Study In Patients With Depression Not Responding to Selective Serotonin Re-uptake Inhibitors

Clinical Evaluation of 323U66 SR in Patients With Depression - Placebo-controlled, Double-blind, Comparative Study in Patients With Depression Who Did Not Respond Sufficiently to Selective Serotonin Re-uptake Inhibitors

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).

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