Lack of beneficial galantamine effect for smoking behavior: A double-blind randomized trial in people with schizophrenia

Abstract

Cigarette smoking is schizophrenia is prevalent and may be due to self-medicating attempts to improve cognitive deficits related to α7 and α4β2 nicotinic receptor dysregulation. Galantamine is an acetylcholinesterase inhibitor that acts as a positive allosteric modulator of nicotine acetylcholine receptors including both the α4β2 and α7 subunits. In a double blind randomized clinical trial galantamine was compared to placebo for its effects on cognitive functioning in people with schizophrenia. This manuscript reports findings for galantamine's effect on smoking behavior in people from this 12-week trial who were smokers (18 galantamine, 25 placebo). Expired CO was measured every 2 weeks and the Fagerström Test for Nicotine Dependence (FTND) was administered at baseline and endpoint. Expired CO measures in galantamine subjects were 23.0 ± 9.7 ppm and 21.1 ± 10.3 ppm at baseline and Week 12, respectively, compared to 20.1 ± 8.5 ppm and 21.0 ±10.3 ppm at baseline and Week 12 in placebo subjects. The mean tau-b correlation between expired CO level and visit was −0.05 ± 0.41 in the galantamine group and 0.13 ± 0.42 in the placebo group (F=0.73, df=1,38, p=0.40), suggesting that there were no trends toward increased or decreased smoking in either group. Mean FTND scores in the galantamine group were 4.9 ± 2.5 at baseline and 5.2 ± 2.2 at week 12, compared to 4.1 ± 2.6 at baseline and 3.7 ± 2.6 at Week 12 in the placebo group (Mantel-Haenszel Χ 2 = 5.53, df=1, p=0.019), for an effect size of 0.4. These results suggest that galantamine has no effect on cigarette smoking and that during galantamine treatment nicotine dependency scores worsen.

Cognitive function during nicotine withdrawal: Implications for nicotine dependence treatment

“…Galantamine has some beneficial effects on cognition and drug use in stimulant abusers (Sofuoglu and Carroll, 2011; Sofuoglu and Mooney, 2009; Sofuoglu et al, 2011) and may improve inhibitory control in abstinent smokers (Sofuoglu et al, 2012). Preliminary studies with cholinesterase inhibitors in alcoholic, methamphetamine-dependent, and schizophrenic smokers show that they are well tolerated but provide mixed results for efficacy with respect to reducing smoking behavior (De la Garza and Yoon, 2011; Diehl et al, 2006; Diehl et al, 2009; Kelly et al, 2008). …”

Optimizing treatments for nicotine dependence by increasing cognitive performance during withdrawal

“…AChEIs also partially substitute for the discriminative stimulus properties of nicotine in humans [46] and rats [47]. Although these findings suggest that AChEIs may prevent smoking relapse, studies examining the effects of AChEIs on tobacco craving and smoking behaviour are mixed [45,46,48-50]. These conflicting clinical results are likely due to different patient populations (i.e., genetic variability, neuropsychiatric disorders, etc), comorbid drug use and small sample sizes.…”

Smoking in male patients with schizophrenia in China: A meta-analysis

“…Smoking patterns can be best understood in the given sociocultural context (Chen et al, 2009;Hou et al, 2011;Kelly et al, 2008;Tang et al, 2007a). Most previous findings on smoking were obtained in Western settings, which may not be applicable to other cultural contexts.…”