Assessing Depression and Mania Symptoms in Ketamine Trials

During the screening patients were rated by the clinician using Montgomery–Åsberg Depression Rating Scale (MADRS) [38 (link)], Young Mania Rating Scale (YMRS) [39 (link)], Columbia–Suicide Severity Rating Scale (C-SSRS) [40 (link)], The Clinician-Administered Dissociative States Scale (CADSS) [5 (link)], Brief Psychiatric Rating Scale (BPRS) [41 (link)] scales. The MADRS is a clinician-assessed measure of depression severity in clinical trials and was developed to provide a measure of depression severity for use in antidepressant response studies. For this purpose, 10 items were selected based on their ability to detect depression change. The YMRS assesses hypomanic/manic symptom severity. It is an 11-item clinician-administered scale, with a total score range of 0 to 60 (≤12 indicates remission, 13–19—minimal symptoms, 20–25—mildly manic, 26–37—moderately manic, and 38–60—severely manic), while the C-SSRS is partially structured clinical history assessing the severity of suicidal thoughts, their intensity, and suicidal behavior. The CADSS was chosen for analysis as it is the most widely used instrument employed in previous mood disorder studies to assess the acute psychoactive effects of ketamine [7 (link)]. The CADSS includes a 19-item scale used to evaluate the patient’s answers (subjective items) and an 8-item scale used by a trained physician to assess the patient’s responses during ketamine intake (objective items). The subjective items include three components: depersonalization, derealization, and amnesia. The BPRS is an 18-item rating scale used to assess a range of psychotic and affective symptoms based on both observation of the subject and the subject’s own self-report. A variant of the BPRS is the four-item BPRS+, which considers the positive symptoms of suspiciousness, hallucinations, unusual thought content, and conceptual disorganization. The BPRS and the BPRS+ are used to assess treatment-emergent psychotic symptoms. In both tests, each symptom is rated on a scale from 0 to 6, where 1 is “not present” and 6 is “extremely severe” (the score of 0 represents a not assessed item). To demonstrate the CADSS and BPRS fluctuations across treatments, CADSS and BPRS scores taken 30 min post drug administration were analyzed.
A subject was defined as a responder at a given time point if the percent improvement from the baseline total MADRS score was at least 50% and the subject did not remit. The patient was defined as a remitter at a given time point if the total MADRS score was ≤10 points [42 (link)]. The final three groups (responders, remitters, and nonremitters) were determined by MADRS score at the follow-up visit, one week after the last ketamine infusion. The study outcome measure is defined per a MADRS score.