Physostigmine, a reversible centrally active acetylcholinesterase inhibitor, was administered over a short period to eight patients with manic symptoms in a double-blind study. Patients were rated using standard manic rating scales.
All exhibited decreased manic symptoms within minutes of receiving physostigmine, and all developed an anergic syndrome. Some patients became depressed. Neither neostigmine methylsulfate (a noncentrally acting cholinesterase inhibitor) nor placebo significantly altered the behavior of the patients. These data are consistent with an adrenergic-cholinergic balance hypothesis of affective disorders.
Janowsky DS, EI-Yousef MK, Davis JM, Sekerke HJ. Parasympathetic Suppression of Manic Symptoms by Physostigmine. Arch Gen Psychiatry. 1973;28(4):542-547. doi:10.1001/archpsyc.1973.01750340072012