Few studies have delineated the real-world, long-term trends of prescription patterns of antidepressants for patients with major depressive disorder (MDD). This study aims to describe their vicissitudes in the nationally representative sample of the US from 1996 to 2015 and explore their characteristics. We used the Medical Expenditure Panel Survey, a nationally representative database of the US population, between 1996 and 2015. We estimated the prevalence of MDD among adults, calculated the proportions of those on antidepressant treatment as well as those on specific drugs through the two decades, and determined their dosages in 2015. We conducted multivariable regression to find possible factors related to their suboptimal prescriptions. The prevalence of adults diagnosed with MDD increased from 6.1% (95% CI, 5.7–6.6%) in 1996 to 10.4% (9.7–11.1%) in 2015. The proportion of patients without any antidepressant therapy decreased but still accounted for 30.6% (28.3–33.1%) in 2015. Sertraline and fluoxetine were among the most frequently prescribed antidepressants throughout the 20 years, while the trend for some new drugs changed dramatically. 16.1% (12.5–20.2%) of patients of MDD on antidepressant monotherapy were prescribed with suboptimal doses in 2015; the risk was lower for those who had higher Body Mass Index (OR 0.94 [0.90–0.99]), longer-term prescriptions (OR 0.92 [0.87–0.97]), and the risk was higher for those who were prescribed with tricyclic antidepressants (OR 11.21 [2.12–59.34], compared with serotonin reuptake inhibitors (SSRIs)), and antidepressants other than SSRIs and serotonin and norepinephrine reuptake inhibitors (OR 4.12 [1.95, 8.73], compared with SSRIs). This study confirmed the growing numbers of patients with MDD and the increase in the antidepressant prescriptions among them. However, the existence of patients without any antidepressant prescriptions or with suboptimal prescriptions and the variable prescription patterns through the decades might suggest some unresolved gaps between evidence and practice.

These are peer-reviewed supplementary materials for the article 'A real-world analysis of antidepressant medications in US veterans aged 60 years and older: a comparative analysis' published in the Journal of Comparative Effectiveness Research.Table S1: Complete list of antidepressantsTable S2: Complete list of non-antidepressant augmentation drugsTable S3: Complete breakdown of baseline comorbiditiesTable S4: Outcomes by treatmentTable S5: Psychiatric hospitalization definitionTable S6: Average number of observation days in study for each treatment for each outcomeTable S7: Psychological hospitalization hazard ratios (reference = sertraline)Table S8: aHR for changing, augmenting, or hospitalization for patients with at least a 90-day observation period, right censored after 730 days (2 years)Aim: To compare the safety and efficacy of antidepressants (AD) among older adults with major depressive disorder (MDD) by assessing treatment change, augmentation and hospitalization rates. Methods: This retrospective study analyzed data from the Veterans Affairs (VA) database, including 142,138 patients aged ≥60 years diagnosed with MDD. Patients prescribed bupropion, citalopram, duloxetine, escitalopram, fluoxetine, mirtazapine, paroxetine, sertraline, or venlafaxine were included. Outcomes were treatment change, augmentation and hospitalization rates. Hazard ratios (aHRs) were calculated using sertraline as the reference. Results: Of the patients, 39.6% required augmentation, 18.1% changed antidepressant treatment and 13.3% were hospitalized. The corresponding incidence rate was 544, 124 and 122 events per 1000 person-years. Compared with sertraline, mirtazapine users had the highest AD change risk (aHR 1.34, 95% CI: 1.29–1.40), while duloxetine users had the lowest (aHR 0.87, 95% CI: 0.83–0.92). Duloxetine also had the lowest augmentation risk (aHR 0.89, 95% CI: 0.86–0.92). Mirtazapine users also had the highest risks of augmentation (aHR 1.15, 95% CI: 1.12–1.18) and hospitalization (aHR 1.14, 95% CI: 1.07–1.23). Bupropion had the lowest hospitalization risk (aHR 0.77, 95% CI: 0.71–0.84). Conclusion: Antidepressant choice significantly influences treatment outcomes in older adults with MDD. Duloxetine demonstrated the best profile with the lowest risks of AD change and augmentation, while mirtazapine posed the highest risks of all three outcomes. Personalized treatment strategies are crucial to improving outcomes in this population.

BackgroundThe United States Food and Drug Administration (FDA) maintains a black-box warning for antidepressants warning of an increased risk of suicidality in children and young adults that is based on proprietary clinical trial data from study sponsors that were submitted for regulatory approval. This article aimed to assess whether the black-box warning for antidepressants is still valid today using recent drug safety data.MethodsPost-marketing adverse drug event data were obtained from the US FDA’s Adverse Event Reporting System (FAERS) for the years 2017 through 2023. Logistic regression analysis was conducted using the case versus non-case methodology and adjusted for gender, age group, drug role (primary drug, secondary drug, interacting drug, and concomitant drug), initial FDA reporting year, reporter country, and a drug*gene*age group interaction.ResultsIn the multivariate analysis, compared to fluoxetine and patients aged 25 to 64 years, children [adjusted reporting odds ratio (aROR) = 7.38, 95% CI, 6.02–9.05] and young adults (aROR = 3.49, 95% CI, 2.65–4.59) were associated with an increased risk of reporting suicidality, but not for the elderly (aROR = 0.76, 95% CI, 0.53–1.09). Relative to fluoxetine, esketamine was associated with the highest rate of reporting suicidality in children (aROR = 3.20, 95% CI, 2.25–4.54); however, esketamine was associated with a lower risk of reporting suicidality in young adults (aROR = 0.59, 95% CI, 0.41–0.84), but not significantly in the elderly (aROR = 0.77, 95% CI, 0.48–1.23). For country-specific findings, relative to the USA, the Slovak Republic, India, and Canada had the lowest risk of reporting suicidality. For the overall study population, desvenlafaxine (aROR = 0.61, 95% CI, 0.46–0.81) and vilazodone (aROR = 0.56, 95% CI, 0.32–0.99) were the only two antidepressants associated with a reduced risk of reporting suicidality.ConclusionThis study shows that with recent antidepressant drug safety data, the US FDA’s black-box warning for prescribing antidepressants to children and young adults is valid today in the USA. However, relative to the USA, 15 countries had a significantly lower risk of reporting suicidality, while 16 countries had a higher risk of reporting suicidality from 38 antidepressants and lithium.