The effects of fenfluramine on sleep and prolactin in depressed inpatients: a comparison of potential indices of brain serotonergic responsivity.

The effects of fenfluramine, an indirect serotonergic agonist, on electroencephalographic sleep and prolactin secretion were assessed in 12 unmedicated inpatients with a primary diagnosis of major depressive episode. Compared to prefenfluramine profiles, sleep studies performed following fenfluramine administration showed a statistically significant reduction of slow-wave sleep (SWS) (p < 0.001) and a corresponding increase in percentage of stage-2 sleep (p < 0.007). Automated delta wave counts per min decreased significantly during the first nonrapid eye movement (NREM) period (p = 0.04), and automated rapid-eye movement (REM) counts were also decreased in the second REM period (p = 0.02). These effects on sleep electroencephalogram (EEG) did not correlate significantly with another measure of serotonergic responsivity, namely peak prolactin level following fenfluramine, nor with the severity of depression. The reductions in SWS and REM counts are proposed to be the result of time-dependent changes in serotonergic neurotransmission following the administration of fenfluramine. These findings are consistent with earlier work suggesting a role for serotonin in initiation and regulation of SWS and REM sleep.