Sequential Therapy for the Treatment of Severe Bipolar Depression.

Inclusion Criteria:A subject will be eligible for inclusion in this study only if all of the following criteria apply:

• Male or female, 18 to 65 years of age, inclusive, at screening.
• Able to read, understand, and provide written, dated informed consent prior to screening. Participants will be deemed likely to comply with study protocol and communicate with study personnel about AEs and other clinically important information.
• Diagnosed with Bipolar Disorder (BD) according to the criteria defined in the DSM-5. The diagnosis of BD will be made by a site psychiatrist and supported by the MINI 7.0.2. The diagnosis will be confirmed by remote, independent raters, via teleconference between the screen visit and the baseline visit.
• Suicidal ideation or behavior of sufficient severity to meet the requirements for a score of 4, or 5 on the C-SSRS (suicide attempt, interrupted attempt, aborted attempt, preparatory actions toward imminent suicidal behaviors, active method, intent +/- plan).
• A score equal to or greater than 20 on the MADRS items of the BISS.
• In good general health, in the opinion of the investigator, as ascertained by medical history, physical examination (PE) (including measurement of seated vital signs), clinical laboratory evaluations, and electrocardiogram (ECG).
• If female, a status of non-childbearing potential or use of an acceptable form of birth control per the following specific criteria:

a. Non-childbearing potential (e.g., physiologically incapable of becoming pregnant, i.e., permanently sterilized [status post hysterectomy, bilateral tubal ligation], or is post-menopausal with her last menses at least one year prior to screening); or

• Childbearing potential, and meets the following criteria:
• Childbearing potential, including women using any form of hormonal birth control, on hormone replacement therapy started prior to 12 months of amenorrhea, using an intrauterine device (IUD), having a monogamous relationship with a partner who has had a vasectomy, or is sexually abstinent.
• Negative urinary pregnancy test at screening, confirmed by a negative urinary pregnancy test at randomization prior to receiving study treatment.
• Willing and able to continuously use one of the following methods of birth control during the course of the study, defined as those which result in a low failure rate (i.e., less than 1% per year) when used consistently and correctly: implants, injectable or patch hormonal contraception, oral contraceptives, IUD, double-barrier contraception, sexual abstinence. The form of birth control will be documented at screening and baseline.
• Body mass index between 18-35 kg/m2.
• Concurrent psychotherapy will be allowed if the type (e.g., supportive, cognitive behavioral, insight-oriented) and frequency (e.g., weekly or monthly) of the therapy has been stable for at least three months prior to screening and if the type and frequency of the therapy is expected to remain stable during the course of the subject's participation in the study.
• Concurrent hypnotic therapy (e.g., with zolpidem, zaleplon, melatonin, benzodiazepines or trazodone) will be allowed if the therapy has been stable for at least 4 weeks prior to screening and if it is expected to remain stable during the course of the subject's participation in the study. Subjects can also continue treatment with benzodiazepines used for sleep or anxiety if therapy has been stable for at least 4 weeks prior to screening and if it is expected to remain stable during the course of the subject's participation in the study.

Exclusion Criteria

A subject will not be eligible for inclusion in this study if any of the following criteria apply:

• Female of childbearing potential who is not willing to use one of the specified forms of birth control during the study.
• Female that is pregnant or breastfeeding.
• Female with a positive pregnancy test at screening or baseline.
• Current diagnosis of a substance use disorde