Cognitive Behavior Therapy May Sustain Antidepressant Effects of Intravenous Ketamine in Treatment-Resistant Depression.

INTRODUCTION: Ketamine has shown rapid though short-lived antidepressant effects. The possibility of concerning neurobiological changes following repeated exposure to the drug motivates the development of strategies that obviate or minimize the need for longer-term treatment with ketamine. In this open-label trial, we investigated whether cognitive behavioral therapy (CBT) can sustain or extend ketamine's antidepressant effects. METHODS: Patients who were pursuing ketamine infusion therapy for treatment-resistant depression were invited to participate in the study. If enrolled, the subjects initiated a 12-session, 10-week course of CBT concurrently with a short 4-treatment, 2-week course of intravenous ketamine (0.5 mg/kg infused over 40 min) provided under a standardized clinical protocol. RESULTS: Sixteen participants initiated the protocol, with 8 (50%) attaining a response to the ketamine and 7 (43.8%) achieving remission during the first 2 weeks of protocol. Among ketamine responders, the relapse rate at the end of the CBT course (8 weeks following the last ketamine exposure) was 25% (2/8). On longer-term follow-up, 5 of 8 subjects eventually relapsed, the median time to relapse being 12 weeks following ketamine exposure. Among ketamine remitters, 3 of 7 retained remission until at least 4 weeks following the last ketamine exposure, with 2 retaining remission through 8 weeks following ketamine exposure. Ketamine nonresponders did not appear to benefit from CBT. CONCLUSIONS: CBT may sustain the antidepressant effects of ketamine in treatment-resistant depression. Well-powered randomized controlled trials are warranted to further investigate this treatment combination as a way to sustain ketamine's antidepressant effects.

Toward understanding the heterogeneity in obsessive-compulsive disorder: Evidence from narratives in adult patients.

BACKGROUND: Current attempts at understanding the heterogeneity in obsessive-compulsive disorder have relied on quantitative methods. The results of such work point toward a dimensional structure for obsessive-compulsive disorder. Existing qualitative work in obsessive-compulsive disorder has focused on understanding specific aspects of the obsessive-compulsive disorder experience in greater depth. However, qualitative methods are also of potential value in furthering our understanding of obsessive-compulsive disorder heterogeneity by allowing for open-ended exploration of the obsessive-compulsive disorder experience and correlating identified subtypes with patient narratives. OBJECTIVE: We explored variations in patients' experience prior to, during and immediately after performing their compulsions. METHOD: Semi-structured interviews were conducted with 20 adults with obsessive-compulsive disorder, followed by inductive thematic analysis. Participant responses were not analyzed within the context of an existing theoretical framework, and themes were labeled descriptively. RESULTS: The previous dichotomy of 'anxiety' vs 'incompleteness' emerged organically during narrative analysis. In addition, we found that some individuals with obsessive-compulsive disorder utilized their behaviors as a way to cope with stress and anxiety more generally. Other participants did not share this experience and denied finding any comfort in their obsessive-compulsive behaviors. The consequences of attentional difficulties were highlighted, with some participants describing how difficulty focusing on a task could influence the need for it to be repeated multiple times. CONCLUSIONS: The extent to which patients use obsessive-compulsive disorder as a coping mechanism is a relevant distinction with potential implications for treatment engagement. Patients may experience ambivalence about suppressing behaviors that they have come to rely upon for management of stress and anxiety, even if these behaviors represent symptoms of a psychiatric illness.

Use of a maze to detect cognitive dysfunction in a porcine model of hypothermic circulatory arrest.

BACKGROUND: Hypothermic circulatory arrest (HCA) can result in cognitive impairment not reflected by histopathology or gross neurologic observation. We tested the sensitivity of two multi-room maze tasks in detecting cerebral dysfunction after HCA in pigs. METHODS: Twenty-seven pigs were studied, divided between two tasks. 13 underwent 90 minutes HCA at 20 degrees C and were trained from postoperative day (POD) 7; 14 were unoperated controls. The maze includes a holding area, 8 rooms, and a center hallway. One piece of apple is placed in each baited room on each of 10 days of learning evaluation. After a pig enters a room, doors to all other rooms close, and the pig must return to the holding area. In task 1, 6 of 8 rooms were baited, and each day's session ended when each baited room had been entered, or after 20 trials. In task 2, initially only the right- or left-sided rooms were baited. Pigs were evaluated each day until they entered 4 baited rooms, or for 15 trials; the process was then repeated, baiting the other side. RESULTS: Intraoperative physiology and postoperative recovery showed no differences between task 1 or 2 pigs. Task 1 did not distinguish between control and HCA groups (p = 0.5), but task 2 revealed significantly (p = 0.04) better learning in controls. CONCLUSIONS: The significantly poorer performance of pigs after HCA suggests that the reversal of baited rooms in task 2 provides the sensitivity to detect cognitive dysfunction. The maze is a promising tool to investigate in pigs the mild cerebral damage often seen after HCA.