Russ WareThe FDA recently published a new public health education page called The Relative Risks of Tobacco Products. For the most part, this page just regurgitates facts that many vapers already understand, i.e. smoking is very harmful, vaping is significantly less harmful, and Nicotine Replacement Therapies (NRTs) such as patches are least harmful.
On the page, the FDA acknowledges that vaping can generally be a lower-risk alternative for adults who smoke cigarettes and that e-cigarettes expose users to fewer harmful chemicals than smoking. Also noted is the fact that despite the science that backs this fact up, many adults believe that e-cigarettes are just as or more harmful than cigarettes.
What isn’t acknowledged is the FDA’s role in driving this misperception by refusing to authorize over 99% of vape products and filling the Center for Tobacco Products (CTP) newsroom with stories of retailers selling unauthorized Elf Bars. But maybe that’s a story for a different article.
What really caught our attention on the Relative Risks page was the suggestion that alongside quitting cold turkey, one of the safest ways to give up smoking tobacco is to use approved prescription drugs like Bupropion and Varenicline. Not knowing much about how effective these approved and allegedly safe medications are for quitting smoking, we decided to take a closer look.
What is Bupropion?
Bupropion is an anti-depressant medication approved for general use by the FDA in 1985. Although it was initially developed to treat depression, it was subsequently found to be effective as a smoking cessation treatment and approved for this use in 1997. It is most commonly prescribed for smoking cessation under the brand name Zyban.
Bupropion works in the brain to change the levels of certain chemicals that influence mood and behavior, including dopamine and norepinephrine. By altering these chemical levels, Bupropion can help reduce cravings for nicotine, decrease withdrawal symptoms, and improve mood, making it easier for people to stick to their quit-smoking plan.
Bupropion is often used in combination with other quit-smoking strategies, such as nicotine replacement therapy (NRT) like patches, gum, or lozenges, counseling, or support groups. A combination of Bupropion and other methods can be much more effective than using Bupropion alone.
Bupropion has proven efficacy for smoking cessation in several clinical trials, helping approximately one in five smokers to stop smoking. It is prescribed tens of millions of times every year in the United States, making it one of the most often prescribed medicines in the country. In contrast, Bupropion is rarely prescribed in countries such as the UK, according to the National Institute of Health and Care Research.
Is Bupropion Safe?
The story of Bupropion as a medicine hasn’t been a smooth ride. It was removed from the market in 1986 due to an increased risk of seizure discovered shortly after it was initially approved. It was reintroduced to the market 3 years later with label adjustments that included a lower maximum daily dose recommendation.
In 2001, as many as 57 deaths were linked to Zyban use in the UK. The British Medicines Control Agency (MCA) and GlaxoSmithKline, the makers of Zyban, pointed out that the link between the medicine and the deaths was unproven.
Those problems occurred a long time ago, but it is worth remembering that anti-depressants are almost always among the most common substance classes involved in human poison exposures. The American Association of Poison Control Centers reported 18,802 Bupropion overdoses in 2022, 18 of which resulted in fatalities. About half of these overdoses (9,708) were from single exposures.
Possible side effects of Bupropion include:
- Constipation
- Dizziness
- Dry mouth
- Loss of appetite
- Nausea
- Tremors or shaking
- Trouble sleeping
- Allergic reactions—skin rash, itching, hives, swelling of the face, lips, tongue, or throat.
- Increase in blood pressure.
- Mood and behavior changes—anxiety, nervousness, confusion, hallucinations, irritability, hostility, thoughts of suicide or self-harm, worsening mood, feelings of depression.
- Redness, blistering, peeling, or loosening of the skin, including inside the mouth.
- Seizures.
- Sudden eye pain or blurry vision, seeing halos around lights, and vision loss.
Serotonin Syndrome
Serotonin syndrome is an uncommon but potentially serious set of side effects linked to some medicines. It happens when the levels of serotonin in your brain become too high. Symptoms can range from mild (shivering and diarrhea) to severe (muscle rigidity, fever, and seizures). Severe serotonin syndrome can even cause death if not treated.
There’s a risk of serotonin syndrome if you take more than your prescribed dose of Bupropion or if you take certain other medicines alongside it.
What is Varenicline?
Varenicline was developed by Pfizer specifically for smoking cessation, although it was subsequently found to also have potential benefits for sufferers of dry eye disease. It was approved by the FDA for its main use in 2006 and was commonly prescribed under the Chantix and Champix brands.
It works by activating the nicotinic receptors in the brain, resulting in the release of dopamine in the brain’s reward center, the nucleus accumbens. This can reduce cravings and withdrawal symptoms associated with quitting smoking. Although not officially classed as an anti-depressant, Varenicline produces what are described as “antidepressant-like effects” and some studies suggest it has potential for use as a true anti-depressant.
A Cochrane Review in 2013 found that varenicline is a highly effective medication for tobacco cessation and that smokers were nearly three times more likely to quit tobacco while taking varenicline than with placebo treatment.
Is Varenicline Safe?
The use of Varenicline appears unlikely to lead to the risk of overdose and it does not appear in The American Association of Poison Control Centers reports as a cause of hospitalization or death. Some studies have suggested that it can increase the risk of adverse cardiovascular events, but the results of various further tests aren’t definitive.
In 2007, shortly after Varenicline was approved, the FDA received reports of suicidal thoughts and behavior, erratic behavior, and drowsiness among users. A boxed warning was then added to the packaging highlighting these potential risks. However. further studies and reviews in 2014 did not find evidence of an increased suicide risk, and the warning was removed in 2016.
Pfizer announced a recall of Chantix in 2021 due to “high levels of cancer-causing agents called nitrosamines in the pills.” This appears not to have been a problem with Varenicline, but rather with Pfizer’s formulation of their branded drug.
Possible side effects of Varenicline include:
- nausea
- constipation
- diarrhea
- gas
- abdominal pain
- vomiting
- heartburn
- bad taste in the mouth
- dry mouth
- increased or decreased appetite
- toothache
- trouble falling asleep or staying asleep
- unusual dreams or nightmares
- headache
- lack of energy
- back, joint, or muscle pain
- abnormal menstrual cycles
- swelling of the face, throat, tongue, lips, gums, eyes, neck, hands, arms, feet, ankles, or lower legs
- hoarseness
- difficulty swallowing or breathing
- rash
- swollen, red, peeling, or blistering skin
- blisters in the mouth
- pain, squeezing, or pressure in the chest
- pain or discomfort in one or both arms, back, neck, jaw, or stomach
- shortness of breath
- sweating
- nausea, vomiting, or lightheadedness with chest pain
- slow or difficult speech
- sudden weakness or numbness of an arm or leg, especially on one side of the body
- calf pain while walking
- seizures
- sleepwalking
Should You Say No to Smoking Cessation Drugs?
We are not saying don’t listen to your doctor if they recommend that you try using Bupropion or Varenicline. Your doctor has (hopefully) years of medical training and experience, while we have none. If they decide it is safe to prescribe these medications to you, who are we to say otherwise.
Both drugs, but Varenicline in particular, should clearly be an option for smokers who have struggled to give up by any other means. Studies have shown that in the right situation, with responsible use, they can considerably improve the chances of quitting.
However, stating that Bupropion or Varenicline “should be the first line of therapeutic treatment for adults seeking to quit smoking”, as the FDA does on its Relative Risks page, feels wrong. There is no mention of the possibility of adverse effects, extreme suicidal thoughts, or risk of overdose, unlike in the section on e-cigarette use which is filled with warnings like “the use of e-cigarettes is not risk-free” and “These products deliver harmful chemicals and contain nicotine, which is highly addictive.”
The almost complete lack of willingness to even consider vaping as a valid smoking cessation aid while simultaneously recommending anti-depressants in a country where an estimated 7% of all adults are already taking them for reasons other than giving up tobacco, seems strange.
Normal, responsible vaping isn’t killing thousands of people each year, but anti-depressants are. Along with opioids and benzodiazepines, anti-depressants were the pharmaceuticals (alone or in combination with other drugs) most commonly involved in pharmaceutical overdose deaths.
Magnetic Brain Pulse Helmets: Also Safer than Vaping?
Although not mentioned on the Relative Risks page, the FDA has also given marketing clearance to a Transcranial Magnetic Stimulation (TMS) device for use as an aid for short-term smoking cessation. Despite Transcranial Magnetic Stimulation being relatively new, little understood, and sounding like something you sign up for at a new-age meditation retreat in California.
TMS treatment, which is also commonly referred to as rTMS, involves applying electromagnetic coils against the scalp to deliver repeated magnetic pulses to the region of your brain involved in mood control and depression.
Common side effects of having TMS treatment include scalp discomfort, headaches, facial spasms, and lightheadedness. Less common side effects include seizures, periods of mania (emotional highs), and hearing loss. Mayo Clinic, the well-respected medical education and research foundation, says:
“Although the biology of why TMS works isn’t completely understood, the stimulation appears to affect how the brain is working. It seems to ease depression symptoms and improve mood. Generally, rTMS is considered safe and well-tolerated. However, it can cause some side effects. More study is needed to determine whether rTMS may have long-term side effects.”
Great, sign me up to have magnetic pulses fired into my brain with unknown long-term side effects because that sounds like a much safer option than vaping.
The Bottom Line
Smoking cessation drugs aren’t inherently dangerous and there are good arguments to be made for developing them and prescribing them in some cases. You are way less likely to be harmed or killed by a two-month course of these drugs than you are by years of smoking. However, just because they are FDA-authorized and handed out by a physician, that doesn’t mean they are 100% safe or that there isn’t a risk of potentially nasty side effects.
Jamie Gann
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