Ketamine-enhanced prolonged exposure therapy in veterans with PTSD: A randomized controlled trial protocol.

BACKGROUND: The 2023 VA/DoD Clinical Practice Guideline for the Management of PTSD recommends individual, manualized trauma-focused such as Prolonged Exposure (PE) over pharmacologic interventions for the primary treatment of PTSD. Unfortunately, clinical trials of trauma-based therapies in the military and veteran population showed that 30% to 50% of patients did not demonstrate clinically meaningful symptom change. Ketamine, an FDA-approved anesthetic with potent non-competitive glutamatergic N-methyl-d-aspartate antagonistic properties, has demonstrated to enhance the recall of extinction learning and decrease fear renewal without interference of extinction training in preclinical studies. METHODS: We plan to conduct a single site RCT comparing three ketamine treatment vs. active placebo (midazolam) adjunct to PE therapy among Veterans with PTSD. Pharmacological phase will start simultaneously with PE session 1. Infusions will be administered 24 h. prior to PE session for the first 3 weeks. After PE is completed (session 10), patients will be assessed during a 3-month follow-up period at various time points. We estimate that out of 100 veterans, 80 will reach time point for primary outcome measure and will be considered for primary analysis. Secondary outcomes include severity of depression and anxiety scores, safety and tolerability of ketamine-enhanced PE therapy, cognitive performance during treatment and early improvement during PE related to the rate of dropouts during PE therapy. DISCUSSION: Results of the proposed RCT could provide scientific foundation to distinguish the essential components of this approach, enhance the methodology, elucidate the mechanisms involved, and identify sub-PTSD populations that most likely benefit from this intervention.

The effects of outcome expectations and satisfaction on weight loss and maintenance: correlational and experimental analyses--a randomized trial.

This study examines the hypothesis that highly favorable outcome expectations promote weight loss and hinder weight maintenance. To investigate the effects of outcome expectations and satisfaction with treatment outcomes on weight loss, 349 adults were randomly assigned to 1 of 2 weight loss programs that emphasize either (a) an "optimistic" message, focusing exclusively on the positive aspects of weight loss, or (b) a "balanced" message, giving equal time to positive and negative aspects of weight loss. Participants changed their weight loss cognitions in response to the intervention, but there was no significant difference between the intervention treatment groups in short-term or long-term (18-month) weight loss. Independent of treatment message, positive outcome expectations and satisfaction were both associated with weight loss.

The impact of expectations and satisfaction on the initiation and maintenance of smoking cessation: an experimental test.

OBJECTIVE: Our primary objective was to test the thesis that the initiation of behavior change is dependent on favorable expectations, whereas maintaining a change in behavior is dependent on satisfaction with the outcomes afforded by behavior change. These hypotheses were tested in the context of a smoking cessation intervention. DESIGN: Adult smokers were randomized to an 8-week smoking cessation program designed to induce either optimistic or modest expectations about cessation. Participants were encouraged to quit smoking after Week 4 and were followed for 15 months after the end of the program. MAIN PROCESS AND OUTCOME MEASURES: The authors focused on participants' expectations about cessation, satisfaction with cessation, and smoking status. RESULTS: The effect of the expectation manipulation on smokers' beliefs about cessation was moderated by their prior cessation success. Those led to hold favorable expectations about cessation were more likely to initiate cessation. Although satisfaction was not affected by initial expectations, it predicted maintained cessation. CONCLUSIONS: Results highlight the challenge of altering how smokers think about cessation and the need for further research on intervention strategies that target different factors for the initiation and maintenance of cessation.

A satisfaction enhancement intervention for long-term weight loss.

OBJECTIVE: To compare the effects of two satisfaction enhancement interventions for weight control on behavioral and weight changes among individuals in a 15-month weight loss program. The primary hypothesis was that long-term weight loss would be improved by an intervention that enhances perceived satisfaction with achieved outcomes. RESEARCH METHODS AND PROCEDURES: Men and women (331) were randomized to weight control programs comprised of diet and exercise counseling and a cognitive intervention that emphasized either comparing experienced outcomes with expectation of ideal outcomes or comparing experienced outcomes with pretreatment status. The latter was expected to cause greater satisfaction with weight loss progress. RESULTS: The intervention manipulation was not successful in influencing cognitions, satisfaction, or weight change. DISCUSSION: The potential for intervening on satisfaction per se for the purpose of achieving greater or more sustained weight loss remains to be demonstrated.