Safety and Efficacy Study Comparing ETS6103 With Amitriptyline in the Treatment of Major Depressive Disorder (MDD)

Inclusion Criteria: * Signed informed consent * Male or female * Age 18-65 years inclusive * Subjects with a current episode of moderate to severe Major Depressive Disorder meeting the criteria of Diagnostic and Statistical Manual of Mental Disorders (DSM) IV -TR and documented using the brief structured interview Mini International Neuropsychiatric Interview (MINI) version 5.0 and with a minimum duration of two weeks and a maximum of twelve months * Minimum Hamilton Depression Scale (HAM-D) 17 items total score of 18 at screening and ≥12 at the end of the lead-in phase prior to randomization. * Female subjects of childbearing potential must have a negative pregnancy test at the Screening Visit and must use an acceptable method of contraception throughout the study and for 30 days after. Male subjects with female partners of child-bearing potential must use an acceptable method of contraception throughout the study and for 30 days after. * Able to understand and comply with the requirements of the study as judged by the investigator Exclusion Criteria: * Considered by the investigator to be at significant risk of suicide or scoring 5 or more on the Montgomery Asberg Depression Rating Scale (c) question 10 * Significant other psychiatric illness which would interfere with trial assessments co-morbid generalized anxiety disorder (GAD) and panic disorder will be permitted where MDD is considered the primary diagnosis * Significant physical illness which would interfere with trial assessments * Recent (within 1 week of screening) antidepressants (except for fluoxetine \[within 4 weeks of screening\] and St John's Wort or Monoamine oxidase inhibitors (MAOI) \[within 14 days of screening\]), * Benzodiazepine or any other psychotropic medication including lithium or other mood stabilizers within 1 week of screening * Oral anticoagulant therapy within one month of screening * Formal psychotherapy or alternative treatments for one week prior to screening or during the study * Reduced hepatic function defined as liver enzyme levels ≥2.5 times upper limit of normal * Renal insufficiency defined as creatinine clearance \<30 mL/min * Epilepsy * Uncontrolled hypothyroidism * Uncontrolled hypertension * Acute porphyria * Urinary retention, prostatic hypertrophy, narrow angle glaucoma or increased intraocular pressure or any other clinically relevant contraindication stated in the Summary of Product Characteristics (SmPC) for citalopram, tramadol or amitriptyline * History of significant cardiac dysrhythmia or history of myocardial infarction within 1 year prior to screening * Significant history of alcohol or substance abuse * Regular alcohol intake above the recommended United Kingdom (UK) guideline of 4 units per day for males or 3 units per day for females * Pregnant or lactating women * Known hepatitis B or C or human immunodeficiency virus (HIV) or syphilis seropositivity. * A corrected QT interval of \>470ms for female subjects of \>450ms for male subjects, calculated using the QTcB (Bazett Correction Formula) , or second degree or higher heart block on an electrocardiography (ECG) recording, at screening. * Allergy to the study drugs or excipients * Treatment with another investigational medicinal product within the 30 days prior to screening.