Zyprexa
The excitement in the field when Clozaril first became available was only matched by the disappointment when we discovered it had such serious side effects that its use would have to be extremely limited. A typical protocol for Clozaril use requires blood tests every two weeks, with only two week supplies of the medicine given at any one time, in order to catch the drop in white blood cell count before it became deadly. Bedsides the unpleasant need for blood tests on such a frequent basis, it was clear this medicine could only be offered to the rare patient with Schizophrenia who was also extremely reliable. It is used these days as a last resort, for intractable symptoms.
Zyprexa was introduced in 1996 and seemed to have none of the serous drawbacks of Clozaril or any of the other, older medications; plus, it was more effective than Risperdal. Its main drawback appeared to be sedation, a side effect that could be turned to our advantage since so many patients when they are acutely ill have trouble sleeping. Zyprexa became the drug of choice for psychotic episodes of all causes.
A digression: There are numerous psychiatric conditions which involve psychotic symptoms, including certain types of Major Depressions, Bipolar Disorders, certain types of personality disorders, drug induced states, etc. Zyprexa was effective at alleviating psychotic symptoms for all these patients. It was safe, effective, and left the patients able to feel the full range of human emotions.
Not unexpectedly, once the drug was in use by millions, rather than a few thousand in clinical trials, the treatment emergent side effects appeared.
I generally wait a year or two before using a new medication because I want to see what "TESE" show up before exposing my patients to the medication. However, Zyprexa was commonly used in hospital settings and I began to see a fair number of patients in the clinic taking Zyprexa. It soon became clear that all was not rosy. Some patients complained of insatiable appetites and had weight gains of over 100 pounds in 6-12 months. Further investigations showed a disproportionate number of patients on Zyprexa were developing abnormal lipid profiles (increases in cholesterol, bad lipoproteins) and some, more than expected by demographics, were becoming diabetic.
Over the course of a year it became clear that we would have to include significant weight gain, and the development of diabetes, as potential side effects of Zyprexa; in a drug that had been available for only a few years, and an illness (diabetes) that can take many years to manifest itself, this was a problem. It was very difficult to assign a risk to the possibility. I could tell a patient that he might develop problems managing sugar and it could become diabetes, but I couldn't tell him how great a risk he was taking.
Two external factors made the Psychiatrist's job much more difficult. Lilly was eager to encourage Doctors to prescribe Zyprexa. On the one hand, they thought, rightly, that they had a medication that could help the sickest of our patients gain a decent quality of life with a low to insignificant risk of the muscle problems seen so often in older drugs and no apparent risk of Tardive Dyskinesia. At the same time, while there were no other medications like it available, the time line for rivals was short (and getting shorter according to a recent, brief note in Technology Review; the note is not yet available on line), and they wanted to recoup their investment and make the tidy profit that seemed to be in store for them. This lead to Lilly tending to down play the risk; since Psychiatrists wanted to allow their patients to continue benefiting, there was a tendency to take a wait and see attitude toward the risk of Diabetes. Exactly how to discuss the risks with patients could be problematic, as well, and is a topic I will address in a later post.
The second problem, not surprisingly, involved lawyers. There are lawyers who genuinely believe they are protecting people from evil corporations and negligent Doctors who have "deep pockets" but just as they blame the corporation's profit motives for skewing data, the lawyers have as much of an incentive to skew data in the opposite direction, in thrall to their own profit motives. Once the hint of malpractice lawsuits permeates through the ether, treatment options become seriously complicated. I would hasten to add that malpractice exists and should be addressed in an expeditious way, but too much malpractice has to do with poor outcomes rather than negligence or poor practice by Physicians. (Perhaps this would be a good topic for another post down the line?)
Another digression: In the 1970's, a class of medications known as MAOI's were found to have a potentially lethal side effect and to be particularly useful for what were known as Atypical Depression. In rare circumstances, the interaction of MAOI's and certain foods (aged cheese, Chianti) produced a hypertensive crisis that could be life threatening. The list of dietary restrictions that were deemed necessary to avoid the (in reality, extremely rare) complication, lead many to avoid the medications altogether. Patients with Atypical Depression, which were often refractory to other treatments, were left without a treatment option that could help them because most Doctors felt it was prudent to avoid the possibility of a lawsuit. The thinking was that if you gave a patient an MAOI and they, despite your advice, or perhaps through bad luck, had a hypertensive crisis, you were likely to be sued; why take the chance? Patients suffered, but lawsuits were avoided. Unfortunately this kind of defensive thinking is common in Medicine and leads to problems of inadequate and unavailable treatment, as well as over treatment, in the interest of avoiding lawyer's attentions.
We are thus left with a similar situation with Zyprexa at the intersection of a unique drug with uniquely effective action, some serious potential side effects, and defensive medicine.
To Be Continued...
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