REVIEW OF: Buspavanich P et al, J ­Affect Disord 2019;251:136–140

TYPE OF STUDY: Prospective, non-randomized controlled trial

Augmentation with lithium has long been established as an effective strategy for refractory depression, but how does it fare in geriatric patients? There is a dearth of evidence on lithium in the geriatric population, which may explain why it is rarely used in older patients. In this multicenter, prospective, non-randomized controlled trial, investigators evaluated the effectiveness of lithium augmentation in geriatric vs non-geriatric patients with major depressive disorder.

The study enrolled 226 patients with moderate to severe major depression (non-bipolar) who had failed at least one antidepressant trial. Lithium was added to their current antidepressant, and those who received at least 4 weeks of lithium were analyzed for response (n = 167), which was defined as ≥ 50% reduction on the Hamilton Depression Rating Scale. These patients were followed for 7–8 weeks. Responses were compared in geriatric (age ≥ 65) and adult patients.

Of the 167 patients analyzed, 22 were geriatric and 145 non-geriatric. The proportion of patients who completed the study was similar in both groups, as were other variables except age of onset, which was higher in the geriatric group. Most patients were female and had been in their current episode for 3 to 12 months. Both groups had similar mean lithium levels at the end of the study (0.61 for geriatric patients and 0.69 for non-geriatric).

Interestingly, geriatric patients had a significantly greater and more rapid response to lithium augmentation than those under age 65 (p = 0.04). Clinical response was 68.2% for geriatric patients and 46.9% for non-geriatric. The authors proposed these differences could be explained by age-related changes in pharmacokinetics and pharmacodynamics. For instance, decline in integrity of the blood-brain barrier with age may allow for quick and sufficient lithium levels. Additionally, lithium has neuroprotective effects, and neurodegenerative processes may play more of a role in the pathophysiology of depression in geriatrics.

While the authors claimed safety and tolerability were implied by the number of patients completing the study, the lack of data on adverse outcomes was a weakness. Plus, the sample size of geriatric patients was small, at least relative to non-geriatric patients. Another weakness was the lack of a non-lithium control group, making it difficult to establish whether these outcomes were unique to lithium.

TCPR’S TAKE
Geriatric patients are usually less responsive to antidepressant therapies than younger cohorts, so these results are a surprise. They lend further support to lithium augmentation in refractory depression. However, older patients are more at risk for adverse effects, drug interactions, and medical problems with lithium. Those risks need to be weighed against the risk of continued depression, which takes a toll on physical as well as mental health.