The effects of galantamine and buspirone on sleep structure: Implications for understanding sleep abnormalities in major depression

Rationale: The serotonergic and cholinergic systems are jointly involved in regulating sleep, but this balance is theorized to be disturbed in depressed individuals. Objective: The goal of this study was to use biological probes in healthy participants, to model the serotonergic/cholinergic imbalance of depression and its associated abnormalities in sleep structure. Methods: We tested 20 healthy female participants 18-30 years of age on four non-consecutive nights. Participants were given galantamine (a cholinergic agent), buspirone (a serotonergic agonist), both drugs together, or placebo before sleeping. Results: Buspirone suppressed tonic rapid eye movement (REM): There was a significant increase in REM latency (p < 0.001). Galantamine increased tonic REM sleep, leading to more time spent in REM (p < 0.001) and shorter REM latency (p < 0.01). Galantamine and buspirone given together were not significantly different from the placebo night by REM sleep measures, but disrupted sleep more than either drug alone. Conclusions: These findings are partially consistent with the cholinergic literature about sleep in depression, notably short REM latency, higher percentage of total sleep time spent in REM and increased sleep fragmentation. The prolonged REM latency and reduced percentage of REM with buspirone resembled the effect of selective serotonin reuptake inhibitor antidepressants on REM sleep.