychiatry 165:395, March 2008 Posted by: Anonymous at May 17, 2009 06:32 PMDr. McMahon replies to Dr. Levinson: http://ajp.psychiatryonline.org/cgi/content/full/165/3/395-a Source: Am J Psychiatry 165:395-a-396, March 2008 Posted by: Anonymous at May 17, 2009 06:54 PMJOL: Which journal article stated that "102 (82%) of the 124 who experienced suicidality on Celexa had NO prior history of suicide attempt"? Posted by: dguller at May 17, 2009 06:55 PM
The STAR*D article from June 2007 - Table 1 Posted by: JOL at May 17, 2009 10:41 PMRe: Laje et al. Genetic Markers of Suicidal Ideation Emerging During Citalopram Treatment of Major Depression. AJP, October 2007. Dr. McMahon replied (AJP, March 2008), "...we agree with Dr. Levinson that it is premature to introduce a test based on these results to the clinic until they are independently replicated..." "...we as a profession need to develop some guidelines as to what clinical genetic tests should be used, when psychiatrists should offer them, and how they should be interpreted in the context of diagnosis and treatment. If we fail to act promptly, then the marketplace will fill the vacuum, which has already begun to occur in other fields of medicine, and psychiatrists may lose the initiative in a debate in which the outcome could have real consequences for our patients and their families." http://ajp.psychiatryonline.org/cgi/content/full/165/3/395-a Then the Federal Register reported on February 29, 2009, “If links between genes and suicidal thinking are validated under a license, depressed individuals at higher risk for suicide could benefit from closer monitoring, alternative treatments, or specialty care while allowing more aggressive treatment in individuals without the increased risk.” http://edocket.access.gpo.gov/2009/pdf/E9-4053.pdf NeuroMark, Inc., plans to develop the Mark-C test: http://neuromark.com/index.html So if every depressed individual had the test, imagine how much money the inventors could make in royalties. I wonder why Laje et al. did not mention they had a patent on the test in their disclosure statements. Posted by: Anonymous at May 17, 2009 11:46 PM"Suicide is a complex malaise," Shneidman said. "Sociologists have shown that suicide rates vary with factors like war and unemployment; psychoanalysts argue that it is rage toward a loved one that is directed inward; psychiatrists see it as a biochemical imbalance. No one approach holds the answer: It's all that and more." http://www.latimes.com/news/obituaries/la-me-edwin-shneidman18-2009may18,0,6007627.story Posted by: Anonymous at May 18, 2009 12:29 AMDear Trail of Tears, JOL: Thanks, I found the table you referred to. You are right that 102 of the 124 subjects who developed treatment-emergent suicidality had no history of prior suicide attempts. I think that it is fairly clear by now that antidepressants do cause an increase in suicidal ideation in certain vulnerable individuals, likely due to the induction of either mixed states or akathasia, at least according to authors that I have read, such as Dr. David Healy. However, looking at STAR*D, without a control arm, it is impossible to know HOW MANY of those who developed suicidal ideation following Celexa use were due to the medication or due to the natural course of the illness. I am NOT saying that there were not any subjects who developed Celexa-induced suicidality, becuase there likely were. But, we cannot know the true incidence of this phenomenon using STAR*D data. That's all. Posted by: dguller at May 18, 2009 07:15 AMTo Trail of Tears, Lawsuits have been brought against the pharma companies because they have not tested the antidepressants in races other than caucasians. The following case from www.SSRIstories.com illustrates the approach that lawyers have taken in these tragic murder-suicides committed by people of races other than causcasians when they were taking an SSRI. http://www.ssristories.com/show.php?item=945 People of Asiatic descent have been "hit hard" by adverse reactions to SSRIs. Here is an excerpt from a lawsuit on a Filipino murder-suicide: happened several years ago in San Deigo, CA: he killed his two sons and himself: this lawuit claims Filipinos have different metabolizing mechanism for SSRIs. 33. On or about April 14, 1997 defendant SmithKline Beecham ("SB") Thursday, May 1, 1997
Computer technician Reynaldo Lacuzong, 35, left a suicide note in his north San Jose home indicating that he had killed his daughter, Rechelle, 9, and his son, Reneil, 5, and then himself, police said. Police were unsure of Lacuzong's motive. The bodies were found by the children's mother, who called 911 in hysterics shortly before midnight. Posted by: Rosie at May 18, 2009 10:22 AM Premature or inappropriate translations, featuring the Laje et al. study... See slide 11 in the following NIH PowerPoint presentation: http://dceg.cancer.gov/files/genomicscourse/khoury-11292007.pdf I propose that NeuroMark rename the Mark-C test "McTest" in honor of the McDonaldization movement in psychiatry. Posted by: Anonymous at May 18, 2009 10:40 AMDr. Healy did note that a 'mixed state' or akathisia might be producing the suicides which occur on SSRIs. However, www.SSRIstories.com has quite a few cases of people killing themselves after starting an SSRI because they suddenly believed they were terminally ill. This was not the presenting symptom when they began taking the SSRI. In fact, one woman on an SSRI killed her husband, two children and herself because she believed that the whole family was terminally ill. She left this explanation in her suicide note. As I have said before, SSRIs cause a new and strange psychosis. The FDA published a General Public Health Advisory on "Worsening Depression & Suicidality in Patient Being Treated with Antidepressant". This was on March 22, 2004. Here is the article from the FDA. It is a good idea to read and reread this occasionally. http://www.fda.gov/cder/drug/antidepressants/AntidepressanstPHA.htm FDA Public Health Advisory Today the Food and Drug Administration (FDA) asked manufacturers of the following antidepressant drugs to include in their labeling a Warning statement that recommends close observation of adult and pediatric patients treated with these agents for worsening depression or the emergence of suicidality. The drugs that are the focus of this new Warning are: Prozac (fluoxetine); Zoloft (sertraline); Paxil (paroxetine); Luvox (fluvoxamine); Celexa (citalopram); Lexapro (escitalopram); Wellbutrin (bupropion); Effexor (venlafaxine); Serzone (nefazodone); and Remeron (mirtazapine). Warning Information Heath care providers should carefully evaluate patients in whom depression persistently worsens, or emergent suicidality is severe, abrupt in onset, or was not part of the presenting symptoms, to determine what intervention, including discontinuing or modifying the current drug therapy, is indicated. Anxiety, agitation, panic attacks, insomnia, irritability, hostility, impulsivity, akathisia (severe restlessness), hypomania, and mania have been reported in adult and pediatric patients being treated with antidepressants for major depressive disorder as well as for other indications, both psychiatric and nonpsychiatric. Although FDA has not concluded that these symptoms are a precursor to either worsening of depression or the emergence of suicidal impulses, there is concern that patients who experience one or more of these symptoms may be at increased risk for worsening depression or suicidality. Therefore, therapy should be evaluated, and medications may need to be discontinued, when symptoms are severe, abrupt in onset, or were not part of the patient’s presenting symptoms. Because antidepressants are believed to have the potential for inducing manic episodes in patients with bipolar disorder, there is a concern about using antidepressants alone in this population. Therefore, patients should be adequately screened to determine if they are at risk for bipolar disorder before initiating antidepressant treatment so that they can be appropriately monitored during treatment. Such screening should include a detailed psychiatric history, including a family history of suicide, bipolar disorder, and depression. Health care providers should instruct patients, their families and their caregivers to be alert for the emergence of agitation, irritability, and the other symptoms described above, as well as the emergence of suicidality and worsening depression, and to report such symptoms immediately to their health care provider. Background Among antidepressants, only Prozac (fluoxetine) is approved for the treatment of pediatric major depressive disorder. Prozac (fluoxetine), Zoloft (sertraline), and Luvox (fluvoxamine) are approved for pediatric obsessive compulsive disorder. None of these drugs is approved as monotherapy for use in treating bipolar depression, either in adults or children. The requested labeling changes are consistent with recommendations made to the Agency at a meeting of the Psychopharmacological Drugs Advisory Committee (PDAC) and the Pediatric Subcommittee of the Anti-Infective Drugs Advisory Committee (Peds AC), held on February 2, 2004. The possibility of suicidality associated with the use of antidepressant drug products in the pediatric population was also the subject of two previous FDA communications (FDA Talk Paper on June 19, 2003, and FDA Public Health Advisory on October 27, 2003). FDA is continuing to review available clinical trial data for pediatric patients with depression and other psychiatric disorders to try to determine whether there is evidence that some or all antidepressants increase the risk of suicidality. Later this summer, the FDA plans to update the PDAC and Peds AC about the results of this review. FDA plans to work closely with each of the nine manufacturers of the antidepressants that are the subject of today’s request to continue investigating how to optimize the safe use of these drugs and implement the proposed labeling changes and other safety communications in a timely manner. To dguller It's sensational enough that 7% of persons who had no history of suicide attempts and no suicidlaity at the start of the study would develop suicidality after some weeks of drug treatment. That finding really deserves to be known. As said "real life doesn't include placebos". How many controlled studies (with placebo) do we have where the researchers ACTIVELY looked for treatment-emergent suicidality (like in this study)? Why? Posted by: JOL at May 18, 2009 11:03 AMRosie, James Torlakson Artist and Father of Elizabeth Torlakson On the morning of March 15, 2004, Elizabeth Torlakson, my daughter, walked into a BART train tunnel and moments later was killed by a train. The San Francisco Medical Examiner's final report states that the presence of her antidepressant Citalopram (Celexa) in her body was the other significant factor contributing to her death (the first being the train). There is mounting and undeniable evidence that SSRI antidepressants induce (cause) high rates of suicide amongst those taking these drugs. Years before Elizabeth’s death, the FDA and the pharmaceutical industry had evidence to this effect, suppressed it, and are still suppressing the full truth. We believe that Elizabeth would be alive today had she been given proper warning in regard to Celexa and its dangers. We believe that this drug, that was supposed to be helping her, killed her. These images, most of which were created to warn the public about the dangers of SSRI antidepressants, may be downloaded and used at no cost. If you need a larger file size for reproduction please contact James Torlakson. This is not a professional medical site. Unsupervised withdrawal from an SSRI antidepressant is extremely dangerous. Any decisions you make in regard to medications should be done under the care and supervision of your trusted doctor. SSRIs and Suicide Results of a MEDLINE Search by Ivan Goldberg, M.D. http://www.psycom.net/depression.central.ssri-suicide.html JOL: There is a difference between suicidal ideation, behaviour, and attempts. It is unclear whether those who never attempted to kill themselves had previous periods in which they displayed suicidal ideation and/or behaviour. It may not have been the case that they never had a suicidal thought prior to Celexa. Again, this is not an argument against SSRI-induced suicidality, because it clearly exists, but only to point out the limitations of this study with regards to determining the true incidence of SSRI-induced suicidality independent of other confounding factors. I believe that there have been placebo-controlled studies that have included suicidality in their outcome data, mainly in the adverse outcomes category. That is where the risk was uncovered after it was noticed in case reports. Posted by: dguller at May 18, 2009 04:04 PM"Will genomics widen or help heal the schism between medicine and public health?" by Muin Khoury. In this videocast Dr. Khoury shows how the Laje, Rush, et al. study data were developed into a product and marketed prematurely. Scroll down to the last videocast on the page at http://www.cdc.gov/genomics/events/special1.htm Posted by: Anonymous at May 18, 2009 09:09 PMPost a comment
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