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Adding another antidepressant to the mix was more helpful than switching agents in older adults with treatment-resistant depression, a two-step, open-label trial suggested.

In the first step of the study which included 619 adults ages 60 and older, those who were randomly assigned to augment their existing antidepressant with aripiprazole (Abilify) saw a 4.83-point improvement in psychological well-being scores at 10 weeks, reported Eric J. Lenze, MD, of Washington University School of Medicine in St. Louis, and colleagues.

This was in comparison with a 4.33-point improvement in the group augmented with bupropion (Wellbutrin) and a 2.04-point improvement in the group that was switched to bupropion, they noted in the .

Findings from this study were also presented at the in New Orleans.

The difference between the aripiprazole-augmented group and the switch-to-bupropion group reached statistical significance (difference 2.79 points, 95% CI 0.56-5.02, P=0.014, with a prespecified threshold P value of 0.017).

"The finding that aripiprazole augmentation was more effective than a switch to bupropion is consistent with of aripiprazole augmentation for treatment-resistant depression in older adults," Lenze and team wrote.

The improvement in well-being scores -- as measured by the National Institutes of Health Toolbox Positive Affect and General Life Satisfaction subscales -- wasn't significantly different between the aripiprazole- and bupropion-augmented groups, nor the bupropion-augmented and bupropion-switch groups.

Rates of depression remission were 28.9% in the aripiprazole-augmented group, 28.2% in the bupropion-augmented group, and 19.3% in the switch-to-bupropion group.

In addition, changes from baseline Montgomery-Asberg Depression Rating Scale (MADRS) score were also greatest in the aripiprazole-augmented group, at -7.60 (95% CI -9.20 to -5.99) versus -7.23 in the bupropion-augmented group (95% CI -8.86 to -5.59) and -4.14 in the switch-to-bupropion group (95% CI -5.81 to -2.48).

Because this was an older patient population, Lenze's group also followed fall rates throughout the trial. During the first phase of the trial, fall rates were highest in the bupropion-augmented group, at 0.55 falls per patient, compared with 0.38 falls per patient in the bupropion-switch group and 0.33 falls per patient in the aripiprazole-augmented group.

"The higher rate of falls with bupropion augmentation than with aripiprazole augmentation may be clinically important, because it included many injurious falls," the authors wrote. "Even in the lowest fall-risk group (augmentation with aripiprazole), we observed a rate of 0.33, which means one fall for every three patients during approximately 10 weeks of treatment."

In an , Gemma Lewis, PhD, and Glyn Lewis, PhD, both of University College London, emphasized the "widespread concerns" about falls in this population.

They noted that while the fall rate difference between the bupropion-augmented and aripiprazole-augmented groups seems "clinically meaningful," the upper boundary of the 95% confidence interval was close to 1 and therefore "may not exclude the possibility that there is little difference in the incidence of falls."

"In this older population, the rate of falls would be expected to be relatively high," they wrote, while also pointing out that this was a relatively "young" older population (mean age 68-69.7). "In a population in which the rate of falls would be expected to be lower, this relative advantage could become less clinically important in absolute terms."

Lewis and Lewis also suggested that lower dosing of the agents than those used in the trial may help to reduce this fall risk, while still maintaining efficacy. Aripiprazole augmentation was started at a 2.5 mg daily dose and increased to a maximum of 15 mg. Extended-release bupropion was started at 150 mg per day, with a target of 300 mg per day and a maximum of 450 mg per day.

Moving on to the second step of the trial, which lasted another 10 weeks, 125 of the original 619 participants from step 1 who did not reach remission were added to a pool of another 123 participants who weren't involved in step 1, likely because they already had a trial of bupropion or aripiprazole. These 248 patients underwent randomization into one of two groups: augmentation with lithium or a switch to nortriptyline (Pamelor).

In the lithium-augmented group, psychological well-being score was improved by 3.17 points, while the nortriptyline-switch group improved by 2.18 points, which was not a significant difference.

As for the secondary outcomes, remission rates were a bit higher in the switch-to-nortriptyline group (21.5% vs 18.9%), as was the drop in MADRS score (-5.33 vs -4.63).

Fall rates were slightly higher in the lithium-augmented group, though not significantly (0.47 per patient vs 0.38).

"The findings from this trial should help clinicians and older adult patients make informed decisions regarding the next steps, in the absence of a response to conventional pharmacologic approaches," the editorialists wrote. While aripiprazole augmentation appeared to be of the most benefit, they advised clinicians to tailor treatment to the patient, keeping in mind side effects associated with these agents -- particularly weight gain with aripiprazole.

Of the 619 patients enrolled in step 1, 211 were assigned to aripiprazole augmentation, 206 to bupropion augmentation, and 202 to a switch to bupropion. Most patients were women and white, and were in their 30s at first onset of depression.

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