Is one or two infusions better in the first week of low-dose ketamine treatment for medication-resistant depression? A post hoc pooled analysis of randomized placebo-controlled and open-label trials.

BACKGROUND: Whether a second ketamine infusion in the first week improves the antidepressant, antisuicidal, and anti-inflammatory effects of the first low-dose ketamine infusion remains unclear. METHODS: A total of 78 patients with medication-resistant depression were allocated to receive two ketamine infusions (n = 30; days 1 and 4), a single ketamine infusion (n = 24; only day 1), or normal saline placebo infusion (n = 24; only day 1). The Montgomery-Asberg Depression Scale (MADRS) and 17-item Hamilton Rating Scale for Depression (HDRS) were administered before and at 40 min, 240 min, day 2, day 4, day 5, and day 7 after infusion. Serum concentrations of interleukin (IL)-2 and tumor necrosis factor (TNF)-α were assessed. RESULTS: Two ketamine infusions improved the overall depressive symptoms (p < 0.001) and melancholic symptoms (p < 0.001) than a single ketamine or placebo infusion. The antisuicidal effect did not differ between the ketamine treatment groups. Two ketamine infusions increased TNF-α levels compared with a single ketamine or placebo infusion (p = 0.015). A single ketamine infusion improved the TNF-α-to-IL-2 ratio, an index of average anti-inflammatory effect, than two ketamine infusions or a single placebo infusion (p = 0.027). DISCUSSION: Repeated low-dose ketamine infusions improved the antidepressant effect, but not the antisuicidal effect, compared with a single infusion. However, repeated ketamine infusions may exert a lesser anti-inflammatory effect than a single infusion.

Antidepressant effects on insulin sensitivity and proinflammatory cytokines in the depressed males.

Growing evidence suggests that mood disorder is associated with insulin resistance and inflammation. Thus the effects of antidepressants on insulin sensitivity and proinflammatory responses will be a crucial issue for depression treatment. In this study, we enrolled 43 non-diabetic young depressed males and adapted standard testing procedures to assess glucose metabolism during 4-week hospitalization. Before and after the 4-week antidepressant treatment, participants underwent oral glucose tolerance test (OGTT) and frequently sampled intravenous glucose tolerance test (FSIGT). Insulin sensitivity (S(I)), glucose effectiveness (S(G)), acute insulin response, and disposition index (DI) were estimated using the minimal model method. The plasma levels of C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and adiponectin were measured. The Hamilton depression rating scale (HAM-D) total scores were reduced significantly during the course of treatment. There were no significant changes in the parameters of S(I), S(G), and DI. Compared to drug naïve status, the level of plasma IL-6 was significantly elevated (0.77 to 1.30 pg/ml; P = .001) after antidepressant therapy. However, the concentrations of CRP, TNF-alpha, and adiponectin showed no differences during the course of treatment. The results suggest that antidepressants may promote stimulatory effect on the IL-6 production in the early stage of antidepressant treatment.

Factors relevant to patient assaultive behavior and assault in acute inpatient psychiatric units in Taiwan.

The purpose of this article was to explore patient assault in acute inpatient psychiatric units and to examine the interplay between the patients, environmental staff factors related to assaults. A log system for recording assault occurrences was used. Four trained research assistants conducted a chart review and interviewed the nursing staff to complete the overt aggression scale, staff observation aggression scale, and environmental assessment questionnaire separately at the four hospitals. The data showed 855 episodes of assaults from 287 patients. The assault incident density ranged from 1.11 to 1.95 per 1,000 patient days. Patient factors (diagnosis, history of assaultive behavior, the duration of admission, and smoking history), environmental factors (patient/nurse ratio and space density) and staff factors (age, length of work experience, training program received in assault prevention and management) were contributing variables to patients' assaultive behavior. This reinforces the complexity of models in predicting assaults among psychiatric in-patients.