Seroquel for Everything and Academic Spokespeople

Part 1. Seroquel for Depression and Anxiety. AstraZeneca is slowly rolling out the PR for Seroquel as a treatment for depression and generalized anxiety disorder. At something called the 7th International Forum on Mood and Anxiety Disorders, AstraZeneca (via academic frontman Stuart Montgomery) has trotted out data from their latest clinical trials which purportedly show that Seroquel beat placebo for depression and GAD. Here's a quote from the detached, independent, non-conflicted academic author, Stuart Montgomery...

Dr. Stuart Montgomery, Imperial College School of Medicine, University of London and author of the [depression] monotherapy study, said: These study results are remarkable -- all of the doses of SEROQUEL XR examined provided improvements in MDD and GAD symptoms. Results from further studies that are still ongoing will add to our understanding of SEROQUEL XR in these conditions.

What is remarkable is not that 'Quell had a slight advantage over placebo but that an "independent" academic psychiatrist is willing to pimp Seroquel so blatantly. It would appear that Dr. Montgomery is aware of who is putting butter on his bread. Finding a modest to perhaps moderate advantage for a drug over a placebo in treating depression and/or anxiety is far from remarkable, given that there are dozens of drugs and psychotherapies that have demonstrated similar or better efficacy. Then again, it is remarkable that Seroquel is related to increased risk of diabetes (1, 2, 3, 4), which is likely not the case for competing depression treatments. Of course, since the movement has now started to treat depression with antipsychotics (1, 2), perhaps we will see many people with depression moving toward an increased risk of diabetes. It might be worth noting that on the MADRS, which was the measure of depression reported in the press release, one question is regarding eating -- the more you eat, the better your score. So an antipsychotic linked to weight gain is set to do well in that those who eat a lot will score better on this item, which is then taken as a sign that they are less depressed.

I've been tracking the Seroquel for everything bandwagon for some time now (1, 2, 3, 4) and I can't wait to see where this is headed next.

Part 2. The Academic Salesperson. As Krusty the Klown might say, "I heartily endorse this event and/or product"...

Here are some other Stuart Montgomery quotes from press releases:

Agomelatine

"Agomelatine is an interesting and potentially very valuable antidepressant that is effective in both moderate and severe depression", says Professor Stuart Montgomery from the Imperial College School of Medicine in London. "The new agent has a unique mode of action, improves sleep without affecting daytime alertness and its efficacy is not compromised by sexual side effects, tolerability problems or discontinuation symptoms.

Escitalopram (Lexapro)

"These results are important because they show we have a treatment at our disposal which is effective without sacrificing the good side-effect profile obviously preferred by patients," commented study author Professor Stuart A. Montgomery, Imperial College School of Medicine, London, United Kingdom. "The ideal combination for any first line treatment is good efficacy and good tolerability - this study shows that escitalopram has all the potency of the non selective SNRIs combined with the good tolerability of the conventional SSRIs," he concluded.

Lexapro (again)

“This consistent advantage really came out as a surprise,” marvelled Prof Montgomery. “These are shocking data that no one was expecting”. He added: “At that stage we already knew that there was something special about the drug”.

Finally, Prof Montgomery mentioned results coming from further studies that he referred to as “staggering” – these were decisive in establishing Lexapro’s long term effectiveness in treating both GAD and SAD.

One more piece on Dr. Montgomery may be of interest to readers (via The Guardian ):

A leading figure in the world of psychiatry gave a pharmaceutical company advice on how to get its new drug approved while he was sitting on the committee which was deciding the licence application.

An internal memorandum from Pfizer, the world's largest drug company, says Stuart Montgomery would be happy to become a paid adviser and declare an interest to the Committee on the Safety of Medicines (CSM) once the drug, an antidepressant to rival Prozac, had been through the licensing process.

Read the whole article and see what you think.

When Dr. Montgomery or other key opinion leaders with similar conflicts of interest speak, we are supposed to view them as independent expert researchers whose enthusiastic product endorsements are based purely based on science. The manner in which every drug company trot out eager academic spokespeople is a sign that academic medicine has become rotten to the core.

Seroquel for Everthing Update: WHAT??

AstraZeneca has reported that its trials with quetipaine (Seroquel) for generalized anxiety disorder and depression are going well, to the point that it plans on filing for FDA approval for said conditions in 2008. As you may recall, Seroquel is currently being studied as a remedy for, well, just about every mental condition (1, 2, 3, 4, 5). Here's what I'm betting is happening...

You conduct enough studies using a drug that is mildly better than a placebo, making sure to usually enroll a large sample of people. At least two of the studies will turn out to be "statistically significant" and who cares what happens in the other studies -- just don't publicize them or include them in your FDA application! If there are seven or eight studies examining Seroquel in depression currently, then we shouldn't be surprised if two of them yield somewhat better results for Seroquel. Considering that some depression rating scales rate an improved appetite as an improvement in depression, then Seroquel-induced weight gain actually counts in its favor.

Hat Tip: Furious Seasons

Cymbalta for GAD: Repeating the Pattern

Lilly's drug Cymbalta (duloxetine, aka Yentreve) was approved by the FDA as a treatment for generalized anxiety disorder today.

Is this good for people with GAD? Is this good for Lilly? Are there any academic cheerleaders in the house?

People with GAD: Sometimes a medication really does a good job in treating symptoms and sometimes there are red flags that the science does not match the marketing. In this case, it took very little digging to find a red flag – just read the press release!

In clinical trials, on average, patients treated with Cymbalta for generalized anxiety disorder experienced a 46 percent improvement in anxiety symptoms compared to 32 percent for those who took placebo, as measured by the Hamilton Anxiety Scale [HAM-A].

I have not seen the full text of what appears to be the only published study of Cymbalta for GAD. I cannot find the other two duloxetine studies on Medline (the press release claims there have been three studies), which seems odd. Perhaps I should dig a little deeper… In any case, let’s move on to the efficacy of duloxetine in the study referenced in the press release.

My guess (from a similar study examining Zoloft for GAD) is that participants averaged about 25 on the HAM-A at the start of treatment. Using the press release’s numbers, the Cymbalta group comes down to an average of 13.5 while the placebo group came down to an average of 17. Is a difference of 3.5 points on the HAM-A noticeable? Could a clinician tell the difference between someone with a 17 and a 13.5 on this measure? I think that in most cases, yes. But it is probably a small difference.

Adverse events reporting in press releases (and often in journal reports) is a joke, so I am not sure about the safety of the compound. The infamous Traci Johnson case suggests that there may be a risk of suicidality with Cymbalta, but I would prefer to see more data before making a firm association. Of course, given the general link between SSRIs (and newer antidepressants) and increased suicidality, my initial instinct is to be leery of Cymbalta in this regard.

Good for Lilly: This is great news for Lilly. As the Zyprexa debacle continues to unfold, Lilly’s search for good news appears to have arrived in Cymbalta. According to the Indianapolis Star, Cymbalta sales hit $1.3 billion in 2006. With the GAD indication and its rapid expansion into the depression market, I’m guessing that we’re looking at least a $2 billion drug for 2007. Not bad for a drug that has no evidence of working better than any of the older, now mostly off-patent SSRIs.

Academics in the House: Dr. Susan Kornstein of Virginia Commonwealth University, whom I have mentioned in the past in relation to her highly positive statements about Lexapro, is back. In the press release, she states:

With this approval, physicians and patients will be happy to know that there is another medication now available to treat this debilitating condition.

Yeah, they’ll be dancing in the streets. With all SSRIs likely showing similar efficacy to Cymbalta and with psychotherapy showing pretty good (but not great) outcomes for GAD (likely better in the long-term than with meds), we needed a more expensive medication because… WHY?

It is amazing how the pattern repeats itself. Show a medication is at least a bit better than a placebo in the short-term, have an “independent” academic give it the stamp of approval, then talk about how it is an important new addition that will prevent untold amounts of grief and suffering. The safety data are often glossed over and the benefits compared to existing treatments are not discussed at all. This helps people (outside of the sponsoring company)… HOW?

Seroquel for Everything Update: GAD

I have mentioned earlier that Seroquel is being studied as a treatment for virtually every psychiatric disorder under the sun. You can now access a very brief outline of the latest Seroquel study for generalized anxiety disorder here.

The official title: An International, Multicenter, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled, Active-Controlled Study of the Efficacy and Safety of Sustained-Release Quetiapine Fumarate (Seroquel SR™ ) in the Treatment of Generalized Anxiety Disorder (SILVER)

Virtually all big drug trials now have cute acronyms. Seroquel has used BOLDER before (here and here) and now it's SILVER. If only the academic researchers associated with these studies put as much thought and time into their work on the data analysis and writeup of these studies as the marketing teams did in coming up with the acronyms.

And how, exactly, did SILVER come from the above title? Seems like a stretch...

But wait, there's more.

Here's another study. In this one, Seroquel will be compared with placebo in the treatment of GAD in elderly folks. And still another study, this one apparently comparing Seroquel to placebo in the treatment of GAD, again. How about another one -- this one comparing Seroquel to Lexapro for GAD.

And another one -- this one apparently will put folks on Seroquel for a while, then follow those who show improvement. Some who improve will get switched to a placebo while some stay on Seroquel. If people switched to placebo show more anxiety, then AstraZeneca and its allied academics will say that Seroquel is a good long-term treatment. Of course, maybe it's just that Seroquel has withdrawal symptoms, and that is what caused the anxiety. Yes, this is all hypothetical, but it is the card that has been played time and time again for other psychiatric disorders.