The smoking cessation medications bupropion and varenicline may both be associated with changes in the way the brain reacts to smoking cues, making it easier for patients to resist cravings, according to two reports posted online today that will appear in the May print issue of Archives of General Psychiatry, one of the JAMA/Archives journals.
“Environmental cues associated with nicotine reinforcement induce cigarette craving, which propagates smoking habits in smokers and relapse in abstinent individuals,” the authors write as background information in one of the articles. “Human brain imaging studies using functional magnetic resonance imaging (fMRI) and positron emission tomography scanning have provided insight into brain regions associated with cue-induced cigarette craving. Nicotine-dependent smokers exhibit activation in brain regions related to attention (prefrontal cortex), emotion (amygdala), reward (ventral tegmental area) and motivation (striatum) while viewing cigarette-related cues.”
Bupropion, originally marketed as an antidepressant, was found to enhance smoking cessation in patients with depression and is now one of the most common therapies for smoking cessation in the world. It is known to reduce cravings in response to smoking cues, but its mechanism for doing so is not well understood. In one study, Christopher S. Culbertson, Ph.D., of University of California, Los Angeles, and colleagues assessed changes in brain activation in response to smoking cues among 30 smokers who were randomly assigned to take either bupropion or placebo for eight weeks.
Participants underwent fMRI scans within one week of joining the study and again at the end of the eight-week treatment period. During the scans, they were shown 45-second videos that contained either smoking cues – actors and actresses smoking in a variety of settings – or neutral cues, with similar settings but no smoking behaviors. Participants also used a response box with five buttons on it to report how strongly they craved cigarettes immediately after watching each video.
Patients who were treated with bupropion reported less craving in response to smoking cues than did patients who received placebo. Those taking bupropion also showed reduced activation in areas of the brain known to be associated with cravings, including limbic and prefrontal regions. Among all the participants, regardless of treatment, reports of cravings aligned with fMRI images – that is, those who showed reduced activation in craving-related areas also reported feeling fewer cravings.
“These results demonstrate that treatment with bupropion is associated with an improved ability to resist cue-induced craving and a reduction in cue-induced activation of limbic and prefrontal brain regions,” the authors conclude.
In a second article, Teresa Franklin, Ph.D., of University of Pennsylvania, Philadelphia, and colleagues studied brain responses to varenicline, another smoking cessation medication. Varenicline reduces symptoms of withdrawal and also reduces the reinforcement received from nicotine while smoking. A total of 22 patients were randomly assigned to receive either varenicline or placebo for three weeks. They also underwent fMRI scans before and after the treatment period, during which they viewed 10-minute video clips that contained either smoking cues or neutral cues and reported their cravings.
In scans performed before treatment, smoking cues activated brain areas known as the ventral striatum and medial orbitofrontal cortex and also elicited reports of cravings, whereas neutral cues did not. After the treatment period, similar patterns persisted in patients who had taken placebo, whereas those treated with varenicline experienced a reduction in both brain activity and reported cravings in response to smoking cues.
In a scan taken while the individuals were at rest before viewing the videos, participants who took varenicline showed a greater activation in the brain area known as lateral orbitofrontal cortex than did those who took placebo. Increased activation in this area predicted a blunted response in the medial orbitofrontal cortex when the cues were shown.
“The results of our study reveal a distinctive new action of varenicline that may contribute to its clinical efficacy,” the authors conclude. “Unsuccessful smoking cessation is more prevalent in individuals with psychiatric illness, suggesting that they have greater difficulty quitting. Varenicline and other medications that can reduce both withdrawal and cue reactivity may be of special benefit to these subgroups.”
Source : Archives of General Psychiatry