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: 1. Male or female, 18 to 65 years of age, inclusive, at screening. 2. 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. 3. 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. 4. 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). 5. A score equal to or greater than 20 on the MADRS items of the BISS. 6. 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). 7. 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. 8. Body mass index between 18-35 kg/m2. 9. 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. 10. 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: 1. Female of childbearing potential who is not willing to use one of the specified forms of birth control during the study. 2. Female that is pregnant or breastfeeding. 3. Female with a positive pregnancy test at screening or baseline. 4. Current diagnosis of a substance use disorder (abuse or dependence, as defined by DSM-5, with the exception of nicotine dependence), at screening or within 6 months prior to screening. 5. Current Axis I disorder, diagnosed at screening with the use of the MINI 7.0.2, that is the primary focus of treatment and BD the secondary focus of treatment for the past 6 months or more. 6. History of schizophrenia or schizoaffective disorders, or any history of psychotic symptoms. 7. History of anorexia nervosa, bulimia nervosa, or eating disorder not otherwise specified, within 5 years of screening. 8. Any Axis I or Axis II Disorder, which at screening is clinically predominant to their BD or has been predominant to their BD at any time within 6 months prior to screening. 9. Has dementia, delirium, amnestic, or any other cognitive disorder. 10. Has a clinically significant abnormality on the screening physical examination that might affect safety, study participation, or confound interpretation of study results according to the study clinician. 11. Participation in any clinical trial with an investigational drug or device within the past month or concurrent to study participation. 12. Current episode of: * Hypertension, Stage 1 as defined by a systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg at screening on two of three measurements at least 15 minutes apart. * Hypertension, Stage 1 as defined by a systolic blood pressure ≥155 mmHg or diastolic blood pressure ≥99 mmHg at the Baseline Visit (Visit 1) within 1.5 hours prior to ketamine infusion on two of three measurements at least 15 minutes apart. * Recent myocardial infarction (within one year) or a history of myocardial infarction. * Syncopal event within the past year. * Congestive heart failure (CHF) New York Heart Association Criteria \>Stage 2 * Angina pectoris. * Heart rate \<50 or \>105 beats per minute at screening or randomization (Baseline Visit). * QTcF (Fridericia-corrected) ≥450 msec at screening or randomization (Baseline Visit). 13. Current history of hypertension, or on antihypertensives for the purpose of lowering blood pressure, with either an increase in antihypertensive dose or increase in the number of antihypertensive drugs used to treat hypertension over the last 2 months. 14. Chronic lung disease excluding asthma. 15. Lifetime history of surgical procedures involving the brain or meninges, encephalitis, meningitis, degenerative central nervous system (CNS) disorder (e.g., Alzheimer's or Parkinson's Disease), epilepsy, mental retardation, or any other disease/procedure/accident/intervention which, according to the screening clinician, is deemed associated with significant injury to or malfunction of the CNS, or history of significant head trauma within the past 2 years. 16. Presents with any of the following lab abnormalities: * Subjects with diabetes mellitus fulfilling any of the following criteria: * Unstable diabetes mellitus defined as glycosylated hemoglobin (HbA1c) \>8.5% at screening. * Admitted to hospital for treatment of diabetes mellitus or diabetes mellitus-related illness in the past 12 weeks. * Not under physician care for diabetes mellitus. * Has not been on the same dose of oral hypoglycemic drug(s) and/or diet for the 4 weeks prior to screening. For thiazolidinediones (glitazones) this period should not be less than 8 weeks. * Any other clinically significant abnormal laboratory result (determined as such by the investigator and medical monitor) at the time of the screening. 17. Any current or past history of any physical condition which in the investigator's opinion might put the subject at risk or interfere with study results interpretation. 18. Positive screening urine test for drugs of abuse at screening: cocaine, amphetamines, barbiturates, opiates. 19. Subjects with exclusionary laboratory values, or requiring treatment with exclusionary concomitant medications as defined in the study manual 20. Subjects on exclusionary concomitant psychotropic medications. 21. Subjects with a lifetime history of illicit PCP/ketamine drug use or previous failed use of ketamine for depression. 22. Liver Function Tests higher than 2.5 times upper limit of normal as defined in the study manual. 23. Known allergies to Lurasidone or Latuda, Cycloserine or Seromycin, Mannitol, Croscarmellose Sodium, Magnesium Stearate, Silicon Dioxide, and/or HPMC (hydroxypropylmethylcellulose) \-