Drug-drug interactions of fluoxetine with tricyclics

The drug-drug interactions with fluoxetine, a pure serotonergic reuptake blocker with a unique profile of side effects, have not been studied adequately. This preliminary report shows that desipramine and nortriptyline plasma levels are markedly increased at steady state (2 to 11 times) when coadministered with fluoxetine. This appears to be the result of the inhibition of the P450 enzyme system of the liver by fluoxetine, resulting in increased plasma levels of drugs metabolized by this system. Research must promptly address drug-drug interactions with fluoxetine since potentially all psychotropic drugs (except for lithium) and many medically indicated drugs could also have significant drug-drug interactions with fluoxetine.