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

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 selectiv ity in vivo. To explore this issue, we carried out a study in which depress ed patients were treated with either the selective serotonin reuptake inhib itor (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 cau sed a significant reduction of platelet 5-HT content. Paroxetine reduced pl atelet 5-HT content to approx. 1% of pretreatment levels (n = 3). The inhib ition of 5-HT uptake by paroxetine appeared to be immediate and complete. D esipramine reduced platelet 5-HT content to 38.7+/-6.2% of pretreatment lev els (n = 5) at a mean plasma level of 195 ng/ml. The percent reduction of p latelet 5-HT content after 6 wk of drug treatment was proportional to the s teady state plasma level of desipramine. The IC50 value of desipramine to r educe platelet 5-HT was 135 ng/ml. These results demonstrate that therapeut ic concentrations of the SNRI desipramine as well as the SSRI paroxetine in hibited serotonin uptake in platelets of depressed patients. If such effect s occur in the brain, desipramine might have some component of its therapeu tic effects due to actions on the uptake of 5-HT.