Clinical doses of fluoxetine and cerebral blood flow in healthy volunteers.

Rationale: Of the specific serotonin reuptake inhibitors (SSRIs), fluoxetine is perhaps the most widely used. Anecdotal reports, mostly in the non-medical press, have suggested that it may positively affect psychological functioning and enhance quality of life in the absence of overt psychiatric disorder. Such widespread use is not supported by scientific data. Objective: This prospective single blind study examined the effects of long term administration of clinical doses of fluoxetine on cerebral blood flow (CBF) in healthy volunteers. Methods: Fifteen healthy subjects were examined by Tc99m HMPAO SPECT after 2 weeks of placebo administration and then after 6 weeks of fluoxetine, administered at 20 mg per day. Blood for fluoxetine and norfluoxetine plasma levels was drawn to ensure compliance. Tc99m HMPAO uptake was analyzed by the region of interest approach, normalized to the cerebellum, and by statistical parametric mapping (SPM). Results: No statistically significant differences between the two conditions were detected by both techniques. Correlation analysis between fluoxetine and norfluoxetine plasma levels and rCBF yielded no statistically significant values. Conclusion: Our findings suggest a differential effect of fluoxetine on CBF under the following conditions: (i) mental health versus psychiatric illness; (ii) acute versus long term administration. Our findings further emphasize the importance of longitudinal studies in elucidating the physiology of the normal brain as well as the pathophysiology of psychiatric disorders.