Abstract
OBJECTIVE: Determine the effects of pimavanserin tartrate [ACP-103; N-(4-flurophenylmethyl)-N-(1-methylpiperidin-4-yl)-N'-(4-(2-methylpropyloxy)phenylmethyl)carbamide], a selective serotonin 5-HT(2A) receptor inverse agonist, on slow wave sleep (SWS), other sleep parameters, and attention/vigilance. METHODS: Forty-five healthy adults were randomized to pimavanserin (1, 2.5, 5, or 20 mg) or placebo in a double-blind fashion (n=9/group). Pimavanserin or placebo was administered once daily in the morning for 13 consecutive days. The effects of pimavanserin were measured after the first dose and again after 13 days. Sleep parameters were measured by polysomnography. Effects on attention/vigilance were measured by a continuous performance task. RESULTS: Compared to placebo, pimavanserin significantly increased SWS following single and multiple dose administration. Pimavanserin also decreased number of awakenings. PSG variables not affected by pimavanserin included sleep period time, total sleep time, sleep onset latency, number of stage shifts, total time awake, early morning wake, and microarousal index. Changes in sleep architecture parameters, sleep profile parameters, and spectral power density parameters were consistent with a selective increase in SWS. Pimavanserin did not adversely affect performance on the continuous performance test measured in the evening before or morning after polysomnography. CONCLUSIONS: These data suggest that pimavanserin selectively increases slow wave sleep and decreases awakenings, an effect that does not diminish with repeated administration.