Inclusion Criteria:
\- Patient Population: Males and females with a diagnosis of major depressive disorder
Inclusion Criteria:
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 eligibility of the study.
2. Males and females aged 18 and 65 years inclusive.
3. Meet DSM-V R criteria 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.
Exclusion Criteria:
1. 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.
