Sunday, December 14, 2008

Anxiety = Psychosis*

That seems wrong, doesn't it? There are plenty of patients who have generalized anxiety disorder who are not psychotic. In fact, I'm not really sure how you'd give someone a diagnosis of schizophrenia and GAD concurrently. To AstraZeneca, however, this difference doesn't matter. They'd like you to give your patients with generalized anxiety disorder an antipsychotic every day, preferably for the rest of their lives.

Confused yet? Don't believe me?

November 2008's American Psychiatry News published an article titled "Study: Quetiapine Monotherapy Works for Generalized Anxiety Disorder" (Vol 1 No 11, p22). The authors discuss data presented on a poster at the meeting of the Anxiety Disorders Association of America, funded, of course, by AstraZeneca, makers of Seroquel XR. The study randomized 234 patients with GAD to receive 50 mg, 150 mg, or 300 mg of extended-release quetiapine versus placebo. The meds were taken for 8 weeks with a 2 week discontinuation taper at the end.

Hamilton Anxiety Rating Scale (HAM-A) scores were used to determine the rate of improvement. Since this isn't the full study, I don't know exactly how anxious the patients were to begin with; this website uses 14-17 for mild symptoms, 18-24 for moderate symptoms, and 25-30 for severe symptoms. The study found that placebo-treated patients improved a mean of 11.1 HAM-A points; 50 mg Seroquel XR patients improved 13.3 points; 150 mg patients improved 13.5 points; and 300 mg patients improved 11.9 points. The 50 mg and 150 mg doses' improvement was statistically significant, p<0.001.>

"The most common adverse events were dry mouth, somnolence, sedation, dizziness, headache and fatigue. During the treatment phase, 15.9% of the patients taking quetiapine XR 50 mg per day withdrew as a result of adverse events, as did 18.1%, 24.4% and 6.4% of those receiving quetiapine XR 150 mg per day, quetiapine XR 300 mg per day and placebo, respectively."
So, the patients taking 50 mg of Seroquel XR improved by 2 extra points on a rating scale, but were 2.5 times as likely to withdraw from the study because they felt the side effects were too severe. That's important here. These patients are saying the improvement in their anxiety was NOT as significant as the addition of the side effects of the medication, given how many of them discontinued the medication.

In the US, you only need to show that your medication is better than a placebo to get FDA approval. Let's ignore the fact that there are multiple good treatments for generalized anxiety disorder, from SSRI's to buspirone to long-acting benzodiazepines to non-pharmacologic therapies like CBT. Let's ignore the fact that AZ is trying to win the approval specifically for Seroquel XR, so if you use plain old Seroquel (expensive enough in its own right) for GAD you'll be using it off-label. Naturally, the drug reps will emphasize the long action and smoothness of XR versus regular (never mind that for most indications, Seroquel can be dosed once daily, which is usually the benefit to using a long-acting form). According to Wikipedia, the Seroquel patent will expire in 2011 in the US, but the XR patent goes until 2017. XR = $$$$$.

*I played a little loose here. The doses of Seroquel XR used in the study were not actually antipsychotic doses (except the 300 mg dose, which was no better than placebo). At 50 and 150 mg doses, you're getting a whole lot of anti-H1, or antihistaminic, effect; some antimuscarinic effect (hence the dry mouth), and probably some anti-serotonergic effect (which likely gives it mood stabilizing properties). No anti-dopaminergic effect. So, using 50 mg Seroquel XR is more akin to using an SSRI + Benadryl than to using Haldol. It's just a LOT more expensive than SSRI + Benadryl. Naturally, we don't have any data to show how Seroquel XR compares to any of our other therapies for GAD, but AZ doesn't have to ascertain this, so they won't. And economically, they shouldn't, if they want to sell shitloads of Seroquel XR.

This is the kind of thing that drives me crazy about psychiatry, medicine, drug companies, etc. There's nothing inherently bad about Seroquel XR; there's nothing wrong with AstraZeneca trying to make money; there's nothing wrong with the article as published, per se. It's just the whole thing put together feels like a huge scam. "Statistically significant" doesn't necessarily mean anything, especially when the clinical effect is small and the side effects were so bothersome that within 2 months 15.9% and 18.1% of patients (at the effective doses) had quit taking the medicine. For those of you who may be in medical school, suffering through evidence-based medicine classes, wondering why in the world do you need to know this crap, THIS IS WHY. So you can be an informed prescriber and consumer of health care dollars and not just take the word of the local drug rep, or even the word of your "Clinical Psychiatrist's News Source".


Dragonfly said...

Interesting. Can imagine patients getting freaked out by the idea of an antipsychotic...

Tiny Shrink said...

Here, anxious person, you need an antipsychotic! No, don't get MORE anxious! It's really for anxiety, I swear!