Clinical trial NCT00789854: Comparing Quetiapine XR Monotherapy and Augmentation With Lithium Augmentation in TRD Patients
Official title: A Randomised, 6-week, Multicentre, Open-label, Rater-blinded Parallel Group Study Comparing Quetiapine Extended Release Monotherapy and Augmentation With Lithium Augmentation in Patients With Treatment Resistant Depression
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Major Depressive Disorder
Treatment Resistant Depression
Keywords: Depression
MDD
TRD
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2008-11-13
Enrollment: 688
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

* Documented clinical diagnosis as confirmed by the M.I.N.I. meeting criteria from the Diagnostic and Statistical Manual of Mental disorders, 4th Edition (DSM-IV) for any of the following:296.2x MDD, Single Episode296.3x MDD, Recurrent Episode
* Current episode of depression present, at least 42 days prior to enrolment but not more than 18 months
* MADRS-Score ≥ 25 at enrolment and randomisation

Exclusion Criteria:

* Patients with a DSM-IV Axis I disorder other than MDD within 6 months of randomisation
* Patients with a diagnosis of DSM-IV Axis II disorder which has a major impact on the patient's current psychiatric status
* Patients who, in the investigator's judgment pose a current serious suicidal or homicidal risk, or have made a suicide attempt within the past 6 months

Primary outcomes:
measure: Change in Depressive Symptoms Between Randomisation and Week 6 Measured by Change in Montgomery Asberg Depression Rating Scale (MADRS) Total Score (Per Protocol Analysis Set)
timeFrame: 6 weeks treatment
measure: Change in Depressive Symptoms Between Randomisation and Week 6 Measured by Change in Montgomery Asberg Depression Rating Scale (MADRS) Total Score (Modified Intention to Treat Analysis Set)
timeFrame: 6 weeks of treatment
Secondary outcomes:
measure: Depression Remission; Montgomery-Asberg Depression Rating Scale MADRS ≤10, All Patients
timeFrame: 6 weeks of treatment
measure: Depression Remission; Montgomery-Asberg Depression Rating Scale (MADRS) ≤10, Patients With One Previous Treatment Failure
timeFrame: 6 weeks of treatment
measure: Depression Remission; Montgomery-Asberg Depression Rating Scale (MADRS) ≤10, Patients With Two Previous Treatment Failure
timeFrame: 6 weeks of treatment
measure: Depression Remission; Montgomery-Asberg Depression Rating Scale (MADRS) ≤8
timeFrame: 6 weeks of treatment
measure: Depression Remission; Montgomery-Asberg Depression Rating Scale (MADRS) ≤12
timeFrame: 6 weeks of treatment
measure: Response Rate; Montgomery-Asberg Depression Rating Scale (MADRS) Score Reduced ≥ 50%, All Patients
timeFrame: 6 week of treatments
measure: Response Rate; Montgomery-Asberg Depression Rating Scale (MADRS) Score Reduced ≥ 50%, Patients With One Previous Treatment Failure
timeFrame: 6 weeks of treatment
measure: Response Rate; Montgomery-Asberg Depression Rating Scale (MADRS) Score Reduced ≥ 50%, Patients With Two Previous Treatment Failure
timeFrame: 6 weeks of treatment
measure: Responder: Clinical Global Impression Improvement (CGI-I) Item 2, All Patients
timeFrame: 6 weeks of treatment
measure: Responder: Clinical Global Impression Improvement (CGI)-I Item 2, Patients With One Previous Treatment Failure
timeFrame: 6 weeks of treatment
measure: Responder: Clinical Global Impression Improvement (CGI-I) Item 2, Patients With Two Previous Treatment Failure
timeFrame: 6 weeks of treatment
measure: Change in Clinical Global Impression Scale (CGI-S), All Patients
timeFrame: 6 weeks of treatment
measure: Change in Clinical Global Impression Scale (CGI-S), Patients With One Previous Treatment Failure
timeFrame: 6 weeks of treatment
measure: Change in Clinical Global Impression Scale (CGI-S), Patients With Two Previous Treatment Failure
timeFrame: 6 weeks of treatment
measure: Change in Beck Depression Inventory (BDI)
timeFrame: 6 weeks of treatment
measure: Change in Pain, Measured by Visual Analog Scale (VAS)
timeFrame: 6 weeks of treatment
measure: Change in Anxiety Measured by Visual Analog Scale (VAS)
timeFrame: 6 weeks of treatment
measure: Change in Anxiety Measured by State-Trait Anxiety Inventory (STAI), State Anxiety Inventory
timeFrame: 6 weeks of treatment
measure: Change in Anxiety Measured by STAI, Trait Anxiety Inventory
timeFrame: 6 weeks of treatment
measure: Change in Sleep Quality Measured by Montgomery Asberg Depression Rating Scale (MADRS), Item 4
timeFrame: 6 weeks of treatment
measure: Change in Sleep Quality Measured by Pittsburgh Sleep Quality Index (PSQI)
timeFrame: 6 weeks of treatment
measure: Change in Quality of Life Measured by Short-form Health Survey (SF-36), Mental Component
timeFrame: 6 weeks of treatment
measure: Change in Quality of Life Measured by Short-form Health Survey (SF-36), Physical Component
timeFrame: 6 weeks of treatment
measure: Change in Quality of Life Measured by Health Questionnaire EQ-5D as Utility
timeFrame: 6 weeks of treatment
measure: Change in Work Productivity and Activity Impairment: General Health (WPAI:GH)
timeFrame: 6 weeks of treatment
measure: Change in Clinical Global Impression (CGI) Item 4 Efficacy and Safety Combined, All Patients
timeFrame: 6 weeks of treatment
measure: Change in Clinical Global Impression (CGI) Item 4 Efficacy and Safety Combined, Patients With One Previous Treatment Failure
timeFrame: 6 weeks of treatment
measure: Change in Clinical Global Impression (CGI) Item 4 Efficacy and Safety Combined, Patients With Two Previous Treatment Failures
timeFrame: 6 week of treatments
Other outcomes:
Locations:
city: Garran
country: Australia
facility: Research Site
state: Australian Capital Territory
city: Brisbane
country: Australia
facility: Research Site
state: Queensland
city: Everton Park
country: Australia
facility: Research Site
state: Queensland
city: Townsville
country: Australia
facility: Research Site
state: Queensland
city: Gilberton
country: Australia
facility: Research Site
state: South Australia
city: Clayton
country: Australia
facility: Research Site
state: Victoria
city: Frankston
country: Australia
facility: Research Site
state: Victoria
city: Heidelberg
country: Australia
facility: Research Site
state: Victoria
city: Malvern
country: Australia
facility: Research Site
state: Victoria
city: Prahran
country: Australia
facility: Research Site
state: Victoria
city: Richmond
country: Australia
facility: Research Site
state: Victoria
city: Graz
country: Austria
facility: Research Site
city: Klagenfurt
country: Austria
facility: Research Site
city: Salzburg
country: Austria
facility: Research Site
city: Wels
country: Austria
facility: Research Site
city: Wiener NEUSTADT
country: Austria
facility: Research Site
city: Wien
country: Austria
facility: Research Site
city: Assebroek
country: Belgium
facility: Research Site
city: Diest
country: Belgium
facility: Research Site
city: Liege
country: Belgium
facility: Research Site
city: Tielt
country: Belgium
facility: Research Site
city: Cerova Koria Village
country: Bulgaria
facility: Research Site
state: Veliko Tarnovo
city: Kardjali
country: Bulgaria
facility: Research Site
city: Pazardjik
country: Bulgaria
facility: Research Site
city: Pleven
country: Bulgaria
facility: Research Site
city: Ruse
country: Bulgaria
facility: Research Site
city: Sofia
country: Bulgaria
facility: Research Site
city: Varna
country: Bulgaria
facility: Research Site
city: Esbjerg N
country: Denmark
facility: Research Site
city: Frederiksberg
country: Denmark
facility: Research Site
city: Odense
country: Denmark
facility: Research Site
city: Aachen
country: Germany
facility: Research Site
city: Achim
country: Germany
facility: Research Site
city: Augsburg
country: Germany
facility: Research Site
city: Bad Homburg
country: Germany
facility: Research Site
city: Bad Honnef
country: Germany
facility: Research Site
city: Bad Saarow
country: Germany
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Bielefeld
country: Germany
facility: Research Site
city: Bochum
country: Germany
facility: Research Site
city: Butzbach
country: Germany
facility: Research Site
city: Chemnitz
country: Germany
facility: Research Site
city: Dresden
country: Germany
facility: Research Site
city: Duren
country: Germany
facility: Research Site
city: Dusseldorf
country: Germany
facility: Research Site
city: Ellwangen
country: Germany
facility: Research Site
city: Erbach
country: Germany
facility: Research Site
city: Gelsenkirchen
country: Germany
facility: Research Site
city: Gutersloh
country: Germany
facility: Research Site
city: Halle
country: Germany
facility: Research Site
city: Hattingen
country: Germany
facility: Research Site
city: Herborn
country: Germany
facility: Research Site
city: Kassel
country: Germany
facility: Research Site
city: Kothen
country: Germany
facility: Research Site
city: Neu-isenburg
country: Germany
facility: Research Site
city: Neubrandenburg
country: Germany
facility: Research Site
city: Nurnberg
country: Germany
facility: Research Site
city: Oldenburg
country: Germany
facility: Research Site
city: Ostfildern
country: Germany
facility: Research Site
city: Schwerin
country: Germany
facility: Research Site
city: Stuttgart
country: Germany
facility: Research Site
city: Westerstede
country: Germany
facility: Research Site
city: Wurzburg
country: Germany
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Gyor
country: Hungary
facility: Research Site
city: Gyula
country: Hungary
facility: Research Site
city: Nyiregyhaza
country: Hungary
facility: Research Site
city: Bressanone
country: Italy
facility: Research Site
state: BZ
city: Brunico
country: Italy
facility: Research Site
state: BZ
city: Cagliari
country: Italy
facility: Research Site
state: CA
city: Pisa
country: Italy
facility: Research Site
state: PI
city: Roma
country: Italy
facility: Research Site
state: RM
city: Bolzano
country: Italy
facility: Research Site
city: Catania
country: Italy
facility: Research Site
city: Napoli
country: Italy
facility: Research Site
city: Roma
country: Italy
facility: Research Site
city: Braga
country: Portugal
facility: Research Site
city: Coimbra
country: Portugal
facility: Research Site
city: Lisboa
country: Portugal
facility: Research Site
city: Santarem
country: Portugal
facility: Research Site
city: Bucharest
country: Romania
facility: Research Site
city: Craiova
country: Romania
facility: Research Site
city: Galati
country: Romania
facility: Research Site
city: Sibiu
country: Romania
facility: Research Site
city: Bratislava
country: Slovakia
facility: Research Site
city: Krupina
country: Slovakia
facility: Research Site
city: Levice
country: Slovakia
facility: Research Site
city: Liptovsky Mikulas
country: Slovakia
facility: Research Site
city: Michalovce Stranany
country: Slovakia
facility: Research Site
city: Presov
country: Slovakia
facility: Research Site
city: Roznava
country: Slovakia
facility: Research Site
city: Zilina-bytcica
country: Slovakia
facility: Research Site
city: Zlate Moravce
country: Slovakia
facility: Research Site
city: Sama de Langreo
country: Spain
facility: Research Site
state: Asturias
city: Salamanca
country: Spain
facility: Research Site
state: Castilla Leon
city: Zamora
country: Spain
facility: Research Site
state: Castilla Leon
city: Barcelona
country: Spain
facility: Research Site
state: Cataluna
city: Vigo
country: Spain
facility: Research Site
state: Galicia
city: Addlestone
country: United Kingdom
facility: Research Site
state: Surrey
city: Winnick
country: United Kingdom
facility: Research Site
state: Warrington
city: Horsham
country: United Kingdom
facility: Research Site
state: West Sussex
city: Coventry
country: United Kingdom
facility: Research Site
city: Glasgow
country: United Kingdom
facility: Research Site
city: Harrow
country: United Kingdom
facility: Research Site
city: Hull
country: United Kingdom
facility: Research Site
city: Winsford
country: United Kingdom
facility: Research Site
Study officials:
affiliation: Germany
name: Michael Bauer, professor
role: PRINCIPAL_INVESTIGATOR
affiliation: AstraZeneca MC Sweden
name: Birgit Ekholm, PhD
role: STUDY_DIRECTOR
References:
citation: Bauer M, Dell'osso L, Kasper S, Pitchot W, Dencker Vansvik E, Kohler J, Jorgensen L, Montgomery SA. Extended-release quetiapine fumarate (quetiapine XR) monotherapy and quetiapine XR or lithium as add-on to antidepressants in patients with treatment-resistant major depressive disorder. J Affect Disord. 2013 Oct;151(1):209-19. doi: 10.1016/j.jad.2013.05.079. Epub 2013 Jun 27.