Overview: Prescription Drugs to Quit Smoking

There are two FDA-approved quit smoking drugs. Bupropion (marketed as Wellbutrin and Zyban), and Varenicline (marketed as Chantix). These medications both require a doctor's prescription.

These medications are different from other quit smoking aids like the patch and nicotine gum because they don't contain any nicotine. Where nicotine replacement products like the patch work by providing a replacement source of nicotine, these FDA-approved quit smoking drugs work in a different way.

There is also a quit smoking vaccine under development which is showing some promise of effectiveness.

Zyban and Chantix

Bupropion, the active ingredient in Zyban, was originally developed as an antidepressant (brand name Wellbutrin) and later approved by the FDA to be used as a quit smoking drug. It appears to improve the chances for successful quitting mainly by reducing withdrawal symptoms, although no one is certain exactly how it does this.

The active ingredient in Chantix is a drug called varenicline, which was actually developed specifically to help people quit smoking. It works on receptors in the brain to do two things: 1) It mimics some of the effects of nicotine in the brain, even though it doesn't contain any nicotine. This is intended to reduce cravings and nicotine withdrawal symptoms. 2) It also blocks the nicotine receptors in the brain, which is intended to make smoking less pleasurable if you do smoke while using this drug. Theoretically, if your brain isn't getting the nicotine 'payoff,' it should be easier to quit.

Success Rates for Zyban and Chantix

Metaanalytic research, which computes the outcomes from multiple research studies, showed that both of these drugs had a similar success rate: About twice as many people who got one of these quit smoking drugs were able to quit and stay quit compared to people who got a placebo or 'fake' medicine. In all of these studies, the participants in both the treatment group and in the control group were on a behavioral plan in addition to the drug or placebo.

My Recommendations

If you are considering a prescription medication to help you quit smoking, choose either Bupropion (Zyban) or Varenicline (Chantix). Both have been shown to improve people's chances of quitting by a factor of about two. None of the other medications to quit smoking have shown any evidence of effectiveness except nortriptyline, which seems to have more side effects than it's worth for most people.

I'd also recommend that you find a good quality behavioral program or plan designed to help eliminate the psychological dependence on smoking.  It's easy to think that prescription medicine is a 'magic pill' that will provide all you need to quit, but for most people, this is simply not true. Even the studies designed to show the effectiveness of these quit smoking drugs included a behavioral program in addition to the drug treatment.

If you are considering using quit smoking medications, read more about Zyban (bupropion) and Chantix (varenicline), and make an appointment to check in with your doctor about whether you are a good candidate for one of them. In the meantime, you'll want to begin researching compatible behavioral programs to help eliminate the psychological addiction. You can read a little about the psychological aspects of smoking here. 

Using Zyban to Quit Smoking

Zyban (bupropion) is one of only two prescription medications that are FDA-approved to help people quit smoking.  (Varenicline, marketed as Chantix, is the other.)  Zyban is the formulation of bupropion that is approved for smoking cessation, and unlike nicotine replacement products like the patch, it does NOT contain nicotine. 

(Wellbutrin is an antidepressant medication with bupropion as the active ingredient.) 

Effectiveness

Metaanalytic research, which computes the outcomes from multiple high-quality research studies, showed that about twice as many people who got bupropion were able to quit and stay quit compared to people who got a placebo or 'fake' medicine.  In these studies, the participants in both the treatment group and in the control group were on a behavioral plan in addition to the drug or placebo.

A Note About Effectiveness The most effective of all of the stop smoking aids or drugs have shown about a 'doubling' effect.  That means that if you use an 'effective' medication or aid, on average you are about twice as likely to quit successfully as someone who tries to quit without it.  What it DOES NOT mean is that the medication alone will "make" you quit.  For example, only about 5% of people who try to quit cold turkey are successful.  So if you use a medication that doubles your chances and then try to quit cold turkey, your chance of quitting successfully ― even WITH the medication ― is only about 10%. I mention this here because it's important to understand what the word 'effective' means when it comes to quit smoking medications, including bupropion.  The bottom line is, to increase your chances of quitting successfully, you'll need to combine whatever you choose with the best quit smoking plan or program you can find.  See 'My Recommendations' below for more advice and links related to this.

How It Works

Bupropion was originally developed as an antidepressant (brand name Wellbutrin) and only later discovered to help people quit smoking.  'Zyban' is the brand name of the bupropion formulation that is approved for smoking cessation.  How it works exactly to help people quit smoking hasn't been proven, but it may work by partially reducing the effect of nicotine in the brain, and reducing some withdrawal symptoms.  An explanation of its chemical properties provides some clues. 

Warning: The information below may fall into the category of 'Way More Than You Wanted to Know' about bupropion.  If you're not interested in a technical explanation of the possible mechanism of action, feel free to skip ahead to 'How to Use Zyban'...

Bupropion acts on two types of neurotransmitters: norepinephrine and dopamine.  For both norepinephrine and dopamine, bupropion acts as a 'reuptake inhibitor' [that is, it keeps the cell from taking the neurotransmitter back in] which has the effect of keeping that neurotransmitter circulating, and increasing its effect.  You can think of the effects of norepinephrine and dopamine as similar to adrenaline - both dopamine and norepinephrine act on the sympathetic nervous system to increase heart rate, glucose release, and other sympathetic nervous system responses.  Bupropion increases these effects.  It's not clear how these effects contribute to bupropion's ability to help people quit smoking, but it may be related to the dopamine effect. 

Nicotinic receptors in the brain (those that respond to nicotine), when stimulated, act in part to stimulate the mesolimbic dopamine system, which scientists believe is the neuronal mechanism for the 'reward' experienced upon smoking.  It may be that the dopamine-related effect of bupropion acts to mask the effect of this stimulation, thereby reducing the 'reward' experienced as a result of nicotinic stimulation, which ultimately should make it easier to quit.

Keep in mind that the 'reward' of nicotine in the brain is only one part of the physical and psychological addiction to nicotine and smoking more generally. 

(BTW, you may read elsewhere that bupropion acts as a nicotinic antagonist - however, the clinical pharmacology information on bupropion published by the FDA does NOT indicate this.)

How to Use Zyban

Using Zyban is pretty simple:  It comes in pill form that you take once a day initially, and then twice a day.  Generally you begin taking it a week or two before the day you plan to quit in order to build up to its maximum effect.  Your doctor may have you continue on Zyban for another 2 to 3 months after you quit. 

Of course, you shouldn't expect the little pill to do all the work by itself ― you'll want to combine it with a good behavioral program for quitting, as well.  (See My Recommendations below for more on this.)

Side Effects

The most common side effects of Zyban (bupropion) are headaches, nausea, dry mouth, and sleep disturbances.  For most people these are relatively minor effects that go away when they quit taking the medication. 

An important potential risk with bupropion is increased risk of seizures.  If you suffer from epilepsy, alcoholism, or any psychiatric condition, including an eating disorder, or if you're on any other medication, especially other antidepressants or antipsychotic drugs, you will want to share that information with your doctor so that the two of you can make an informed decision about whether or not Zyban (bupropion) is a good option for you.  

The FDA also recently issued a warning that, for children and teenagers, any antidepressant may increase the risk of thinking about suicide.  Even though Zyban is formulated as a smoking cessation medication, its active ingredient, bupropion, acts as an antidepressant, so it will be important to discuss this with your doctor if you are a teenager, or are considering asking your doctor to prescribe it to a teenager in your care.

Pros and Cons

What are the pros and cons of using bupropion to help quit smoking? 

 Pros:

• The success rate for Zyban is at least as good as other 'effective' quit smoking aids such as nicotine replacement products.

• Unlike nicotine replacement products, Zyban and Chantix allow you begin the treatment a week or two prior to your quit attempt.  This allows you to integrate a quit smoking program with the treatment while you are still smoking, and may help you with a natural tapering or 'nicotine fading' technique that can help minimize withdrawal symptoms.

• It's easy to use -- it is simply a pill that you take a couple of times a day.  (However, don't be fooled into thinking that the pill will do the job all by itself.)

Cons:

• Zyban (bupropion) requires a doctor's prescription, so it may be less convenient than some of the other options.  Cost to you depends upon whether you have insurance that will cover the doctor visit and all or part of the cost of the prescription. 

• As with most medications, Zyban (bupropion) has some side effects and risks associated with it, and is not recommended for people with certain conditions, especially anything that increases your risk of seizures.  (See side effects, above.)

My Recommendations

Bupropion is one of the two prescription quit smoking medications that have been shown to be effective, so as long as you aren't one of the people who should NOT take it (primarily because of increased risk of seizures), it may be worth exploring this option with your doctor.  You may want to also read about Varenicline (Chantix) for comparison purposes.

Of course, it will be important to decide on a behavioral program for eliminating the psychological dependence on smoking, too.  Remember that a 'doubling' of the usual 5% cold turkey success rate only yields a 10% success rate.  Stack the deck in your favor as much as possible by using a good behavioral program, too.  As much as we'd all like it to be, bupropion is not a 'magic pill' for quitting smoking. 

Using Chantix to Quit Smoking

Chantix (active ingredient varenicline) is one of only two prescription medications that are FDA-approved to help people quit smoking.  (Bupropion, marketed as Zyban, is the other.)  Unlike nicotine replacement products like the patch, neither of these medications contain nicotine. 

Effectiveness

Like other medications, the effectiveness of Chantix (varenicline) was also examined using metaanalytic techniques.  (Metanalysis is a a statistical research technique used to combine the outcomes from multiple high-quality studies to get the most accurate answer.)  The effectiveness was similar to Zyban: about twice as many people who got Chantix were able to quit and stay quit compared to people who got a placebo or 'fake' medicine.  In these studies, the participants in both the treatment group and in the control group were on a behavioral plan in addition to the drug or placebo.

(In head-to-head studies comparing the effectiveness of varenicline and bupropion, Chantix appeared to have a slight edge.  It's worth noting that these studies were conducted by its manufacturer, Pfizer.)

A Note About Effectiveness The most effective of all of the stop smoking aids or drugs have shown about a 'doubling' effect.  That means that if you use an 'effective' medication or aid, on average you are about twice as likely to quit successfully as someone who tries to quit without it.  What it DOES NOT mean is that the medication alone will "make" you quit.  For example, only about 5% of people who try to quit cold turkey are successful.  So if you use a medication that doubles your chances and then try to quit cold turkey, your chance of quitting successfully ― even WITH the medication ― is only about 10%. I mention this here because it's important to understand what the word 'effective' means when it comes to quit smoking medications, including varenicline.  The bottom line is, to increase your chances of quitting successfully, you'll need to combine whatever you choose with the best quit smoking plan or program you can find.  See 'My Recommendations' below for more advice and links related to this.

How It Works

Unlike bupropion, varenicline was developed specifically to help people quit smoking.  It works by both mimicking and blocking the effects of nicotine in the brain.  It may seem odd that both mimicking and blocking the effects of nicotine could work to help people quit, but it actually makes sense.  By mimicking the effects of nicotine, varenicline may reduce some of the withdrawal symptoms (although by no means all of them) that people experience when they quit.  And by partially blocking the effects of nicotine, it helps to reduce the 'reward' of nicotine intake, making at a little bit easier to give it up.

Warning: The information below may fall into the category of 'Way More Than You Wanted to Know' about varenicline.  If you're not interested in a technical explanation of the mechanism of action, feel free to skip ahead to 'How to Use Chantix'.

OK, here's the technical part:  The brain has neurotransmitter receptor cells that have been labeled 'nicotinic' receptors because they are stimulated by nicotine.  Varenicline acts on these cells as an 'agonist,' which means that it binds to these cells and stimulates them in a similar way to nicotine.  (The effects are not as strong as nicotine, however.)  Because the drug is in effect 'parked' at the receptor sites on these cells, it also partially blocks nicotine from activating them, thereby reducing the effect of nicotine in the brain from smoking, and helping to reduce the 'reward' associated with smoking.

A note about addiction:  One of the reasons smoking is so psychologically addictive is because the method of delivery - smoke - has an immediate effect on your system.  In other words, you are 'rewarded' right after the behavior - not 5 minutes later, or half an hour later.  Psychological research shows that rewards or punishments that follow the action quickly have a much greater effect than rewards or punishments that are delayed.  So the act of lighting up is immediately rewarded, and it becomes a very strong behavior, making it very difficult to quit. 

Applying that principle to the action of  varenicline, it's clear that its effectiveness is related to the fact that 1) varenicline [partially] mimics the effect of nicotine, but in a steady, all-the-time way, NOT as a response to lighting a cigarette, and 2) it [partially] blocks the effects of real nicotine, so that the act of lighting up a cigarette doesn't feel as 'rewarding' as before. 

Keep in mind that the 'reward' of nicotine in the brain is only one part of the physical and psychological addiction to nicotine and smoking more generally.  There are many other aspects of smoking dependence that should be addressed by psychological and behavioral techniques designed to help eliminate their effects.

If you're interested in digging even further into the technical details of Chantix, you can look at the clinical pharmacology of Chantix here.

How to Use Chantix

Using Chantix (varenicline) is not complicated.  Your doctor will probably give you instructions to help you gradually 'ramp up' your dosage during the first week or so until you're on a 'full' dosage of a 1 mg tablet in the morning and one in the evening.  The ramp up process helps minimize side effects from the drug.  Chantix should be taken after eating and with a full glass of water.

Generally, you doctor will advise you to plan your quit date to coincide with the ramp up to the full dosage - so quit date should fall a week or so after you begin taking Chantix, although some people need a few weeks for Chantix to work best.  Initially you'll probably take it for about 3 months, and provided you quit smoking, your doctor may prescribe another three months' worth to help you solidify your success, for a total of 6 months maximum.

BTW, if your doctor's recommendations differ from what I've described above, of course you should follow your doctor's recommendations.  The information above is how Chantix is 'usually' used, based on the manufacturer's testing and recommendations.  Your doctor's recommendations, on the other hand, should be tailored to your specific situation.  That said, don't hesitate to ask your doctor questions if there is something you don't understand.  Especially if your doc is doing something different from the norm, it may help you to understand why s/he has made that decision for you.  I always say, an informed patient is a healthier, happier patient! 

Also, keep in mind that, like other quit smoking medications, Chantix is just ONE element of a successful quit smoking attempt.  You'll want to combine it with the best behavioral program for quitting you can find, to maximize your chances for success.  (See My Recommendations below for more on this.)

Side Effects

The most common side effect of varenicline is nausea (feeling sick to your stomach).  For most folks it is fairly mild and doesn't last, but for some people it can be more severe.  If you have bad nausea using this drug, reducing your dose might help - check with your doctor.  Other side effects include sleep disturbances, including insomnia and strange dreams,  headaches, constipation, vomiting, and being gassier that usual. 

Varenicline hasn't been tested on pregnant or breastfeeding women, or on children, so it is unknown whether it could have harmful effects in these circumstances.

Before your doctor prescribes Chantix to help you quit smoking, you should be sure to let him or her know if you:

• have kidney problems or get kidney dialysis.

• are pregnant or plan to become pregnant.

• are breastfeeding.

• are taking any other medications, including vitamins or herbal supplements. 

Pros and Cons

What are the pros and cons of using Chantix (varenicline) to help quit smoking? 

 Pros:

• The success rate for Chantix is at least as good as other 'effective' quit smoking aids such as nicotine replacement products or bupropion (Zyban).

• Unlike nicotine replacement products, Chantix allows you begin the treatment a week or two prior to your quit attempt.  This allows you to integrate a quit smoking program with the treatment while you are still smoking, and may help you with a natural tapering or 'nicotine fading' technique that can help minimize nicotine withdrawal symptoms.

• It's easy to use ― it is simply a pill that you take a couple of times a day.  (However, don't be fooled into thinking that the pill will do the job all by itself.)

Cons:

• Chantix (varenicline) requires a doctor's prescription, so it may be less convenient than some of the other options.  Cost to you depends upon whether you have insurance that will cover the doctor visit and all or part of the cost of the prescription. 

• As with most medications, varenicline has some side effects and risks associated with it, and is not recommended for people with certain conditions.  (See side effects, above.)

My Recommendations

Chantix is one of only two prescription quit smoking medications that have been shown to be effective, so if you're considering using prescription medication to help quit smoking, it's certainly worth exploring this option with your doctor.  It appears to be at least as effective as Zyban (bupropion), and doesn't have the seizure risk that is associated with bupropion.  For these reasons (as well as the 'pros' listed above), I would consider Chantix the first choice for prescription medication options. 

Don't forget to choose or devise a behavioral strategy for eliminating the psychological dependence, too.  Although Chantix should help reduce some of the 'reward' effect via its action on brain chemicals, for most people it is not a 'magic pill' that will 'make' you quit.  Increase your chances of success by supporting your quit attempt with the best behavioral/psychological program you can find. 

A Vaccine to Quit Smoking?

If you've been paying attention to the news, you may have read about a quit smoking injection designed to help people quit smoking.  It's called NicVAX, and it's being developed by Nabi Biopharmaceuticals.  It's not available yet - the manufacturer is still conducting clinical trials to show whether or not it works, in order to get it approved by the FDA.  However, I'll review the information that's available now, so you know what's coming down the pipeline.  Technically, it is a 'vaccine' since it works by stimulating antibody production. 

Effectiveness

Generally I use metaanalytic research to draw conclusions about the effectiveness of a drug treatment, because this technique combines the outcomes from several research studies to draw the most accurate conclusion possible.  However, since the quit smoking injection hasn't been FDA approved yet, the only research that is available is what has been done by the manufacturer so far as they collect data to be used in the process of getting it approved by the FDA.

Here's what that research shows so far

Overall, comparing people who got the most effective dose and dosing schedule of NicVAX, a little more than twice as many were able to quit and stay quit compared to people who got a placebo or 'fake' shot to quit smoking.  This is about the same as most of the other quit smoking products that show any sign of effectiveness. 

Specifically, about 6% of people who received a placebo (fake shot) stayed quit for a year, compared to around 16% of people who got the real quit smoking shot.  It's worth noting that the vaccine was more helpful for some people than for others.  When they compared people on the basis of who showed the greatest antibody effect (which is the mechanism of action for this vaccine), the top third showed about a 16% success rate compared to the bottom two-thirds, which showed a rate of about 8% - not significantly different from the rate of 6% for the placebo group. 

If you look at only the people who received the most effective dose and schedule, the results are a little more encouraging: 21% compared to 13%, vs. 6% for the placebo group.  However, at this point in the research it's not possible to tell whether the difference between the bottom two thirds (13%) and the placebo group (6%) are just due to random variation, or if they really reflect the effectiveness of the vaccine.  Hopefully more research will help to clarify this.

If you'd like to take a look at the data presented by the manufacturer at the American Heart Association Scientific Sessions in November 2007, you can see that here:  quit smoking vaccine presentation.

My conclusions

Based on the research so far, it looks like the quit smoking shot can actually make a difference for some people, but the percentages overall are still pretty low - in other words, this quit smoking injection, if/when it becomes available, will not be a magic bullet - it won't make quitting 'effortless.'  It may help some people quit smoking, but you'll still have the best chance if you combine it with other techniques, including a method to help deal with the psychological and behavioral aspect of quitting. 

Other Potential Quit Smoking Drugs

Besides Wellbutrin, another antidepressant, nortriptyline, has also been shown to help people quit, but it has not been FDA-approved as a medication to quit smoking, and is not usually prescribed because it has more severe side effects than other drugs that work about as well.

Other antidepressants such as Effexor (venlafaxine), Paxil (paroxetine), Prozac (fluoxetine), and Zoloft (sertraline) work by a different mechanism and have NOT been shown to help people quit smoking.

Anti-anxiety drugs have also been tested, under the theory that reducing anxiety would be helpful for people quitting. However, there is no evidence that anti-anxiety medication help people quit smoking, and these drugs are addictive and have their own side-effects.

Conclusions

None of these are good options to try. If you're going to try a prescription medication, stick with Zyban or Chantix, and be sure to couple it with a complete behavioral program, as well.