Antidepressant effect of femoxetine and desipramine and relationship to the concentration of amine metabolites in cerebrospinal fluid

Abstract

The antidepressant and biochemical effects of femoxetine, a selective serotonin uptake inhibitor, and desipramine, a selective nor-adrenaline uptake inhibitor, have been compared in a double-blind study in 42 outpatients with depressive illness. The patients were allocated at random to treatment with either 600 mg femoxetine or 150 mg desipramine daily for 6 weeks. The total depression score showed a significant decrease in both groups, indicating an overall improvement in depressive symptoms. The patients treated with femoxetine reported significantly less severe anticholinergic effects during the whole treatment period than the desipramine patients. Both drugs, decreased the level of 5-HIAA in CSF, whereas no consistent changes were found in the MHPG and HVA levels. The pretreatment level of the metabolites had no predictive value for the outcome of the treatment with either drug. No significant correlation was found between therapeutic effect and the plasma concentration of the active compounds.

Cardiovascular (ECG and systolic time intervals) and anticholinergic effects of repeated doses of femoxetine‐a comparison with amitriptyline and placebo in healthy men.

“…The results are consistent with side effects observed in therapeutic studies (Dahl et al, 1982;Tamminen et al, 1982;Ahlberg et al, 1982).…”

“…Spontaneously reported adverse effects due to anticholinergic activity (dry mouth, constipation, difficulty in micturition) were reported 3 and 16 times during femoxetine and amitriptyline periods respectively, reflecting the lower anticholinergic potency of femoxetine. The results are consistent with side effects observed in therapeutic studies (Dahl et al, 1982;Tamminen et al, 1982;Ahlberg et al, 1982).…”

“…Plasma concentrations of femoxetine and norfemoxetine, in contrast, showed marked intersubject variability: they were consistently below the limit of detection in one subject and were close to it in three subjects. Similar variability has been observed previously (Dahl et al, 1982) and measurement of plasma femoxetine concentrations is evidently not a satisfactory indication of compliance. Measurement of whole blood concentrations of 5-HT indicates at least fair compliance with femoxetine treatment: 5-HT concentrations fell in all 12 subjects compared with values obtained during placebo treatment.…”

“…In contrast to the tricyclic Correspondence: Dr B. K. Skrumsager, Ferrosan Research Division, DK-2860 Soeborg, Denmark antidepressants, femoxetine has only a weak inhibitory effect on noradrenaline uptake into peripheral organs, and has little or no central and peripheral anticholinergic action (Buus Lassen et al, 1975). The clinical efficacy of femoxetine is comparable with that of amitriptyline and desipramine (Dahl et al, 1982;Tamminen et al, 1982;Ahlberg et al, 1982) and it is believed to have little effect on the cardiovascular system (Nielsen, 1982).…”

Multiple approaches in neuronal activity for treating depression: More effective, more types of receptors?

“…Typical neuroleptics such as chlorpromazine or haloperidol are also Rose and Westhead, 1964Lauritsen and Madsen, 1974Rickels er al., 1981Santonastaso et al, 1979Stassen et al, 1993Lecrubier et af., 1980Brogden et a/., 1978Angst et al, 1977Kampman et al. 1978Montgomery et al, 1981Laursen et af., 1985Gravem et al, 1987Dominguez et al, 1985Bremner, 1984Reimherr et al, 1990Naylor and Martin, 1985Dahl et al, 1982LOO et al. 1993Fabre, 1990Jenkins et nl., 1990Heller et al, 1990Brogden et al, 1979 antagonists for several neuronal receptors.…”