The psychopharmacological effects of repeated doses of fluvoxamine, mianserin and placebo in healthy human subjects

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Abstract
Summary The psychopharmacological effects of fluvoxamine, 50 mg twice a day, were compared with those of mianserin, 20 mg twice a day, and placebo, each given for 8 days in a double-blind crossover design to 9 healthy human volunteers. At least one week was left between the 8-day courses of drugs. Testing was carried out before and 3 h after taking the morning dose on Days 1 (predrug), 4, and 8, and comprised EEG, cognitive and psychomotor tasks, and self-ratings of mood and bodily symptoms. Fluvoxamine had no effect on any of the EEG wavebands, but mianserin increased voltages in the slow wavebands as compared with placebo. This effect was particularly pronounced on Days 4 and 8. Mianserin significantly decreased critical flicker fusion frequency and speed of reaction time, and slowed down tapping rate; digit symbol substitution and symbol copying test performances were also impaired by mianserin. These effects were most marked after the first dose and had lessened somewhat later in the week. Symbol copying was the only task impaired by fluvoxamine as compared with placebo. Mianserin caused drowsiness after the first dose but this effect declined by Day 8. By contrast, fluvoxamine induced feelings of anxiety, sweatiness, trembling, nausea, loss of appetite, restlessness, muscle tension, irritability, tiredness, headache, and dizziness; these effects were most evident in the middle of the week and relatively reduced at the end of the week. Mianserin produced a few of these effects but they tended to be maximal on Day 1 or 4 and then to wear off. It was concluded that fluvoxamine is much less likely to produce psychomotor and cognitive impairment on repeated usage than is mianserin, but that some adverse effects, particularly nausea, may be troublesome. Fluvoxamine would seem more appropriate in patients in whom sedation is not required, mianserin in those in whom initial sedation is acceptable.