Effect of fluoxetine on circadian rhythm of melatonin in patients with major depressive disorder.

OBJECTIVES: The purpose of this study is to explore the response of melatonin circadian rhythm to fluoxetine treatment and its relationship with clinical therapeutic effect.

METHODS: This study investigated salivary melatonin in 13 outpatients with major depressive disorder and age- and sex-matched healthy controls. Depressed patients received six weeks fluoxetine (20 mg/day) treatment, and saliva was collected before and four weeks after treatment. In sampling days, a total of 12 time-point salivary melatonin was measured over 24-hours. Multioscillator cosinor model was used to fit the rhythms.

RESULTS: There was no difference of circadian melatonin rhythms in depressed patients, and melatonin was not significantly lower after fluoxetine treatment. To our surprise, the melatonin amplitude (Before minus After) was positively correlated with the improvement in Hamilton Depression Rating Scale (HDRS) scores at day 42 whereas there was no such correlation at day 28.

CONCLUSIONS: Melatonin rhythms were similar between depressed patients and matched healthy controls. The interesting finding that the difference of salivary melatonin amplitude was correlated with the clinical improvement after six weeks fluoxetine treatment deserve further study.