Lithium augmentation of venlafaxine: an open-label trial.

The authors conducted an open-label study of the efficacy and tolerability of venlafaxine and of lithium augmentation in outpatients with depression who were not responding to venlafaxine. Outpatients aged 18 to 70 years were eligible if they had a minimum baseline score of 16 on the 17-item Hamilton Rating Scale for Depression (HAM-D). Patients were started on venlafaxine 37.5 mg twice daily for 1 week. For weeks 2 through 4, the dose of venlafaxine was increased to 75 mg twice daily, and for weeks 5 through 7, the dose was further increased to 75 mg three times daily. At the end of the 7-week treatment period, patients with a <50% decrease in their HAM-D scores from baseline were given lithium carbonate 600 mg once daily. The dose of lithium carbonate was adjusted to maintain plasma levels in the range of 0.6 to 1.0 mmol/mL. Efficacy was assessed with the 17-item HAM-D, Montgomery-Asberg Depression Rating Scale, and the Clinical Global Impressions Scale. Data were analyzed on an intent-to-treat basis. At the end of the 7-week treatment period, 35% of patients showed a > or = 50% decrease in their HAM-D scores from baseline. Lithium augmentation was initiated in 23 patients. The results showed that the addition of lithium was well-tolerated and led to a further decrease in the HAM-D scores, with eight patients responding and two of them presenting a remission. The addition of lithium to venlafaxine was found to be a well-tolerated strategy in treatment-resistant patients.

Predictors of (non-) response in depressed outpatients treated with a three-phase sequential medication strategy.

The predictive value of eight domains or sets of variables including sociodemographic aspects, premorbid history, symptomatology, personality, social and diagnostic data are evaluated in depressed outpatients with a Hamilton Rating Scale for Depression (HRSD) score of at least 14. Patients were treated using a three-phase sequential treatment strategy. Of the 119 patients, 88 completed the trial. The HRSD-score at the end of phases I, II or III was used as an outcome measure. Patients with an initially high HRSD-score and an obsessive-compulsive personality had a greater chance of recovery, while patients with somatization and a passive-aggressive personality had less of a chance of recovery. Variables involving psychiatric history, premorbid history or symptomatology of the depression, were not significantly related to outcome. The endogenous/non-endogenous distinction was not a predictor of response.

Brofaromine versus lithium addition to maprotiline. A double-blind study in maprotiline refractory depressed outpatients.

Depressed outpatients (n = 51) resistant to treatment with maprotiline were treated in a blind, randomized, single-centre study, for 6 weeks with either the reversible and selective monoamine oxidase A-inhibitor (MAO-A-I), brofaromine or lithium addition to maprotiline. The Hamilton Rating Scale for Depression was scored by an independent rater before and after the 6 week treatment period. No significant differences in efficacy were found between the two treatment regimes. In the patients who completed the trial, brofaromine was well tolerated with the exception of insomnia. Anticholinergic effects as well as thyroid dysfunctions (17 out of 20) were more frequent in the maprotiline/lithium group.

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.