Study to Assess Clinical Response of Duloxetine in Patients Hospitalized for Severe Depression
Condition: Depressive Disorder, Major
MeSH terms: Depressive Disorder; Depressive Disorder, Major
Intervention: Duloxetine; Placebo
Intervention description: Capsule; Capsule
Intervention MeSH terms: Duloxetine Hydrochloride
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Enrollment: 339.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      Study to assess efficacy of Duloxetine 120 mg and Duloxetine 60 mg in patients hospitalized
      for severe depression after 4 weeks of treatment. To evaluate the rescue option in
      non-responding patients. Safety of Duloxetine will also be assessed.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Male or female patients of 18 years of age at the screening visit or older

          2. Meet criteria for severe Major Depressive Disorder (MDD)

          3. Montgomery-Asberg-depression rating scale (MADRS) total score ≥ 30 and the 6-item
             Hamilton Depression scale (HAMD-6) score ≥12 at both screening (V1) visit and baseline
             (V2) visits

          4. Clinical Global Impression of Severity (CGI-Severity) score ≥4 at both screening visit
             and baseline visit.

          5. Requirement of hospitalization (not for social or other non-medical reasons) at
             screening visit and at least up to Visit 4

          6. Patient willing and able to comply with the requirement for hospitalization and with
             all scheduled visits, tests and procedures required by the protocol

          7. Have a level of understanding sufficient to provide informed consent and to
             communicate with the investigators and site personnel. Informed consent document must
             be signed at screening visit, in accordance with Good Clinical Practice (GCP) and
             local regulatory requirements, prior to any study procedure

        Exclusion Criteria:

          1. More than two previous episodes of major depression that did not respond to adequate
             doses and duration (minimum of 6 weeks) of two different antidepressant therapies

          2. Lack of response to at least two antidepressant therapies given at adequate doses for
             at least 6 weeks for the current depressive episode

          3. Concurrent presence of symptoms fulfilling criteria for any Axis I disorder other than
             anxiety disorders (with exception of the Obsessive-Compulsive Disorder (OCD)) or Major
             Depressive Disorder, in the investigator's judgment

          4. Any previous diagnosis of a bipolar disorder, schizophrenia or OCD

          5. Depression with catatonic features, depression with post-partum onset, or organic
             mental disorders

          6. The presence of an Axis II disorder

          7. MDD with psychotic features requiring neuroleptic treatment and/or interfering with
             patient's ability to provide informed consent, at investigator's discretion

          8. History of substance abuse or dependence within the past year, excluding nicotine and
             caffeine, but including alcohol or benzodiazepines

          9. Positive urine screen for drug abuse (cannabinoids, cocaine, opiates including
             methadone, or amphetamines) at screening

         10. Epilepsy or a history of seizure disorder or of a treatment with anticonvulsant
             medication for epilepsy or seizures

         11. Patients with acute liver injury (such as hepatitis) or severe cirrhosis (such as
             Child-Pugh Class C)

         12. Known diagnosis of congenital galactosaemia, glucose or galactose malabsorption
             syndrome, or lactose deficiency

         13. Patient with a known diagnosis of raised intraocular pressure, or at known risk of
             acute narrow-angle glaucoma

         14. Serious medical illness or clinically significant laboratory abnormalities that, in
             the judgment of the investigator, are likely to require intervention/exclusion of
             study medication during the course of the study: cardiovascular (e.g. uncontrolled
             hypertension, abnormal initial ECG findings according to investigator judgement),
             respiratory, haematological, hepatic or gastrointestinal

         15. End stage renal disease (estimated creatinine clearance ≤30 mL/min) and undergoing
             dialysis

         16. Abnormal thyroid-stimulating hormone (TSH) concentrations, based on the performing
             laboratory's reference ranges. Patients must be clinically and chemically euthyroid at
             the time of randomization. Patients may be taking thyroid replacement therapy provided
             their dose is stable and their compliance is good for at least three months before the
             screening visit

         17. Pregnancy (to be excluded by urine pregnancy test at screening visit) or
             breast-feeding

         18. Sexually active woman of childbearing potential (i.e. not 6 months post-menopausal, or
             not surgically sterilized) not using a medically approved method of birth control
             (i.e. oral contraceptives, intrauterine device, or double-barrier) for at least one
             month prior to the screening visit and throughout the study

         19. Participation in another clinical trial within 30 days prior to screening visit

         20. Current treatment with Duloxetine for any indication and previous treatment with
             Duloxetine for psychiatric indications

         21. Known hypersensitivity to Duloxetine or any of the inactive ingredients

         22. History of oversensitivity to psychotropic drugs, in the investigator's judgment

         23. Electro-convulsive Therapy (ECT) or Transcranial Magnetic Stimulation (TMS) within one
             year prior to screening visit and during the study

         24. Initiation or discontinuation of depression-oriented psychotherapeutic treatment (e.g.
             behaviour therapy, psychoanalytic therapy, cognitive therapy, etc) within 6 weeks
             prior to screening visit, or planned use of such treatment at any time during the
             study

         25. Treatment with a Monoamine Oxidase Inhibitor (MAOI) within 14 days prior to baseline
             visit or the potential need to use an MAOI during the study or within 5 days after
             discontinuation of duloxetine

         26. Treatment with Fluoxetine within 30 days prior to baseline visit

         27. Treatment with any excluded medication listed in the protocol