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Drugs thought to be selective inhibitors of either the uptake of serotonin (5-HT) or norepinephrine (NE) are known to be effective antidepressants. In general, a relative selectivity for NE vs. 5-HT uptake inhibition greater than 50-fold in vitro is thought to be sufficient to maintain such selectivity in vivo. To explore this issue, we carried out a study in which depressed patients were treated with either the selective serotonin reuptake inhibitor (SSRI) paroxetine or the selective norepinephrine reuptake inhibitor (SNRI) desipramine. Patients were treated with either drug or placebo for 6 wk. Drug levels in plasma and platelet 5-HT content were measured 12 times during the treatment period using HPLC procedures. Both drug treatments caused a significant reduction of platelet 5-HT content. Paroxetine reduced platelet 5-HT content to approx. 1% of pretreatment levels (n = 3). The inhibition of 5-HT uptake by paroxetine appeared to be immediate and complete. Desipramine reduced platelet 5-HT content to 38.7+/-6.2 % of pretreatment levels (n = 5) at a mean plasma level of 195 ng/ml. The percent reduction of platelet 5-HT content after 6 wk of drug treatment was proportional to the steady state plasma level of desipramine. The IC50 value of desipramine to reduce platelet 5-HT was 135 ng/ml. These results demonstrate that therapeutic concentrations of the SNRI desipramine as well as the SSRI paroxetine inhibited serotonin uptake in platelets of depressed patients. If such effects occur in the brain, desipramine might have some component of its therapeutic effects due to actions on the uptake of 5-HT.

Reduction of platelet serotonin content in depressed patients treated with either paroxetine or desipramine