Efficacy and Safety of Ramelteon Sublingual in Adult Patients With Acute Depressive Episodes Associated With Bipolar I Disorder

Q-LES-Q -SF is a self-administered, 16-item questionnaire to assess the degree of enjoyment and satisfaction experienced by participants in various areas of daily functioning, such as social relationships, living/housing, physical health, medication, and global satisfaction. The questionnaire consists of 16 items rated by the participants on a 5-point scale. Of these, 14 items are summed to produce a total quality of life score with a maximum of 70 points. In addition, there are two global items that are scored individually. These items rate satisfaction with study medication and overall life satisfaction. The questionnaire is usually scored as a percent of total possible score, with higher scores indicating better health status. A positive change from Baseline indicates improvement. A MMRM model was used for analysis with baseline*week, pooled center, week, treatment, baseline, and week*treatment as factors in the analysis.

MADRS is a 10-item clinician rated scale to measure overall severity of depressive symptoms (i.e., apparent sadness, reported sadness, inner tension, etc.) rated on a 7-point Likert scale from 0 (normal) to 6 (most abnormal) with a total score range from 0 to 60. Higher scores indicate greater severity of symptoms.

The YMRS total score at week 6 relative to baseline. YMRS is a four item scale to assess manic symptoms, rated on a scale from 0 (symptom not present) to 8 (symptom extremely severe), with 7 items rated on a scale from 0 (symptom not present) to 4 (symptom extremely severe) with higher scores reflecting greater levels of mania. The YMRS total score is calculated as the sum of the 11 individual item scores and ranges from 0-60. Higher scores indicate greater severity of symptoms. A negative change from Baseline indicates improvement. A MMRM model was used for analyses with baseline*week, pooled center, week, treatment, baseline, and week*treatment as factors in the analysis.

The CGI-I assesses the clinician's impression of the participant's state of mental illness improvement and consists of one question for the investigator: "Compared to his condition at the start of the study, how much has this patient changed?" which is rated on a seven-point scale (1=very much improved; 2=much improved; 3=minimally improved; 4=no change relative to baseline; 5=minimally worse; 6= much worse; 7=very much worse). Higher scores indicate greater severity of illness. A MMRM model was used for analysis with baseline*week, pooled center, week, treatment, baseline, and week*treatment as factors in the analysis.

The CGI-S at week 6 relative to Baseline. The CGI-S assesses the clinician's impression of the participant's current state of mental illness and consists of one question for the investigator: "Considering your total clinical experience with this particular population, how mentally ill is the patient at this time?" which is rated on a seven-point scale (1=normal, not ill at all; 2=borderline mentally ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill). Higher scores indicate greater severity of illness. A MMRM model was used for analysis with baseline*week, pooled center, week, treatment, baseline, and week*treatment as factors in the analysis.

MADRS is a 10-item clinician rated scale to measure overall severity of depressive symptoms (i.e., apparent sadness, reported sadness, inner tension, etc.) rated on a 7-point Likert scale from 0 (normal) to 6 (most abnormal) with a total score range from 0 to 60. Higher scores indicate greater severity of symptoms.

The 16 item QIDS-SR16 version is designed to assess the severity of depressive symptoms. The QIDS-SR16 assesses all the criterion symptom domains designated by the American Psychiatry Association Diagnostic and Statistical Manual of Mental Disorders - 4th edition, DSM-IV, to diagnose a major depressive episode. QIDS-SR16 assessment has been used to screen for depression and also to measure symptom severity. This scale is also used to distinguish response from remission, as well as to quantify between group treatments effects in open label and randomized controlled trials. The patient is asked to rate the severity and frequency of specific symptoms present over the last 7 days. The QIDS-SR16 total scores range from 0 to 27. Higher scores indicate greater severity of impairment. A negative change from Baseline indicates improvement. A MMRM model was used for analysis with baseline*week, pooled center, week, treatment, baseline, and week*treatment as factors in the analysis.

The SDS comprises patient-rated items designed to measure the extent to which the subject's life is impaired by panic, anxiety, phobic, or depressive symptoms. The participant rates the extent to which his or her (1) work, (2) social life or leisure activities, and (3) home life or family responsibilities, are impaired by his or her symptoms on 10-point visual analogue scales from 0 (not at all) to 10 (extremely) with a total score range from 0 to 30. Higher scores indicate greater severity of impairment. There are verbal descriptors for the points on the scales as well as numerical scores that provide more precise levels of the verbal descriptors. In addition, the SDS addresses the number of days lost and the number of days under-productive due to the symptoms. A negative change from Baseline indicates improvement. A MMRM model was used for analysis with baseline*week, pooled center, week, treatment, baseline, and week*treatment as factors in the analysis.