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.

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.

The purpose of this study was to demonstrate efficacy, safety and clinical benefit of Trazodone Contramid® OAD (Once A Day) in the treatment of Unipolar Major Depressive Disorder (MDD).

This two-arm, multicentre, randomized, placebo-controlled, double-blind, parallel-design study consisted of a baseline phase (screening and wash-out) and a double-blind randomized phase (randomization to Trazodone Contramid® OAD or placebo). The total study duration including wash-out of prohibited medications was approximately 11 weeks; the total duration of the randomized phase was 8 weeks (titration: 2 weeks + treatment: 6 weeks).

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 the Mini-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, must demonstrate MDD as the primary disorder.
• The current episode of MDD should have lasted for a minimum of 1 month, whether the patient 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 at screening and baseline.
• Oral and written language comprehension at a level sufficient to comply with the protocol 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 study participation.

Exclusion Criteria:

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

• Presence of any of the following DSM-IV Axis I disorders: generalized anxiety disorder, panic disorder, social phobia, obsessive-compulsive disorder, post-traumatic stress disorder, eating disorder, bipolar disorder, alcohol/substance abuse or dependence (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 no therapeutic response to two prior courses of at least one month of conventional antidepressant drug treatment in adequate dosages.

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

• Meet criteria for high suicide risk on the MINI suicide scale, or in the opinion of the investigator is inappropriate for the trial due to clinically significant suicidal or 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), laboratory parameters.

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

• Unwilling to discontinue use of prohibited medications for a minimum of 5 drug half-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 3 months 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 treatment with trazodone due to Adverse Events.

• Bowel disease causing malabsorption.

• Serious, unstable illnesses during the 3 months before screening including but not limited to: hepatic, renal, gastroenterologic, respiratory, cardiovascular (including ischemic heart disease), endocrinologic, neurologic, immunologic or hematological disease.

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

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

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

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