Pristiq's FDA Chances: Depression – Yea; Menopause – Nay

As more info on Pristiq continues to roll out, I'll do my best to track them quite closely.

While Wyeth scrambles to resolve issues in its Puerto Rico plant to meet FDA standards, Ms. Kathleen Kerr of Newsday recently reported on Pristiq's potential to be approved for use in depression and hot flashes resulting from menopause. I was so excited to see some decent reporting on a mental health issue in a paper other than the NYT. It was also nice to see that it didn't end with "Shares of Wyeth fell 38 cents Friday to close at $51.50 on the New York Stock Exchange."

"If Pristiq wins Food and Drug Administration approval, it will be the first antidepressant and only non-hormonal remedy marketed specifically for hot flashes. But Pristiq isn't without problems – it poses rare suicide risks in young people."

I've scoured the Internet and have found scant information regarding
Wyeth's clinical trials on Pristiq (generic name: desvenlafaxine).
Please e-mail me if
there's specific information regarding the "rare suicide risks" posed
in those under 18. (I can only assume that this statement comes from
the general black-box warning assigned all antidepressants .)

Wyeth, according to the Newsday article, is still in the middle of clinical trials. (From what I can see, they are in Phase III.)
Wyeth currently is testing the drug at 50 mg for effectiveness. About
half of the patients in the clinical trial felt nauseous in doses
higher than 100 mg. The highest dosage that I know of is 400 mg.

"It turns out anti-depressants like Effexor XR (venlafaxine), another
Wyeth drug already on the market for depression, can somewhat control
hot flashes, and some doctors already prescribe it for that purpose.
Doctors may prescribe drugs approved for one ailment for others – a
practice called off-label use."

So doctors already prescribe Effexor for off-label use. This means one
of two things: Wyeth has sales reps pushing Effexor for off-label usage
regarding hot flashes in menopause (vasomotor symptoms, I presume) or
doctors are reporting that Effexor helps their patients who suffer from
these menopausal symptoms. I'd hate to think it's the former.
Especially not with what has gone down with Eli Lilly and Zyprexa. But
do many of the patients using Zyprexa really know where their side
effects are coming from? I digress…

"Pristiq is not chemically identical to Effexor XR but does contain its active metabolite, O-desmethylvenlafaxine."

OK – not chemically identical. Just, uh, similar. Venlafaxine
hydrochloride, desvenlafaxine succinate. Please note: desvenlafaxine
succinate also operates under the clinical trial name DVS-233. Nice to
have handy when the generic name isn't used in clin. trial results.
(I've noticed.)

"'They [Pristiq and Effexor] have some of the same ingredients,' Wyeth spokeswoman Gwen Fisher said. 'The FDA has deemed it a separate drug and required separate clinical trials.'"

Ms. Gwen Fisher, bless her heart, is innocently (term used loosely) defending Pristiq's individuality, we shall say. "Pristiq does not equal Effexor." Since Pristiq's molecules are structured somewhat differently, the FDA requires new trials and data for the drug to be approved for its intended use. I love the following paragraph:

"To retain sales, pharmaceutical companies often develop new drugs that
mimic older ones facing loss of patent protection. The idea is to keep
customers who might otherwise switch to new generic drugs."

It gets better, of course:

"Financial analyst Dr. Jon LeCroy of Manhattan's Natexis Bleichroeder investment bank says if Pristiq is approved, Wyeth could be looking at another blockbuster, but he doesn't expect its sales to rival Effexor's. LeCroy said Pristiq will probably have more success treating depression than hot flashes.

The problem with Pristiq has been its high level of nausea,' LeCroy
said, noting other side effects like sweating and jitteriness. 'The big
market here is as an antidepressant.'"

I can already hear Pristiq's cha-chings not rivaling those of Effexor's. Dr. LeCroy's theory would mean that Pristiq won't be the Godsend that Wyeth hopes it to be if the menopausal market isn't safely in their corner.

Here's the thing: Wyeth's marketing strategy for Pristiq is to hail it as the "new" antidepressant drug, which can also serve as medicine that staves off vasomotor symptoms. Once Effexor goes generic, chances are that Wyeth will not be able to retain most of the consumers they had on Effexor. Doctors will be hesitant to prescribe Pristiq, at first, until more data comes out about its efficacy. Drug reps will convince doctors that,  "Hey! Pristiq is no different than Effexor! It's just structured differently." Not only that, the reps can point out, "Look – Effexor was prescribed off-label by doctors for hot flashes. Pristiq is much better for that, FDA-approved, and specifically targets those menopausal symptoms." If Pristiq is somehow FDA-approved with the data of low-dosage trials, doctors may avoid prescribing the med because of overwhelming evidence pointing to nausea at higher doses. What menopausal woman needs nausea with hot flashes? Ugh.

Imagine this scenario: A patient with – heck – or without healthcare needing antidepressant medication. The patient with healthcare may be denied coverage of Pristiq because its generic, venlafaxine by this point, is cheaper. (Something like this happened to me with Paxil a few years ago.) A patient without healthcare wants the cheapest generic antidepressant that the doctor prescribes. Enter venlafaxine once again. Wyeth's market share immediately plummets for all quarters of 2010.

"Some physicians are not so sure Effexor provides relief for hot flashes and they wonder whether Pristiq really can.

Dr. Benjamin Goldman, an associate attending physician in obstetrics and gynecology at North Shore University Hospital in Manhasset, says he has prescribed Effexor for menopausal mood swings and anxiety but not for hot flashes.

'I wouldn't tell you off the bat it was good for hot flashes," Goldman said. "I really don't have patients that say Effexor helps with vasomotor symptoms.'"

It'd be interesting if the majority of attending physicians feel the same way. Ms. Kerr was a smart cookie and grabbed a rebuttal from spokeswoman Fisher.

"Fisher of Wyeth says the company has done 'really thorough trials for women for vasomotor symptoms [like hot flashes].'"

Nice quote to give, Fisher. The FDA will give its nay or yea in April. It wouldn't surprise me if they said yea to antidepressant use and nay to vasomotor use because of lack of evidence in improved symptoms. Clinical trials send to last somewhere between 6-12 weeks so it would still remain to be seen whether Pristiq would drop off for long-term use.

And lastly:

"Dr. Eric Hollander, chairman of the psychiatry department at Manhattan's Mount Sinai School of Medicine, cautions that antidepressants like Effexor can, on occasion, switch people who are bipolar into manic episodes.

'You want to screen [patients] for bipolar disorder," Hollander said. "They need to be aware of side effects.'"

Dammit. Thank you, Dr. Whoever-You-Are at my behavioral hospital for diagnosing me properly. [sarcasm]