Study supports aripiprazole augmentation for treatment-resistant depression in older adults

By Dr Michael Doris MB BS

Compared with bupropion, aripiprazole may be a better choice of augmentation for treatment-resistant depression in older adults, a recent study published in The New England Journal of Medicine has shown.

The study recognised the prevalence of major depression in older adults and its persistence despite appropriate first-line treatment, with those with unremitting depression (despite two trial uses of antidepressant medication) defined as having treatment-resistant depression. Strategies for treatment-resistant depression include augmentation – addition of a medication to an existing antidepressant – or switching the class  of the existing antidepressant. Few studies have compared these strategies in older people.

The researchers therefore conducted a two-step, open-label study, investigating adults aged 60 years or over with treatment-resistant depression. In step 1, 619 patients were randomly assigned in even numbers to augmentation of existing antidepressant medication with aripiprazole, augmentation with bupropion, or a switch from existing antidepressant medication to bupropion. Those who did not benefit from, or were ineligible for, step 1 were randomly assigned to step 2, with even distribution of 248 patients to either augmentation with lithium or a switch to nortriptyline. Each step lasted about 10 weeks.

Results were similar between augmentation with aripiprazole and augmentation with bupropion, with wellbeing scores improving by 4.83 points and 4.33 points, respectively. Augmentation with either agent was more effective than a switch to bupropion in several areas, including remission of depression (28.9% remission for augmentation with aripiprazole and 28.2% for augmentation with bupropion vs 19.3% with switch to bupropion).

Of note, the researchers recognised a significantly lower  rate of falls in patients augmented with aripiprazole (0.33 falls per patient) compared with patients augmented with bupropion (0.55 falls per patient). In patients in step 2, improvements in wellbeing and the incidence of remission were low, but similar with lithium augmentation or a switch to nortriptyline.

Professor Philip Mitchell, Scientia Professor of Psychiatry at UNSW Sydney and Director of the Mood Disorders Service at Sydney’s Ramsay Clinic Northside, commented, ‘This study will provide important evidence-based guidance for both GPs and psychiatrists.’

He said the findings suggested that augmentation of an ineffective antidepressant with aripiprazole (or similar partial dopamine agonist) was the preferred (and more simple) step before considering switching to a different antidepressant class.

‘A caveat needs to be noted,’ he said. ‘Even aripiprazole augmentation only led to a remission rate of just under 30%. While for a treatment-resistant population this is a meaningful reduction, this finding highlights the current limitations in our treatments for these very impaired patients.’

N Engl J Med  2023; doi: 10.1056/NEJMoa2204462.