This just in: In July, Lurasidone, originally approved for Schizophrenia, was approved by the FDA for treatment of Bipolar 1 depression.
You can now prescribe Latuda for your depressed, bipolar patients. I can't think of "Latuda" without hearing, "Latuda Matata".
Here's a link to the AJP in Advance abstract for Lurasidone Monotherapy in the Treatment of Bipolar I Depression: A Randomized, Double-Blind, Placebo-Controlled Study. The primary outcome measure was the MADRS, and the study was sponsored by Sunovion.
"Lurasidone treatment significantly reduced mean MADRS total scores at week 6 for both the 20–60 mg/day group (−15.4; effect size=0.51) and the 80–120 mg/day group (−15.4; effect size=0.51) compared with placebo (−10.7)"
According to a Wikipedia article that may be wrong,
"An effect size calculated from data is a descriptive statistic that conveys the estimated magnitude of a relationship without making any statement about whether the apparent relationship in the data reflects a true relationship in the population. In that way, effect sizes complement inferential statistics such as p-values."
I'm not sure what it means for an effect size to be 0.51, or for the placebo score not to be recorded with an effect size.
Once again, I went to ClinicalTrials.Gov, and lo and behold, I found:
Lurasidone HCI - A 6-week Phase 3 Study of Patients With Bipolar I Depression (PREVAIL3)
Now, I don't know for sure if this is the same trial they're talking about, but since it was last verified in August 2013, it seems likely (and it was first received in January 2011).
And miracle of miracles, the results are listed.
This may be a little hard to read, but the primary outcome result for Lorasidone 20-120mg is -11.8, and for placebo, -10.4. And the p value is 0.176, which, last I checked, is larger than 0.05.
The abstract had the difference for lorasidone as -15.4, but grouped into two separate dosage groups, 20-60mg, and 80-120mg. This appears to be a subgroup analysis, where you chop up your results into smaller groups after the study is over, and which is a no-no because it can yield spuriously positive results for individual subgroups (I'll get to how this works in a later post).
So the results on clinicaltrials.gov seem to indicate that there was no significant difference.
It turns out, there was another trial listed on clinicaltrials.gov, entitled, Lurasidone - A 24-week Extension Study of Patients With Bipolar I Depression. this study was first received in March 2009, and last verified in February 2013. There were no results reported for this study on the site.
So we have a 24 week study, conducted earlier than the 6 week study, with no results reported. And we have a 6 week study with conflicting results, depending on where you look.
I could be wrong about how to interpret this data. What do you think?
I have found that the scientific department of the company involved can get you the most accurate data and the data that was used for the trials that led to FDA approval for a specific indication. I gave a CME course on the newer atypicals when they first came out and got very good scientific data from all of the companies involved.
ReplyDeleteOn the issue of effect size, there are various approaches. The number posted suggests that it is Cohen's D and an effect size of 0.4-0.7 is considered "moderate".
A look at all of the data for approval of atypicals for bipolar depression would be very interesting if it has not already been published because every company making these drugs tried to get that indication and most of them failed.
Thank you, that was helpful. I have to admit, I'm surprised you were able to get the data from the various companies, given all the problems with disclosure of data that have been in the public eye, lately.
DeleteThe data for atypicals for Bipolar depression would be VERY interesting. It's not at all clear to me why Latuda's data should have been better than all the others.