The effects of an orally administered cholinergic agonist on REM sleep in major depression

Centrally active cholinergic agents such as arecoline and physostigmine shorten rapid eye movement (REM) latency, reduce REM interval times, or both and do so preferentially in patients with depression. We tested an orally administered cholinergic agonist (donepezil HCL 10 mg [Aricept]) to determine whether this agent also alters REM timing in depressed patients (n = 8) compared with age- and gender-matched control subjects (n = 8). All subjects were studied for 3 consecutive nights in the sleep laboratory. The design was a fixed-order placebo-donepezil protocol to accommodate the long half-life of donepezil. Night 1 served as an adaptation night. On night 2, placebo was administered at 8:00 PM. On night 3, donepezil was administered at 8:00 PM. The cholinergic challenge distinguished the groups. In depressed patients REM latency was reduced compared with baseline (47.6 vs. 64.4, p =.04) following administration of donepezil. Control subjects showed no response: REM latency after donepezil was virtually identical to baseline REM latency (71.7 vs. 69.3). These data indicate that donepezil is likely to be useful in testing hypotheses related to cholinergic function in mood disorders.