Antidepressant Strategies for Treatment of Acute Depressive Episodes Among Veterans.

OBJECTIVE: The 2016 VA/DoD Clinical Practice Guideline for Management of Major Depressive Disorder offers consensus-based recommendations when response to the initial antidepressant medication is suboptimal; however, little is known about "real-world" pharmacological strategies used by providers treating depression in the Veterans Affairs Health Care System (VAHCS). METHODS: We extracted pharmacy and administrative records of patients diagnosed with a depressive disorder and treated at the Minneapolis VAHCS between January 1, 2010 and May 11, 2021. Patients with bipolar disorder, psychosis-spectrum, or dementia diagnoses were excluded. An algorithm was developed to identify antidepressant strategies: monotherapy (MONO); optimization (OPM); switching (SWT); combination (COM); and augmentation (AUG). Additional data extracted included demographics, service utilization, other psychiatric diagnoses, and clinical risk for hospitalization and mortality. RESULTS: The sample consisted of 1298 patients, 11.3% of whom were female. The mean age of the sample was 51 years. Half of the patients received MONO, with 40% of those patients receiving inadequate doses. OPM was the most common next-step strategy. SWT and COM/AUG were used for 15.9% and 2.6% of patients, respectively. Overall, patients who received COM/AUG were younger. OPM, SWT, and COM/AUG occurred more frequently in psychiatric services settings and required a greater number of outpatient visits. The association between antidepressant strategies and risk of mortality became nonsignificant after accounting for age. CONCLUSIONS: Most of the veterans with acute depression were treated with a single antidepressant, while COM and AUG were rarely used. The age of the patient, and not necessarily greater medical risks, appeared to be a major factor in decisions about antidepressant strategies. Future studies should evaluate whether implementation of underutilized COM and AUG strategies early in the course of depression treatment are feasible.

Dose-related effects of ketamine for antidepressant-resistant symptoms of posttraumatic stress disorder in veterans and active duty military: a double-blind, randomized, placebo-controlled multi-center clinical trial.

This study tested the efficacy of repeated intravenous ketamine doses to reduce symptoms of posttraumatic stress disorder (PTSD). Veterans and service members with PTSD (n = 158) who failed previous antidepressant treatment were randomized to 8 infusions administered twice weekly of intravenous placebo (n = 54), low dose (0.2 mg/kg; n = 53) or standard dose (0.5 mg/kg; n = 51) ketamine. Participants were assessed at baseline, during treatment, and for 4 weeks after their last infusion. Primary analyses used mixed effects models. The primary outcome measure was the self-report PTSD Checklist for DSM-5 (PCL-5), and secondary outcome measures were the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) and the Montgomery Åsberg Depression Rating Scale (MADRS). There were no significant group-by-time interactions for PTSD symptoms measured by the PCL-5 or CAPS-5. The standard ketamine dose ameliorated depression measured by the MADRS significantly more than placebo. Ketamine produced dose-related dissociative and psychotomimetic effects, which returned to baseline within 2 h and were less pronounced with repeated administration. There was no evidence of differential treatment discontinuation by ketamine dose, consistent with good tolerability. This clinical trial failed to find a significant dose-related effect of ketamine on PTSD symptoms. Secondary analyses suggested that the standard dose exerted rapid antidepressant effects. Further studies are needed to determine the role of ketamine in PTSD treatment. ClinicalTrials.gov identifier: NCT02655692.

Antidepressant Effect of the VA Weight Management Program (MOVE) Among Veterans With Severe Obesity.

INTRODUCTION: Obesity is prevalent among users of Veteran's Health Administration services, where it is comorbid with depression, post-traumatic stress disorder, type 2 diabetes, cardiovascular disease, colon, and breast cancer. Among obese subjects, severe obesity represents a subpopulation with the highest risk of depression. We investigate the antidepressant effect of a local VA weight management program (Managing Overweight Veterans Everywhere - MOVE) among depressed veterans with severe obesity. MATERIAL AND METHODS: In a 10-week prospective pilot study, 14 clinically depressed veterans with severe obesity were recruited from: (1) the 2-week residential based intense MOVE program (IMP) (N = 7) and (2) the 10-week educational module of self-management MOVE program (SMP) (N = 7). Subjects had a Beck Depression Inventory, 2nd edition (BDI-II) score > 12 and BMI > 40 or BMI > 35 with associated to comorbid conditions. Concurrent treatment for depression such as medications or psychotherapy was excluded. The primary efficacy endpoint was the change in BDI-II score form baseline to week 10. Analysis consisted of linear mixed model with baseline BDI-II score as a covariate, and level of MOVE intervention (IMP vs. SMP), time, and time by treatment interaction as fixed effects, and random patient effect. Pearson's correlation examined the relationships between clinical and demographic variables and change in severity of depression by BDI-II scores. Secondary outcomes include weight loss and energy expenditure. RESULTS: The sample was composed by 14 subjects (IMP = 7; SMP = 7) mostly unemployed (N = 9), married (N = 10), mid-aged (mean = 58.2, SD = 8.4), Caucasian (N = 13), male (N = 12), with recurrent depression (N = 11), and a mean overall duration of current depressive episode of 13.5 months (SD = 10.2). Out of 14 participants; seven had a family history of mood disorder, two had previous psychiatric hospitalization, three had a previous suicidal attempt, and eight had a history of substance use disorder. There was a significant decrease in severity of depression among all 14 (F3,36.77 = 5.28; P < 0.01); antidepressant effect favored the IMP compared to SMP at day 12 (F1,15.10 = 9.37, P = 0.01) and week 6 (F2,27.34 = 4.26, P = 0.03), but effect fell short of significance at week 10. The change in severity of depression measured by BDI-II score significantly correlated with total weight loss (r = -0.60; P = 0.04) and daily energy expenditure at 12 days (r = -0.67; P = 0.01), week 6 (r = -0.59; P = 0.03), and week 10 (r = -0.71; P = 0.01). CONCLUSIONS: Depressed veterans with severe obesity improved their depressive symptoms by participating in the MOVE program. Veterans in the IMP had greater but short-term antidepressant effect as compared to educational intervention for obesity. Future studies with larger sample size may elucidate the underlying mechanisms of weight reduction to improve depression and, more importantly, sustain response among veterans with severe obesity.