title: First administration of cytidine diphosphocholine and galantamine in schizophrenia: a sustained alpha7 nicotinic agonist strategy.
abstract: Converging lines of evidence suggest pathophysiology of alpha7 nicotinic acetylcholine receptors (alpha7 nAChRs) in schizophrenia. This pilot study was designed to test the tolerability, safety, and preliminary efficacy of chronic administration of an alpha7 nAChR agonist strategy involving combination treatment of cytidine diphosphocholine (CDP-choline; 2 g/d), a dietary source of the alpha7 nAChR agonist choline, and galantamine (24 mg/d), a positive allosteric modulator of nAChRs that was prescribed to prevent choline from becoming a functional antagonist and improve the efficiency of coupling the binding of choline to channel opening. The combination of CDP-choline and galantamine was administered to 6 schizophrenic patients with residual symptoms in a 12-week, open-label trial. Patients were maintained on stable dose regimens of antipsychotic medications for 4 weeks before study entry and for the trial duration. All reached target doses of both agents and completed the trial. Transient side effects resolved without slowing of dose titration. Gastrointestinal adverse effects were most common. Of the 6 patients, 5 showed reduction in Clinical Global Impressions severity scores and Positive and Negative Syndrome Scale total scores. Three patients requested continuation of the adjunctive combination at the end of the trial. These results suggest further investigation of the combination of CDP-choline and galantamine as an alpha7 nAChR agonist intervention.
authors.affiliation: Mental Health Service Line, Department of Veterans Affairs Medical Center, Washington DC 20422, USA. Stephen.Deutsch@med.va.gov
authors.forename: Stephen I
authors.initials: SI
authors.lastname: Deutsch
authors.forename: Barbara L
authors.initials: BL
authors.lastname: Schwartz
authors.forename: Nina R
authors.initials: NR
authors.lastname: Schooler
authors.forename: Richard B
authors.initials: RB
authors.lastname: Rosse
authors.forename: John
authors.initials: J
authors.lastname: Mastropaolo
authors.forename: Brooke
authors.initials: B
authors.lastname: Gaskins
mesh_terms: D000328:Adult; D003566:Cytidine Diphosphate Choline / Q000627:therapeutic use*; D005260:Female; D005702:Galantamine / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018722:Nicotinic Agonists / Q000627:therapeutic use*; D018697:Nootropic Agents / Q000627:therapeutic use; D010865:Pilot Projects; D011978:Receptors, Nicotinic / Q000378:metabolism*; D012559:Schizophrenia / Q000188:drug therapy* / Q000378:metabolism; D064569:alpha7 Nicotinic Acetylcholine Receptor
chemical_list: C579167:Chrna7 protein, human; D018722:Nicotinic Agonists; D018697:Nootropic Agents; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; D005702:Galantamine; D003566:Cytidine Diphosphate Choline