Treatment strategy in depression. I. Non-tricyclic and selective reuptake inhibitors in resistant depression: a double-blind partial crossover study on the effects of oxaprotiline and fluvoxamine.

Antidepressants are ineffective in about 30% of patients with major depression. Some authors then advise treatment of non-responders with (non-tricyclic) more selective reuptake inhibitors. In a double-blind, partial crossover study, 71 patients were selected for treatment during 4 weeks with oxaprotiline and/or fluvoxamine, two non-tricyclic antidepressants that are selective reuptake inhibitors or noradrenaline and serotonin respectively. All patients had failed to respond to earlier treatment with cyclic antidepressants during the current episode. Only 13% of the patients responded, with 27% of them responding to oxaprotiline and none to fluvoxamine. Moreover, a low response of 27% was also obtained in the crossover phase, which included all non-responders to the first treatment, oxaprotiline being effective in 39% and fluvoxamine in 10% of the patients. The results indicate that selective reuptake inhibitors are not an effective alternative for non-responders to other cyclic antidepressants and that non-responders to "noradrenergic" antidepressants do not appear to have much chance of responding to "serotonergic" antidepressants and vice versa.

Treatment strategy in depression. II. MAO inhibitors in depression resistant to cyclic antidepressants: two controlled crossover studies with tranylcypromine versus L-5-hydroxytryptophan and nomifensine.

Antidepressants are ineffective in about 30% of the patients with major depression. Besides electroconvulsive therapy (ECT) and lithium, MAO inhibitors have been suggested as an alternative in such patients. In 2 controlled, partial crossover studies involving 47 patients with major depression who had already been treated unsuccessfully with at least 2 cyclic antidepressants, the effect of the MAO inhibitor tranylcypromine was studied. The first study was an open comparison with L-5-hydroxytryptophan (L-5HTP), the second study a double-blind comparison with nomifensine. Neither the patients treated with L-5HTP nor the patients treated with nomifensine, except one, improved. In contrast, tranylcypromine was effective in 50% of the patients. The depressions of the responders to tranylcypromine appeared to be more endogenous (according Newcastle Scale II) and of shorter duration than those of the non-responders. It is concluded that MAO inhibitors such as tranylcypromine are an effective alternative to ECT and lithium in patients with major depression who have failed to respond to cyclic antidepressants.

L-5HTP in depression resistant to re-uptake inhibitors. An open comparative study with tranylcypromine.

L-5HTP and tranylcypromine were compared in an open, but controlled and cross-over study, in patients suffering from major depression; all were non-responders to several reuptake inhibitors, including oxaprotiline and fluvoxamine. After four unsuccessful sleep-deprivations, L-5HTP or tranylcypromine were given during four weeks in a crossover design. Of 17 patients given L-5HTP during both treatment periods, none responded, whereas of 26 patients treated with tranylcypromine, 15 responded. Thus, L-5HTP is not a therapeutically effective alternative in depressed patients who have not responded to reuptake inhibitors.