Tuesday, April 14, 2009

Seroquel gets the Abilify FDA Treatment

The FDA's Psychopharmacological Advisory Committee voted last week to recommend that Seroquel be approved as an adjunctive treatment for depression, but it rejected AstraZeneca's request that the drug be approved as monotherapy treatment for depression or generalized anxiety disorder.

According to this
article in The Philadelphia Inquirer, "Panel members, including scientists from outside the FDA and consumer advocates, said Seroquel's risks in depression and anxiety outweighed its benefits."

One of the panel members, Richard Malone, explained that "the risks are fairly well-documented, and I don't think they are acceptable for this use."


While I agree with the committee's rejection of two indications, I'm concerned that they were inappropriately impressed by the Seroquel augmentation data. As far as I know, the augmentation studies have not been published, but a summary can be found on page 27 of AZ's briefing document. It looks like they used the same research design as BMS did in their Abilify augmentation studies, and that the Seroquel results were equally unimpressive (see this article at Clin Psych for a slam of the Abilify data). Seroquel reduced the MADRS depression score by about 15 points, while placebo decreased it by about 12 points. This 3 point advantage is tiny, considering that the MADRS is a 60 point scale. Personally, I don't think that this 5% advantage (3 divided by 60 possible points) is worth Seroquel's side effects.

Particularly since this recently published
randomized trial showed that when Seroquel was added to Prozac, it yielded no advantages over placebo, aside from helping patients sleep better over the first few weeks. This was not a study of treatment-resistant patients (unlike the FDA data) but it nonetheless shakes my confidence in the potency of the medication.

If the full FDA decides to go along with the committee's recommendation, AZ will mount the kind of mega direct-to-consumer marketing campaign that we have seen with Abilify (for background, see two excellent LA Times pieces
here and here), and consequently there will be a little epidemic of obesity among depressed patients. Now that's what I call depressing!

9 comments:

Marilyn Mann said...

Totally agree.

Nancy Frugé said...

Thank you for this, Dr. Carlat.

I am still puzzled by the fact that the formula quetiapine b6 maleate is not mentioned in the company’s briefing document. The FDA brief includes this information.

In regard to The Philadelphia Inquirer article, who was providing the medical care for these patients?

When the CATIE study results were published, Carol Tamminga, M.D., highlighted the obvious need—and reportedly unfilled need in some cases—to adequately monitor patients for whom psychotropic medications were prescribed (Am J Psychiatry 163:563-565, April 2006):

“As long as psychotropic medications were considered relatively free of side effects, psychiatrists could practice in settings appropriate to other mental health counselors. However, medication treatments with high side effect burden demand clinical settings that are capable of detecting and managing serious side effects. This knowledge means that the clinician’s office needs to be equipped to efficiently monitor antipsychotic drug side effects. Blood pressure cuffs, scales, body tape measures, a process for plasma chemistry monitoring and electrocardiograms, and qualified consultants for medical questions become important components of practice. Dynamic information of drug side effects needs to take a prominent place in a patient’s psychiatric chart. Medical consequences of psychiatric drugs are real, preventable, and require focused monitoring. Clinicians will need to have systems for the effective monitoring of drug side effects to maintain and promote physical health among patients as well as psychiatric health.”

In an online CME activity I viewed last fall [1], scant data were presented to support the efficacy of quetiapine XR as adjunct therapy to antidepressants in the treatment of MDD. A single study of quetiapine XR was cited, a poster presented at the 2008 APA meeting [2]. Assuming that this was the best data the speakers could provide for quetiapine XR, I wondered why the drug was even included in the discussion. AstraZeneca provided funds for the CME activity.

[1] CME Outfitters, LLC, Course Materials for Atypical Antipsychotics in Major Depressive Disorder: When Current Treatments Are Not Enough and After the Show, December 3, 2008. Downloaded from http://www.cmeoutfitters.com on November 27, 2008.
[2] El-Khalili N, et al. Poster NR3-088. Presented at APA 2008.

Steven Reidbord MD said...

As bad as this is (and I agree that marketing atypicals to augment antidepressants has a terrible risk/benefit ratio), I believe we dodged a deadlier bullet this time. FDA approval of an atypical for G.A.D. monotherapy would have been a disaster. Or will be, if it happens in the future.

Anxiety is very common at all ages, and drug treatments (e.g., benzodiazepine tranquilizers) are routinely prescribed by non-specialists. Imagine the massive marketing blitz for a "non-habit forming" alternative in the form of an atypical, and the readiness of primary care doctors to embrace this "sensible" alternative. As I noted, this wouldn't be the first time an antipsychotic was marketed this way — but there would be a lot more money behind it this time. Avoiding the addiction potential of benzos by substituting the far more serious medical risks of, say, Seroquel would result in a public health tragedy.

therapyfirst said...

To Dr Reidbord, amen!

Astra Zeneca is out of control, I have to say even Lilly hasn't been this disgusting in a greedy reach.

Don't wait for PCPs to start thinking about using this drug, they are already getting the pitches. And it shows, to me at least, how disgusting pharma overall can be.

Gina Pera said...

I won't pretend to understand all your points, Nancy, but thank you for making them. I find your posts always helpful and informative.

I would be surprised, however, if 1 in 100 psychiatrists take the steps outlined in monitoring drug side effects.

For example, when the wrong choice in psychotropic medication results in hypertension, many physicians simply tack on an antihypertensive, according to reports I hear on a regular basis. (But the hypertension is seldom detected by the psychiatrist.)

Again, do we blame Big Pharma or do we blame poor training of these physicians -- or worse: arrogance, denial, apathy, ignorance. or the lack of accountability?

therapyfirst said...

Furious Seasons is posting today that Astra Zeneca is now looking for an indication to treat Anorexia Nervosa with Seroquel.

"we don't have weight gain issues" circa early 2000, now they want to use this side effect to their advantage?

And I thought Lilly was scum? AZ keeps going and going. Lower!

Paul said...

TF,

Using side effect to advantage? Where do think Viagra came from...?

International Regulatory Affairs said...

Thanks for this useful post.....

Anonymous said...

The Seroquel fad is appalling. Is it's sedative effect not due primarily to histamine H1 antagonism? Non-addictive sleep aids are cheap and available OTC at every drug store and supermarket in the country, and while diphenhydramine can leave you a bit groggy in the morning, it's no worse than Seroquel in that respect!