AstraZeneca(Atacand, Crestor), GlaxoSmithKline (Advair, Boniva) and Pfizer (Benadryl, Lipitor) have all already begun to scrap projects, while others like Sanofi-Aventis (Allegra, Plavix) are about to pick up the trend and start making cuts.

The cuts come as no surprise, as big pharma companies have been seeing there pipelines shrink since 1998, when the trend to buy out drug rights from smaller bio-tech companies began.

Despite the increased cost efficiency of buying drugs from smaller bio-techs, I am not so sure that big pharma is going to like the end result of their decision.

Stephen Foley raises some excellent questions in a recent post, saying

those calculations about the benefits of in-licensing over in-house could change rapidly if the competition for licensing deals, which has been getting more ferocious for several years, increases dramatically. It could be that they will regret swinging cuts to their R&D budgets sooner rather than later.

And there is another reason for executives to pause. There are very great political benefits from drug companies being able to trumpet the life-changing discoveries that have emerged from their research labs and their scientific trials. Yes, these are companies that have manipulated the publication of scientific data, made over-reaching claims for their drugs, and practiced price gouging of government health and insurance services, but they are also companies that lower our cholesterol, shrink tumors, keep diabetes in check and lift the burdens of depression. In the UK, there is an explicit compact with the government on this score: drug prices charged to the National Health Service are set to allow for investment in research. In the US, the good works of drug research help keep in check the demands for re-importation of drugs from lower-priced Canada, and other cost-cutting measures.

It sounds like big pharma is trying to have their cake and eat it too; outsourcing research and development to cut costs while still maintaining control over patents on drugs to protect their profits.

Cutting the cost of research and development is like cutting off your leg to lose weight. Why not cut the fat of advertisement out first. After all, aren’t doctors suppose to tell us the medicines we need?

After they get rid of the cost of research and development, what excuse will big pharma have left to overcharge consumers?

Earlier this month, a closely-watched trial over the osteoporosis drug Fosamax ended in mistrial, to the frustration of nearly everyone involved. The trial was marked by great tension, with a deadlocked jury, reports of threats of physical violence, and a judge-ordered cooling-down period.

What could cause such intense drama? Well, this was just one of approximately 900 state and federal cases pending against Fosamax, alleging that that medication causes osteonecrosis of the jaw (the death of jawbone tissue). In large part, the tension in the Manhattan courtroom was that this trial — the first — was supposed to be an indicator of how these hundreds of similar cases might proceed. The other major factor is that it is notoriously difficult to “prove” drug-related injuries, and this difficulty was definitely shown in the frustration and tension among jury members.

Millions of women have taken Fosamax (alendronate), a Merck drug that was approved in 1995 to treat osteoporosis associated with menopause, and in 1997 to prevent osteoporosis itself. Until the recent introduction of some competing medications, it was one of the most popular drugs in the U.S. It is still prescribed millions of times per year to women suffering from bone loss.

In short, Merck’s defense on this topic is that there is no definitive evidence that Fosamax causes the death of jaw tissue, while plaintiffs and their lawyers insist that Merck overpromoted Fosamax without warning doctors about the potential for jaw injury. Obviously, no conclusions were reached.

Of course, this is of great interest to women who may have taken, or are considering taking, Fosamax. Only your doctor can decide what is the right choice for you, but we thought we would enumerate the other medications available for treating osteoporosis for those doing research on Fosamax alternatives. One very important thing to be aware of it is that Fosamax is not the only osteoporosis drug in this class (the bisphosphonates), which all have a similar mode of action. Fosamax is being talked about most in the media, but all are associated with some amount of risk of damaging the jaw.

If you do choose to take a bisphophonate, know these facts:

• A high proportion of jaw injuries occur following high-dose intravenous administration, so that is a particularly risky way to take the medication.
• As many as 60% of the cases are preceded by a dental surgical procedure involving the jaw. In short, women who are expecting major dental work should consider delaying treatment with Fosamax, Boniva, Actonel or similar drugs until after their dental surgery.

Here are the main alternatives on the market for Fosamax:

1. Actonel (risedronate) is a bisphosphonate manufactured and marketed by Procter & Gamble and Sanofi-Aventis. It belongs to the same family of drugs as Fosamax, and may be associated with the same jaw side effects.
2. Boniva (ibandronate) is also a bisphosphonate, manufactured and marketed by GlaxoSmithKline and Roche Laboratories. It is a competitor to Fosamax, and may also affect the jaw tissue.
3. Evista (raloxifene) is NOT a bisphosphonate , but rather an oral selective estrogen receptor modulator from Eli Lilly and Company that affects bones through estrogen. Evista may be an interesting alternative for women concerned about their jaw health or planning oral surgery.

Also this month, The Wall Street Journal published an article called “From the Osteoporosis Front, Updates on Potential New Drugs.” These are the up-and-comers in clinical trials and going before the FDA. The story covers the latest news about Wyeth’s Viviant, Pfizer’s Fablyn, Amgen’s denosumab, and other upcoming treatments for osteoporosis.

If you are interested in following the Fosamax case that ended in a mistrial, it is expected to be re-tried in the spring. The name of the case is “In re Fosamax Products Liability Litigation, U.S. District Court, Southern District of New York (Manhattan), No. 06-1789.”

However, people suffering from atypical depression — characterized by hunger and sleepiness, rather than loss of appetite and insomnia — may have different needs in an antidepressant and should discuss with their doctor options such as Bupropion (familiarly known by its GlaxoSmithKline trade name, Wellbutrin), which could help where popular SSRIs might fail.

That is because SSRIs — Selective Serotonin Reuptake Inhibitors — work on the neurotransmitter Serotonin, while Wellbutrin — an NDRI — is a Norepinephrine and Dopamine Reuptake Inhibitor. This change of focus in the affected neurotransmitter may make all the difference for those individuals who suffer depression in an atypical manner.

Atypical depression differs from regular, “melancholic” depression primarily in energy and appetite. It is often characterized by “reversed vegetative symptoms” such as over-eating (regular depressives have little appetite) and/or over-sleeping (regular depression is usually characterized by sleeplessness).It is estimated that up to 40% of people suffering from depression have atypical symptoms.

Wellbutrin reportedly has a more enlivening affect than the SSRIs, so it is often considered for those who are sleeping abnormally long amounts. (For this reason, it is not advised for those suffering anxiety or agitation.) It is also one of the only antidepressants that is not associated with weight gain, and for this reason is also suitable for atypical depressives who may be overeating.

Even successful users of SSRIs have reason to consider Wellbutrin. SSRIs have widely-known sexual side effects that trouble some patients, even if the SSRI is curing their depression. This may make them turn to their physician for refinement of the prescription. Says Ray Sahelian, M.D.:

Since bupropion raises dopamine levels, it actually can enhance sexuality rather than depress libido as do many SSRIs. Bupropion has been shown to have a favorable effect on sexual dysfunction. Several reports and small, short-term trials have examined bupropion as an adjunct or substitute for other antidepressants in sexually dysfunctional patients. This means that Wellbutrin is often prescribed for sufferers of atypical depression, but it is also prescribed as an add-on for people using SSRIs who would like to try to combat the sexual side effects of SSRIs.

In other words, Wellbutrin is often prescribed as an add-on to an SSRI for the express purpose of relieving some of the SSRI’s sexual side effects (usually loss of libido or functioning).

Depression is not the only condition that Bupropion has been approved to treat. In 1997, it was approved by the FDA as a smoking cessation aid under the name Zyban. And in 2006, Wellbutrin XL was approved as a treatment for Seasonal Affective Disorder. Because both Wellbutrin (prescribed for depression) and Zyban (prescribed for smoking cessation) are essentially Bupropion, patients should not take both at the same time; they would be doubling their dose.

Caution: The most well-known side effect of Bupropion is that it lowers seizure thresholds. Doctors have worked around this with lower dosages (it is highly dose-dependent) and controlled-release formulations. Still, those with seizure disorders should avoid Bupropion. Other common side effects are nervousness/ agitation and insomnia. As with any antidepressant, people suffering from increased depressive symptoms or thoughts of suicide should contact their doctor immediately.

Some formulations of Bupropion are available as generics in the United States and Canada.

U.S. Brand Names

• Budeprion SR®
• Budeprion XL®
• Buproban™
• Wellbutrin SR®
• Wellbutrin XL®
• Wellbutrin®
• Zyban®

Canadian Brand Names

• Novo-Bupropion SR
• PMS-Bupropion SR
• RATIO-Bupropion SR
• SANDOZ-Bupropion SR
• Wellbutrin XL®
• Wellbutrin®
• Zyban®

A couple of years ago, actor Tom Cruise was dismissed as a kook for ranting against antidepressants and other psychiatric drugs. But in light of what we’re now learning about SSRIs, is it possible that we collectively owe Cruise an apology?

First, let me say that I still think Cruise is an odd guy. And I know that his bashing of SSRIs is not rooted in scientific research, but in the strange tenets of Scientology — including an irrational hatred of the field of psychiatry.

Second, I strongly believe that antidepressants can help people. I’ve seen their positive effects on people personally. But I also believe the FDA should take further steps to ensure the safety of these medications, and to curb the greed-fueled marketing of SSRIs by drugmakers.

With those caveats, there’s no question that across a number of fronts, Cruise is receiving a level of vindication regarding SSRIs.

As Evelyn Pringle reports in Scoop:

The demolition of the giant “psycho-pharmaceutical complex” appears to be on the horizon … The antidepressants known as selective serotonin reuptake inhibitors, or SSRI’s, such as Prozac, Paxil, Zoloft, Celexa and Lexapro are at the center of the storm. These drugs have been prescribed to more Americans than any other class of medications over the past two decades. Cymbalta, Effexor and Wellbutrin are often referred to as SSRI’s, but they are slightly different chemically. However, the drugs all carry similar side effects and warnings….

The top sales pitch for SSRI’s has been the “chemical-imbalance-in-the-brain” myth. “There is no evidence whatsoever that depression is caused by a biochemical imbalance,” says Dr. Peter Breggin, one of the world’s leading experts on psychiatric drugs and author of the new book, “Medication Madness.”

People take for granted pronouncements such as, “You have a biochemical imbalance,” and “mental disorders are like diabetes,” he explains in the book. “In reality,” Dr. Breggin writes, “these are not scientific observations – they are promotional slogans, so adamantly repeated in the media … that people assume them to be true … Reluctant patients by the millions are pushed into taking drugs by doctors who tell them with no uncertainty that they need medication.”

While Dr. Breggin’s view is still in the minority, anti-SSRI sentiment is gaining traction — thanks in large part to the questionable actions of drugmakers.

At the moment, all eyes are on Paxil maker GlaxoSmithKline due to reports that the company is under investigation by the US Department of Justice, as well as the Senate Finance Committee … The report that led to the investigation … was submitted by Dr Joseph Glenmullen, a Clinical Instructor in Psychiatry at Harvard Medical School and author of “The Antidepressant Solution” and “Prozac Backlash: Overcoming the Dangers of Prozac, Zoloft, Paxil, and Other Antidepressants with Safe, Effective Alternatives”…

The report shows that Glaxo knew in 1989, long before Paxil was FDA approved, that people taking the drug were 8 times more likely to engage in suicidal behavior than people given a placebo, or sugar pill. Now, it stands to reason that even the most depressed person would decline to take Paxil if given these facts. Also, parents certainly would decline if they were told about the risks.

Dr Glenmullen explains that, by submitting what he refers to as “bad” Paxil numbers to the FDA, Glaxo was able to avoid adding a warning about suicide to the label when the drug was approved…

As Charles Grassley of the Senate Finance Committee puts it: “Essentially, it looks like GlaxoSmithKline bamboozled the FDA.” And this may only be the beginning, as Big Pharma’s marketing practices — including paying off academic researchers and physicians — come under closer scrunity.

As the Glaxo scandal unravels, the public will learn that other antidepressant makers such as Eli Lilly, Pfizer, Wyeth and Forest Laboratories are equally guilty … Shrinks on the take are so addicted to industry money that it’s impossible to embarrass them … Overall, estimates indicate that the drug industry spends $19 billion annually on marketing to physicians in the form of gifts, travel, meals and other consulting fees…

The scary part is, even though all this scrutiny may cost Big Pharma by reducing the overprescribing of SSRIs, the families affected by suicides or other SSRI-related tragedies may never get their day in court — if the Supreme Court rules in favor of Wyeth in the Wyeth v. Levine case now before the court.

More on the interview from Furious Seasons. More on Garnier here.

Wow, what a nailbiter. That’s enough to give Glaxo execs a heart attack (or at least increase the risk of one by, oh, 43 percent.)

(Via Reuters.)

The widely used but controversial diabetes drug Avandia will now have a strong “black box” warning on its label, advising users of an increased risk of heart failure, the U.S. Food and Drug Administration announced late Tuesday. Another four diabetes drugs from the same class, including Actos, will also carry a similar black-box message, which is the agency’s strongest label warning. The FDA and the drug manufacturers, GlaxoSmithKline and Takeda Pharmaceuticals, have been negotiating the label changes since May.

Studies have suggested that Avandia (rosiglitazone), made by Glaxo, and Actos (pioglitazone), made by Takeda, raise patients’ odds for heart failure. Other research has suggested that Avandia might possibly raise users’ risk for heart attack, though the FDA has said that more investigation on that issue is needed.

“Under FDA’s post-marketing surveillance program, we carefully monitor new safety information for marketed drugs and take appropriate action when necessary to inform patients and health care providers of new information,” Dr. Steven Galson, director of the FDA’s Center for Drug Evaluation and Research, said in a prepared statement.

How about a little PRE-marketing surveillance, FDA?

GlaxoSmithKline on Wednesday took some of the attention away from disappointing sales of diabetes drugs by announcing it was lifting its stock buyback authorization to 12 billion pounds ($24.7 billion).

Experts expected to see Glaxo report a $200 million revenue plunge in sales of Avandia, its diabetes medicine that’s been linked to an increased risk of heart attacks. According to The Times of London, analysts, on average, predicted that global sales of the drug during the three months to June 30 had fallen by 23 per cent to £367 million, compared to £477 million in 2006. (You can double those numbers for the impact in U.S. dollars.)

The drop in sales was even worse, though — to £349 million.

Nonetheless, with the buy-back news, the stock was up Wednesday.

What’s interesting to me is that Alli’s embarrassing side effects have done little to dissuade potential users from buying the product.

Glaxo says to expect “gas with oily spotting” and “more frequent stools that may be hard to control.” Glaxo also says that it is just “the excess fat that passes out of your body and is not harmful. In fact, you may recognize it as something that looks like the oil on top of a pizza.”

TMI, dudes.

Then there’s this helpful tip from the drug’s official Web site:

“It’s probably a smart idea to wear dark pants, and bring a change of clothes with you to work.”

A commenter on the Wired Science blog provided his own characterization:

Lemme tell ya what! I tried this product when it was a prescription, Xenical…yeah… after a dash into a public bathroom, having to throw away my underwear, and then a dash home – that cured me of taking it again! “Oily discharge” is an understatement; I guess if you could call what happened to the Exxon Valdez an “oily discharge” then you would be on target! I will be curious to see how many people buy this a second time……