Naked Medicine

Let's Face It: Medicine is Business

Category: Science and Research

Is taurine in Red Bull harmful?

Question on Quora asks about taurine: “It’s the ingredient in Red Bull. I’m aware that each Red Bull contains the amount of caffeine a cup of coffee would have but what about the taurine ingredient?”

According to a pubmed citation – this one specifically examines the effects of energy drinks containing Taurine and other additives on a pediatric and adolescent population:

“Energy drinks have no therapeutic benefit, and many ingredients are understudied and not regulated. The known and unknown pharmacology of agents included in such drinks, combined with reports of toxicity, raises concern for potentially serious adverse effects in association with energy drink use. In the short-term, pediatricians need to be aware of the possible effects of energy drinks in vulnerable populations and screen for consumption to educate families. Long-term research should aim to understand the effects in at-risk populations. Toxicity surveillance should be improved, and regulations of energy drink sales and consumption should be based on appropriate research.”

http://www.ncbi.nlm.nih.gov/pubm…

I read the conclusion as, “it doesn’t do much good and we don’t know what harm it can do, we need to study this some more.”

Even though the question asks about taurine in isolation as a key ingredient in Red Bull, I think the question needs to be answered in the context of the form and method of delivery of the taurine in question. Thus I believe the above March 2011 study is closest to giving a clinical conclusion to what the effects of taurine may be when taken as an energy drink. The confounding effects would come from other additives including caffeine on the subjects studied.

[link to quora question]

Medicines and Drugs – Do Doctors and Scientists Know What They’re Talking About?!

I think an accurate description would be, “doctors and scientists mostly understand one or few aspects of how the active compound of a drug could/should work for a particular biological pathway that has been attributed to causing or contributing to a particular condition.”

If you look at the prescribing information (also called a package insert or PI) of many drugs, it will often say that how the drug actually works is unknown – “the mode of therapeutic action {for a drug} in {a condition} is not known” – I think you would be shocked at how prevalent this statement is for all the drugs available on market today.

We don’t know all of the pathways that the drug may be acting on, and we can’t even begin to uncover all of the compensatory or countering pathways that will be activated as a result of this drug being introduced into our bodies (or at least, that’s why we have “post-marketing surveillance and post-marketing studies”) once the drug is released into the general public and gets into thousands and thousands of patients.

One example is a class of novel anti-cancer biological drugs that target the angiogenesis (blood vessel creating) pathways of cancer cells. Oncologists were excited by the prospect that now we have “targeted” therapies and can now go after specific pathways that cancer cells appear to have hijacked or show dominance in the body, and our desire is that, by going after cancer-specific pathways, we can then design treatments or find drugs that specifically affect cancer cell pathways but not “normal” cell pathways.

Another hope for the advent of these targeted therapies is the better side effect profile as opposed to the traditional chemotherapies that kill all cells that have fast replication (cancer cells, hair cells, stomach lining cells), giving rise to a very difficult-to-tolerate side effect for the patient receiving treatment. It turned out that these targeted therapies, while appearing to have more favorable side effect profiles compared to traditional chemotherapy, have other side effects that scientists did not anticipate or see until late in clinical trials, including cardiovascular side effects that were potentially fatal.

This is one “common” illustration of how what we see in the laboratories and even in preclinical studies and in vivo animal models are not completely predictive of what we will see once the drug goes into the human body.

Another illustration of how scientists “make do” with the little that they can feasibly understand during the timeline of drug development is how the “side effect” of some drugs have become the de facto “Indication” approved for treating another condition for which the drug was originally not studied to treat. Viagra (sildenafil) is one such serendipitous blockbuster drug. The compound was originally studied for treating hypertension, and scientists saw quite a rousing side effect (pun intended) and realized that the side effect of the drug may very well be the key use of the drug.
[link to the quora question]
[link to my original answer]

How Pharma Employees Rip Off Their Employers

Not sure if this adds up much to the costs of drugs, but it does bloat the overhead that is paid by pharma companies to keep its employees.

For example, a pharma field manager wants to do a “ride along” with her subordinate. Sounds logical, yes? Only she wants to go to a state where the subordinate really has very little business there.

That makes no sense, wouldn’t you want to go on a ride-along with your subordinate to a place where he’s got a ton of business, so you can see how he performs and what he’s doing?

Turns out that it’s because the manager has a hobby – let’s say – trains – and there happens to be a train festival going on in the “state that has little or no business”.

The plot thickens.

The pharma manager is just using this “ride-along” as a pretext for her hobby with trains.

Now, what’s the harm in that? Other than the company having to pay for that managers plane ride, hotel say, all “business meals”, transportation… that easily comes up to maybe $1000-$2500 a trip.

Stealing from your employer.

All in the name of managing.

Kids Not Getting Enough Cholesterol?

I had no idea that September National Cholesterol Education Month, but it is, and I saw a press release about nonprofit nutrition education organization Weston A. Price Foundation on getting consumers to recognize the importance of cholesterol.

The press release made sense to me, but it seriously will meet lots of antagonism because of the prevalent trend of obese children in the USA these days. I bet these kids have ridiculously high cholesterol levels – and certainly not from eating too much “nutrient dense” foods. So while I as a scientist and also as mother of a toddler who needs lots of “good fats” can sympathize, I don’t think the argument here can stand up to even one voice saying “… then what about all this concern with childhood obesity?”

I sent my query off to the publicist, who got in touch with the Sally Fallon Morell, president of the Weston A. Price Foundation to respond to my challenge above. Sally’s response is here.

I followed the links given as references, including the one from the Foundation itself:
Dietary Recommendations for Children –A Recipe for Future Heart Disease?

“Just Say No!”
When it comes to feeding their children, parents should “just say no!” to the governments dietary guidelines. Children need a diet rich in traditional fats in order to achieve optimum growth and development, as well as protection from heart disease later in life.

I wished it had addressed additionally the issue of fast foods – because this is the reality of “kids’ diets” these days… if saturated fat plays a role in children’s growth, at what point do parents draw the line in where that source of saturated fat comes from? (this question was answered by another link that Sally’s response included, but I wished the above information would address it immediately rather than me having to look at another (non-related to the foundation) link.

I also found the Swedish study findings interesting, mostly because I’ve been drinking more whole milk (full fat) since that’s what I give to my child, who is almost 2 at this writing. Our pediatrician had told us that at this point, we should cut back milk for him because it doesn’t really do much for him other than the calcium and vitamin D that he can be easily getting from other sources.

I don’t know how much this would convince you as a consumer about the benefits of cholesterol in children. On an objectivity scale, I would have preferred that the links I received were original source citations (i.e. links to the original scientific studies published – such as from PubMed) rather than what appears to be commercial pages or user-contributed pages.

Acai Miracle Berries is Mostly Miracle Marketing

In experiments conducted by the US Dept of Agriculture, volunteers were asked to ingest large quantities of fruits that have been identified as having high levels of antioxidants, and their blood were subsequently tested for antioxidant capacity. One important note is the large amount of fruit required per ingestion – for example – volunteers in the Kiwi fruit group must eat 4 kiwis. The cherry group? 45 cherries. This should give consumers an idea of the potential “starting” dose needed to gain an antioxidant benefit – and this is PER DOSE. (imagine eating 45 * 3 cherries a day – if you want to get the benefit of cherries’ antioxidant properties with every meal.)

This does make for an attractive commercial market to give consumers “concentrated” forms of antioxidants – except most of companies providing these types of nutrition products are not regulated by the FDA – that branch of the government regulating food and drugs to make sure that you as a consumer aren’t being ripped off or worse – physically harmed by ingesting unsafe products. Unfortunately, history has shown that the FDA only steps in when enough people get sick or if a few people begin to die from the so-called “nutraceutical” – just look at the ephedrine cases in the multi-billion dollar weight-loss industry.

Currently there is no agreed projection of antioxidant intake because this can fluctuate based on individual energy intake, caloric consumption, and especially environmental or confounding health related factors like exposure to cigarette smoke or disease (increasing body’s oxidation burden). There are researchers who are trying to determine what these individual needs may be, but for the most part, consumers have been inundated by commercial entities eager to profit on a perceived benefit of “high antioxidant intake”. For example, via Quackwatch:
http://www.quackwatch.com/01QuackeryRelatedTopics/PhonyAds/acai.html

The verdict? If you like to drink exotic berries for the taste, there’s no problem with indulging yourself but if you’re looking for some of these commercial products for bona fide healthcare benefits, require the claims to be backed up by randomized, double-blind placebo controlled clinical trials, with full disclosure of side effect profiles experienced by the human subjects.

(…and if there is really some miracle plant bearing amazing therapeutic properties, the pharma companies would outrun anyone to isolate the agents, synthesize/mass produce, and submit it through the proper legal govt channels for commercialization! that was how we got cancer drugs from the pacific yew tree.)

Which Side Are You Really On, Jane Chin?!

I received what is probably the most passionate email from a reader of this blog that I’ve ever gotten since creating NakedMedicine.com in 2006. The email concludes with this:

I can’t figure out what your agenda is Ms Chin. Are siding with the poor hard working physicians who are fighting a losing battle with their idiot patient’s lifestyles? Are you siding with the tirelessly industrious pharmaceutical scientists who are selflessly dedicating their efforts to cure our ills? Are you siding with the poor neglected suffering individuals who are bravely pushing onward in their lives, struggling with disease, possible disease, possible pandemics, or just plain plainness requiring cosmetic medicine? Doctors, business, persons, for whom are you advocating?

I was shocked by the email, because this reader “hit the nail on the head”! He can’t figure out what my agenda is, because my agenda is in NONE of those sides he described. In other words, if I were guilty of picking “a side”, it wasn’t part of the “usual suspects”.

Here’s my very long response to my reader, to whom I’m grateful, because he took the time and effort to share with me this question that obviously is frustrating him.

******

You wrote what you felt, and I don’t fault you for that. I can sense a real feeling of frustration from you, and I don’t blame you for feeling frustrated about the healthcare system that seems to be broken in many ways.

I want to address specific points you brought up – first one being ‘cures’. I genuinely don’t think that the drug industry is prevented from, or are resistant to, discovering cures for diseases. It’s not about ‘cure’ versus ‘not the cure’ that is the problem. It is often the economy of scale that is the problem, and a very understandable one when you consider that the drug industry is – and has to run like a business – in order to remain in business. I have no doubt that the drug industry would love to find a cure – because they can charge for the price of a ‘cure’ and be justified in charging such a price.

The problem on the one hand is that many times we simply cannot find ONE underlying factor of a disease, especially the chronic diseases like diabetes and heart disease (in fact, many diabetics die of a heart attack and don’t live long enough to die of diabetes complications, especially those consuming a western diet). It is not like a bacterial infection where we can pinpoint ONE origin of the disease and target that specifically, the way we can target an infecting bacteria with an antibiotic and ‘cure’ the patient.

The other problem is about the number of people with a certain disease. For example, there may be fewer companies willing to research rare diseases that may be ‘repaired’ let alone ‘cured’, simply because the companies need to get the money somehow to do all the experiments and clinical trials necessary to jump through regulatory hurdles to even get the drug approved. When i was a graduate student, doing what are pretty simple experiments (and not even in people – i worked off the petri dishes), i was often using reagents that cost my employer thousands of dollars to purchase from reagent companies. Each of my experiments has to cost at least a thousand bucks, and many of my experiments failed and produced no result.

These prices are nothing compared to the amount of money it costs to run a clinical trial at the scale required by the FDA. Now the drug companies have to pay for the drugs, the cost of mountains of paperwork needed to get the clinical trials started, the doctors who do the clinical trials (and some doctors get really snobby and brag to each other about how much $ they can muscle out of drug companies “per patient” to enroll in the drug companies’ trials), not to mention the “overhead” that the academic institutions charge the drug companies because their doctors work there (and these overhead costs can mean more than 50% of the total study budget).

And then most of the drugs end up not passing the FDA’s requirements and fail to get approved. So if you’re running a company, you will tend to want to go into areas where you will likely have more customers – heart disease for example – just so you stand a better chance of keeping your company operating should it succeed in getting a drug treating that disease approved. This is also why the government has to create incentives for companies that are willing to go into rare or “orphan” diseases – for example, Gaucher’s disease is a rare lysosomal storage disease affecting maybe 1 in 40,000 people. A drug company that competes in this market will be happy selling 1 prescription every 3 months.

I honestly do not view drug companies as entities that profit from the suffering of others, because of the logic of this assumption: If drug companies are creating diseases in people in order to make drugs for the very diseases they created, then that to me qualifies for the statement. However, drug companies happen to offer the tools to treat the disease, not unlike device companies making scalpels and surgical tools to allow doctors to cut us open should our illnesses demand it. It seems illogical to me to accuse device companies for profiting from people having tumors that require scalpels to operate and excise the tumors – unless we’re also implying that the scalpel companies are putting tumors in people that only their brand of scalpel can remove.

Additionally, I have observed that for the most part, people in our society today tend to prefer that we “have a pill to treat XYZ”, so that they do not have to do the hard work required to get their own health back on track. And then you add to the fire media agencies that charge pharma companies millions of dollars to come up with brainless gimmicky advertisements, and it is no wonder why many people feel like the drug companies are “profiteers of suffering.” Some years ago, there was a government funded study that shows that rigorous diet and exercise will help reduce diabetes risk at a very real level – in fact – the study patients who had diet and exercise regimen did as well in reducing their diabetes symptoms as study patients who took an anti-diabetic drug.

But why hasn’t the government or the doctors (not the drug companies – their responsibility is in making drugs) done anything about this amazing result? Because the of costs involved to the clinics in order to make “diet and exercise” possible in patients at a therapeutic level. Clinics would need to hire case workers and nurses whose job is to counsel and support and follow each and every single patient who opts for this “natural and effective” treatment. OK then, how about asking patients themselves to do this? Seriously, if you are a patient at risk for diabetes (i.e. risk factors are there, but patient is still “pre-diabetic” and not yet requiring drugs to control their blood sugars), you have everything you need at your disposal to go for the natural and effective (and less expensive than prescription drugs) cure! why aren’t patients doing this? because willpower and discipline are key – and you’re going to need both for a lifetime to prolong the onset of disease.

I can share this true experience – my husband had prediabetic blood work results some years ago when I urged him to see an endocrinologist, because his side of the family also suffers from diabetes. the endocrinologist told him that because he was so young (not yet 40 at the time), she preferred that he try the old fashioned diet and exercise, and see if he could get the risk factors down, before she put him on a drug. He happens to have a level of willpower and discipline that even I don’t have – and he altered his lifestyle dramatically – and it was enormously difficult. 6 weeks later he went back and the endocrinologist was so impressed with his results that she told him that most of his blood work results were approaching normal numbers. But she also told us that not every patient she sees can make this happen – and often she is forced to give the patient drugs to make sure that the patient doesn’t end up with uncontrolled diabetes symptoms (resulting in all sorts of nasty things including death).

I see drugs as exactly what you said you wished to see – repairs and cures. However, the reality is, few are truly cures because of the complexities of most diseases, and repairs don’t always “fix” things without creating new problems (called side effects) EXACTLY because of the complexities of most diseases.

The doctors’ hands are tied not by pharma companies, but by insurance companies as well as their own malpractice lawsuit concerns. Your average primary care doctor has to track how many patients he sees everyday because he needs to make sure he breaks even. That’s not the drug companies doing, but the insurance companies that capitate how much doctors are paid for doing what. So you also have a system that don’t reward doctors for spending more time with patients – in fact – you’re making it very bad business for the doctor to spend too much time because then he’ll lose money that day – and this does not do well to cultivate trust with patients who then need to heed the doctors’ advice about doing the hard things they need to do to steer their health status back on track.

I hope my email begins to help you understand where I am coming from – perhaps I can’t take any sides because I don’t think there are any sides that I can reasonably take without acknowledging that there are other entities that also need to be held accountable. the healthcare ‘system” is truly a “system” and a staggering, complex one at that. the best I can do is to help the consumers – people like you and me – to think for ourselves about what is being “sold” to us whether it’s from the drug companies, insurance companies, the government, the doctors, even patient groups. If I am guilty of siding with anything, it will be on the side of “critical thinking” about the system of healthcare with all of its players.

Best wishes,
Jane Chin

Provenge and FDA’s Etiology For Not Approving

By Dan Abshear

Terminal patients are those who are not expected to live due to usually illness such as advanced prostate cancer (cT3). If the patient has 6 months or less to live, those patients are considered terminally ill. Regardless, if a patient is terminal, they are without a cure or tolerable treatment for their illness. Since such patients will likely die in a short period of time, treatment options, even if unproven, are often desired by such patients. This is understandable, because at such a severe stage of illness, such as prostate cancer, possible extension of their lives with comfort is worth it to them, regardless of lack of evidence of proof of whatever treatment that may be advantageous to them regarding these issues. The FDA, however, claims authority on the treatment options of such patients, although that administration has proven itself over the years to be rather inadequate with its frequent drug recalls and black box warnings, and they do these things only under pressure from the public, usually.

Prostate cancer is a rather frequent occurrence- with between 10 to 20 percent of men predicted to acquire the disease during their lifespan, resulting in about 30,000 deaths a year from this disease of the one million men who have prostate cancer in the United States. Furthermore, there are different stages of prostate cancer, and the more severe the prostate cancer cases are which is determined by such methods as bone scans and Gleason’s scores, which is a score that assesses prostate tissue after it is biopsied and if it is determined that the stage of cancer is severe by this and to estimate proper treatment options if proven to be malignant. Typically, the initial suspicion of prostate cancer is determined by the results of what is called a PSA (Prostate Specific Antigen) blood test, as PSA is a protein produced by prostate cancer cells. If the PSA blood test is above normal limits, a prostate biopsy is performed to determine and confirm not only the presence of cancer, but also the severity of the disease on such a patient.

Yet fortunately, and as you will read, innovation still exists in medicine. A few years ago, a small Biotechnology company called Dendreon was working on a conceptually new treatment for the worst prostate cancer patients, and this treatment therapy created by Dendreon was named Provenge. Provenge is the first immunotherapy biologic treatment for the progressed prostate cancer patients, and has proven to be a very novel and innovative treatment option for advanced prostate cancer patients who are terminally ill. Usually, these patients are unresponsive to usual treatment methods for prostate cancer, and are left with chemotherapy as their only treatment option at such a traumatic stage of prostate cancer. Understandably, most patients at this stage refuse treatment entirely, largely due to the brutal side effects of such chemotherapy treatments as Taxotere (Sanofi Aventis, docetaxel). The immunotherapy method developed by Dendreon required the removal of white blood cells of the diseased patient and, after altered, are re-injected into this patient now designed to attack what is called PAP, which is on prostate cancer cells only. This treatment required only three such injections in a period of six weeks. This resulted in life extension twice that of chemotherapy treated prostate cancer patients of this severity, and without the concerning side effects of chemotherapy. The medical community and survivors of prostate cancer were elated and waited with great anticipation for access to this treatment method.

Fortunately, as the years passed, Provenge, by 2007, had convinced others of its safety and efficacy in its benefit for severe prostate cancer patients. This caused great joy to such patients and their families. Perhaps greater elation was experienced by the caregivers and specialists of such a disease, such as urologists and oncologists who treat such patients. While Provenge was on fast track status at this time at the FDA, the FDA panel thankfully recommended with clarity the approval of Provenge based on its proven and substantial efficacy and safety demonstrated in its performance in past trials. The FDA announced this to the public in the early Spring of 2007, I believe.

Now for the bad news: With great shock and surprise, the FDA agency rejected the approval of this great treatment for very sick patients due to, they said, ‘lack of data’ in May of 2007. This contradicts their favorable opinion of Provenge weeks before delivering this terrible news. Especially when one considers the FDA Commissioner is a prostate cancer survival himself!

Soon after this judgment was passed by the FDA, conflicts of interest were discovered by others. For example, a member of the FDA agency who was evaluating Provenge, Dr. Scher, was found to have a financial commitment to a future competitor of Provenge that was being produced by a company called Novacea, and this company had signed a co-promotion agreement with Schering with this similar prostate cancer drug being developed by this company. Dr. Scher never disclosed this conflict during the approval process of Provenge. As it turns out, this anticipated prostate cancer drug made by Novacea was discovered to have serious flaws, and Schering pulled out of the agreement with Novacea. In addition to this incident and before May of 2007, baseless letters were anonymously delivered to the FDA stating negative qualities about Provenge that were without merit and speculative claims about the treatment. Yet overall, the disapproval by the FDA of Provenge angered many, and a newly formed advocacy group called Care to Live filed a lawsuit against the FDA for their clear lack of protocol or knowledge about such complex treatment agents as Provenge at the end of last year.

Terminal patients, I surmise, desire comfort during their progressive disease that has placed them in the last chapter of their lives, and certainly should have a right to choose any treatment that possibly could benefit them. At this stage of such a patient, one could argue, safety of any treatment option is not of concern to these patients, because they are going to die anyway. Yet the FDA, with reckless disregard and overt harshness for these very ill patients, ultimately harmed others more by not approving Provenge with deliberate intent.

The FDA does in fact presently have the ability to grant what is called conditional approval for such treatment methods as Provenge, and why they have not expanded this approval process to all terminally ill patients remains completely unknown. What is known is that they are harming those they pledged to protect so long ago by depriving such patients in need of treatment, as no other options are viable presently that are as safe and effective with great tolerability associated with Provenge. So now the FDA appears to be a bought, corrupt, and incompetent administration without loyalty and dedication to the public and its health. This needs to be corrected in any way possible for the lives of others. A terminally ill patient has a personal right to obtain and access such treatments upon their own volition as well as the discretion of their doctor, just as a terminally ill patient is granted an individual right to die, if they choose to do so. It is an individual decision in such cases that should be void of interference from others.

“Facts do not cease to exist because they are ignored.” — Aldous Huxley

Patients Adrift in a Sea of Clinical Trials

By Sally Satel, M.D.

On the front page of the Washington Post last week was a headline geared to spark the ire of those who have a congenital animus toward pharmaceutical companies–“Comparison of Schizophrenia Drugs Often Favors Firm Funding Study“.

The Post article noted that, according to a recent study, nine out of ten head-to-head company-funded clinical trials of antipsychotic medications were found to favor the drug whose maker funded the study.

The study, published in the February issue of the American Journal of Psychiatry by German and American psychiatrists, reviewed 30 drug trials of second-generation antipsychotics, also called atypicals, published between 1966 and 2004. Five drug companies were responsible for underwriting these 30 trials.

Aside from its headline, the Post article was well done and revealed important lessons from the study. For instance:

  1. From a clinical standpoint today, it doesn’t matter much which drug wins a horse race.
  2. The company studies provide useful information, not pabulum.
  3. Most important, we need more research.

Let’s look at these points one by one.

In the real world of practice trial results are less important than you think. In modern psychiatry, there are no first-line drugs. Years ago, by contrast, lithium was the pharmaceutical of choice for maintenance treatment of the manic symptoms of bipolar illness. Today, the FDA has approved several mood–stabilizers (anticonvulsants) for treatment and suppression of mania, not to mention off–label drugs.[1] Take posttraumatic stress disorder. Today, only two SSRI–type drugs are FDA approved for PTSD but they are not dazzlingly effective. In fact, because the condition varies so much from patient to patient, other medications that are not approved for the condition (e.g., low-dose antipsychotics, anticonvulsants and benzodiazepines) can be very helpful in certain individuals.

Why do doctors struggle so much to find effective treatments? The state of the art in prescribing effective antipsychotic drugs is still pretty poor and, as a result, doctors are often forced to take a trial and error approach. When starting a depressed patient on an antidepressant or an antipsychotic, doctors typically choose the drug they are most skilled in using. This is a perfectly reasonable choice, given our rather slim knowledge about how to tailor medications for each patient.

The largest and most recent government–funded studies tend to be enormously humbling for physicians and companies alike. Data from the new STAR*D Study (Sequenced Treatment Alternatives to Relieve Depression) show that only 25-33% of subjects achieved full remission with antidepressants.[2] (Granted, a higher percentage of patients had partial relief, and sometimes that is enough to improve daily functioning significantly. Still, higher rates of full-remission are surely desirable.)

Another study, CATIE (Clinical Antipsychotic Trials of Intervention Effectiveness Study) found that three-fourths of all subjects asked to stop their antipsychotic, either because it was not helping or because side-effects were unacceptable to them.[3] The CATIE study lasted an unprecedented duration (18 months) and enrolled an unprecedented number of subjects (nearly 1500), thus permitting a fuller picture than most other clinical trials.[4]

For the record, psychiatrists do have some guideposts in selecting drugs. In my own practice, I rely on four rules of thumb for using (or avoiding) a specific drug. I use a particular treatment (1) if the patient had a good response to it during a prior treatment episode, and (2) if a close relative benefited from that drug (aka: the pharmacogenetic rationale).

I avoid treatments if (1) the patient says he would find a side-effect totally unacceptable, such as weight gain. If the medication poses a sizeable risk of causing a medical complication, such as worsening hypotension, diabetes or high cholesterol, I still might use it but watch the patient very carefully. I also avoid treatments if (2) a drug is very expensive–and the patient has to pay out of pocket. In that case, I use a first generation, generic antipsychotic and follow for signs of tardive dyskinesia, a movement disorder that can emerge with long-term use.

Company funded studies still provide useful information. It is no mystery (or conspiracy) why studies comparing the same drug can come out differently. In short, they are conducted using different designs, different statistical tests, and/or different outcome measures. Anyone can read the published studies and see for themselves how they differ. There is transparency here, but the psychiatrist must take time to read the entire study, not just the abstract.

Some factors that can favor one or another drug are: the doses used (e.g., a low-dose of a clearly superior drug will make it seem lame when compared to a standard dose of an inferior one), the duration of the study (i.e., trials may be only four weeks long but different drugs may have different times to maximum effectiveness), and outcome measures (i.e., reduction of psychosis but not behavioral withdrawal, or vice-versa).

One can be forgiven for wondering whether some trials have been conveniently engineered to make the sponsor look better–for example, when a low dose of a competitor’s drug is used or when the researcher doesn’t seem to look too hard for side effects or doesn’t report all of them. On the other hand, often researchers truly don’t know to look for a novel side effect or do not know what the optimal duration of study should be. Why? Because we need to know more!

We need more research. This is the main conclusion physicians, patients, and the media should take away from February’s American Journal of Psychiatry study. The main limitation of so many clinical trails is that the data they yield don’t help the clinician with a specific patient. The kinds of information psychiatrists need are how to home in on a medication that will be best for a particular patient. Switching around medications and dealing with bad side-effects take large tolls on patients. Not only do they cause suffering or vast inconvenience, these adverse events problems can cause poor compliance or outright refusal to try any other drug. It is demoralizing to a patient to continue to be sick and to go from one drug to the next; he starts to fear he will never get better. And, of course, it is a problem, though a routine one, for the physician.

Legitimate concerns about clinical trials abound. For instance, how do the findings of clinical trials compare to patients that physicians see everyday (who are, generally speaking, more likely to have other mental and physical problems)? Clinical trials typically enroll subjects who have classic symptom constellations and are medically relatively healthy. As well, such subjects are able to give informed consent; very psychotic patients often cannot. Also, do differences in drugs justify differences in cost and how do those differences vary across patient subtypes? And, of vast importance, what drugs really help the patient get better, not in just alleviating symptoms, but in terms of day-to-day functioning?

Pharmaceutical companies may not be interested in these questions. Either the National Institutes of Health or some other government or non-profit entity could conduct these trials. Currently, only NIH can sponsor studies large enough to involve a sufficiently large number of patients that the results yield more clinically-relevant information. That’s a major weakness of company-sponsored trials, no matter how well done. An additional virtue of non-industry funding is that the specter of conflict of interest is erased.[5]

Schizophrenia is one of the most mysterious and vexing diseases in psychiatry. The most afflicted often give up their lives to it. They are desolately lonely and tormented by hallucinations and paranoia. Neuroscientists have made tangible progress but the etiology or etiologies of the disease (the most popular theory is that gene mutations lead to abnormal development of neural circuits, particularly in the context of external stress, but a number of respected researchers have even suggested a viral cause) remain murky. This makes it difficult for physiology to inform drug development.

There is no question that some patients have Lazarus-like recoveries when the right medication is found. The search, though, can be a time-consuming pharmaceutical odyssey. Worse, however, is that not enough patients get excellent results. Clearly, we need more evidence about the medications we have now and even better drugs in the future.

We shouldn’t become cynical about the companies pursuing these cures. Competition between competing therapies broadens our understanding of mental illness and can help researchers chart a course towards the next generation of treatments. In a sea of uncertainty, that’s the best we can hope for.

Dr. Sally Satel is a resident scholar at AEI.

Notes
[1] Some psychiatrists consider clozapine (now off patent) to be a first line drug for schizophrenia. It has been clearly demonstrated to be superior to other atypical antipsychotics but is not very popular because of the necessary blood monitoring. Also, because it is generic, there is no pharmaceutical advertising behind it. See Tamminga, C. Practical Treatment Information for Schizophrenia American Journal of Psychiatry 163:563-565, 2006. Of interest, now lithium is making a comeback. A number of new studies have shown that it has a significant suicide-prevention effect, see Tondo L., Hennen J., Baldessarini R.J Lower suicide risk with long-term lithium treatment in major affective illness: a meta-analysis. Acta Psychiatrica Scandinavica, vol. 104, Number 3, September 2001, pp. 163-172(10); Cipriani A, Pretty H, Hawton K, Geddes JR. Lithium in the prevention of suicidal behavior and all-cause mortality in patients with mood disorders: a systematic review of randomized trials. Am J Psychiatry. 2005 Oct;162(10):1805-19; Kessing LV, Sondergard L, Kvist K, Andersen PK. Suicide risk in patients treated with lithium. Arch Gen Psychiatry. 2005 Aug;62(8):860-6;Muller-Oerlinghausen B, Felber W, Berghofer A, Lauterbach E, Ahrens B.The impact of lithium long-term medication on suicidal behavior and mortality of bipolar patients. Arch Suicide Res. 2005;9(3):307-19.

[2] Rush AJ, Trivedi MH, Wisniewski SR, Stewart JW, Nierenberg AA, Thase ME, Ritz L, Biggs MM, Warden D, Luther JF, Shores-Wilson K, Niederehe G, Fava M; STAR*D Study Team. Bupropion-SR, sertraline, or venlafaxine-XR after failure of SSRIs for depression. N Engl J Med. 2006 Mar 23;354(12):1305-7;Rubinow DR Treatment strategies after SSRI failure–good news and bad news. N Engl J Med. 2006 Mar 23;354(12):1305-7.

[3] Lieberman JA, Stroup TS, McEvoy JP, et. al. Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) Investigators. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia.N Engl J Med. 2005 Sep 22;353(12):1209-23.

[4] And, still, patients on first generation, or typical, antipsychotics were not followed long enough to track emergence of tardive dyskinesia, the major aversive side-effect from long term use.

[5] Other suggestions: perhaps the FDA could require a new medication be included in at least one large, long-term trial funded by the company and designed and conducted by an independent group at the expense of that company or jointly supported by NIH. Alternatively, one could have the FDA require that as part of Phase IV (post-FDA approval) that companies would be obligated to contribute to CATIE-like studies to see how effective medications are when used they way clinicians use them for the patients that they treat. Since these would be head-to-head studies, several companies would contribute and this would combat any bias that could be alleged when a single company pays.

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