June 1, 2023

Dr. Andrew Pipe explains the effects of Bupropion and Varenicline in smoking cessation therapies.

I’m going to sit make a couple of comments about briona only to note that this drug serendipitously was found to be able to help people stop smoking there are contraindications which you’re probably far more aware of than most clinicians to the use of this agent which is obviously fundamentally originally an antidepressant but many patients will report that taking

The conventional doses of these products they don’t kind of like the way that they feel or that they have a dry mouth or a skin rash well in any other area of clinical practice when patients have side effects which are dose related we adjust the dose in reducing the dose of bupropion in the face of these kinds of side effects generally addresses the side effects

Without significantly attenuating its ability to help or maintain smoking cessation so once again that point about titration and when you pro prion was first first arrived it was shown in contrast to to nicotine replacement therapy to be very significantly more efficacious and when used in combination the first hints about combination therapy was more efficacious

Again so final comment about an agent varenicline which is modification of a naturally occurring substance that occurred in the rose apartment is found in the leaves of a shrub which grew in western eurasia during the second world war people smoked the leaves of the shrub as a tobacco substitute post second world war the iron curtain eastern bloc pharmaceutical

Industry used the leaves of this shrub as a smoking cessation aid the active ingredient cytosine not cytosine cytosine binds to the alpha 4 receptor but not well but if you modify that cytosine structure you get varenicline which binds avidly to this particular receptor except that when it stimulates this receptor the receptor only opens partway you get overall less

Flow of ions overall in aggregate less depolarization of underlying neurons and therefore in aggregate less release in the forebrain of dopamine and etc etc etc but smokers perceive this is hmm i don’t really feel like i need a cigarette because i’m feeling ok i got nicotine receptor stimulation producing dopamine another transmitter release and by the way this is

Occupying that that particular receptor site and so if i do smoke a cigarette i don’t really kind of feel that i so now we are able to use if you will molecular biology principles to address some of these issues now that is not to say that this is the answer but we are certainly a whole lot further along the road than we were in the past the most common side effects

Of varenicline and anything which stimulates nicotine receptors are nausea and sleep disturbances why because you’ve got nicotine receptors in your gut if you stimulate them constantly you’re gonna get nauseated in exactly the same way if you chew nicotine gum very avidly and swallow the saliva nausea will will follow so if you’re using a systemic agent which is

Omnipresent around-the-clock you’re gonna have perhaps nausea you’re certainly perhaps initially going to have some sleep disturbances some insomnia some unusual dreams because those nicotine receptors are not used to being stimulated during the night those symptoms pardon me generally pass fairly quickly in fact it’s kind of intriguing many of the responses we get

From patients on varenicline are yeah i’m having unusual dreams but you know what they’re kind of cool and i can’t wait to go to bed at night because i wonder what’s going to appear appear this evening but then there were the questions of neuropsychiatric and cardiovascular issues and so clearly one of the zone zombie concepts that is persisted is that varenicline

Causes psychiatric problems despite the fact that following the initial pharmacovigilance type signals which are unbelievably sensitive but not specific if you look at the use of varenicline in large populations or in communities where varenicline has been used for for a considerable period of time you find that there is no evidence to to substantiate the view that

These caused psychiatric disorders and that evidence comes from a variety of sources in a variety of communities the us military health system published this in late nineteen 2008 2012 comparing varenicline with with nrt patch no increase in newer psychiatric hospitalizations over all reduced rates of inpatient and outpatient neuropsychiatric diagnosis consistent

With studies using nrt and varenicline uses and other settings showed no increased risk of self-harm depression etc etc etc at this point let me digress i live and work and play in a cardiovascular setting i am old enough to be able to remember when statins which are now the mainstay of the management of coronary artery disease were first introduced and i remember

Being in toronto at the toronto can conference centre in hearing very learned clinicians and scientists say hang on a second there’s evidence that statins are making people depressed and having suicidal thoughts and suicidal ideation and we better be you don’t hear a single word about that now not because we’re reckless in our use of statins but because it’s a

Common phenomenon when products are introduced that these pharmacovigilance instruments pick up these kinds of signals which are frankly more noise than that then signal so i think one can clearly say that there the evidence about the concern of varenicline causing psychiatric problems has been as is now dissipating this zombie had its origin in canada because

In an article which appeared in the cma j which was purportedly a meta-analysis of a sort the author’s suggested that the risk of cardiovascular events in a meta-analysis of studies using varenicline and cardiovascular patient populations with 0.82% in the placebo group and 1.0 6% in the varenicline group now in most cardiovascular pharmacology clinical trials an

Adverse cardiovascular event or you know and this can just include irregular heartbeat for two seconds and the whole pantheon okar this is pretty low but this was interpreted by the authors as a 72% risk of serious adverse cardiovascular events in those that used varenicline why you did this exercise pipe so much well because i was involved in what was the largest

Single trial of varenicline cardio in a cardiovascular setting the largest group of patients in this meta-analysis came from our trial and all of our cardiovascular side-effects notwithstanding that this trial wasn’t powered to be a safety trial all of our cardiovascular side effects were independently reviewed and we found no signal whatsoever in that particular

Meta-analysis so we were kind of a little perturbed by this but fortunately the british medical journal one year later published a more complete more appropriate meta-analysis looking at the risk of cardiovascular side effects from varenicline and concluded no significant increase in cardiovascular serious adverse events associated with varenicline use so there’s

A lot of no pun intended smoke that swirls around the academic discussions of smoking cessation pharmacotherapy and very often it takes some time for the smoke to clear and that evidence just continues to accumulate

Transcribed from video
Bupropion and Varenicline By CAMH Professionals Videos