Patients will be classified into 3 levels by their past therapeutic histories:
Level 1: Patients who do not receive an appropriate treatment for their current major depressive episode.
Level 2: Patients who never showed a satisfactory response to an adequate dosage of Paroxetine during a sufficient period of their current major depressive episode.
Level 3: Patients without a satisfactory response to two or more antidepressants including one of Paroxetine or Escitalopram for a sufficient period.
A satisfactory response means baseline HAM-D17 score was reduced over 50% or HAM-D17 score 10 or below and a sufficient period means 6 weeks.
Patients will be randomly assigned to the following treatment groups. Patients in level 1 will be randomly assigned to treatment groups among Paroxetine monotherapy, Escitalopram monotherapy, or Venlafaxine monotherapy.
Patients in level 2 will be enrolled who were medicated Paroxetine monotherapy in level 1 and assigned to one of the following 4 groups; Escitalopram monotherapy, Venlafaxine monotherapy, Paroxetine combined with Venlafaxine, or Paroxetine augmented with Lithium.
Patients in level 3 will be randomly assigned to one of the following 4 groups: 1) Either Paroxetine combined with Lamotrigine or Paroxetine combined with Bupropion if they resist two antidepressants including Paroxetine. 2) Either Escitalopram combined with Mirtazapine or Escitalopram combined with Aripiprazole if they resist two antidepressants including Escitalopram. 3) Patients who does not respond to both Paroxetine and Escitalopram will be randomly assigned to either 1) or 2).
