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MDD in Older Adults
Switch and Augmentation Treatment Strategies for Older Adults With Depression

Released: August 04, 2023

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Key Takeaways
  • In addition to implementing evidence-based prescribing practices, effective treatment of late-life depression includes attending to cognitive impairment, medical comorbidities and associated disability, extraneous medications and polypharmacy, and geriatric-relevant concerns (eg, fear of falling, bereavement, social isolation), as well as engaging family and caregivers.
  • Augmentation with aripiprazole or bupropion may be more effective than switching to bupropion in older adults with depression. However, augmentation with aripiprazole may be associated with a lower risk of falls than augmentation with bupropion in this patient population.
  • Using a measurement-based approach to depression care provides objective data to support switch vs augmentation strategies.

Imagine this: You are in your clinic, treating a 78-year-old patient for depression. This is the patient’s third lifetime major depressive episode, and this specific episode started 6 months ago. You have prescribed 2 different selective serotonin reuptake inhibitors (SSRIs), both of which are taken at the maximum dose advised in the prescribing information. After 8 weeks of this regimen, there is limited clinical improvement.

In addition to maximizing SSRI doses, you are following best practices for depression care in older adults by deprescribing extraneous medications. In the case of this patient, unnecessary and potentially unsafe medications include the as-needed use of hydroxyzine for anxiety and the rare use of diazepam for periodic insomnia. You also have excluded other causes for depression exacerbation by clarifying with the patient that they do not misuse alcohol, marijuana, or other drugs; that their cardiac disease and diabetes are optimally managed; that they are not bereaved; and that their cognition is not impaired (as evidenced by a Montreal Cognitive Assessment score of 27 and complete independence in all instrumental activities of daily living). You also have screened the patient for obstructive sleep apnea with the STOP-BANG questionnaire, inquired about any problems with chronic pain, ruled out other psychiatric conditions other than mild generalized anxiety disorder, and confirmed that there are no major stressors related to the patient’s finances, housing, social connections, and engagement in meaningful activities.

Because you practice measurement-based care—which, in this scenario, includes administering the Patient Health Questionnaire‒9 (PHQ-9) and inquiring about the common adverse events of the patient’s antidepressant(s) at every visit—you note that the patient has achieved <20% improvement from their baseline PHQ-9 score. Their score at baseline was 24, and it has not budged beyond 19 in the past 16 weeks of treatment. The patient is feeling frustrated with the lack of improvement and requests another medication change. Because there has been <30% improvement in the patient’s depression with both SSRIs, you agree that a switch to another class of medication is warranted. Thus, you prescribe duloxetine, a serotonin‒norepinephrine reuptake inhibitor (SNRI), at 30 mg/day; after 10 days, the dose is increased to 60 mg/day. After 3 weeks of this regimen, the patient notices an improvement in symptoms, and their PHQ-9 score has decreased from 19 to 13. Both you and the patient are delighted with this progress. Furthermore, you encourage the patient to increase their daily walks from 30 minutes to 45 minutes and suggest planning at least 1 social event every week. The patient agrees to try these changes and plans to return to your clinic in 4 weeks.

Upon return, the patient feels less anxious, is sleeping better, and has more energy than when they first saw you. However, the patient shares that they still are not where they want to be. The patient’s PHQ-9 at this visit is 12, and they request that you make another medication change, saying, “I’m improved, but this is still no way to live.”

What Do You Do Now?
You already have switched the patient’s medication 3 times now. The first 2 changes had minimal benefit on the patient’s symptomatic improvement. The third switch to an SNRI resulted in an improvement in the patient’s PHQ-9 score and a subjective report that they felt “improved but not yet well.” In this instance, the next pharmacologic approach is to augment the SNRI with another antidepressant agent.

Two studies are worth considering at this stage which support augmentation as the next best step (vs another medication switch). Although there are some differences in the VAST-D and OPTIMUM studies (of note, in the lower age limit of participants, veterans vs nonveterans, and duration of exposure), both studies identify augmentation with either bupropion or aripiprazole as superior to another medication switch (in the case of these studies, switching to bupropion). 

In these large studies, augmentation with either bupropion or aripiprazole resulted in remission for approximately 30% of patients who received an adequate dose and treatment for at least 10 weeks. The VAST-D study reported the following remission rates at 12 weeks: 22.3% for the switch to bupropion group, 26.9% for the augmentation with bupropion group, and 28.9% for the augmentation with aripiprazole group. The OPTIMUM study reported the following remission rates at 10 weeks: 19.3% for the switch to bupropion group, 28.2% for the augmentation with bupropion group, and 28.9% for the augmentation with aripiprazole group. These remission rates are remarkably similar. Falls were an a priori safety outcome of interest in the OPTIMUM study, with the highest risk ratio for falls observed in the augmentation with bupropion group.

Back to our case: Because this patient does not have a history of falls, denies a history of seizure disorder, has normal gait, feels steady, exercises regularly, and does not misuse drugs or alcohol, you and the patient decide that augmentation with bupropion extended release is a reasonable next step. Your titration approach is to start at 150 mg/day, which is then increased to 300 mg/day at Week 4. The patient is tolerating the medication regimen well and has incremental benefit with initiation and subsequent dose increase, so at Week 6 you increase the dose again to 450 mg/day.

Why did we choose bupropion augmentation over aripiprazole? Although augmentation with aripiprazole in late-life depression has been shown to be relatively safe for measures of cardiac and metabolic health, there is still an increased risk of extrapyramidal symptoms—such as akathisia, parkinsonism, and tardive dyskinesia—with atypical antipsychotics compared with antidepressants.

Your Thoughts?
In summary, following a stepped-care approach in the treatment of depression in older adults should include attention to medical, prescription, and social determinant contributors to treatment nonresponse; consideration of percent improvement using measurement-based care and patient self-report of improvement; and contemplation of both efficacy and safety when choosing between switch and augmentation strategies. In your practice, how do you decide whether to use switch or augmentation strategies when treating older adults with depression? Join the discussion by answering the polling question and posting a comment below.

Bibliography

  • Lenze EJ, Mulsant BH, Blumberger DM, et al. Efficacy, safety, and tolerability of augmentation pharmacotherapy with aripiprazole for treatment-resistant depression in late life: a randomised, double-blind, placebo-controlled trial. Lancet. 2015;386:2404-2412.
  • Lenze EJ, Mulsant BH, Roose SP, et al. Antidepressant augmentation versus switch in treatment-resistant geriatric depression. N Engl J Med. 2023;388:1067-1079.
  • Mohamed S, Johnson GR, Chen P, et al. Effect of antidepressant switching vs augmentation on remission among patients with major depressive disorder unresponsive to antidepressant treatment: the VAST-D randomized clinical trial. JAMA. 2017;318:132-145.
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In your practice, how do you decide whether to use switch or augmentation strategies when treating older adults with depression?

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