Controlled cross-over study of a 5-HT uptake inhibiting and an NA uptake inhibiting antidepressant

A double-blind comparison of zimelidine, a potent and fairly selective 5-hydroxytryptamine (5-HT) uptake inhibitor, and desipramine, a noradrenaline (NA) uptake inhibitor, was carried out in hospitalized patients with endogenous depression. The patients were randomized into parallel groups receiving either zimelidine 100 mg b.i.d. or desipramine 75 mg b.i.d. Forty patients completed the study, twenty in each treatment group. Patients who did not respond adequately to one drug after 4 weeks were treated with the other drug (cross-over design) after a washout period. For evaluation of the therapeutic efficacy Hamilton Rating Scale for Depression, Comprehensive Psychopathological Rating Scale for Depression, Beck's Inventory and Global Rating Scales were used. All ratings indicated greater effectiveness for zimelidine as compared with desipramine, although the differences were not generally statistically significant. Only "somatic anxiety" on the Hamilton scale was significantly (P less than 0.05) in favour of zimelidine. Although both zimelidine and desipramine were well tolerated, the zimelidine patients reported significantly less severe anticholinergic adverse reactions. Of five patients who did not improve on zimelidine, three were then given desipramine but only one recovered completely. Of 10 patients who were switched over to zimelidine, 6 recovered completely and one moderately. Zimelidine produced strong inhibition of the uptake of 5-HT in platelets and a decrease in blood 5-HT after 2 weeks or longer treatment. The uptake of 5-HT in rat hypothalamic synaptosomes was reduced by about 50% and that of NA about 20% when incubated in the patients' plasma. All these effects seem to be mainly due to norzimelidine. Desipramine produced strong inhibition of the uptake of NA in hypothalamic synaptosomes but weak effect on the 5-HT uptake. Urinary MHPG tended to decrease during desipramine treatment but was not affected or tended to increase during zimelidine treatment.