title: Valproate attenuates dextroamphetamine-induced subjective changes more than lithium.
abstract: Dextroamphetamine administration in healthy controls produces a range of subjective and physiological effects, which have been likened to those occurring during mania. However, it is uncertain if these can be attenuated by lithium since conflicting results have been reported. To date there have been no previous studies examining the effects of valproate on dextroamphetamine-induced mood and physiological changes. The current study was a double-blind, placebo-controlled, study in which volunteers received either 1000 mg sodium valproate (n=12), 900 mg lithium (n=9), or placebo (n=12) pre-treatment for 14 days. Subjective and physiological measures were then obtained prior to administration of a 25 mg dose of dextroamphetamine, and at two time points after administration. Differences in the response to dextroamphetamine were assessed between the three treatment groups. The results of this study show that pre-treatment with lithium only significantly attenuated dextroamphetamine-induced change in happiness, while valproate pre-treatment significantly attenuated the effects of dextroamphetamine on happiness, energy, alertness and on the diastolic blood pressure. These results suggest that lithium and valproate do not have the same mechanism of action on dextroamphetamine-induced changes, and this finding may relate to differences in their mechanism of action in mood disorders.
authors.affiliation: Department of Biomedical Engineering, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Morgan C
authors.initials: MC
authors.lastname: Willson
authors.forename: Emily C
authors.initials: EC
authors.lastname: Bell
authors.forename: Sanjay
authors.initials: S
authors.lastname: Dave
authors.forename: Sheila J
authors.initials: SJ
authors.lastname: Asghar
authors.forename: Brent M
authors.initials: BM
authors.lastname: McGrath
authors.forename: Peter H
authors.initials: PH
authors.lastname: Silverstone
mesh_terms: D000293:Adolescent; D000328:Adult; D000339:Affect / Q000187:drug effects; D000927:Anticonvulsants / Q000494:pharmacology*; D018692:Antimanic Agents / Q000494:pharmacology*; D001714:Bipolar Disorder / Q000139:chemically induced / Q000523:psychology; D000697:Central Nervous System Stimulants / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D003913:Dextroamphetamine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008094:Lithium / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D014635:Valproic Acid / Q000494:pharmacology*
chemical_list: D000927:Anticonvulsants; D018692:Antimanic Agents; D000697:Central Nervous System Stimulants; D014635:Valproic Acid; D008094:Lithium; D003913:Dextroamphetamine