Sodium valproate increases pupillary responsiveness to a cholinergic agonist in responders with mania.
BACKGROUND
The cholinergic hypothesis of affective disorders predicts that mania is a hypocholinergic state relative to monoaminergic activity. Treatments that increase cholinergic sensitivity are expected to improve manic symptoms. Valproic acid is an effective treatment for mania. Little, however, is known about the cholinergic effects of this agent.


METHODS
Ten male hypomanic or manic patients were treated with valproic acid (1500-2000 mg) for 2 weeks. Cholinergic sensitivity was assessed before, and after treatment using graded concentrations of pilocarpine eyedrops (0.03-2.0%). Pupil size changes were quantified using an infrared pupillometer and ED50 values were referenced to maximal dilation with 0.5% tropicamide.


RESULTS
Valproate treatment decreased Bech mania ratings and ED50 values (p < .0001). Improvements in mania after treatment were closely correlated with decreases in ED50 (r = .76; p < .01). This relationship was indistinguishable from one previously observed after lithium treatment.


CONCLUSIONS
These results provide support for the cholinergic-adrenergic hypothesis. Moreover, similar pupillary reactions to valproic acid and lithium treatments suggest that these agents may share a common action on muscarinic receptors.
DeMet
E M
EM
Mental Health Care Group, Veterans Affairs Medical Center, Long Beach, California 90822, USA.
Sokolski
K N
KN
D000328:Adult; D001714:Bipolar Disorder / Q000188:drug therapy* / Q000523:psychology*; D018679:Cholinergic Agonists / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018721:Muscarinic Agonists; D010862:Pilocarpine; D011976:Receptors, Muscarinic / Q000187:drug effects; D012025:Reflex, Pupillary / Q000187:drug effects*; D016896:Treatment Outcome; D014635:Valproic Acid / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use*
D018679:Cholinergic Agonists; D018721:Muscarinic Agonists; D011976:Receptors, Muscarinic; D010862:Pilocarpine; D014635:Valproic Acid