The Me-Too Drug Ripoff

antipharma

In addition to the billions of health care dollars drug companies waste on disease mongering (see earlier posts), billions more are wasted on developing and marketing hundreds of “me-too” drugs. By definition, a “me-too” or “copycat” drug is a very slight variation of a drug already on the market.

The main downside of me-too drugs that they drive up health care costs  – the exorbitant cost of medical care is the main reason millions of Americans can’t afford a doctor when they’re ill. Other drawbacks of Big Pharma’s fixation with copycat drugs include the neglect of hundreds of potentially treatable illnesses and hundreds of cases of premature death and/or permanent disability related to inadequate safety profiling. Nearly all the major drug recalls in the last few years have involved copycat drugs that were assumed safe because they were chemically similar to medications already on the market.

An Issue First Raised by Ralph Nader

To the best of my recollection, Ralph Nader was the first to raise the issue of “me-too” drugs in his 2000 presidential campaign. Dr Marcia Angell, Harvard Senior Lecturer in Social Medicine, also covers the subject extensively in The Truth About the Drug Companies: How They Deceive Us and What To Do About It (2004) and in “Excess in the pharmaceutical industry” in the Canadian Medical Association Journal

According to Angell, it’s quite common for a drug company to manufacture their own copycat drugs when their patent is about to expire. The idea is to persuade doctors not to opt for cheaper generics when brand named drugs lose their patent protection. She gives the example of AstraZeneca reformulating the ulcer drug Priloxec to bring out Nexium, a nearly identical replacement. The company also shrewdly increased the price of Prilosec to get people to switch.

Three virtually identical cholesterol lowering drugs, Provochol, Zocor and Lipitor were introduced soon after Lipitor (introduced in 2002) became the best selling pharmaceutical in history . The latter was the first statin, a class of drugs that inhibits cholesterol formation in the liver. There are now eight virtually identical statin medications, excluding combination medications that contain it.

Billions Spent on Marketing Identical Drugs

OF all the drugs the FDA approved between 1993 and 2003, 78% were similar to already marketed drugs. Even more shocking, 68% weren’t even new compounds but a reformulation (change from capsule to tablet, short to long acting, etc) or a recombination of existing drugs.

Angell also laments the billions of dollars drug companies spend persuading doctors (and now patients through direct-to-consumer advertising) that their new me-too drug is more effective or safer than the older versions on the market. In most cases, they do this without a shred of scientific evidence. The FDA only requires pre-approval trials to compare me-too drugs to placebo and not to existing medications.

Big Pharma’s View on Me-Too drugs

Pharmaceutical companies want us to believe that me-too drugs enhance health care delivery. They allege that copycat drugs lower prescription costs by increasing competition. They also assert that doctors need a range of back-up drugs when the first-line medication doesn’t work or isn’t tolerated.

The claim about lowering prescription costs is utter rubbish. Copycat drugs are always priced the same or higher than the older drugs they supposedly compete with. And drug companies never, ever market their me-too drugs to doctors or patients on the basis of cost savings. As the price for brand name prescription drugs soars through the roof, only the easy availability of quality generics keeps prescription costs affordable for patients.

To justify the value of providing doctors a range of similar drugs to choose from, drug industry analysts give the example of the numerous copycat SSRIs available for treating depression. In doing so, they claim that some patients who fail to respond to Prozac, may respond to Paxil, Zoloft, Celexa, Priligy, Lexapro, Zelmid, Viibyrd or Upstene.

This is yet another marketing claim unsubstantiated by scientific research. After prescribing SSRIs for 25 years, I, like most of my colleagues, have never found a differential response to different brands. In fact my clinical experience coincides very closely to a recent literature review of SSRI effectiveness. This meta analysis revealed that only 35-38% of patients (only slightly higher than the rate of placebo response) get a positive response to any SSRI. The other 60+% fail to improve or experience horrible side effects.

What the Congressional Budget Office Found

In 2004, Angell could only estimate what drugs companies were spending on marketing, as this is considered proprietary corporate information. However in 2008, the Congressional Budget Office investigated and came up with the following findings:

  • Drug companies spent approximately $20.5 billion on promotional activities (10.8% of total revenue) in 2008.
  • Drug marketing costs, which grew rapidly between 1988 and 2006 had slowed and had been steady for three years at 10-11%. The CBO felt this was directly related to decreased rate of new drugs coming to market.
  • In 2008 drug companies spent only slightly more on promoting new drugs than they did marketing copycat drugs.

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Medicalizing the Menstrual Cycle

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I have blogged previously (see Menopause: Made in the USA) about the negative effects of the “corporatization” of health care in the US. “Disease mongering” is a particularly nasty one. This occurs when pharmaceutical companies “medicalize” common conditions in order to market drugs that supposedly treat them.

Thanks to skillful marketing, Eli Lilly has turned premenstrual syndrome (PMS) into a profit-making commodity nearly as lucrative as menopause and “childhood bipolar disorder” (see Drug Companies: Killing Kids for Profit).

In 1994, the American Psychiatric Association (APA) included premenstrual dysphoric disorder (PMDD) in their diagnostic manual “as a possible mental disorder requiring more research.” They have continued the diagnosis in DSM V. Although DSM IV lists PMDD as a strictly “research” diagnosis, Eli Lilly immediately seized on it as a genuine disorder and devised a marketing strategy to profit from it.

The Difference Between PMS and PMDD

Approximately 80-90% of women worldwide report physical and emotional changes in the 7-10 days prior to the onset of menstruation. For most women, these consist of minor physical changes similar to those of early pregnancy (water retention, breast swelling and tenderness and abdominal bloating).

Approximately 1/3 of women note mental and emotional changes (aka PMS) – depression, anxiety, fatigue, irritability, insomnia, difficulty concentrating – that have a minor impact on their daily functioning.

Although the APA has yet to agree PMDD even exists as a disorder, there are numerous claims in psychiatric and women’s health literature that approximately 3-8% of women suffer from it. By definition, a woman can only qualify for a PMDD diagnosis if they experience a “marked” decrease in normal functioning due to premenstrual mood changes. A rigorous Swedish study ascertained that the true percentage of women experiencing a “marked” decrease in functioning before their period closer to 1.3%.

A Golden Marketing Opportunity for Eli Lilly

Once the patent on a drug expires, other manufacturers are free to produce cheaper generic versions, resulting in plummeting sales of the original brand name drug. In 1999 Lilly, facing the expiration of its patent on Prozac, exploited the new “diagnosis” of PMDD by re-branding Prozac as a feminine pink and purple tablet called Sarafem.

In 2001, the FDA approved Sarafem for “PMDD,” on the basis of double blind studies involving several hundred women. Lilly reported a 60% response rate in women who took it for five cycles, with greater effectiveness in women who took it continuously throughout the month (as opposed to 7-10 days before their period).

Hopefully psychiatrists aren’t quite so gullible as the FDA, given Prozac’s limited effectiveness in treating depression. Thirty years of double blind studies reveal that depressed patients who take Prozac have an average response rate of 38-40%. In fact, statistical analysis of all randomized controlled trials reveal that all SSRI’s (i.e. Prozac, Zoloft, Paxil, citalopram, etc) are only slightly more effective than a placebos, which works 33-37% of the time.

Skillful Marketing Adds Billions to US Health Care Bill

Charging three dollars per dose for their pink and purple Sarafem tablets (in contrast to 41 cents per dose for generic fluoxetine), Lilly launched a massive marketing campaign to convince women they suffered from PMDD. In 2001, the year Serafem came out, nearly 100,000 prescriptions were sold, reaping Lilly $85 million in profits.

Given the soaring cost of health care in the US (the main reason millions of Americans go without medical care), it strikes me as unethical and immoral to trick doctors and women into wasting nearly a billion dollars on pink and purple pills with a fancy name, when generic fluoxetine would have been equally effective at 1/9 the cost.

Research Evidence for “Natural” Treatments

What I find really fascinating about the PMS/PMDD controversy is that it’s one of the few women’s health “conditions” in which there are more double blind placebo trials of “alternative” or “natural” treatments than medication trials. The three “alternative” treatments that have shown clear effectiveness in randomized controlled trials are omega 3 supplements, Vitamin D and the chaste tree berry or chasteberry. In fact, much of this research suggests that PMS-related mood changes may actually represent a nutritional deficiency of omega 3 and/or Vitamin D.

Omega 3 oil is the most studied in PMS-related mood changes, largely owing to its proven efficacy in depression and large cross cultural studies revealing that populations (for example Asians and Norwegians) consuming large amounts of fish (a primary source of omega 3) in their diets have an extremely low incidence of depression.

Vitamin D, has also proved helpful for depression in double blind studies, especially in elderly depressives suffering from documented Vitamin D deficiency. Other studies show that 1,000 – 2,000 international units of Vitamin D is helpful in alleviating premenstrual symptoms.

This finding correlates with an extremely low incidence of PMS in Asian women. The same oily fish that are a rich source of omega 3 are the only natural food source of Vitamin D (the majority of us derive Vitamin D from exposure to sunlight).

Three double blind studies in the British Medical Journal, the Archives of Gynecology and Obstetrics and the Journal of Women’s Health and Gender-based Medicine reveal that chasteberry helps approximately 52% of women with PMS. Chasteberry is an herbal remedy used by Hippocrates in ancient Greece for pre-menstrual symptoms. It’s believed to work by lowering prolactin (a pituitary hormone influencing milk production). High prolactin levels are a recognized, but infrequent, cause of depression.

Take Home Message: Try Natural Remedies First

In light of all the above studies, common sense would dictate that women who suffer from PMS should try a combination of omega 3 and 1,000-2,000 IU of Vitamin D for a minimum of six months before resorting to either Sarafem or generic fluoxetine. Both have potentially serious long term side effects. Owing to their effect on serotonin receptors in the brain, SSRI’s can be very difficult to stop. Moreover they are associated with a loss of bone density, which increases the risk of osteoporosis and hip fracture in later life, and possibly linked to breast and ovarian cancer

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