A Randomized, Double-blind, Two-arm Study Comparing the Efficacy and Safety of Trazodone Contramid® OAD and Placebo in the Treatment of Unipolar Major Depressive Disorder.

Inclusion Criteria:

• Males or females.

• Aged 18 years or older.

• Fulfills Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV)criteria for Unipolar Major Depressive Disorder (MDD) (Axis I) as confirmed by theMini-International Neuropsychiatric Interview (MINI).

• The primary DSM-IV Axis I diagnosis should be MDD (296.22, 296.23, 296.32, 296.33);any subject meeting criteria for another, non excluded Axis I disorder, mustdemonstrate MDD as the primary disorder.

• The current episode of MDD should have lasted for a minimum of 1 month, whether thepatient has been diagnosed with one single or recurrent episodes.

• Presence of dysphoria for most days over the past four weeks.

• Montgomery-Åsberg Depression Rating Scale (MADRS) total score of at least 26 atscreening and baseline.

• Oral and written language comprehension at a level sufficient to comply with theprotocol and to complete study-related materials.

• Sign and date a written Informed Consent Form (ICF) approved by a Research Ethic Board (REB) which has also been signed and dated by the Investigator prior to studyparticipation.

Exclusion Criteria:

• DSM-IV Major Depressive Disorder Specifiers: [a] With Catatonic Features; [b] WithPostpartum Onset; [c] With Seasonal Pattern;

• Presence of any of the following DSM-IV Axis I disorders: generalized anxietydisorder, panic disorder, social phobia, obsessive-compulsive disorder, post-traumaticstress disorder, eating disorder, bipolar disorder, alcohol/substance abuse ordependence (caffeine and nicotine allowed), any psychotic disorder.

• Depression secondary to stroke, cancer or other severe medical illnesses.

• Positive urine drug screen at screening visit.

• History or present condition of any DSM-IV Axis II disorder.

• History of treatment refractory major depressive episodes defined as incomplete or notherapeutic response to two prior courses of at least one month of conventionalantidepressant drug treatment in adequate dosages.

• Currently in psychotherapy (at least one session in the past month with a plan forcontinuing) with a licensed/registered/certified mental health provider, marriagecounselor, or family therapist.

• Meet criteria for high suicide risk on the MINI suicide scale, or in the opinion ofthe investigator is inappropriate for the trial due to clinically significant suicidalor homicidal potential.

• Require hospitalization for treatment of the current episode of depression.

• Uncorrected hypo- or hyperthyroidism.

• A history of seizures other than pediatric febrile seizure.

• A history of cardiac arrythmias requiring therapy.

• A history of myocardial infarction within 1 year before screening.

• Clinically significant abnormal findings of Electrocardiography (ECG), laboratoryparameters.

• Unwilling to discontinue use of any antidepressants, including herbal remedies, for aminimum of 5 drug half-lives prior to screening.

• Unwilling to discontinue use of prohibited medications for a minimum of 5 drughalf-lives prior to screening.

• Treatment within the last 3 weeks with Monoamine Oxidase (MAO) inhibitors.

• Use of the following concomitant treatment during the study:

• medications causing QT prolongation (e.g. amiodarone, droperidol, erythromycin).

• medications causing PR prolongation (e.g. digoxin).

• Anti -psychotics (e.g. haloperidol).

• protease inhibitors such as ritonavir and indinavir.

• Hormonal treatment (e.g. estrogen, oral contraceptives) which has started within 3months of study entry.

• Treatment with another investigational agent within the last 30 days.

• Known and documented allergy to trazodone or any structurally similar drugs.

• Previous failure of treatment with trazodone, or previous discontinuation of treatmentwith trazodone due to Adverse Events.

• Bowel disease causing malabsorption.

• Serious, unstable illnesses during the 3 months before screening including but notlimited to: hepatic, renal, gastroenterologic, respiratory, cardiovascular (includingischemic heart disease), endocrinologic, neurologic, immunologic or hematologicaldisease.

• Pregnant or lactating, or is of childbearing potential and not willing to use anapproved method of contraception.

• Significant liver disease, defined as active hepatitis or elevated liver enzymes >3times the upper boundary of the normal range.

• Significant renal disease, defined as Blood Urea Nitrogen (BUN) and/or creatinine >3times the upper boundary of the normal range clearance.

• Any other condition that, in the opinion of the investigators, would adversely affectthe patient's ability to complete the study or its measures.