Emergence of mania in two middle-aged patients with a history of unipolar treatment-refractory depression receiving vagus nerve stimulation.

OBJECTIVES: We report on two patients who experienced emergence of full manic symptoms while receiving vagal nerve stimulation (VNS). METHODS: Two patients, both with a well-documented and verified history of longstanding unipolar depression, were initiated on VNS for treatment of their severe major depressive episodes. RESULTS: The two patients had emergence of full manic symptoms after 8 and 9 months of VNS, respectively. Manic symptoms were adequately managed with standard treatments (mood stabilizer and electroconvulsive therapy) and VNS was continued in the two subjects for up to 5 years without any further occurrences of manic/hypomanic episodes. CONCLUSIONS: These cases suggest that some patients with treatment-resistant depression may have a previously unrecognized bipolar disorder, triggered only by VNS. This report also provides evidence that VNS-induced manic switches, however serious and troubling to patients, can be managed safely, and that VNS maintenance can be continued for an extended period of time without manic relapses. Although the mechanism of action of VNS is not known, emerging evidence supports central nervous system dopaminergic and possibly cholinergic system involvement.

Nitrous Oxide for Treatment-Resistant Major Depression: A Proof-of-Concept Trial.

BACKGROUND: N-methyl-D-aspartate receptor antagonists, such as ketamine, have rapid antidepressant effects in patients with treatment-resistant depression (TRD). We hypothesized that nitrous oxide, an inhalational general anesthetic and N-methyl-D-aspartate receptor antagonist, may also be a rapidly acting treatment for TRD. METHODS: In this blinded, placebo-controlled crossover trial, 20 patients with TRD were randomly assigned to 1-hour inhalation of 50% nitrous oxide/50% oxygen or 50% nitrogen/50% oxygen (placebo control). The primary endpoint was the change on the 21-item Hamilton Depression Rating Scale (HDRS-21) 24 hours after treatment. RESULTS: Mean duration of nitrous oxide treatment was 55.6 ± 2.5 (SD) min at a median inspiratory concentration of 44% (interquartile range, 37%-45%). In two patients, nitrous oxide treatment was briefly interrupted, and the treatment was discontinued in three patients. Depressive symptoms improved significantly at 2 hours and 24 hours after receiving nitrous oxide compared with placebo (mean HDRS-21 difference at 2 hours, -4.8 points, 95% confidence interval [CI], -1.8 to -7.8 points, p = .002; at 24 hours, -5.5 points, 95% CI, -2.5 to -8.5 points, p < .001; comparison between nitrous oxide and placebo, p < .001). Four patients (20%) had treatment response (reduction ≥50% on HDRS-21) and three patients (15%) had a full remission (HDRS-21 ≤ 7 points) after nitrous oxide compared with one patient (5%) and none after placebo (odds ratio for response, 4.0, 95% CI, .45-35.79; OR for remission, 3.0, 95% CI, .31-28.8). No serious adverse events occurred; all adverse events were brief and of mild to moderate severity. CONCLUSIONS: This proof-of-concept trial demonstrated that nitrous oxide has rapid and marked antidepressant effects in patients with TRD.

Harnessing the Undiscovered Resource of Student Research Projects.

This article suggests that undergraduate research can help advance the science of psychology. We introduce a hypothetical "question-list paradigm" as a mechanism to do this. Each year, thousands of undergraduate projects are completed as part of the educational experience. Although many of these studies may not contain sufficient contributions for publication, they provide a good test of the replicability of established findings across populations at different institutions and geographic locations. Thus, these projects could meet the needs of recent calls for increased replications of psychological studies while simultaneously benefiting the student researchers, their instructors, and the field in general.