Effect of Antidepressant Switching vs Augmentation on Remission Among Patients With Major Depressive Disorder Unresponsive to Antidepressant Treatment: The VAST-D Randomized Clinical Trial.

IMPORTANCE: Less than one-third of patients with major depressive disorder (MDD) achieve remission with their first antidepressant. OBJECTIVE: To determine the relative effectiveness and safety of 3 common alternate treatments for MDD. DESIGN, SETTING, AND PARTICIPANTS: From December 2012 to May 2015, 1522 patients at 35 US Veterans Health Administration medical centers who were diagnosed with nonpsychotic MDD, unresponsive to at least 1 antidepressant course meeting minimal standards for treatment dose and duration, participated in the study. Patients were randomly assigned (1:1:1) to 1 of 3 treatments and evaluated for up to 36 weeks. INTERVENTIONS: Switch to a different antidepressant, bupropion (switch group, n = 511); augment current treatment with bupropion (augment-bupropion group, n = 506); or augment with an atypical antipsychotic, aripiprazole (augment-aripiprazole group, n = 505) for 12 weeks (acute treatment phase) and up to 36 weeks for longer-term follow-up (continuation phase). MAIN OUTCOMES AND MEASURES: The primary outcome was remission during the acute treatment phase (16-item Quick Inventory of Depressive Symptomatology-Clinician Rated [QIDS-C16] score ≤5 at 2 consecutive visits). Secondary outcomes included response (≥50% reduction in QIDS-C16 score or improvement on the Clinical Global Impression Improvement scale), relapse, and adverse effects. RESULTS: Among 1522 randomized patients (mean age, 54.4 years; men, 1296 [85.2%]), 1137 (74.7%) completed the acute treatment phase. Remission rates at 12 weeks were 22.3% (n = 114) for the switch group, 26.9% (n = 136)for the augment-bupropion group, and 28.9% (n = 146) for the augment-aripiprazole group. The augment-aripiprazole group exceeded the switch group in remission (relative risk [RR], 1.30 [95% CI, 1.05-1.60]; P = .02), but other remission comparisons were not significant. Response was greater for the augment-aripiprazole group (74.3%) than for either the switch group (62.4%; RR, 1.19 [95% CI, 1.09-1.29]) or the augment-bupropion group (65.6%; RR, 1.13 [95% CI, 1.04-1.23]). No significant treatment differences were observed for relapse. Anxiety was more frequent in the 2 bupropion groups (24.3% in the switch group [n = 124] vs 16.6% in the augment-aripiprazole group [n = 84]; and 22.5% in augment-bupropion group [n = 114]). Adverse effects more frequent in the augment-aripiprazole group included somnolence, akathisia, and weight gain. CONCLUSIONS AND RELEVANCE: Among a predominantly male population with major depressive disorder unresponsive to antidepressant treatment, augmentation with aripiprazole resulted in a statistically significant but only modestly increased likelihood of remission during 12 weeks of treatment compared with switching to bupropion monotherapy. Given the small effect size and adverse effects associated with aripiprazole, further analysis including cost-effectiveness is needed to understand the net utility of this approach. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01421342.

Voluntary childlessness is increased in women with inflammatory bowel disease.

BACKGROUND: The women's health aspect of inflammatory bowel disease (IBD) is a newer area of study; childbearing issues have received little attention despite the fact that IBD affects women predominantly during their childbearing years. The aim of this study was to better understand patients' considerations about pregnancy-related issues and to examine trends in childbearing so that physicians are able to better tailor their advice to IBD-specific concerns. METHODS: Data were gathered from specific questions in 3147 surveys mailed anonymously to all members of the Crohn's and Colitis Foundation of America (CCFA) Illinois Carol Fisher chapter. The subjects were provided a pre-addressed, pre-stamped return envelope and were instructed to return their completed surveys with no identifying information. Subjects were from the Illinois community. Females IBD patients were 15-44 of age and were members of the CCFA Illinois Carol Fisher chapter. RESULTS: In this study, 169 females age 15-44 years with IBD, 110 with Crohn's disease (CD) and 59 with ulcerative colitis (UC), were identified. Most subjects were white. IBD patients had a higher rate of voluntary childlessness (CD 18%, UC 14%) than the 6.2% seen in the general population (P = 0.001 for CD, P = 0.08 for UC). Women with UC had a lower rate of temporary childlessness (CD 28%, UC 13.6%) than the general population (33%) (P = NS and P < 0.0001 for UC). The rates of nonvoluntary childlessness in IBD were similar to the general population. Women with IBD also had fewer children than their state and national counterparts. The state of the patients' IBD, including those who had gone through a previous pregnancy with IBD, did not alter their resolve to have children. The educational level of our subjects was higher than the nationwide and statewide levels; 76% of the subjects used contraception before diagnosis of IBD, and 82% used it after diagnosis. The most common choices were oral contraception, barrier methods, and abstinence. This study was unable to compare the lifetime rates of complications of pregnancy with population-based controls because such data were unavailable. Furthermore, their findings in this study may not be generalized to all ethnic groups because our population was mostly white. CONCLUSIONS: Women with IBD had a higher rate of voluntary childlessness and fewer children than the general population. These observations are likely attributable to a higher educational achievement and to racial background of the patients rather than to IBD-related reasons. Although contraception use in patients with IBD was lower that in the general population, use was higher after the diagnosis of IBD than before the diagnosis. Contraceptive choices and adoption rates were similar to the general population. Women with CD were more affected by miscarriages after diagnosis with IBD than those with UC.

The education and employment status of patients with inflammatory bowel diseases.

Inflammatory bowel disease (IBD) has the propensity to affect patients who are in their late teens and early 20s, an age when most people decide on their educational and career directions. This review describes the effects that IBD has on the continuum of education and employment. Patients with Crohn's disease and ulcerative colitis attain a similar level of education as that of the general population. The quality of life of such patients in school, as measured by both patients' and teachers' perceptions, indicates that, despite the difficulties that students face in terms of missed school time and physical inconveniences, teachers are generally perceived by students to have favorable attitudes toward helping them. Even though earlier work in the area of employment has suggested that the occurrence of IBD is clustered among people in white-collar positions, recent data have suggested that certain environmental risks for IBD (i.e., sedentary or indoor jobs) may be associated with jobs classified as being white-collar, and therefore having a white-collar job may in itself not be a risk factor for the development of IBD. Patients with IBD have a higher rate of nonparticipation in the labor force, and the participation rate seems to maintain steady levels over time. A majority of patients with IBD continue in the same employment positions over a period of years. Patients with IBD, especially those who have undergone surgery, took more sick leave than their counterparts without IBD. A majority of patients with IBD favored the disclosure of their diagnosis to their employers and perceived little discrimination in the workplace. Furthermore, most employers were perceived by their employees with IBD as having fair attitudes toward the compensation provided for their employees with IBD.