Conditions: Major Depressive Disorder Treatment Resistant Depression
Keywords: Depression MDD TRD
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 688
Healthy volunteers: no

Brief summary:
The primary objective of the study is to evaluate the efficacy of Quetiapine extended release (XR) in combination with an selective serotonin reuptake inhibitor (SSRI) or Venlafaxine versus Lithium in combination with an selective serotonin reuptake inhibitor or Venlafaxine versus Quetiapine extended release monotherapy in subjects with treatment resistant depression as assessed by the changes from randomisation to week 6 in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score. As an independent objective, the primary objective will also be evaluated in two subgroups of patients: (1) patients who were resistant to two previous antidepressant therapies and (2) in the subgroup of patients with one previous failure.

Detailed description:
The secondary objectives of the study are to compare the effects of the three different treatment regimen as assessed by the following variables and, if applicable, by their changes from randomisation to week 6 (end of study). Additionally the time of onset of therapeutic effect will be assessed by evaluating efficacy data after the first four days (Day 4) of treatment as well as after the first week of treatment (Day 8). These analyses will also be performed in the subgroups of patients with 2 failed previous antidepressants and patients with 1 failure.

Arms:
arm 1: Selective serotonin reuptake inhibitors (SSRI) or Venlafaxine from previous therapy + add-on treatment with quetiapine XR, 300mg tablet once daily (od).

From previous anti-depressant treatment 64% of the patients had SSRI and 35% had Venlafaxine at baseline. arm 2: Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with lithium, approximately 900mg tablet once daily (od).

From previous anti-depressant treatment 67% of the patients had SSRI and 33% had Venlafaxine at baseline. arm 3: Switch from previous treatment with SSRI or venlafaxine to quetiapine XR monotherapy, 300mg tablet once daily (od)

Interventions: intervention 1: Quetiapine XR intervention 2: Lithium carbonate intervention 3: SSRI/Venlafaxine
Intervention descriptions: intervention 1: 300 mg once daily (od) intervention 2: 900 mg once daily (od) intervention 3: SSRI - doses within label, Venlafaxine dose up to 225 mg/day

Protocol document: