Patient description: The patient is a 47-year-old Asian woman complaining of persistent feelings of sadness. She lost interest in activities she used to enjoy. She states that her mood is mostly depressed for the past 3 weeks. She also lost her appetite , which led to about 5kg weight loss. She complains of loss of energy and feelings of worthlessness nearly every day. She is not using any drugs and she does not smoke. She doesn't drink alcohol. She used to exercise every day for at least 30 min. But she doesn't have enough energy to do so for the past 3 weeks. She also has some digestive issues recently. She is married and has 4 children. She is menopausal. Her husband was recently diagnosed with colon cancer and he is starting his chemotherapy. There is nothing remarkable in her past medical history and her drug history is only positive for Vit D3 1000 units daily. Her family history is negative for any psychologic problems. Her HAM-D score is 20.

Clinical trial eligibility criteria: eligible ages (years): 18.0-75.0,  Acute Depressive Episode In the opinion of the investigator, the participant is capable of understanding and complying with protocol requirements. 2. The participant or, when applicable, the participant's legally acceptable representative signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures. 3. The participant is a man or woman aged between 18 and 75 years, inclusive. 4. The participant suffers from Bipolar I Disorder, Most Recent Episode Depressed as the primary diagnosis according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) (classification code 296.5x) and confirmed by the Structured Clinical Interview for DSM Disorders (SCID). 5. The reported duration of the current Major Depressive Episode (MDE) is at least four weeks and less than 6 months. 6. The participant has a Young Mania Rating Scale (YMRS) score of ≤10 both at the Screening and Baseline visits. 7. The participant has a Montgomery-Åsberg Depression Rating Scale (MADRS) total score ≥24 at the Screening and Baseline Visits. 8. The participant has a Clinical Global Impression Scale Severity (CGI-S) score of ≥4 at the Screening and Baseline Visits. 9. Hamilton Rating Scale for Anxiety (HAM-A) score is ≤21 at Screening and Baseline visits. 10. The participant has a lithium and/or valproate levels within therapeutic range (0.6 - 1.2 mEq/L for lithium or 50-125 mcg/ml for valproate) at screening. If the patient does not have a lithium and/or valproate level within therapeutic range at screening, they must have a lithium and/or valproate levels within the therapeutic range between Day to Day -30 of screening. 11. A female participant of childbearing potential who is sexually active and agrees to use routinely adequate contraception from signing of informed consent throughout the duration of the study and for 30 days after the last dose. 12. A male participant who is nonsterilized and sexually active with a female partner of childbearing potential agrees to use adequate contraception from signing of informed consent through the duration of the study and for 30 days after the last dose  The participant has received any investigational compound <30 days before Screening or 5 half-lives prior to Screening. 2. The participant has received ramelteon in a previous clinical study or has ever used ramelteon. 3. The participant is an immediate family member, study site employee, or is in a dependent relationship with a study site employee who is involved in conduct of this study (e.g., spouse, parent, child, sibling) or may consent under duress. 4. The participant has one or more of the following Any current psychiatric disorder other than Bipolar I Disorder, Most Recent Episode Depressed as defined in the DSM-IV-TR, as assessed by the SCID Current or history of: schizophrenia, unipolar depression with psychotic features, bipolar depression with psychotic features, any other psychotic disorder (with the exception of psychosis associated with a manic episode), mental retardation, organic mental disorders, or mental disorders due to a general medical condition as defined in the DSM-IV-TR Current diagnosis or history of alcohol or other substance abuse or dependence (excluding nicotine or caffeine) as defined in the DSM-IV-TR that has not been in full and sustained remission for at least one year from the day of screening. (Participant must also have negative urine drug screen prior to Baseline) Presence or history of a clinically significant neurological disorder (including epilepsy) Neurodegenerative disorder (Alzheimer disease, Parkinson disease, multiple sclerosis, Huntington disease, etc) Any Axis II disorder that might compromise the study History of Rapid Cycling Bipolar Disorder: Patients who have more than 8 episodes of mood disorder per year. 5. The participant experienced the first episode of mood disorder after the age of 65 years. 6. The current depressive symptoms of the participant are considered by the investigator to have been resistant to 2 adequate treatment trials with any of the mood stabilizers (specifically started to treat the current depressive episode) and/or antidepressant medications of at least 6 weeks duration each. 7. The participant is on any other psychotropic medications except for lithium (serum levels 0.8 to mEq/L) or valproate (serum levels 50 to 125 mcg/ml) at the Screening visit. 8. The participant is on lithium and/or valproate for less than 30 days prior to screening. 9. If the participant is on antidepressant medications and/or antipsychotic medications (used as a mood stabilizer) and the patient is considered appropriate by the PI, these medications must be washed out for at least 2 weeks prior to the Screening visit. 10. The participant has received electroconvulsive therapy, vagal nerve stimulation, or repetitive transcranial magnetic stimulation within 6 months prior to Screening. 11. The participant has started receiving formal cognitive or behavioral therapy, systematic psychotherapy within 30 days prior to screening or plans to initiate such therapy during the study. 12. The participant has a significant risk of suicide according to the investigator's clinical judgment or has a score ≥ 5 on item 10 (suicidal thoughts) of the MADRS or has made a suicide attempt in the previous 6 months. 13. The participant has taken or is anticipated that the participant will take at least 1 of the disallowed concomitant medications. 14. The participant has a clinically significant unstable illness, for example hepatic impairment or renal insufficiency, or a cardiovascular, pulmonary, gastrointestinal, endocrine, neurological, rheumatologic, immunologic, hematological, infectious, dermatological disorder or metabolic disturbance as determined by Investigator. 15. The participant has a history or current diagnosis of Fibromyalgia, Chronic Fatigue Syndrome, Chronic Pain Syndrome or Sleep apnea. 16. The participant has a previous history of cancer that had been in remission for less than 5 years prior to the first dose of study medication. This criterion does not those participants with basal cell or stage I squamous cell carcinoma of the skin. 17. The participant has 1 or more laboratory value outside the normal range, based on the blood or urine samples taken at the Screening Visit, that are considered by the investigator to be clinically significant; or the participant has any of the following values at the Screening Visit A serum creatinine value >1.5 times the upper limits of normal (xULN) A serum total bilirubin value >1.5 xULN