Study In Patients With Depression Not Responding to Selective Serotonin Re-uptake Inhibitors
Condition: Depressive Disorder
MeSH terms: Depression; Depressive Disorder
Intervention: 323U66 (Bupropion Hydrochloride Sustained Release); Placebo
Intervention description: Subjects with Major Depressive Disorder who were randomized to take 100mg of Bupropion SR in the morning and placebo in the evening for one week. Week 2 subjects were given 100mg dose of Bupropion morning and evening. Weeks 3 thru 12 received 150mg dose morning and evening. Week 1=dose level 1, 100 mg. Week 2=dose level 2, 200 mg. Weeks 3 - 12=dose level 3, 300 mg.; Subjects with Major Depressive Disorder who were randomised to placebo to match Bupropion SR during the treatment period.
Intervention MeSH terms: Bupropion
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 325.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: depression; double-blind; placebo-controlled; bupropion hydrochloride; SSRI; comparative study; non-responder

Summary:

      This study is designed to evaluate the efficacy and safety in depressive patients who did not
      respond sufficiently to selective serotonin re-uptake inhibitors (SSRI).
    

Eligibility criteria:

        Inclusion criteria:

          -  [At the start of the pretreatment phase]

          -  Target disease: Patients diagnosed as having the following primary disease on the
             basis of DSM-IV-TR criteria.

          -  Major Depressive Disorder, Single Episode (296.2x) (excluding with psychotic features)

          -  Major Depressive Disorder, Recurrent (296.3x) (excluding with psychotic features)

          -  HAM-D (17 items) total score is >=16.

          -  Patients who have been treated with marketed paroxetine (Paxil®) at 20mg/day to
             40mg/day for 4 weeks and more at the start of the pretreatment phase.

          -  Age: >=18 years old (at the time of informed consent) , <65 years old (at the start of
             treatment phase )

          -  Gender: Male or female.

          -  Inpatients or outpatients: Either

          -  Informed consent: The subject himself/herself must give written informed consent.
             However, if the subject is under 20 at the time of giving consent, both the subject
             himself/herself and his/her legally acceptable representative must give written
             informed consent.

        [At the end of the pretreatment phase]

          1. HAM-D (17 items) total score is ≥14.

          2. Percentage of change from the start of the pretreatment phase in the HAM-D (17 items)
             total score is <50%

        [At the start of the treatment phase]

          1. HAM-D (17 items) total score is ≥14.

          2. Percentage of change from the start of the pretreatment phase in the HAM-D (17 items)
             total score is <50%

        Exclusion Criteria:

        [At the start of the pre-treatment phase]

          -  Patients with a complication of glaucoma

          -  Patients concomitantly using a drug increasing the risk of bleeding and patients with
             bleeding tendency or predisposition to bleeding

          -  Patients with predisposition to seizure (who currently have or have a past history of
             seizure, febrile convulsive seizure in infancy, cerebral tumour, cerebrovascular
             disorder or head injury, who have a family history of idiopathic seizure, patients
             with diabetes who have been treated with oral hypoglycaemics or insulin, or who use
             drugs lowering the threshold of seizure).

          -  Patients who currently have or have a past history of the following disorders:

          -  Anorexia nervosa (DSM-IV-TR 307.1)

          -  Bulimia nervosa (DSM-IV-TR 307.51)

          -  Patients with a history of manic episode

          -  Patients with a past or current DSM- IV-TR diagnosis of schizophrenia or other
             psychotic disorder

          -  Patients with a current DSM-IV-TR Axis II diagnosis (e.g., antisocial or borderline
             personality disorder)

          -  Patients starting psychotherapy (except for supportive psychotherapy not aimed at
             therapeutic efficacy and unlikely to affect efficacy evaluation) and formal cognitive
             behaviour therapy within 5 weeks prior to the start of the pre-treatment phase

          -  Patients with a diagnosis of substance abuse (alcohol or drug) by the DSM-IV-TR
             criteria or with a diagnosis of substance dependence within 1 year prior to the start
             of the pre-treatment phase

          -  Patients who have received electroconvulsive therapy within 17 weeks prior to the
             start of the pre-treatment phase

          -  Patients who have taken MAO inhibitors (selegiline hydrochloride) within 2 weeks prior
             to the start of the pre-treatment phase

          -  Patients who have taken another investigational drug within 12 weeks prior to the
             start of the pre-treatment phase

          -  Female patients who are pregnant, possibly pregnant or are nursing, and those who want
             to become pregnant before 30 days after the last dose of the investigational product

          -  Patients who have attempted suicide within 17 weeks prior to the start of the
             pre-treatment phase, or patients for whom the score of suicide-related item No. 3 of
             HAM-D is >=3, or patients in whom the risk of suicide is judged to be high by the
             investigator (sub-investigator)

          -  Patients in whom the risk of homicide is judged to be high by the investigator
             (sub-investigator)

          -  Patients with a history of hypersensitivity to 323U66 and/or paroxetine

          -  Patients with serious cerebral disease

          -  Patients who have ECG or clinical evidence of any cardiac condition that the
             investigator (sub-investigator) feels may predispose the subject to ischemia or
             arrhythmia

          -  Patients with serious physical symptoms (i.e. cardiac/hepatic/renal disorder,
             hematopoietic disorder) The index of seriousness is Grade 3 of "Criteria for
             classification of seriousness of adverse drug reactions to pharmaceutical products,
             etc." (PAB/PSD No.80 in 1992).

          -  Patients with a history or complication of cancer or malignant tumour.

          -  Patients whose major depressive disorder is due to direct physiological effects of a
             general medical condition (for example, hypothyroidism, Parkinson's disease, chronic
             pain)

          -  Patients with systolic blood pressure of >=160 mmHg or diastolic blood pressure of
             >=100 mmHg

          -  Patients who are inappropriate for participating in the study in the judgement of the
             investigator (sub-investigator)

        [At the start of the treatment phase]

          1. Patients whose compliance of paroxetine during the pretreatment phase is less than
             70%.

          2. Patients who have ECG or clinical evidence of any cardiac condition that the
             investigator (sub-investigator) feels may predispose the subject to ischemia or
             arrhythmia

          3. Patients with systolic blood pressure of >=160 mmHg or diastolic blood pressure of
             >=100 mmHg