Electroencephalographic and psychomotor effects of chlorpromazine and risperidone relative to placebo in normal healthy volunteers

Aims To investigate the effects of single oral doses of chlorpromazine (50 mg) and risperidone (2 mg) relative to placebo on topographical electroence phalometry (CATEEM(TM)) and psychomotor tests in 12 healthy male volunteers . Methods A double-blind, placebo-controlled, three-way crossover design usin g a double dummy blinding technique was utilized. Chlorpromazine was select ed as representative of the 'typical' neuroleptics, being also highly sedat ive. Risperidone has been suggested as representative of the newer 'atypica l' neuroleptics and is claimed to be only minimally sedative. Volunteers we re dosed on 3 separate days with a minimum of 7 days interval between trial days. On each trial day volunteers were dosed twice. Dose 1 consisting of either chlorpromazine 50 mg or placebo to chlorpromazine, and dose 2 either risperidone 2 mg or placebo to risperidone. The volunteers were randomized so that each received either chlorpromazine or risperidone (or neither), b ut not both on an individual trial day. A 17 electrode quantitative topogra phical electroencephalograph (EEG) recording was taken for each volunteer b efore and after each dosing period. Seven psychomotor function tests were u sed to determine the effects of each treatment on psychomotor performance. Results The data confirm the cited reports of sedation following single ora l doses of chlorpromazine 50 mg. However, 7 of the 12 volunteers dosed with risperidone 2 mg also reported drowsiness/lethargy which was of greater se verity and duration than 5 of the 12 volunteers who reported somnolence fol lowing dosing with chlorpromazine 50 mg. Objective assessment of psychomoto r impairment using a short battery of psychomotor function tests mirrored t he subjective reports of somnolence in that the impairment in volunteers do sed with risperidone 2 mg was greater in extent and magnitude than in volun teers dosed with chlorpromazine 50 mg. With respect to the cortical quantit ative electroencephalogram, both chlorpromazine (50 mg) and risperidone (2 mg) increased power (4.75-6.75 Hz) in keeping with cited effects of other n euroleptics on the quantitative EEG. In addition, there was a statistically significant increase (P<0.05) in alpha(1) (7.0-9.5 Hz) and beta(1) (12.75- 18.5 Hz) wavebands in volunteers dosed with risperidone 2 mg. Furthermore, based on estimates of variability, we propose that a 3 min eyes open and 3 min eyes closed quantitative EEG recording is sufficient to maintain adequa te power for this technique, whilst allowing its application to early volun teer trials of novel neuroleptic agents. Conclusions This study demonstrates that quantitative EEG can be utilized i n the profiling of neuroleptic agents, and could be readily applied to the early profiling of novel neuroleptics in Limited numbers of volunteers, ear ly in drug development. The chosen battery of psychomotor tests has clearly demonstrable sensitivity to the quantification of the subjective reports o f somnolence secondary to both chlorpromazine and risperidone.