February 5, 2008

FDA Discovers That Anticonvulsants Cause Suicide, Too

Or so they find in a preliminary review.

You probably think this is an example of the new FDA, the new anti-Pharma FDA, more attentive to public health, getting their act and their data together for the benefit of Americans.

Ha.  Wrong.

I.

The New York Times reports the story, which of course is only half the story.

According to the FDA website, an analysis of almost 200 clinical trials of 11 antiepileptic drugs finds that the suicide rate is almost double that of placebo. 

On first glance, this seems like the FDA went to the semiotic school of medicine:  "if SSRIs double the rate of suicide, and SSRIs are antidepressants, then antiepileptics, which are also antidepressants, should also double the rate... holy crap, we'd better check."

Popper would be appalled, but psychiatry lives in this world, and so does the FDA.  It's insane, but if that's their  worldview at least they should be true to it and look for suicide in "logical" places.

Nope.  Not even honest in their wrongness.  Semiotics isn't what drove the FDA to these conclusions-- it was even more basic than that.

Lawyers.

One lawyer, anyway.  Andrew Finkelstein, personal injury lawyer from NY, was handling some Neurontin suicides.  How do you make big money?  First, you send the FDA all the adverse event reports you can get; then ask them to put a black box warning on it.  Black box warning is gold: it means the suicide link exists, it's true-- indisputably so (preposterousness of it aside, of course.)  Sprinkle in a dash of off label promotion by Big Pharma and you have yourself a lawsuit masquerading as a self-righteous public service announcement...

It helps to pretend to be for the little guy: "The FDA's complete inaction in protecting the health and safety of United States' citizens from a known serious risk..."

And so, the FDA got cracking...

II.

Let's take a look.  The FDA report finds the risk of suicidal thoughts and behaviors is double that of placebo-- just like the doubling of suicide rates for antidepressants.

But not really.  The rate increased from 0.22% placebo to 0.43% for anticonvulsants.  That's tiny.  But it's also not comparable to antidepressants, because the number needed to harm for antidepressants is 50, for anticonvulsants it's 500.  In other words, antidepressants are ten times more likely to cause suicide than anticonvulsants.

In the 28,000 people in the seizure drug arms, only 4 committed suicide (none on placebo did.) 

I'm not buying the increased suicide risk with SSRIs, but I am sure as hell not buying this nonsense for anticonvulsants.

III. 

So, why did it take 4 years to release the data?  (Finkelstein has been at them since at least 2004.)

I'm not sure I should even mention this because I do not fully understand it, but I will, if only to give a starting point to others with more time.

Russell Katz, MD is the FDA's chief of neurologic drugs; it is his report on anticonvulsants and suicide that is on the FDA website.  He also handled the antidepressant-suicide investigation.

According to an old story (2004) from my San Francisco Chronicle, Dr. Katz may have been involved in suppressing/delaying the release of the antidepressant-suicide data.

Make of that what you will.  I'm going to bed.















Comments

Then again, some of these n... (Below threshold)

February 5, 2008 3:04 AM | Posted by Eigemacx: | Reply

Then again, some of these new, weird anticonvulsants like Neurontin and Topamax are notorious for both causing anxiety and showing no apparent efficacy against placebo, right?

I'm actually under the impression that Topamax divides bipolar disorder in two different conditions, one that responds to it and one that doesn't. But Topamax is a weird, woefully under-studied drug that could have driven me to suicide if I didn't have the space to modulate my clonazepam, but OTOH made me realize I had autistic/schizoid traits beneath the weird bipolar shit that was probably harming me more than the fucked up mood swings.

But why do I digress? Because if you've succesfully built a shield, no matter what weird axis I disorder is happening on top of it, you might be fine but as soon as something starts messing with that shield, you might just get panicky enough. I know I do get morbid thoughts. But hey, I've got music, I've got lamotrigine, I've got clonazepam, couldn't ask for anything more.

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I don't have much to add; j... (Below threshold)

February 5, 2008 9:12 AM | Posted by Steve: | Reply

I don't have much to add; just kudos for a great post.

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It is very strange that you... (Below threshold)

February 5, 2008 9:40 AM | Posted by Phil McCubbin: | Reply

It is very strange that you have invoked Popper here- especially in this way. I find your dismissal of the potential of SSRIs to cause suicide kind of strange. But everything in life is uneven- people we admire for their views on one topic will turn out to have some strange or illogical views on other topics...

But I would love to see a post on the utility of Popper in psychiatry...


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Okay, we have medications w... (Below threshold)

February 5, 2008 4:24 PM | Posted by Will: | Reply

Okay, we have medications with a large incidence of side effects causing a small increase in suicidal thinking. What if the patients' thinking goes like this: "Gee, it already sucked that I have epilepsy, and now I have to be on this awful medication that makes me sleepy and gain weight. I wonder if it would just be easier to kill myself." Can somebody please look at several medications with unpleasant side effects given for some chronic medical illnesses, and see if the incidence of suicidal thinking is greater? We know it's true for dialysis. This is a much better explanation than anticonvulsants and SSRIs somehow "causing" suicidal thinking.

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Why do you call yourself "t... (Below threshold)

February 6, 2008 11:38 AM | Posted by Joe: | Reply

Why do you call yourself "the last" psychiatrist?

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Ah, I get it: "Wovon man ni... (Below threshold)

February 6, 2008 11:41 AM | Posted by Joe: | Reply

Ah, I get it: "Wovon man nicht sprechen kann, daruber muss man schweigen" But Wittgenstein is sooo 20th century you know.

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I tend to agree with you. T... (Below threshold)

February 6, 2008 12:49 PM | Posted by William: | Reply

I tend to agree with you. The anticonvulsant numbers look very weak for FDA to say there is a suicide risk.

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fyi: when I click on Digg, ... (Below threshold)

February 6, 2008 7:57 PM | Posted by Joe: | Reply

fyi: when I click on Digg, I get the registration page, not the login page.

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Just so I'm reading the sta... (Below threshold)

February 7, 2008 8:48 AM | Posted by Anonymous: | Reply

Just so I'm reading the statistics correctly, if the number needed to harm is 500, i.e., 500 people have to be treated with an anticonvulsant before suicidal ideation or behaviour can be ascribed to it, but 1,000,000 (say) of people take these meds, then ~1,000,000/500 = 2,000 people can be expected to have SI and behaviour induced by the anticonvulsant.

Right? I think?

So while it sucks to be one of the 2000, if these meds due in fact control epilepsy and bipolar and mania for the rest of the one million, it's still worth it. At least if you're someone paying the costs of these illnesses and making the call.

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While the gross figures may... (Below threshold)

February 7, 2008 3:53 PM | Posted by Jody: | Reply

While the gross figures may not be staggering, the epidemiology setting forth an increased risk of more than 2.0 is still persuasive. Also, I read that FDA official Russel Katz denied that a lawyer sparked the FDA investigation. In Neurology Today, (June 2005) it stated the basis for the review:

"It came about because a company came to us after looking at their controlled trial database. They thought they might have seen a signal for increased suicidal behavior. Dr. Katz said he could not name the drug at this time. But, he said, there is another anticonvulsant drug that already has been linked with a slight increase in suicide risk. Zonisamide has on its label a rate of 1.1 % suicide attempt vs. 0.4 % for placebo, Dr. Katz said. So, taken together with this second drug, whose sponsor felt might have a signal, we suggested that we might look back at all the new anticonvulsants."

What this means is that other pharma companies sought out the FDA regarding a potential safety hazard. Why didnt Pfizer?

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Why didn't Pfizer ? ... (Below threshold)

February 23, 2008 11:28 AM | Posted by Ricoh Pauli: | Reply


Why didn't Pfizer ? That is the real question. While it is true that the figures may not be staggering from a "number needed to harm" perspective, they are substantial enough that FDA was moved to issue A WARNING. A warning is not a definitive statement on causality; it is a statement to the effect that there is an association between use of a drug or class of drugs and a given undesirable outcome and that there is biological plausability.

They are not laying down an academic treatise. They are issuing the warning so that prescribers and patients can, ideally, make more informed risk-benefit analyses before committing to a course of Rx.

Some will argue -- and the drug manufacturers will -- that the warning may do more harm than good by keeping 'life saving medicines' out of the hands of patients, but even with a BLACK BOX WARNING the medication can still be used but the onus is then on the prescriber to weigh the plusses and minuses, convey informed consent, and document that.

That may sound like more work than is reasonable for the docs, but in our thoroughly over-medicated society maybe it is good for the prescribers to think longer and harder.

The drugs companies by and large don't want that. They want the psychiatrists and family doctors to be fast and loose with their preescription pads.

Many of the drug companies are on record as having marketing plans for psychotropics that make the drugs look so benign that docs are more likely to prescribe off-label for various & sundry disorder(the intent of the marketing is of course to lower the threshold for off-lable prescription).

There is no more flagrant example of this than in the case of Pfizer's Neurontin [see the literature stemming from Discovery in the David Franklin Whistleblower case if there are any doubts about this].

The fact that the impetus to search the anticonvulsant clinical trial data base appears to have come from a 'tip' form a drug manufacturer is particularly telling.

Liability issues are of course at the center of all of this, but to suggest that a lawyer with a boxful of MedWatch reports induced the FDA into action, as Last Psychiatrist did, is a cartoon.

-Ricoh

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It is easy to dismiss the f... (Below threshold)

January 11, 2009 2:12 PM | Posted by Anonymous: | Reply

It is easy to dismiss the findings when you have no personal experience with the matter. My daughter was hospitalized after having a few seizures. She became suicidal once she started her medication. The suicidal thoughts remained until we strted weening her off of the meds. Whe was not depressed about having seizures or having to take medication. She just had many adverse effects: psychosis, temors, suicidal thoughts, etc...

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Look back at all the drugs ... (Below threshold)

July 27, 2010 2:39 PM | Posted by L K Tucker: | Reply

Look back at all the drugs that are claimed to cause suicide. Doesn't it raise suspicion? How is it possible so many different drugs seem to do that?

Did you ever consider that something else is at work?

The problem begins when drugs are allowed to be sold with only a statistical probability of effective use.

Two positive controlled trials are necessary but the drug company can say which of the the test results are entered into the record. In the case of six antidepressive drugs an independent group filed a FOIA request to get the raw data that had been sent to the FDA. It turned out that forty-seven tests had been performed to get the two per drug needed, or twelve tests. None of the companies were required to factor in the failed trials. When this data is considered placebo beats all the drugs, pick any antidepressant drug.

Read these threads to find posters that believe their drug of choice either helped or hurt them. Impossible! What is happening? A little known phenomenon discovered forty years ago when it caused mental breaks for office workers is the likely explanation.

Subliminal Distraction is unknown and unrecognized by any mental health authority. It is closely held information among designers and engineers who work with 'Systems Furniture,' cubicles.

If you have the symptoms from SD exposure you will be diagnosed as mentally ill. Treatment will begin and you will improve or decline. If you do not improve a second drug will be tried. This will repeat until you show improvement. But there is no way to test the effectiveness of any of the drugs. In fact you will improve only if your Subliminal Distraction exposure stops. Whatever drug or treatment being used will be credited with your recovery. With no way to know better you believe what the white coated doctor tells you.

In 1783 London the mentally ill were confined and fed because there was nothing that could be done for them. Surprise, surprise, surprise they recovered with no treatment. It is called Spontaneous Remission. No one knows what it is or why it happens.

It is not possible to determine if Spontaneous Remission happened while someone was under treatment.

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