A Remarkable Medicine And Its Champion

One of my Frequently Asked Questions is “why do you hate prescription drugs so much?”

And the answer is, I DON’T.  Not at all.  I have used, and will continue to use, prescription drugs whenever they are the best treatment for an individual.

What I DO hate is the way they are mis-used, and the way some companies push their drugs for inappropriate purposes, or in dosages that are harmful when they could be helpful in (usually lower) doses.

I also hate the way the 3^rd-party-payers (private insurance, welfare agencies, the government programs like Medicare and the military or prison systems) try to control who gets them, for what reason and how much.

Other than that — No Problemo!

One thing that has really puzzled me is a certain drug I used frequently in my neurology and neurosurgery training — Dilantin (phenytoin).

This drug has potentially overwhelming utility and is so cheap and easy and effective that it has become the world’s most popular anticonvulsant. It has long been the drug of choice to control epilepsy.

Bioavailability ( the ability of it to get in the blood stream and be effective) does not change appreciably with the eating of food, although the length of time for which it is available to the body does; from 12 hours without to 24 hours with. So somebody can easily take it in the morning for breakfast and be fine for the day, once their blood level has been checked.

It is generally wildly effective on “tonic clonic” seizures, the kind where people flap their arms and legs rapidly but can’t remember doing so.  It may be some help on the partial complex seizure, the kind you can actually see in psychiatry more often, with more complex symptoms, but which can often end up being “tonic-clonic” anyway.

Epilepsy is taken very seriously by the government. In every state known to me, the person who suffers seizures (and is treated with medication) is expected not to drive until a year later when medical control of the event has been established and there are no more losses of consciousness. This extremely sensible measure, which generally makes patients quite angry, has saved countless lives.

I was near to completing my residency and preparing for my written boards when I got a free, slim, hardcover book in the mail with the title “A Remarkable Medicine Has Been Overlooked.”

At the time, I was cramming knowledge into my little skull, and yet I took the time to read this awesome book.

It was not written by a medical doctor or a research scientist.  It was written by a billionaire.  Jack Dreyfus, founder of Dreyfus & Co, and the Dreyfus Fund, solely financed the Dreyfus Health Foundation to research the benefits of phenytoin.

Why would he do this?  Why didn’t the government do it, or the company that had invented, patented and was successfully making a fortune selling the drug?

First of all – the government?  HA!  Lotsa luck with that one.

The company?  Parke-Davis was reluctant to invest in a drug nearing the end of its patent life. In other words, by the time they finished, it would be generic and other people would profit – not their shareholders.

So Dreyfus spent a lot of his personal fortune and the rest of his life vainly trying to get the medical profession to use this “wonder drug” for alternative purposes — depression, anxiety, mania, repetitive thinking, various types of pain, cardiac arrhythmias, neuromuscular disorders, impulsive aggression, cocaine abuse, Alzheimer’s disease, burns, and wound and skin ulcer healing, just to name some of the 70 or so uses his scientists discovered.

Almost every doctor’s office in the land was sent a free copy.

Did it make a difference?

Well, you know the answer – otherwise I wouldn’t be writing this essay!

Any licensed medical doctor can use any FDA approved medication any way he or she pleases without any kind of risk of malpractice or other problems.  It’s called “off-label” prescribing.  We do it all the time.

Other anticonvulsants were widely used in psychiatry as antipsychotics (tegretol, for example) long before the FDA approved the drug for that use.

Aspirin has NEVER been FDA approved as a blood thinner, and yet you hear every doctor in the country recommend a half-aspirin or a baby aspirin each day for certain patients to avoid blood clots and strokes.

Dreyfus died at age 95 in 2009 after spending 40 years pushing the use of Dilantin in many alternate conditions, writing several books, and of course, financing more private research than many pharmaceutical companies ever do.

Dreyfus was lucky – he stumbled onto phenytoin to help the severe depression that affected him in the late 1950s.  With the depression gone, he went on to become the most successful money manager of the era (he sold the company in the 1970s) and to do many other achievements outside the financial world.

But though Dreyfus may have been frustrated by the medical world’s refusal to listen to solid research, I kept this knowledge in that mysterious gray mass between my ears – even at a time when I had so much input to my head that it threatened to tumble out of any opening I had!

The physical book itself has long since vanished – over twenty years and a bunch of moves through a bunch of states.  However, I know where I can get another copy any time I want to consult it.

I have learned that one of the richnesses of pharmacology in general is that people market a drug at a specific dose or series of doses, and the FDA approves it for a specific use.  But at different doses, plenty of drugs have wildly different actions than those intended. Generally in my experience, dosages far lower than what the drug company and the original researchers had in mind are the most effective.  Generally what are given to little children and geriatrics.  More is definitely not always better.

One that comes to mind immediately is doxepin, which first saw the light of day as one of the early antidepressants. For many years, it was one of the best antidepressants available. Also, it could be a bit anxiolytic (tranquilizing) and sedating.

For many years, I thought anybody who used it without getting a blood level was a doctor who needed his (or her, less of them) head examined.  The list of side effects was a frightening at best – cardiac problems, possibly blood count, low blood pressure, plenty of constipation and yes, people died sometimes. I reviewed lots of charts of folks on this drug back in the day.

It seems this is, in local use, a potent anti-itch cream.  Once I talked to a dermatologist who insisted it was the best thing going. I have also heard that when used in micro-doses (It was not unusual to see people on about 200mg. every evening back then) like under 10mg. it is a totally different medicine.

As a matter of fact, it is subject for a separate patent application.

The history of Dilantin development is notable for the roles played by serendipity, not strange in science.  Before anyone actually thought of it as an anticonvulsant, it had to survive years on the shelf because it just was not a very good sleeping pill.

Dilantin is available any which way you could want it — elixir, or even intravenously, to prevent seizures from happening in the course of neurological surgery. It’s been a long time, but I have been there and done that.  It is even possible to give a “loading dose” if it is tough to stop someone from seizing and you have to get an effective blood level quickly.  Of course, you do not do this in folks who have kidney or liver problems.

Remember, although the FDA may have approved something for a specific use, a doctor who knows what he or she is doing can always use this drug in any “off label” way they feel is justified.

For someone who has a difficult-to-treat condition, Dilantin might could work and may be worth a trial.  It depends on research reports and numbers and the like, but I feel strongly that anyone who has a chronic pain syndrome, and the current treatment does not seem to be helping, should at least ask about Dilantin. After all, the alternative — if management with pills is the only thing a patient finds acceptable — can all too often end up on the slippery slope of addiction to opiates, morphine-like stuff.

The Bandolier has long been one of my favorite journals.  I will admit I do like their mascot, reminiscent of a Mexican type freedom fighter. My love for this emblem is clearly reinforcing my status as a “renegade.”

But the real reason for which I love this, is because the journal, British in its inception, is evidence-based. It is really hard to make medicine even look like — let alone be considered — science, in a world where a lot of doctors really do decide which medicine to prescribe, based on what drug rep visited last.  Given that many drug reps got their jobs by winning beauty contests and know about as much about pharmacology as a neurologically impaired chipmunk, something like “Bandolier” is very precious.

Dilantin has a narrow therapeutic index, which means that the difference between a too-small-to-be-effective dose and an overdose is very slight. Anybody who takes it should have a blood level drawn, no matter what the doctor says. This being said, I have seen cases where it has been effective in doses far lower than the doses generally required to stop seizures.

It is important to fight on this one.  Dilantin has a fair amount of side effects sometimes and nothing can be the answer all the time, but there are plenty of stories of it having helped people with chronic pain syndromes. Enough so it is worth a shot a lot more often than most doctors think about it.

It seems to be helpful in conditions that involve the central nervous system.  Things like migraine headaches. It also seems to have been helpful with “tic douloureux,” a pretty horrible facial pain that people mostly treat with carbamazepine (Tegretol by brand name) that seems to me to be a lot more complicated drug with a lot of interactions and the capacity to cause a bit more harm.  “Tic douloureux” is a pain in the trajectory of a nerve that connects directly to the brain.

Dilantin seems also to have been helpful in cases of peripheral neuropathy — pain in the arms and legs, sometimes secondary to metabolic type problems, which is often considered near-impossible to treat.

Now there are certainly other ways to treat all of the conditions listed above.  Some mainstream, some alternative.  Things like anti-oxidants, or TENS units (transdermal nerve stimulation) or Emotional Freedom Technique.

The major question in my mind, however, is given the very good (for a prescription drug) history and safety profile, the low cost, even the need for a blood test (plenty of useful older drugs, like valproic acid, need them for top-line safety) is why more people don’t try this, or look into it, or even talk about it, for some of the harder cases?

I have actually called general physicians and asked them to consider it.  I doubt residents are getting taught about it, or they magically forget about it.  So few general, internal or family doctors even return my calls anymore. We are not talking about the numbers for a research study.

So I am appealing to the only people who have the power to do anything meaningful with medical care –the patients.

YOU or your loved one who is suffering and getting no relief.

If the pain from some kind of a nerve just will not stop, and you cannot afford to or do not want to think about other means than prescription drugs, ask about Dilantin.

Now I will admit I have not used it in psychiatry — not so much because individual research is not exactly overwhelming, because I would still try it if a patient were really unresponsive to treatment. My problem is the use of polypharmacy in psychiatry, for most everyone has a medication they think is helping at least in part, and they don’t want to give it up.  It is usually something that would interact with Dilantin, and make it hard to use.

As I said, Jack Dreyfus was not even an amateur pharmacologist. He stumbled onto something he thought was worth looking into and he invested – by some estimates – over $100 million into research (which continues today after his death).

Perhaps this is one case where the amateur could see what the professional could not.  In science, they call it “anecdotal” evidence.  But this is a man who put his money where his mouth is, for his is still getting results and publishing them.

Anecdotal evidence can be a reason a doctor prescribes something, although a certain level of compulsion and of informed consent is to be expected.

There are some people who are suffering where Dilantin could work.