Patient description: A 46-year-old Asian woman with MDD complains of persistent feelings of sadness and loss of interest in daily activities. She states that her mood is still depressed most of the days. She complains of loss of energy and feelings of worthlessness nearly every day. She is on anti-depressants for the past 6 months, but the symptoms are still present. She does not drink alcohol or smoke. 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 diagnosed with colon cancer a year ago and is undergoing chemotherapy. Her past medical history is unremarkable. Her family history is negative for any psychologic problems. Her HAM-D score is 20.

Clinical trial eligibility criteria: eligible ages (years): 18.0-65.0,  Major Depressive Disorder (MDD) Patient Population: Males and females with a diagnosis of major depressive disorder 1. Signed an Institutional Review Board (IRB) approved informed consent document indicating that they understand the purpose of and procedures required by the study and are willing to participate in the study and comply with all study procedures and restrictions. Informed consent must be obtained from the patient and/or a designated representative prior to initiating screening procedures to evaluate of the study. 2. Males and females aged 18 and 65 years inclusive. 3. Meet DSM-V R for major depression, single episode or recurrent episode, with or without melancholia and without psychotic features (296.21, 296.22, 296.23, 296.31, 296.32, or 296.33). 4. Had a total score of > 18 on the HAM-D (17-item version), and a score of > 2 on the depressed mood item of the HAM-D at the screening visit and at the baseline visit. 5. Patients who are currently not on any antidepressants or, Patients on antidepressants and agree to the appropriate washout period (certain antidepressants with prolonged effects (e.g., fluoxetine) may need longer than 2 weeks post-discontinuation to obtain relatively uncontaminated baseline evaluation). 6. Agreed not to start psychotherapy or behavior therapy during the trial. Patients currently on these types of therapy for at least 3 months are eligible for the study and could continue to receive therapy during the trial  Women who are pregnant, or lactating; or taking a low-estrogen "mini-pill" contraceptive. 2. Individuals who are currently taking either study medication (pramipexole and/or ondansetron). 3. Renal and hepatic dysfunction with Total Bilirubin: >1.5 x UNL AST: >2.5 x UNL ALT: >2.5 x UNL Serum Creatinine: >1.5 x UNL Creatinine Clearance: <30 mL/min (calculated by Cockcroft and Gault equation) 4. Hypersensitivity to any component of either study medication. 5. Lifetime history of hypomania/mania, psychotic disorder, dementia and borderline or antisocial personality disorders. 6. History of a serious suicidal attempt in the past 12 months; presence of serious suicidal tendencies/potential; modified C-SSRS >4. 7. Positive urine screen for benzodiazepines, cocaine/cocaine metabolites, cannabinoids, amphetamines, barbiturates, and opiates or history of moderate or severe substance dependence (drugs or alcohol, DSM-V-R criteria) within the past 6 months of the screening visit. 8. Non-responders to at least two trials of antidepressant treatment in the past. (Therapeutic dose for at least 6 weeks) 9. Patients currently taking or have taken the following medications within the past 6 months Centrally acting dopamine antagonists MAOI 10. Patients considered unlikely to co-operate in the study, and/or poor compliance anticipated by the investigator. 11. Patients who have clinical significant hypotension or any clinical significant ECG abnormality at screening. 12. Any other clinically relevant acute or chronic diseases which could interfere with patients' safety during the trial, or expose them to undue risk, or which could interfere with study objectives. 13. Patients who have participated in another clinical trial with an investigational drug within previous 30 days or 5 half-lives whichever is longer