AstraZeneca Releases Limited Seroquel Data For Depression

About two months ago, AstraZeneca filed three separate new drug applications with the FDA to have Seroquel XR--the extended release version of bad old Seroquel--approved as a treatment for depression as monotherapy, adjunct therapy, and maintenance therapy. I noted at the time that using antipsychotics for depression would represent an huge tectonic shift in treating depression and that it was odd that AZ hadn't released any efficacy data for Seroquel XR's performance versus placebo in treating depression (or Major Depressive Disorder, as AZ has it). AZ yesterday released limited performance data for the drug during a poster session at the American Psychiatric Association's convention. This data has not been published yet in a peer-reviewed journal, so I have no information to share on drop outs as well as whatever statistical methodology may have been used. So it's still Missouri time as far as I am concerned.

Here's the lowdown on the poster session:

1. "In a six-week, multicenter, double-blind study, 723 patients were randomized to receive SEROQUEL XR 50 mg/day, SEROQUEL XR 150 mg/day, SEROQUEL XR 300 mg/day, or placebo. At Week 6, all SEROQUEL XR groups had significantly reduced mean MADRS score versus placebo (-11.07): -13.56 (p<0.05) for 50 mg/day; -14.50 (p<0.001) for 150 mg/day; and -14.18 (p<0.01) for 300 mg/day. By Day 4, all SEROQUEL XR groups significantly reduced mean MADRS score versus placebo (-3.27): -4.91 (p<0.01) for 50 mg/day; -5.43 (p<0.001) for 150 mg/day; and -5.35 (p<0.001) for 300 mg/day. The most common adverse events (AEs) (>5% and double the rate of placebo in any SEROQUEL XR dose group) were dry mouth, sedation, somnolence, dizziness, constipation, back pain, irritability, and myalgia."

2. "In a six-week, multicenter, double-blind study, 446 patients were randomized to receive antidepressant (AD) plus SEROQUEL XR 150 mg/day, SEROQUEL XR 300 mg/day, or placebo. SEROQUEL XR 300/mg day plus an antidepressant showed statistically significant advantage versus placebo plus an AD for 1) change in MADRS total score at Week 6 (-14.70 versus -11.7; p<0.01); 2) improvement in MADRS from Week 1 onwards; 3) response (58.9% versus 46.2%; p<0.05); and 4) remission (42.5% versus 24.5%; p<0.01). For SEROQUEL XR 150 mg/day plus AD, improvements in these variables were not significantly different versus placebo, except for MADRS improvement at Weeks 1 and 2. The most common adverse events (AEs) (>5% and double the rate of placebo in any SEROQUEL XR dose group) were dry mouth, somnolence, sedation, dizziness, constipation, fatigue, and weight increased."

3. "In a time-to-event, double-blind, randomized-withdrawal, parallel-group, maintenance study, 787 patients were randomized to SEROQUEL XR or placebo and dose-adjusted as clinically indicated. The mean daily dose of study drug at randomization (last open-label dose) was similar for the SEROQUEL XR group (176.6 [95.5] mg/day) and the placebo group (177.9 [90.8] mg/day). In total, 89.0% (n=348) of SEROQUEL XR patients were receiving the same doses at study end as at open-label baseline, 5.1% (n=20) were receiving a higher dose, and 5.9% (n=23) a lower dose. The risk of a depressed event was significantly reduced for SEROQUEL XR compared with placebo suggesting increased time to event (HR = 0.34 [0.25, 0.46]; p<0.001). In total, 55 (14.2%) SEROQUEL XR-treated patients and 132 (34.4%) placebo-treated patients experienced a depressed event."

The basic story here is that Seroquel improved MADRS scores by about two or three points over placebo (if I am reading things correctly), and got about a 30 percent effect size over placebo (although I'll need the published study for a final number). Two or three points improvement on the MADRS scale doesn't really impress me much (it may impress others), especially given the many, many problems associated with the use of this drug.

But the Seroquel XR story at the APA doesn't end there. Researchers also rolled out data for the use of Seroquel XR in treating generalized anxiety disorder. AZ announced that it would file a new drug application with the FDA before the end of June seeking approval of the drug for treating GAD.

Here's my prediction: the FDA will soon approve Seroquel XR for use in treating depression (it's already approved for "bipolar depression"), AZ will market the hell out of the drug as a new wave anti-depressant for tough to treat cases, doctors will prescribe the drug (which is already well saturated in the marketplace), and soon enough the stories of even more patients packing on the pounds and unable to be wakeful throughout the day will come rolling in. Along with the stories of even more teens using Seroquel as a drug of abuse.

I hope I'm wrong but I doubt that I will be.