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.

Patterns of opioid prescribing by dentists in a pediatric population: a retrospective observational study.

BACKGROUND: Dentists are regular prescribers of opioid analgesic medications; however, there are few published data on their prescribing practices for children. The aim of this study was to assess opioid prescribing practices of dentists for pediatric patients. METHODS: We conducted a retrospective study (2011/12 to 2017/18) using administrative health data of opioid prescribing practices of dentists in Nova Scotia for children and adolescents (age < 18 yr). The main variables of interest were opioid "type" and "load" dentists prescribed (number of dispensed prescriptions/yr, days supplied/prescription and dosage/d per prescription in milligrams of morphine equivalents [MME]). RESULTS: Dentists accounted for a mean of 18.3% (standard deviation 1.5%) of all opioid prescribers for the pediatric population annually but were responsible for 59.9% of all opioid prescriptions and 48.6% of total MME dispensed during the 7-year study period. Oral and maxillofacial surgeons were responsible for 80.7% of all dental-related opioids dispensed. Codeine was most frequently prescribed (78.6% of total MME), followed by oxycodone (11.1%). There were significant downward trends over the study period in the total amount of opioid analgesics dispensed (r = -0.903, p < 0.01), primarily due to a reduction in the total amount of codeine dispensed and number of days supplied per prescription (r = -0.837, p < 0.05). Few opioids were dispensed to children less than 12 years. INTERPRETATION: Dentists in Nova Scotia reduced prescriptions of opioids in the pediatric population between 2011/12 and 2017/18, which may indicate that current opioid prescribing principles are influencing dentists' prescribing habits. Nonetheless, patients and parents should receive appropriate counselling as to the proper use, risks, storage and potential for misuse of opioids when prescribed.