A preliminary investigation into the effects of doxazosin on cognitive functioning in tobacco-deprived and -satiated smokers

Abstract

Objective: To test the effects of doxazosin, an α1 antagonist, on cognitive functioning during tobacco withdrawal in smokers.

Methods: Participants (n = 35) were randomly assigned to receive placebo, 4-mg/day, or 8-mg/day doxazosin. They completed a continuous performance task and self-reported their withdrawal symptoms at baseline and twice following a medication titration period: once in a tobacco-deprived state and again in a nondeprived state. Ability to resist smoking was assessed using a laboratory smoking-lapse paradigm.

Results: Participants showed poorer cognitive performance on most measures taken from the continuous performance task when tobacco deprived. Eight-mg/day doxazosin improved inhibitory control during the nondeprivation session but did not affect sustained attention or reaction time. Participants receiving doxazosin reported fewer withdrawal symptoms during deprivation than those on placebo. Those showing the greatest improvement of inhibitory control under doxazosin were better able to resist smoking (i.e., latency to smoke) during a smoking lapse task. Self-reported withdrawal symptoms also were negatively associated with time to smoking.

Conclusions: Doxazosin reduced symptoms of tobacco withdrawal according to self-report and cognitive assessment and improved inhibitory control above predrug levels. This research identifies potential mechanisms by which doxazosin might improve smoking outcomes.

Keywords: doxazosin; inhibitory control; smoking cessation; tobacco withdrawal; α1 antagonist.

Figure 1

Effect of doxazosin and tobacco deprivation on commission errors on the CPT. Capped vertical bars represent SEM. Broken line crossing Y axis at 0 represents pre-medication baseline performance. Non-tobacco deprived sessions were conducted within 1 hour of smoking. Tobacco deprived sessions were conducted following at least 11 hours of abstinence. * above bar shows significant difference from premedication baseline, p < 0.05.

Figure 2

Effects of doxazosin and tobacco deprivation on withdrawal symptoms on the Minnesota Nicotine Withdrawal Symptoms Scale. Capped bars represent SEM. Broken line crossing Y axis at 0 represents pre-medication baseline performance. Non-tobacco deprived sessions were conducted within 1 hour of smoking. Tobacco deprivation sessions were conducted following at least 11 hours of abstinence. Symbol above bar shows significant increase from premedication baseline within that treatment condition, *p < 0.05, **p < 0.01.

Figure 3

Relation between degree of increase in Minnesota Withdrawal Scale score during deprivation session relative to baseline and number of cigarettes smoked during the free access phase of the smoking lapse task. Dashed line is least squares linear regression line for combined sample. The association is significant at p < 0.05.