Methodology
The open-label trial included adults aged 60 and over with drug-resistant depression. During an initial 10-week phase, subjects were randomized into 3 groups to receive a dose increase of existing treatment with aripiprazole (aripiprazole group), bupropion (bupropion group), or switch from existing treatment to bupropion (switch bupropion).
Patients who did not respond to the first phase treatments or who were ineligible for them (in particular those who were already on one of these two molecules) went directly to phase 2 of the trial. They were then randomized into two groups. In one, lithium was added to their existing treatment (lithium group). In the other, the subjects switched from their existing treatment to nortriptyline (switch nortriptyline group), also over 10 weeks.
The main evaluation criterion was the evolution of psychological well-being evaluated by two sub-scores of the National Institutes of Health Toolbox Emotion Battery regarding positive emotions and life satisfaction.
Principle results
Between inclusion and the end of phase 1 (n=619), psychological well-being was increased by 4.83 [3,28-6,38]4,33 [2,76-5,91] et 2,04 [0,43-3,66] points in the three groups aripiprazole, bupropion and switch bupropion respectively.
The difference between the aripiprazole group and the bupropion switch group was significant, reaching 2.79 points [0,56-5,02] at the end of phase 1 (p=0.014). On the other hand, that between the bupropion and switch bupropion groups, and that between the aripiprazole and bupropion group, were not.
At the end of phase 2 (n=248), the improvement in psychological well-being was 3.17 [1,12-5,22] points in the lithium group and 2.18 [0,10-4,26] in the switch nortriptyline group, with no significant difference between the two groups.
In phase 1, remission was achieved in 28.9% of patients in the aripiprazole group, 28.2% of those in the bupropion group and 19.3% of those in the switch bupropion group. In phase 2, it concerned 18.9% of patients in the lithium group and 21.5% of those in the switch nortriptyline group.
In terms of safety, the relative risk of falling was lower in the aripiprazole group than in the bupropion group (RR 0.59 [0,38-0,92], p=0.02). In phase 2, the risk of falling was similar in the lithium group and in the switch nortriptyline group.
