Pharmacodynamic and pharmacokinetic interactions of selective serotonin re-uptake inhibiting antidepressants (SSRIs) with other psychotropic drugs

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Abstract
Selective serotonin re-uptake inhibitors are often combined with tricyclic antidepressants (TCA) in the aim of optimalizing pharmacotherapy of the psychiatric patient. However, the real clinical benefit is still not well documented, but it is known, that fluoxetine and fluvoxamine interact with TCAs by increasing their plasma levels. Several reports describe the manifestation of severe adverse effects during such combination therapies. Case studies with citalopram correlate with in vitro investigations, in that citalopram is less likely to interact with TCAs at the pharmacokinetic level. Clinical studies are needed to evaluate the risk and benefit of a combination of other SSRIs such as paroxetine and sertraline, which are also potent inhibitors of cytochrome P-4502D6, an isozyme implicated in the metabolism of TCAs.