Chronic Treatment with Fluvoxamine, Clovoxamine, and Placebo: Interaction with Digoxin and Effects on Sleep and Alertness

The influence of 17 days of administration of fluvoxamine or clovoxamine, two new antidepressant agents, on the kinetics of a single intravenous dose of digoxin, and on self-rated parameters of sedation, mood, and sleep, was evaluated in a series of healthy volunteers. In the fluvoxamine study, subjects received fluvoxamine, 100 mg daily, or matching placebo for 17 consecutive days in a crossover design. For the clovoxamine study, subjects received clovoxamine, 150 mg daily, or placebo for 17 days. All treatments were double blind. At the end of each treatment, digoxin kinetics were evaluated following a single 1.25 mg intravenous dose. Compared to the placebo condition, fluvoxamine had no significant influence on digoxin elimination half-life (57 vs 47 hours), volume of distribution (10.5 vs 10.3 liters/kg), total clearance (2.4 vs 3.0 ml/min/kg), or 72 hour urinary excretion (33 vs 37 percent of the dose). Likewise clovoxamine did not alter digoxin elimination half-life (39 vs 40 hours), volume of distribution (10.7 vs 10.2 liters/kg), or total clearance 3.4 vs 3.4 ml/min/kg). 72 hour urinary excretion of digoxin was slightly increased by clovoxamine (41 vs 50 percent of the dose, P < .05). Self-ratings indicated a sedating effect of fluvoxamine, with reports of difficulty attaining morning alertness. These effects were not reported with clovoxamine. Thus clovoxamine and fluvoxamine appear to have differential effects on sleep and alertness in healthy volunteers. However, neither have an important influence on the kinetics of digoxin.