As if integration issues from the large acquisition of Wyeth weren't enough, here's another reason to worry about Pfizer (NYSE:PFE): The Food and Drug Administration failed to approve Lyrica as a treatment for generalized anxiety disorder. Again.

The pharmaceutical giant originally got a "not-approvable letter" for using Lyrica as a treatment for anxiety back in 2004. Under the new terminology, this time around, the company received a "complete response letter." By any name, it's still a rejection.

As is typical with pharmaceutical companies, Pfizer didn't elaborate much on the rejection, simply saying that the FDA felt that "data contained in the [New Drug Application] were insufficient to support approval." Whether that means an additional trial is needed remains to be seen.

Pfizer is still holding out hope that the FDA will approve the drug as an add-on therapy for anxiety, even though it wouldn't approve it as a monotherapy.

Lyrica is currently approved as a treatment for fibromyalgia, nerve pain, and as an add-on treatment for seizures. Its biggest rival, Eli Lilly's (NYSE:LLY) Cymbalta, is already approved to treat generalized anxiety disorder and depression, so trying to get Lyrica approved for mood disorders isn't particularly weird.

It is rather weird, though, that Pfizer couldn't get Lyrica past the FDA. Large pharmaceutical companies like Pfizer, Merck (NYSE:MRK), GlaxoSmithKline (NYSE:GSK), and AstraZeneca (NYSE:AZN) usually have a pretty good feeling for what the FDA needs to approve a drug, especially after they've seen a candidate get rejected in the past.

Maybe the FDA has moved the goalposts for approval -- it wouldn't be the first time -- but Lyrica's latest rejection just seems like one more stumble from giant Pfizer. You know what they say: The larger they are, the harder they fall.

For a contrarian view, Adam Wiederman explains why pessimism can be a good indicator for successful investing.