What is Effective? People who were not responding to their current antidepressant were assigned to receive risperidone or placebo as an add-on to their current antidepressant treatment. On average, people taking Risperdal improved by 2.8 points on the Hamilton Depression Rating Scale (HAM-D) relative to people taking placebo. Look over the scale and tell me if you think 2.8 points is a very meaningful difference. Decide for yourself. Yes, the difference was statistically significant, and when a sample size contains 268 people spilt between two groups, it is common for a small difference to be statistically significant. Similarly small (in some cases moderate), but statistically significant, differences were found on other measures assessing overall mental health, disability, and life satisfaction. Results in terms of response to treatment (i.e., getting 50% better or more) and remission (no significant symptoms of depression) were a little more encouraging, but not overwhelmingly so. In sum, risperidone worked better than placebo as an add-on to antidepressant treatment by a small to moderate margin. So far, so good.
Lies, Damned Lies, and Statistics: Here's two quotes from the discussion section:
In our study, risperidone augmentation offered statistically significant benefit on multiple measures within 1 week, and the magnitude of benefit appeared to increase steadily throughout the study...
Our findings suggest that risperidone augmentation is well tolerated and has beneficial effects early in the course of treatment among patients who do not respond to initial therapy. Investigators have reported that early symptom improvement (during the first week of therapy) may predict eventualremission, a key ultimate treatment objective...Not to be a stickler for details, but at the end of Week 1, the average patient on Risperdal was 1.5 points better off on the HAM-D (see above) compared to the average patient on placebo. Yes, it's statistically significant, but it's pretty close to meaningless. Oh, and at week 2, the difference had shrunk to 1.2 points and was no longer statistically significant. So how did "the magnitude of benefit appear to increase steadily throughout the study" when the benefit decreased from week 1 to week 2? The benefit of risperidone over placebo did improve from a measly 1.9 points on the HAM-D at week 4 to a questionably meaningful 2.8 points at week 6 -- not sure that is a steadily increasing benefit worthy of much mention.
Enter Invega: Here's another piece from the discussion...
Although not evaluated in this trial, a new medication closely related to risperidone, extended-release paliperidone, has hypothetical advantages related to its metabolism and delivery system, including reduced serum fluctuation, reduced peak exposure, and fewer cytochrome P450–related drug–drug interactionswith widely used antidepressants.Awesome! I was hoping they'd mention Invega (paliperidone), the Son of Risperdal and I was not disappointed. As you likely know, Invega is the patent extender for Janssen, as generic risperidone will soon make branded Risperdal into a has-been. This is clearly an attempt to link the present study's modestly positive results to Invega. You can bet your life savings that Janssen reps will be pounding down doors attempting to convince docs that Invega is just like Risperdal but better because of some trumped-up advantages, which will include some of the "hypothetical advantages" mentioned above. So the study, published in a highly respected journal, goes to show that a product just like Invega works as an antidepressant, but Invega gives you the efficacy of Risperdal in a new, improved formulation.
Note to Peer Reviewers: You're not actually obligated to run marketing tripe for Janssen. There was not a single reference cited to support the "hypothetical advantages" of Invega. Not one. In the future, I think such statements that lack supporting data should be excluded from your journal. This is supposed to be about science, not marketing, right?
Where did the Key Opinion Leaders Go? A previous trial examined risperidone as an antidepressant, generally finding the drug ineffective, though one had to look closely to notice the use of tricky statistics (1, 2) in the trial. The prior trial was also noteworthy for its authorship line, which apparently included people whose contributions to the study seemed minimal. In addition, the order of the authors switched around in suspicious ways as the data moved around from being presented at conferences to being published (3, 4).
In the present study, key opinion leaders are nowhere to be found in the authorship line. I know that people at Janssen read my prior posts regarding the prior study -- perhaps they have learned that someone is watching them and that adding authors for the sake of marketing (lending a veneer of "independence" and credibility to an industry funded study) may well become public knowledge, making them look like used car salespeople. In any case, I appreciate that there were no academic authors thrown on the authorship line as a means of boosting the credibility of the present study.
Now I'm off to snort a couple of Seroquel to deal with all of this marketing trickery. Rumor has it that Seroquel can be a pretty good high...