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Posts Tagged ‘zyban’

The genetics of quitting smoking- Bupropion and nicotine metabolism

October 18th, 2010

If you’ve been reading A3 for a while, you know that we’re big supporters of scientific progress in addiction treatment. While it may be true that addicts need to want recovery in order to truly turn their lives around, the choice is hardly ever that simple and if we can tip the balance in the favor of treatment, or a better way of life, I say let’s go for it. When it comes to genetics and addiction, I’ve normally talked only about the fact that a person’s genetic code may predispose them to addiction or to other related conditions (like depression, anxiety, and so on). Aside from a single mention of pharmacogenomics, I don’t think I’ve spoke much about the way genetics can help us tailor addiction treatment to individual needs. We’re about to fix that.

Replacement therapies and quitting smoking

You’ve heard of nicotine patches and gums, right? In the research community, those are all known as Nicotine Replacement (NR) therapy and they’ve proven to be some of the most helpful tools for those who are quitting smoking. By allowing smokers to still get the nicotine their body craves (even though there are thousands of other chemicals in cigarettes that likely make them even more satisfying) without having to light up, these NR methods let cigarette addicts get their NIC fix while slowly lowering their dose and getting away from the habit of putting a cigarette in their mouth. Like methadone, buprenorphine, and other replacement therapies, the idea is to move addicts one step away from the actual addictive behavior and allowing them to begin adopting a healthier way of living. Replacement therapies are very successful, even if some people hate the idea of giving drugs to drug addicts, and nicotine replacement works well by itself for some people (though only about 20%).

But when it comes to nicotine, like with many other drugs, different people metabolize the stuff at different rates. The individual variability in the internal processing of nicotine greatly affects how many cigarettes individuals smoke and also the probability that they will become addicted to tobacco (people who metabolize nicotine more quickly smoke more and are more likely to become addicted to smoking). Fast metabolizers are also half as likely to be able to use nicotine replacement alone to quit smoking (1). However, when you put all of the addiction research together, it becomes pretty obvious that the same variability in nicotine metabolism can also help us determine the best course of treatment for tobacco addiction.

Metabolism, treatment, and the best way to quit smoking

Bupropion helps fast metabolizers increase their quitting chancesFortunately for smokers, the only research finding in this area hasn’t been that slow metabolizes have a much better chance of quitting smoking with nicotine replacement therapy. The same group of addiction researchers (led by Caryn Lerman of University of Pennsylvania), also found that buporopion, the smoking cessation medication everyone knows as Zyban (and the antidepressant called Wellbutrin), could help those fast metabolizers catch up with the slow metabolizers when it came to quitting (see the figure on the left taken from the actual study – you see that the dark bars, who are the bupropion patients, do as well as the white bars regardless of their metabolism rate, which is on the bottom). The researchers found that while slow matabolizers of nicotine did much better with simple smoking cessation therapy and fast metabolizers did very poorly (30% versus 10% quit respectively in each of the groups), adding bupropion made all groups look essentially the same (2). The moral? While those slow metabolizers don’t really get much of a benefit from using bupropion since they do pretty well with talk therapy or nicotine replacement alone, the fast metabolizers really need it to even their chances of quitting – and once they get bupropion, they do pretty well!

Genetics and addiction treatment – is this just the beginning?

Hopefully you’re now convinced that genetics can really help us determine what treatment course will best suit a specific person over another. There’s little question that this sort of approach is in its infancy, and you certainly can’t go to a doctor right now and get your metabolism rate for a drug analyzed (unless you’re part of a research study), but this sort of work shows great promise in improving the outcomes of addiction treatment. When you look back at that original paragraph, and the quite common thinking that addicts need to WANT to be better – I would argue that those fast metabolizers probably wanted to quit smoking as much as anyone else in the study, and their physical makeup just made it that much more difficult for them. I think that if you look at the science of addiction closely, you’ll find that this supposed lack-of-motivation is sometimes more of a myth than a reality. Many addicts want to get better, they want to stop behaving in ways that specifically mess up their lives but they just find it incredibly difficult. My hope is that this is where science can truly make a difference, by making it just a little bit easier…

Hopefully one day we’ll be able to specifically adjust addiction treatment programs according to individual patients’ needs, including the use of medications, specific behavioral treatments, and more.

Citations:

1) Robert A. Schnoll, Freda Patterson, E. Paul Wileyto, Rachel F. Tyndale, Neal Benowitz, & Caryn Lerman. Nicotine metabolic rate predicts successful smoking cessation with transdermal nicotine: A validation study (2009).

2) F Patterson, RA Schnoll, EP Wileyto, A Pinto, LH Epstein, PG Shields, LW Hawk, RF Tyndale, N Benowitz & C Lerman1. Toward Personalized Therapy for Smoking Cessation: A Randomized Placebo-controlled Trial of Bupropion (2008).


Posted in:  Education, Medications, Treatment
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ADD and ADHD medications: Lessons from a crystal meth experiment

April 11th, 2010

I’ve recently completed a study that I presented at the Society For Neuroscience (SFN) meeting in DC. The study was actually aimed at looking at the usefulness of two medications in interfering with the rewarding qualities of methamphetamine. The thinking was the if we could figure out a way to interfere with crystal meth being perceived as rewarding by the brain, we may be able to help addicts from continued use after a relapse.

Two prescription stones but only one hits crystal meth

The two medications are atomoxetine and bupropion, though you may know them as Strattera and Wellbutrin or Zyban. Their mechanisms of action are similar, but distinct enough that we wanted to test them both. The results of the study, in one sentence, were that atomoxetine (or Strattera), but not bupropion (or Zyban) succeeded in eliminating animals’ preference for meth if given along with it. The implication is that in the future, these, or other, similar, medications, may be given to newly recovering addicts. The hope would be that by taking the drug, they may be somewhat protected in the case of a relapse. If they don’t enjoy the drug during the relapse, they may have a better chance of staying in treatment.

More to these medications than meets the eye

I learned some other interesting things while preparing, and then carrying out, the study. While Zyban could, by itself, be liked by the animals, Strattera did not seem to produce any sort of preference. Given the common use of these drugs in the treatment of ADHD, the difference may be very important. As you may recall, I’ve talked before about the connection between impulse control problems and being predisposed to developing addiction. Given this relationship, it would seem that we’d want to be especially careful about using drugs that can cause abuse with this population. Many of the stimulants used to treat ADD and ADHD can indeed lead to abuse, as their effects are very similar to speed, or crystal meth (Adderall and Ritalin come to mind). Zyban’s abuse liability is definitely lower, given the greatly reduced preference animals develop for it. Still, it seems that Strattera’s abuse potential is almost zero. In trial after trial, animals given atomoxetine fail to show a preference for the drug.

To my mind, this means that as long as it’s successful in treating the attention problems, atomoxetine is the better candidate. All in all, I’d think the first choice should be the one that helps the symptoms of ADHD while having a reduced likelihood of dependence. Obviously, if the drug is not able to treat the problem, other options should be selected, but it seems to me that given the known relationship between attention deficit problems and addiction, the question of abuse liability should play a significant role in the selection of medication.

Once again, this doesn’t mean that all users of Adderall, Ritalin, or the other stimulant ADHD medications will develop an addiction to their prescription. In fact, we know that rates of addiction to prescriptions are generally relatively low. Nevertheless, I’d consider ADHD patients a vulnerable population when it comes to substance abuse so I say better safe than sorry.


Posted in:  Education, Medications, Treatment
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