Severe depressive episode with psychotic symptoms
Conditions
Interventions
The study was designed to include 30 participants, 15 in each intervention group. In a crossover design, patients will be randomized between the intervention and placebo groups using an electronic ran
Sponsors
Universidade Federal da Bahia
Hospital Universitário Professor Edgard Santos
Eligibility
Age
18 Years to 65 Years
Inclusion criteria
Inclusion criteria: Patient aged between 18 and 65 years, diagnosed with unipolar depression with psychotic symptoms, according to clinical evaluation and diagnostic criteria for unipolar depression of the Diagnostic and Statistical Manual of Mental Disorders 5th Edition (DSM-5), evaluated using MINI 7.0.2 (The Mini International Neuropsychiatric Interview), with a score of 20 or more on the MADRS scale at baseline; The assessment of psychotic symptomatology will be performed using item 15 of the BPRS, including patients with scores greater than or equal to 3 (i.e., without belief change after reality testing); The duration of the current depressive episode must be at least 4 weeks.
Exclusion criteria
Exclusion criteria: Patients diagnosed with primary psychotic disorders - such as schizophrenia, schizoaffective disorder, brief psychotic disorder - will be excluded, as well as patients with bipolar affective disorder, current substance use disorder according to DSM-5 criteria; patients in a state of mutism or catatonic stupor; patients with dementia or intellectual disability; pregnant or lactating patients; patients with uncompensated general medical conditions or general medical conditions whose psychotic and/or depressive symptoms may be a direct manifestation; and first-degree family members of investigators. Furthermore, patients with depressive symptoms attributed mostly to other psychiatric diagnoses other than MDD will be excluded, as in the case of patients with severe personality disorders; Patients undergoing treatment with electroconvulsive therapy (ECT) in the current episode will also be excluded; Hypertensive patients who are decompensated and refractory to antihypertensive measures at pre-infusion times will be excluded.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To compare the change in depressive symptoms between the intervention (esketamine) and placebo (midazolam) groups based on the reduction in Montgomery-Asberg Depression Rating Scale (MADRS) scores 24 hours after the last infusion, compared to pre-infusion scores ( baseline). A linear mixed-effects model will be used to examine differences between treatment groups between baseline and 24h after the last infusion. Such a model will have as independent variables the period levels (beginning and end). Restricted maximum likelihood estimation will be used to analyze any incomplete data. Significant effects will be examined with simple effects tests. Significance is assessed at p < 0.05 (two-tailed). | — |
Secondary
| Measure | Time frame |
|---|---|
| Evaluate the change in MADRS scores pre- and post-infusion at the other evaluation times: 24 hours after the first infusion and 7 days after the last infusion. The same statistical model described for the primary outcome will be adopted in this case;;Assess the proportion of patients achieving therapeutic response criteria (reduction of at least 50% in MADRS scale scores) and remission (MADRS score less than or equal to 10) within the intervention and control groups 24 hours after the first and last infusions and 7 days after the last infusion. The proportion of respondents in each period will be evaluated using a simple logistic regression model with binomial distribution, with period and drug as interacting predictors.;Evaluate possible changes in psychotic symptoms in the study population, evaluating the pre- and post-infusion scores of the Brief Psychiatric Rating Scale (BPRS). For this, the same statistical model described for the primary outcome will be adopted;;Verify the safety of the intervention both in the intervention group and in the placebo group using the Clinician Administrated Dissociative States Scale (CADSS), administered during and after the infusions;;Evaluate possible associations between clinical characteristics of patients and the propensity to present worsening of psychotic symptoms during the treatment protocol or dissociative episodes during treatment. For this, simple linear regression models with binomial distribution will be used, adopting different clinical characteristics as possible predictors of BPRS and CADSS scores, respectively;;Evaluate the cognitive effects of esketamine administration through neuropsychological assessments before and after the protocol, using the same model as the primary outcome;;Measure levels of cytokines (IL-1B, IL-6), C-reactive protein (CRP) and brain-derived neurotrophic factor (BDNF) and their correlation with depressive symptoms at baseline in this population. Pearson's correlation analysis will be us | — |
Countries
Brazil
Contacts
Public ContactLucas Quarantini
Hospital Universitário Professor Edgard Santos
Outcome results
None listed