Paroxetine, a new, potent and selective serotonin (5-HT) uptake inhibitor has been evaluated in an open study for its clinical effect as well as its effect on the 5-HT concentration in whole blood in 19 patients with depressive illness. Paroxetine was administered in daily doses of 20 to 60 mg. The global evaluation after six to eight weeks showed a marked improvement in 11 patients, a moderate improvement in four and no change in four patients. Assessment with the Hamilton Rating Scale for Depression in ten patients showed a reduction from a mean score of 22.7 to 6.6 in six weeks. Maximal reduction was, however, first seen in three of the patients after 8 to 12 weeks. No correlation between the antidepressant effect and plasma concentrations of paroxetine was found. The only side effects noted with paroxetine were that two patients complained of dry mouth in the beginning of the treatment and a further patient experienced a burning sensation together with periodical light headache. Generally laboratory examinations did not show any trend towards pathological values except in one patient, where a moderate leucopenia was observed. Crista puncture/biopsy showed, however, no specific bone marrow reaction. The 5-HT concentration in whole blood was reduced to about 0.02 micrograms/ml indicating a total depletion of 5-HT from the thrombocytes. The present study indicates that paroxetine possesses a good antidepressive effect in combination with a very low frequency of side effects.

In a 12-week double-blind study with 36 patients with major depressive episode (DSM-III), paroxetine (Seroxat, Aropax) showed significantly quicker onset of efficacy on the Melancholia Scale, and better tolerance than imipramine. Plasma concentration analyses showed no clear concentration-efficacy correlation in either treatment group. During long-term treatment paroxetine seemed to be superior to imipramine in preventing relapse; both treatments were well tolerated. A significant correlation between baseline plasma tryptophan: large neutral amino acids ratio and final Hamilton Rating Scale for Depression (HRSD) score and a trend towards an inverse correlation between this ratio and percentage reduction in HRSD score were seen in the paroxetine group but not in the imipramine group. In line with previous studies, these results support the hypothesis that paroxetine is an effective and well tolerated antidepressant.

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