The influence of acute and subchronic administration of various antidepressants on early morning melatonin plasma levels in healthy subjects: increases following fluvoxamine.

The influence of various antidepressants on the morning levels of plasma melatonin was studied in human volunteers after acute and subchronic administration in weekly increasing doses over a period of three weeks. Two monoamine oxidase (MAO) inhibitors (tranylcypromine: irreversible type A and B; pirlindole: reversible type A), two reuptake inhibitors (maprotiline: selective for noradrenaline; fluvoxamine: selective for serotonin) and an alpha 1/alpha 2-adrenergic and serotonin S2-receptor antagonist (mianserin) were administered to groups of 4 to 7 healthy volunteers each. Two hours after a single oral dose at 9 a.m., at the end of each week and one week after the last dose, morning levels of melatonin were measured using a radioimmunological method. In addition, platelet MAO activity and the uptake of 14C-5-HT into platelets were determined. Plasma melatonin concentrations at 9 a.m. were significantly increased after the intake of 150 mg fluvoxamine the night before; whereas, administration of the same dose in the morning did not lead to increases in melatonin during the day. Following subchronic administration, plasma melatonin levels were significantly increased after the 1st (50 mg/day), 2nd (100 mg/day) and 3rd (150 mg/day) week of fluvoxamine intake in comparison to pre-drug levels. No changes in early morning levels of plasma melatonin were measured in the subjects receiving the other antidepressants, after acute as well as after subchronic administration. The results seem to indicate that following fluvoxamine intake at night, the early morning decline of melatonin is delayed. It is suggested that the underlying mechanism leading to a rise in morning melatonin levels cannot be explained solely on the basis of an inhibition of 5-HT reuptake and that other pharmacological properties of fluvoxamine may be involved.