Systematic review and meta-analysis of second-generation antidepressants for the treatment of older adults with depression: questionable benefit and considerations for frailty.

BACKGROUND: Frail older adults are commonly prescribed antidepressants. Yet, there is little evidence to determine the efficacy and safety of antidepressants to treat depression with concomitant frailty. To better understand this issue, we examined the efficacy and safety of second-generation antidepressants for the treatment of older adults with depression and then considered implications for frailty. METHODS: Due to the absence of therapeutic studies of frail older adults with depression, we conducted a systematic review and meta-analysis of double-blind, randomized controlled trials that compared antidepressants versus placebo for adults with depression, age 65 years or older. We searched PubMed/MEDLINE, Cochrane Library, reference lists from meta-analyses/studies, hand searches of publication lists, and related articles on PubMed. Outcomes included rates of response, remission, and adverse events. After evaluating the data, we applied a frailty-informed framework to consider how the evidence could be applied to frailty. RESULTS: Nine trials were included in the meta-analysis (n = 2704). Subjects had moderate to severe depression. For older adults with depression, there was no statistically significant difference in response or remission to second-generation antidepressants compared to placebo. Response occurred in 45.3% of subjects receiving an antidepressant compared to 40.5% receiving placebo (RR 1.15, 95% CI: 0.96 - 1.37, p = 0.12, I2 = 71%). Remission occurred in 33.1% with antidepressant versus 31.3% with placebo (RR 1.10, 95% CI: 0.92 - 1.31, p = 0.30, I2 = 56%) (Figure 2 and 3). There were more withdrawals due to adverse events with antidepressants, 13% versus 5.8% (RR 2.30, 95% CI: 1.45-3.63; p < 0.001; I2 = 61%; NNH 14, 95% CI:10-28). IMPLICATIONS FOR FRAILTY: Subjects in the meta-analysis did not have obvious characteristics of frailty. Using framework questions to consider the implications of frailty, we hypothesize that, like older adults, frail individuals with depression may not respond to antidepressants. Further, observational studies suggest that those who are frail may be less responsive to antidepressants compared to the non-frail. Given the vulnerability of frailty, adverse events may be more burdensome. CONCLUSIONS: Second-generation antidepressants have uncertain benefit for older adults with depression and cause more adverse events compared to placebo. Until further research clarifies benefit, careful consideration of antidepressant prescribing with frailty is warranted.

Evidence-informed guidelines for treating frail older adults with type 2 diabetes: from the Diabetes Care Program of Nova Scotia (DCPNS) and the Palliative and Therapeutic Harmonization (PATH) program.

Clinical practice guidelines specific to the medical care of frail older adults have yet to be widely disseminated. Because of the complex conditions associated with frailty, guidelines for frail older patients should be based on careful consideration of the characteristics of this population, balanced against the benefits and harms associated with treatment. In response to this need, the Diabetes Care Program of Nova Scotia (DCPNS) collaborated with the Palliative and Therapeutic Harmonization (PATH) program to develop and disseminate guidelines for the treatment of frail older adults with type 2 diabetes. The DCPNS/PATH guidelines are unique in that they recommend the following: 1. Maintain HbA1c at or above 8% rather than below a specific level, in keeping with the conclusion that lower HbA1c levels are associated with increased hypoglycemic events without accruing meaningful benefit for frail older adults with type 2 diabetes. The guideline supports a wide range of acceptable HbA1c targets so that treatment decisions can focus on whether to aim for HbA1c levels between 8% and 9% or within a higher range (ie, >9% and <12%) based on individual circumstances and symptoms. 2. Simplify treatment by administering basal insulin alone and avoiding administration of regular and rapid-acting insulin when feasible. This recommendation takes into account the variations in oral intake that are commonly associated with frailty. 3. Use neutral protamine Hagedorn (NPH) insulin instead of long-acting insulin analogues, such as insulin glargine (Lantus) or insulin detemir (Levemir), as insulin analogues do not appear to provide clinically meaningful benefit but are significantly more costly. 4. With acceptance of more liberalized blood glucose targets, there is no need for routine blood glucose testing when oral hypoglycemic medications or well-established doses of basal insulin (used alone) are not routinely changed as a result of blood glucose testing.Although these recommendations may appear radical, they are based on careful review of research findings.