Selective serotonin reuptake inhibitors fluoxetine and fluvoxamine induce hyperglycemia by different mechanisms

The effects of the selective serotonin reuptake inhibitors, fluoxetine and fluvoxamine, on plasma glucose levels were investigated in mice. Both fluoxetine and fluvoxamine elicited significant hyperglycemia, while a selective noradrenaline reuptake inhibitor maprotiline had no effect. Fluoxetine and fluvoxamine did not change serum insulin levels, although they elicited hyperglycemia. Pretreatment with the serotonin (5-hydroxytryptamine, 5-HT) depleter, p-chlorophenylalanine (pCPA), abolished fluvoxamine-induced hyperglycemia, although pCPA did not affect the fluoxetine-induced glycemic effects. These results suggest that the selective serotonin reuptake inhibitors fluoxetine and fluvoxamine induce hyperglycemia by inhibition of insulin release. Moreover, our findings indicate that the glycemic effects of these drugs are differentially associated with serotonergic mechanisms.