Lack of beneficial galantamine effect for smoking behavior: a double-blind randomized trial in people with schizophrenia.
Cigarette smoking is in schizophrenia is prevalent and may be due to self-medicating attempts to improve cognitive deficits related to alpha7 and alpha4beta2 nicotinic receptor dysregulation. Galantamine is an acetylcholinesterase inhibitor that acts as a positive allosteric modulator of nicotine acetylcholine receptors including both the alpha4beta2 and alpha7 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 chi2=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.
Maryland Psychiatric Research Center, University of Maryland School of Medicine, Box 22147 Baltimore, MD 21228, United States. dkelly@mprc.umaryland.edu
Deanna L
DL
Kelly
Robert P
RP
McMahon
Elaine
E
Weiner
Douglas L
DL
Boggs
Dwight
D
Dickinson
Robert R
RR
Conley
Robert W
RW
Buchanan
D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use; D001944:Breath Tests; D002248:Carbon Monoxide / Q000032:analysis; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005702:Galantamine / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018697:Nootropic Agents / Q000627:therapeutic use*; D011569:Psychiatric Status Rating Scales; D011618:Psychotic Disorders / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D011978:Receptors, Nicotinic / Q000187:drug effects; D012559:Schizophrenia / Q000175:diagnosis / Q000188:drug therapy*; D012565:Schizophrenic Psychology; D012651:Self Medication; D016540:Smoking Cessation; D064569:alpha7 Nicotinic Acetylcholine Receptor
D014150:Antipsychotic Agents; C579167:Chrna7 protein, human; D018697:Nootropic Agents; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; C403531:nicotinic receptor alpha4beta2; D005702:Galantamine; D002248:Carbon Monoxide