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.

Muscle fatigability and control of force in men with posttraumatic stress disorder.

INTRODUCTION: Acute stress can increase fatigability and decrease steadiness of sustained low-force contractions that are required for functional tasks in upper limb muscles. Whether motor performance is more impaired in people with a chronic stress disorder is not known. PURPOSE: This study compared the fatigability and steadiness (force fluctuations) of handgrip muscles in veterans with posttraumatic stress disorder (PTSD) and civilian controls in the presence and absence of varying levels of cognitive demand. METHODS: Eighteen veterans with PTSD and 21 healthy controls (33 ± 9 yr) attended three randomized experimental sessions to perform an isometric fatiguing contraction (20% of maximal strength) with the handgrip muscles. Two sessions involved performing a cognitive task during the fatiguing contraction: 1) difficult mental math task (stressor) and 2) a simple mental math task (mental attentiveness). A third session involved a fatiguing contraction with no mental task (control). RESULTS: Stress elevated heart rate, blood pressure, and levels of anxiety in veterans with PTSD (P < 0.05) but blunted cortisol levels (P < 0.05). Time to failure was briefer (7.2 ± 2.5 vs 9.3 ± 5.2 min, P = 0.03), and force fluctuations increased at a greater rate for veterans with PTSD than for controls (P < 0.05). Cognitive stress did not influence time to failure or force fluctuations for either group (P > 0.05). CONCLUSIONS: Veterans with PTSD demonstrated greater fatigability and loss of steadiness (greater force fluctuations) of the handgrip muscles compared with healthy controls. SIGNIFICANCE: Male veterans with PTSD demonstrated altered neuromuscular function of arm muscles that potentially affects functional tasks during daily, ergonomic, and military activities.

Characteristics of patient encounters that challenge medical students' provision of patient-centered care.

BACKGROUND: Medical educators need to effectively engage and teach medical students to provide patient-centered care (PCC). There is limited appreciation for the issues that clinical students identify as challenges in providing PCC. METHOD: As part of a required half-day PCC workshop in 2007, medical students authored critical incident scenarios on patient encounters where PCC was difficult. The authors analyzed 131 scenarios using qualitative memo technique to identify features associated with these encounters. Categories and themes were identified using constant comparative methodology. RESULTS: Commonly cited PCC challenges were student's/patient's emotional responses (63%/44%), patient's/family's perception of the care plan (54%), conflicting expectations (35%), communication barriers (30%) and patient's social circumstances (29%). Sixty-three percent of incidents identified PCC-appropriate responses to these challenges. CONCLUSIONS: Student-authored critical incidents regarding difficult patient encounters can be analyzed to identify key features that students perceive as challenges to providing PCC and can inform curriculum development.

Nonpsychotic, nonparaphilic self-amputation and the internet.

The literature suggests that self-amputation is an outgrowth of either psychosis or paraphilia. In the case we present, the patient was neither psychotic at the time of amputation, nor did he ascribe a sexual motivation for his act. Instead, he had a long-standing idea that being an amputee was a critical aspect of his identity. The patient used the internet to research the method for his amputation and sought support from individuals with the same desire via e-mail, web sites, and Usenet news groups.

Differences Between First and Second Electroconvulsive Treatments Given in the Same Session.

For the first and second of two bilateral ECTs given under the same anesthesia, judgments were made of the durations of four seizure-induced phenomena: tonic-clonic motor activity, paroxysmal EEG activity, EEG spike waves, and tachycardia. A total of 36 pairs of treatments were given to 14 patients. Pearson correlation coefficients between each of six possible pairs of these four measures were higher for the first ECTs than for the second ECTs (p < 0.05 to p < 0.001). These results suggest that the seizure associated with the second ECT under the same anesthesia is physiologically different from that of the first ECT and is less well generalized through the brain.