Pipamperone/Citalopram (PNB01) Versus Citalopram (CIT) and Versus Pipamperone (PIP) in Major Depressive Disorder (MDD)

Inclusion Criteria:

1. Patient is informed and given ample time and opportunity to think about her/hisparticipation and has given her/his written informed consent.
2. Patient understands the investigational nature of the trial and is willing and able tocomply with the trial requirements.
3. Patient is male or female, aged ≥ 18 years.
4. Patient has MDD according to the DSM IV-R criteria with an existence of depressed mood (DSM-IV-R Crit. A1) and loss of interest/anhedonia (DSM-IV-R Crit. A2) as confirmed bythe MINI, lasting for at least 4 weeks and no longer than 18 months (78 weeks) for thecurrent episode, and causing significant functional impairment (DSM-IV-R MDD C-criterion).
5. CGI-S rating of at least 4 and a minimum MADRS total score of 26 using IVRS ePRO atBaseline.

Exclusion Criteria:

1. Patient is pregnant, nursing, or is a woman of child-bearing potential who is notsurgically sterile, 2 years postmenopausal, or who does not consistently use 2combined effective methods of contraception (including at least 1 barrier method),unless sexually abstinent.
2. Existence of Mood Disorder with psychotic features and/or high suicidality risk, asconfirmed by MINI.
3. Concomitant diagnosis of any additional primary Axis I disorder and presence of any ofthe following co-morbid disorders: (Hypo)manic episode, Panic Disorder (limitedsymptom attacks allowed), Obsessive Compulsive Disorder, Post-traumatic StressDisorder, Alcohol dependence, any other Substance abuse and/or dependence, PsychoticDisorder, Eating Disorder, or General Anxiety Disorder, as confirmed by MINI.
4. Concomitant diagnosis of any primary Axis II disorder.
5. Patient is hospitalized.
6. Patient has a clinically relevant renal dysfunction (e.g. GFR <60mL/min).
7. Patient has hepatic dysfunction (total bilirubin >2.0mg/dL or alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) greater than 2 times the upper limit ofthe reference range).
8. Patient has a malignant neoplastic disease, a documented history of epilepsy (juvenileconvulsions excepted) or a documented, in the opinion of the investigator, clinicallyrelevant risk of bleeding (eg. severe bleeding disorder, treatment with warfarin, …).
9. Patient with a documented history or concomitant diagnosis or significant risk ofcardiac arrhythmia or dysrhythmia, including a QTc interval of ≥500 ms at Baseline.
10. Patient has any other medical or psychiatric condition, which in the opinion of theinvestigator, can jeopardize or would compromise the patient's ability to participatein this trial or that would interfere with trial assessments.
11. Patient with documented alcohol or drug abuse, or having a positive standard screenfor alcohol or drugs (including benzodiazepines and opioids).
12. Patient received, in the past 7 days treatment with any psychoactive drug prior torandomization, including typical and atypical antipsychotics, hypnotics,antidepressants, anxiolytic drugs, anticonvulsive therapy, opioids, monoamine oxidase (MAO) inhibitors, sedative antihistamines, psychostimulants or amphetamines, dopamineD2 receptor antagonists, butyrophenones, metoclopramide, lithium, anticonvulsants,benzodiazepines, or barbiturates. If patient has received such therapy, a washoutperiod of at least 7 days prior to baseline is required before inclusion in this trial (except fluoxetine: 4 weeks, and St John's Wort or MAO inhibitors: within 2 weeks).
13. Concomitant treatment with diuretics, QT prolongation drugs, or dopamine agonists.
14. Resistant depression defined as having failed to respond to either: a/ 2 previousantidepressants at an adequate dose administered for at least 4 weeks during thecurrent episode; b/ augmentation therapy with any atypical antipsychotic drug
15. Electroconvulsive therapy (ECT) or repetitive Transcranial Magnetic Stimulationtherapy (rTMS) within the last 6 months; Vagus Nerve Stimulation (VNS) or Deep BrainStimulation (DBS) ever.
16. Formal psychotherapy or alternative treatment for 1 week prior to or during the study.
17. Patient has participated in another trial of an investigational agent (includingmedical device) within the last 3 months prior to baseline or is currentlyparticipating in another trial of an investigational drug.
18. Known hypersensitivity to any of the study drugs