obsessive-compulsive disorder
Conditions
Interventions
In a crossover design, all participants will receive an infusion of 0.045mg/kg midazolam (active placebo) and another infusion of 0.5mg/kg esketamine, with an interval of two weeks between procedures.
Dakwar, 2020
Rothberg, 2020), with data in the literature proving the safety of its use in OCD patients (Bloch 2012, Rodriguez 2017).
The sample size cannot be estima
Sponsors
Hospital Universitário Professor Edgard Santos
Universidade Federal da Bahia
Eligibility
Age
18 Years to 65 Years
Inclusion criteria
Inclusion criteria: Female or male subjects, 18 to 65 years of age; Each participant must have a sufficient level of understanding to understand all procedures and the informed consent form; Participants must complete for Obsessive-Compulsive Disorder in accordance with the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders, for at least one year, as assessed by a structured diagnostic interview, The Mini International Neuropsychiatric Interview, version 7.0.2, with a Yale-Brown Obsessive-Compulsive Scale score of at least 16 points ;Treatment resistance defined as at least one prior attempt at an adequate dose and duration of a serotonin reuptake inhibitor or clomipramine and/or cognitive behavioral therapy with exposure and response prevention or having refused these treatments for individual reasons;Individuals should not have changes in the dosage of selective serotonin reuptake inhibitors or clomipramine by pe least two months before enrollment in the study
Exclusion criteria
Exclusion criteria: Patients with severe depression defined by a Montgomery-Asberg Depression Rating Scale score greater than or equal to 34; Patients with imminent risk of suicide defined by a score greater than or equal to 4 on item 10 (suicidal thoughts) of the Montgomery-Asberg Depression Rating Scale; Use of other glutamate modulating agents; Current or past diagnosis of any psychotic disorder as defined in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders; Patients with a history of bipolar disorder as defined in the DSM-5; Individuals with a history of substance use disorder (except nicotine or caffeine) within the last 3 months according to the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders; Participants who are pregnant or breastfeeding; Serious and unstable medical illnesses; History of seizures without a clear and resolved etiology; Treatment with a monoamine oxidase inhibitor within 4 weeks prior to the study; Treatment with any other concomitant medication that may interfere with the evaluation of the results and/or safety of the participant; Presence of any medical disease that may alter the morphology and/or physiology of the brain; Investigators or their immediate family members; Patients who have started cognitive behavioral therapy with exposure and response prevention in the last 8 weeks prior to study enrollment; Patients who, after randomization, need to change the standard treatment by withdrawing or adding new drugs to their treatment regimen for Obsessive Compulsive Disorder should be excluded from the study to minimize potential biases caused by differences between groups
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To compare of obsessive-compulsive symptoms between the control group and the placebo group from the reduction in the Yale-Brown Obsessive-Compulsive Scale score 24h after the infusion, compared to the score before each procedure. It is expected to find a significant reduction, i.e. greater than or equal to 35% in the total score on the Yale-Brown Obsessive-Compulsive Scale. A mixed linear fixed effects model will be used to examine the differences between esketamine and midazolam treatment. A composite symmetry covariance structure appears to be the best fit to the data. The constrained maximum likelihood estimate will be used to analyze incomplete data. Significant effects will be examined with simple effects tests. Significance is assessed at P < 0.05, two-tailed. | — |
Secondary
| Measure | Time frame |
|---|---|
| To assess the change in the Yale-Brown Obsessive-Compulsive Scale total score before each infusion to 7 and 14 days after the procedure between the placebo group and the control group. We will use the same method described for the primary outcome; ;To assess the proportion of responders (participants who achieved a reduction of at least 35% of symptoms by the Yale-Brown Obsessive-Compulsive Scale) of the placebo group and the control group after 24h, 7 and 14 days after each infusion. To assess the proportion of individuals who respond or remit at each point, a McNemar test will be used at each point for the participants and the results will be Bonferroni corrected for the number of points examined. Wilcoxon Rank Sum test will be used to compare severity of obsessive-compulsive symptoms, severity of depressive symptoms (if any) and percentage of cumulative reduction of obsessive-compulsive symptoms compared to percentage of reduction of depressive symptoms;;To assess changes from baseline scores for 24h, 7, and 14 days after each infusion in the placebo and control groups on the Clinical Global Impression for Severity and Improvement and the Montgomery-Asberg Depression Rating Scale. We will use the same method described for the primary outcome;;To verify the safety of the intervention both in the placebo group and in the control group through the instruments Clinician Administrated Dissociative States Scale, Brief Psychiatric Assessment Scale and Young Mania Scale;;To evaluate clinical and biological markers (peripheral biomarkers such as BDNF, IL-1, IK6, TNF-alpha, IFN, microRNAs and serum esketamine level) and their correspondence with therapeutic response. We will use t-tests to assess differences in the dosages of these markers at different collection periods and between treatment groups. Pearson's correlation analysis will be used to determine the relationship between Yale-Brown Obsessive-Compulsive Scale scores and serum marker levels. Finally, a linear regre | — |
Countries
Brazil
Contacts
Public ContactLucas Quarantini
Hospital Universitário Professor Edgard Santos
Outcome results
None listed