Saturday, November 21, 2009

Are We Keen on the Nicotine Vaccine?

From the Internet last week:

Nicotine Vaccine May Help Smokers Quit

The National Institute on Drug Abuse, a division of the National Institutes of Health, gave Nabi BioPharmaceuticals a $10 million grant to take its anti-nicotine vaccine, NicVAX, to clinical trials. Officials want to confirm its effectiveness, monitor side effects, compare it to commonly used treatments and collect information that will allow the drug treatment to be used safely…

NicVAX is designed to stimulate the immune system to create antibodies that latch onto nicotine molecules in a smoker's bloodstream, preventing nicotine from entering the brain. Trapped outside the brain, the too-large molecules of nicotine can’t trigger the addictive pleasure chemicals invoked by smoking tobacco. …

The results of initial trials on 1,000 patients has been promising and caused few side effects. Nabi BioPharmaceuticals reports that 35 percent of those given the vaccine have been able to remain smoke-free compared with only 10 percent of patients who received a placebo.

(Nicole Straff, AOL Health, November 13, 2009)

I’ve written previously on The Blog about the benefits of vaccinations, and about the need for patients to assume some degree of responsibility for their own health behaviors. So when I read the on-line notice as I sipped my early morning Dunkin’ Donuts Vanilla Chai (Note to Company: Why can’t I get any size larger than medium?), my interest was piqued. The idea of a vaccine for nicotine addiction, and the use of a quick technological fix to prevent the health effects of cigarette use, appealed to every public health bone in my body. (Admittedly, these moments are getting fewer and fewer as I get farther from that phase of my life. Yet every now and then one of these residual ossicles lodges in my throat and I have to resort to the Heimlich Maneuver of Public Concern to get it out.)

Pharmacologic therapy for addictions is not a new idea. There are lots of therapies out there to help manage acute overdoses of medications such as narcotics (Codeine, Lortab, and Percocet) and benzodiazepines (Valium and Ativan). There are also a host of treatments to help manage both narcotic and alcohol withdrawal symptoms, and specific pharmacologic regimens have been developed to provoke acute withdrawal in a supervised setting under sedation or anesthesia to speed up the detoxification process. (This is actually a pretty good business as well; an outfit in Michigan offers a one hour detox under anesthesia for only $6,700. The on-line brochure notes that operators are available 24 hours a day, 7 days a week. And of you order now, we’ll throw in the Showtime Rotisserie Oven and this amazing spiral slicer. Call today!)

Less common, however, are medications that are given on the front end to inhibit the addictive behavior. Many people are familiar with the fact that heroin addicts are often treated with methadone, an artificial analogue of the street drug prescribed by a physician. In theory this takes the addict off the street and facilitates a slow and gradual withdrawal; in reality, it substitutes one addictive drug for another, and while it does take folks off the street it puts them into the ED on nights and weekends when the Methadone Depot is closed. (True story: About three months ago I was working a night shift and the police brought in an empty shipping carton containing twelve one liter bottles of methadone elixir. But it’s not addictive, right?). There are implants that can provide some assistance by blocking the effect of opiates as well, but their long-term success in preventing recidivism is not yet established. And while certain antidepressants (Chantix) have been used to assist with smoking cessation, it’s uncertain whether their effect is really related to the antagonism of nicotine or on managing the mild situational depression that often accompanies attempts at lifestyle change.

There is also a medication out there to prevent alcohol abuse. It’s called disulfiram (Antabuse), and its use was quite the rage when I was in training. What it does is block the metabolism of alcohol so when a person taking the drug uses alcohol, there’s a buildup of acetaldehyde formaldehyde in their system. Acetaldehyde is the main ingredient of a hangover, and the patient who swigs a beer while on the drug has an immediate (5-10 minute) and quite potent hangover complete with sweating, shaking, flushing, nausea, violent retching, and a feeling of being generally unwell (I use that term because I’m not sure “crappy” is a word befitting medicine, and I can’t in good conscience refer to a bowel-product in a family publication.) Recall that the closely related formaldehyde is the stuff they use to pickle dead fish and fetal pigs in jars on the wall in high school biology, and you can figure that you probably don’t want any of that in you. Disulfiram isn’t used much anymore. The official reason is that there are so many products with alcohol in them (mouthwash, liquid medications, etc), that patients were inadvertently pushed into reactions, which was admittedly unfair to them. However, my own theory is that nobody takes it anymore because it stops alcoholics from drinking, and if I’m an alcoholic the last thing I’m going to do is take something that going to make me sick when I drink. In my experience, most alcoholics would like to have their hangover the old-fashioned way, so compliance with Antabuse is usually abysmal. Personally, I wish it would make a comeback, and specifically that they would develop an injectable form for use in the ED. I can’t help but think that if we could induce a violent hangover in some of our more chronic alcoholic patients rather than just letting them sleep it off, they might be more motivated for treatment.

(To be frank, there are other examples of punitive theory in which I fervently believe. For example, gonorrhea can be treated equally well with either a painful injection in the posterior or with a dose of oral medication. If you’re the one passing the disease around, or if you’re just being a jerk, guess which therapy you get?).

But there’s never been a vaccine that regulates behavior leading to long-term health problems. The concept is fascinating. By blocking the passage of nicotine through the blood-brain barrier, we stop the stimulation of nicotine receptors in the brain. If the receptors are blocked, there’s no pleasure from smoking. The idea opens the door to a world of possibilities. Can we do the same for the metabolic products of alcohol, preventing them from affecting the brain and blocking the pleasant feelings of Cap’n Jack? How about narcotics? A biochemical stimulant that produces obesity? Sound waves at the frequency of Glenn Beck’s voice?

Like most things, the idea of a vaccine against behavior is easier said than done. This use of technology also opens up an entire spectrum of ethical issues. Let’s say that we are, in fact, able to regulate behavior with vaccines. Do we want to? Is it right to do so? How do you give informed consent for behavioral change when the end result may be permanent? What does it do to the concepts of autonomy and free will? And as our knowledge of immunology and neurochemistry gets more specific, can we develop vaccines to block other behaviors not related to poor health? I don’t know that I’d go as far as to invoke George Orwell’s 1984, but it’s pretty easy to see where the argument is headed. Clinically, there’s a problem here as well. It’s entirely possible that a drug addict who got an anti-narcotic vaccine has a broken leg six months later. Even I’d be hard pressed to say that the patient should be denied the beneficial effects of pain medication simply because the vaccine is already “on board” and doing its stuff. (I think the people I work with would tell you I’m a relatively hard person to get narcotics from, but I do have my limits. My theory has always been if you break something, lose something, bleed somewhere, have cancer, or let me stick a sharpened piece of stainless steel somewhere into your body, you can have all the pain medication you want.)

There’s also a flip side to the coin. Vaccines designed for clinical purposes can be perceived as facilitating undesirable behavior. We’ve seen this with the advent of the Human Papilloma Virus (HPV) vaccine. Clinically, this is great thing. We know that cervical cancer is a leading killer of young women, and that cervical cancer is caused in large part by infection with HPV. HPV, in turn, is fairly ubiquitous in our society, so it makes sense to offer the HPV vaccine to all girls and young women in order to diminish their risk of cancer. While there are still some issues to work out…namely if there are long-term effects, and if boys who are carriers of HPV should get vaccinated as well…this is a wonderful innovation and the first in what we hope will be a virtual cornucopia of preventive immunotherapies for malignant disease.

How can something this good get tuned on its head? Well, HPV is contracted through sexual contact. And if we make unprotected sex safer, that might encourage more teenagers and unmarried people to have sex. That’s not right. And if that happens, there might be more abortions. That would also be wrong. Clinically, I would argue (and have done so) that while it’s true that there may be less risk of cervical cancer, there are still plenty of other reasons to discourage sex outside of a long-term monogamous relationship. Things like unwanted pregnancy, gonorrhea, syphilis, hepatitis, and AIDS come to mind. But you can see the politics at work here, can’t you?

In the long run, I suspect the story of the nicotine vaccine (at least the form currently in trials) will be a lot like the tale of the gastric banding procedure. The “fatpass” (official medical term) decreases the size of the stomach so less food can be taken in at each meal, therefore decreasing total caloric intake and inducing weight loss. That being said, I’ve seen hosts of patients who had the procedure and, after initially losing poundage in the triple digits, have put most of it right back on. This happens because their underlying issues with food and lifestyle cannot be solved with surgery, and so they learn to compensate for the procedure by eating the same volume of food, but eating smaller amounts more frequently. (One of my ED doc colleagues is a perfect example of this. The day after his gastric bypass, someone called to see how he was doing. He was eating a pan of brownies, but with the bypass he could only eat them only one at a time.)

The article described a success rate of 35% in getting patients to remain nicotine-free. Checking out the company’s web site, the trials have lasted only 6-12 months. And while a short-term return of 35% is surely better than nothing, it’s still only 35%. People who are successful with permanent weight loss after gastric bypass surgery are those who also change their diet, lifestyle, social circles, and self-perceptions. If the vaccine helps only a minority of smokers to quit, there must be a host of other reasons for tobacco use besides the nicotine kick. While the vaccine can be part of the solution…and if it passes clinical trials, I’ll be proud to be a cheerleader…it is a single piece of the puzzle which also includes higher prices on tobacco products, clean indoor air legislation, enforcement of underage tobacco purchases, expansion of smoking cessation programs, and public education. My fear is that in this technology-happy, quick-fix society, those strategies shown to have real impact on the health effects of tobacco use will be lost.

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