Clinical trial NCT01725308: A Study to Evaluate the Efficacy of FK949E in Bipolar Disorder Patients With Major Depressive Episodes
Official title: Phase II/III Study of FK949E: Placebo-controlled, Double-blind, Parallel-group Comparative Study and Open-label, Non-controlled Extension Study in Bipolar Disorder Patients With Major Depressive Episodes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Bipolar Disorder
Keywords: FK949E
Major depressive episode
patients
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
First posted: 2012-11-12
Enrollment: 431
Sex: ALL
Minimum age (years): 20
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: In period I, the treatment effect of FK949E was compared with that of placebo in a blind manner in bipolar disorder patients with major depressive episodes. In period II, the long-term safety and efficacy of FK949E was evaluated.

Detailed description: This study consisted of two parts. In Treatment Period I, FK949E or placebo was administered orally in a blind manner to bipolar disorder patients with major depressive episodes, with the aim of evaluating the superiority of FK949E over placebo and the dose response of two doses of FK949E based on changes in Montgomery-Asberg Depression Rating Scale (MADRS) total score. In Treatment Period II, the long-term safety, efficacy and pharmacokinetics of open-label FK949E was evaluated in patients who completed Treatment Period I. An analysis was performed for data in Treatment Period I and another analysis was done for data in combined Treatment Periods I and II.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of bipolar I or II disorder as specified in the Diagnostic and Statistical Manual of Mental Disorders Ver. 4 Text Revision (DSM-IV-TR,) with a major depressive episode
* The Hamilton Depression Rating Scale (HAM-D17) total score of 20 points or more and HAM-D17 depressed mood score of 2 points or more
* Able to participate in the study with understanding of and compliance with subject requirements during the study in the investigator's or subinvestigator's opinion

Exclusion Criteria:

* Concurrent or previous history of DSM-IV-TR Axis I disorders, except bipolar disorder, within the last 6 months before informed consent
* Concurrence of DSM-IV-TR Axis II disorder that is considered to greatly affect patient's current mental status
* The Young Mania Rating Scale (YMRS) total score of 13 points or more
* Nine or more mood episodes within the last 12 months before informed consent
* Lack of response to at least 6-week treatment with at least 2 antidepressants for the current major depressive episode in the investigator's or subinvestigator's opinion
* History of abuse or dependence of alcohol or substances other than caffeine and nicotine
* Treatment with a depot antipsychotic within the last 42 days before primary registration
* Unable to stop taking mood stabilizers (lithium carbonate and/or sodium valproate), lamotrigine, antipsychotics, or antidepressants from 7 days before secondary registration
* Unable to stop taking antiepileptics (except lamotrigine and sodium valproate), antianxiety agents, hypnotics, sedatives, psychostimulants, antiparkinsonian agents, cerebral ameliorators, antidementia agents, or anorectics, except those specified as conditionally-allowed concomitant drugs, after primary registration
* Electroconvulsive therapy within the last 76 days before primary registration
* The current major depressive episode persisting for more than 12 months or less than 4 weeks before informed consent
* A possible need of psychotherapy during the study period (unless the therapy has been commenced at least 76 days before primary registration and been maintained on a fixed level at fixed frequency)
* Documented or suspected conditions such as renal failure, hepatic failure, serious cardiac disease, hepatitis B, hepatitis C, or acquired immunodeficiency syndrome (AIDS) (or to be a carrier of hepatitis B, hepatitis C, or AIDS)
* Concurrence of malignancy or history of cured malignancy within 5 years
* Concurrence of uncontrolled hypertension (defined as a systolic blood pressure of 180 mmHg or more, or a diastolic blood pressure of 110 mmHg or more at primary registration) or unstable angina that may worsen with the study or may affect the study results based on the clinical judgment of the investigator or sub-investigator
* Concurrence of hypotension (defined as a systolic blood pressure of less than 100 mmHg at primary registration) or orthostatic hypotension
* History of transient, idiopathic orthostatic hypotension, with or without pre-syncope symptoms or syncope, or a current condition susceptible to transient hypotension, such as dehydration and decreased blood volume
* Concurrent or previous history of cerebrovascular disease or transient ischemic attack (TIA)
* Abnormal laboratory or electrocardiographic findings considered clinically significant in the investigator's or subinvestigator's opinion (in reference to grade 3 of the Adverse Drug Reactions Severity Grading Criteria \[Notification No. 80 of the Safety Division, Pharmaceutical Affairs Bureau, Ministry of Health and Welfare dated 29 June 1992\])
* Participation in another clinical study or post-marketing study within the last 12 weeks before informed consent
* History of quetiapine therapy during the current major depressive episode
* Pregnant or lactating women

Primary outcomes:
measure: Change From Baseline to End of Treatment Period I in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score
timeFrame: Baseline and Week 8
Secondary outcomes:
measure: Change From Baseline in MADRS Total Score (Treatment Period I)
timeFrame: Baseline and Weeks 1, 2, 3, 4, 6, 8
measure: Change From Baseline in MADRS Total Score (Combined Treatment Period I and II)
timeFrame: Baseline (Week 0 for FK949E 150 mg/FK949E & FK949E 300 mg/FK949E and Week 12 for Placebo/FK949E) and Weeks 1, 2, 3, 4, 6, 8, 10, 12 13, 14, 16, 18, 20, 24, 28, 32, 36, 40, 44, 48, 52
measure: Number of Participants With MADRS Response (Treatment Period I)
timeFrame: Baseline and Weeks 1, 2, 3, 4, 6, 8
measure: Number of Participants With MADRS Response (Combined Treatment Period I and II)
timeFrame: Baseline (Week 0 for FK949E 150 mg/FK949E & FK949E 300 mg/FK949E and Week 12 for Placebo/FK949E) and Weeks 1, 2, 3, 4, 6, 8, 10, 12, 13, 14, 16, 18, 20, 24, 28, 32, 36, 40, 44, 48, 52
measure: Number of Participants With MADRS Remission (Treatment Period I)
timeFrame: Weeks 1, 2, 3, 4, 6, 8
measure: Number of Participants With MADRS Remission (Combined Treatment Period I and II)
timeFrame: Weeks 1, 2, 3, 4, 6, 8, 10, 12, 13, 14, 16, 18, 20, 24, 28, 32, 36, 40, 44, 48, 52
measure: Change From Baseline in Hamilton Depression Rating Scale (HAM-D17) Total Score (Treatment Period I)
timeFrame: Baseline and Weeks 1, 2, 3, 4, 6, 8
measure: Change From Baseline in HAM-D17 (Combined Treatment Period I and II)
timeFrame: Baseline (Week 0 for FK949E 150 mg/FK949E & FK949E 300 mg/FK949E and Week 12 for Placebo/FK949E) and Weeks 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 28, 36, 40, 44, 52
measure: Number of Participants With HAM-D17 Response (Treatment Period I)
timeFrame: Baseline and Weeks 1, 2, 3, 4, 6, 8
measure: Number of Participants With HAM-D17 Response (Combined Treatment Period I and II)
timeFrame: Baseline (Week 0 for FK949E 150 mg/FK949E & FK949E 300 mg/FK949E and Week 12 for Placebo/FK949E) and Weeks 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 28, 36, 44, 52
measure: Change From Baseline in Clinical Global Impression-Bipolar Disorder-Severity (CGI-BP-S): Mania (Treatment Period I)
timeFrame: Baseline and Weeks 1, 2, 3, 4, 6, 8
measure: Change From Baseline in CGI-BP-S: Mania (Combined Treatment Period I and II)
timeFrame: Baseline (Week 0 for FK949E 150 mg/FK949E & FK949E 300 mg/FK949E and Week 12 for Placebo/FK949E) and Weeks 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 28, 32, 36, 40, 44, 48, 52
measure: Change From Baseline in CGI-BP-S: Depression (Treatment Period I)
timeFrame: Baseline and Weeks 1, 2, 3, 4, 6, 8
measure: Change From Baseline in CGI-BP-S: Depression (Combined Treatment Period I and II)
timeFrame: Baseline (Week 0 for FK949E 150 mg/FK949E & FK949E 300 mg/FK949E and Week 12 for Placebo/FK949E) and Weeks 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 28, 32, 36, 40, 44, 48, 52
measure: Change From Baseline in CGI-BP-S: Overall Bipolar Illness (Treatment Period I)
timeFrame: Baseline and Weeks 1, 2, 3, 4, 6, 8
measure: Change From Baseline in CGI-BP-S: Overall Bipolar Illness (Combined Treatment Period I and II)
timeFrame: Baseline (Week 0 for FK949E 150 mg/FK949E & FK949E 300 mg/FK949E and Week 12 for Placebo/FK949E) and Weeks 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 28, 32, 36, 40, 44, 48, 52
measure: Clinical Global Impression-Bipolar Disorder-Change (CGI-BP-C): Mania (Treatment Period I)
timeFrame: Weeks 1, 2, 3, 4, 6, 8
measure: CGI-BP-C: Mania (Combined Treatment Period I and II)
timeFrame: Weeks 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 28, 32, 36, 40, 44, 48, 52 (Placebo/FK949E only from week 12, FK949E 150 mg/FK949E & FK949E 300 mg/FK949E from week 1)
measure: CGI-BP-C: Depression (Treatment Period I)
timeFrame: Weeks 1, 2, 3, 4, 6, 8
measure: CGI-BP-C: Depression (Combined Treatment Period I and II)
timeFrame: Weeks 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 28, 32, 36, 40, 44, 48, 52 (Placebo/FK949E only from week 12, FK949E 150 mg/FK949E & FK949E 300 mg/FK949E from week 1)
measure: CGI-BP-C: Overall Bipolar Illness (Treatment Period I)
timeFrame: Weeks 1, 2, 3, 4, 6, 8
measure: CGI-BP-C: Overall Bipolar Illness (Combined Treatment Period I and II)
timeFrame: Weeks 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 28, 32, 36, 40, 44, 48, 52 (Placebo/FK949E only from week 12, FK949E 150 mg/FK949E & FK949E 300 mg/FK949E from week 1)
measure: Number of Participants With Adverse Events (Treatment Period I)
timeFrame: Up to 8 weeks
measure: Number of Participants With Adverse Events (Combined Treatment Period I and II)
timeFrame: Up to 54 weeks (Placebo / FK949E, from week 12 to week 52, for FK949E 150 mg / FK949E & FK949E 300 mg / FK949E groups, from week 0 to week 52)
measure: Change From Baseline in Drug Induced Extra-Pyramidal Symptoms Scale (DIEPSS): Total Score (Treatment Period I)
timeFrame: Baseline and Weeks 4, 8
measure: Change From Baseline in DIEPSS: Total Score (Combined Treatment Period I and II)
timeFrame: Baseline (Week 0 for FK949E 150 mg/FK949E & FK949E 300 mg/FK949E and Week 12 for Placebo/FK949E) and Weeks 4, 8, 12, 16, 20, 28, 36, 44, 52
measure: Change From Baseline in DIEPSS: Parkinsonism (Treatment Period I)
timeFrame: Baseline and Weeks 4, 8
measure: Change From Baseline in DIEPSS: Parkinsonism (Combined Treatment Period I and II)
timeFrame: Baseline (Week 0 for FK949E 150 mg/FK949E & FK949E 300 mg/FK949E and Week 12 for Placebo/FK949E) and Weeks 4, 8, 12, 16, 20, 28, 36, 44, 52
measure: Change From Baseline in Young Mania Rating Scale (YMRS) (Treatment Period I)
timeFrame: Baseline and Weeks 1, 2, 3, 4, 6, 8
measure: Change From Baseline in YMRS (Combined Treatment Period I and II)
timeFrame: Baseline (Week 0 for FK949E 150 mg/FK949E & FK949E 300 mg/FK949E and Week 12 for Placebo/FK949E) and Weeks 1, 2, 3, 4, 6, 8, 10, 12, 13, 14, 16, 18, 20, 24, 28, 32, 36, 40, 44, 48, 52
measure: Number of Participants With an Affirmative Response to Columbia Suicide Severity Rating Scale (C-SSRS): Suicidal Ideation (Treatment Period I)
timeFrame: Weeks 4, 8
measure: Number of Participants With an Affirmative Response to C-SSRS: Suicidal Ideation - Wish to be Dead (Combined Treatment Period I and II)
timeFrame: Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 (Placebo/FK949E only from week 12, FK949E 150 mg/FK949E & FK949E 300 mg/FK949E from week 4)
measure: Number of Participants With an Affirmative Response to C-SSRS: Suicidal Ideation - Suicidal Thoughts (Combined Treatment Period I and II)
timeFrame: Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 (Placebo/FK949E only from week 12, FK949E 150 mg/FK949E & FK949E 300 mg/FK949E from week 4)
measure: Number of Participants With an Affirmative Response to C-SSRS: Suicidal Ideation - Suicidal Thoughts With Method (Combined Treatment Period I and II)
timeFrame: Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 (Placebo/FK949E only from week 12, FK949E 150 mg/FK949E & FK949E 300 mg/FK949E from week 4)
measure: Number of Participants With an Affirmative Response to C-SSRS: Suicidal Ideation - Suicidal Intent Without a Plan (Combined Treatment Period I and II)
timeFrame: Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 (Placebo/FK949E only from week 12, FK949E 150 mg/FK949E & FK949E 300 mg/FK949E from week 4)
measure: Number of Participants With an Affirmative Response to C-SSRS: Suicidal Ideation - Suicidal Intent With a Plan (Combined Treatment Period I and II)
timeFrame: Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 (Placebo/FK949E only from week 12, FK949E 150 mg/FK949E & FK949E 300 mg/FK949E from week 4)
measure: Number of Participants With an Affirmative Response to C-SSRS: Suicidal Behaviors (Treatment Period I)
timeFrame: Weeks 4, 8
measure: Number of Participants With an Affirmative Response to C-SSRS: Suicidal Behaviors - Suicide Attempt (Combined Treatment Period I and II)
timeFrame: Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 (Placebo/FK949E only from week 12, FK949E 150 mg/FK949E & FK949E 300 mg/FK949E from week 4)
measure: Number of Participants With an Affirmative Response to C-SSRS: Suicidal Behaviors - Self-injury Behavior Without Intent (Combined Treatment Period I and II)
timeFrame: Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 (Placebo/FK949E only from week 12, FK949E 150 mg/FK949E & FK949E 300 mg/FK949E from week 4)
measure: Number of Participants With an Affirmative Response to C-SSRS: Suicidal Behaviors - Discontinued Attempt (Combined Treatment Period I and II)
timeFrame: Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 (Placebo/FK949E only from week 12, FK949E 150 mg/FK949E & FK949E 300 mg/FK949E from week 4)
measure: Number of Participants With an Affirmative Response to C-SSRS: Suicidal Behaviors - Interrupted Attempt (Combined Treatment Period I and II)
timeFrame: Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 (Placebo/FK949E only from week 12, FK949E 150 mg/FK949E & FK949E 300 mg/FK949E from week 4)
measure: Number of Participants With an Affirmative Response to C-SSRS: Suicidal Behaviors - Preliminary Act to Suicide (Combined Treatment Period I and II
timeFrame: Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 (Placebo/FK949E only from week 12, FK949E 150 mg/FK949E & FK949E 300 mg/FK949E from week 4)
measure: Number of Participants With an Affirmative Response to C-SSRS: Suicidal Behaviors - Suicidal Behavior (Combined Treatment Period I and II)
timeFrame: Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 (Placebo/FK949E only from week 12, FK949E 150 mg/FK949E & FK949E 300 mg/FK949E from week 4)
measure: Number of Participants With an Affirmative Response to C-SSRS: Suicidal Behaviors - Completed Suicide (Combined Treatment Period I and II)
timeFrame: Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 (Placebo/FK949E only from week 12, FK949E 150 mg/FK949E & FK949E 300 mg/FK949E from week 4)
Other outcomes:
Locations:
city: Aichi
country: Japan
facility: Site JP00030
city: Aichi
country: Japan
facility: Site JP00031
city: Aichi
country: Japan
facility: Site JP00052
city: Aichi
country: Japan
facility: Site JP00055
city: Aichi
country: Japan
facility: Site JP00072
city: Aichi
country: Japan
facility: Site JP00092
city: Akita
country: Japan
facility: Site JP00003
city: Chiba
country: Japan
facility: Site JP00008
city: Chiba
country: Japan
facility: Site JP00009
city: Fukuoka
country: Japan
facility: Site JP00002
city: Fukuoka
country: Japan
facility: Site JP00037
city: Fukuoka
country: Japan
facility: Site JP00038
city: Fukuoka
country: Japan
facility: Site JP00039
city: Fukuoka
country: Japan
facility: Site JP00040
city: Fukuoka
country: Japan
facility: Site JP00041
city: Fukuoka
country: Japan
facility: Site JP00058
city: Fukuoka
country: Japan
facility: Site JP00082
city: Fukuoka
country: Japan
facility: Site JP00083
city: Fukuoka
country: Japan
facility: Site JP00091
city: Fukuoka
country: Japan
facility: Site JP00094
city: Fukuoka
country: Japan
facility: Site JP00095
city: Fukuoka
country: Japan
facility: Site JP00096
city: Fukuoka
country: Japan
facility: Site JP00097
city: Fukuoka
country: Japan
facility: Site JP00098
city: Fukushima
country: Japan
facility: Site JP00004
city: Gifu
country: Japan
facility: Site JP00028
city: Gunma
country: Japan
facility: Site JP00006
city: Gunma
country: Japan
facility: Site JP00007
city: Hiroshima
country: Japan
facility: Site JP00035
city: Hiroshima
country: Japan
facility: Site JP00056
city: Hiroshima
country: Japan
facility: Site JP00067
city: Hokkaido
country: Japan
facility: Site JP00001
city: Hokkaido
country: Japan
facility: Site JP00059
city: Hokkaido
country: Japan
facility: Site JP00061
city: Hokkaido
country: Japan
facility: Site JP00062
city: Hokkaido
country: Japan
facility: Site JP00068
city: Hokkaido
country: Japan
facility: Site JP00069
city: Hokkaido
country: Japan
facility: Site JP00073
city: Hokkaido
country: Japan
facility: Site JP00074
city: Hokkaido
country: Japan
facility: Site JP00076
city: Ibaraki
country: Japan
facility: Site JP00005
city: Kagawa
country: Japan
facility: Site JP00049
city: Kanagawa
country: Japan
facility: Site JP00021
city: Kanagawa
country: Japan
facility: Site JP00022
city: Kanagawa
country: Japan
facility: Site JP00023
city: Kanagawa
country: Japan
facility: Site JP00024
city: Kanagawa
country: Japan
facility: Site JP00025
city: Kumamoto
country: Japan
facility: Site JP00042
city: Kumamoto
country: Japan
facility: Site JP00050
city: Kyoto
country: Japan
facility: Site JP00032
city: Kyoto
country: Japan
facility: Site JP00084
city: Miyagi
country: Japan
facility: Site JP00077
city: Nagano
country: Japan
facility: Site JP00027
city: Nara
country: Japan
facility: Site JP00075
city: Oita
country: Japan
facility: Site JP00053
city: Okayama
country: Japan
facility: Site JP00054
city: Okayama
country: Japan
facility: Site JP00079
city: Okinawa
country: Japan
facility: Site JP00043
city: Okinawa
country: Japan
facility: Site JP00046
city: Osaka
country: Japan
facility: Site JP00033
city: Osaka
country: Japan
facility: Site JP00034
city: Osaka
country: Japan
facility: Site JP00047
city: Osaka
country: Japan
facility: Site JP00063
city: Shizuoka
country: Japan
facility: Site JP00029
city: Tokushima
country: Japan
facility: Site JP00036
city: Tokyo
country: Japan
facility: Site JP00010
city: Tokyo
country: Japan
facility: Site JP00011
city: Tokyo
country: Japan
facility: Site JP00012
city: Tokyo
country: Japan
facility: Site JP00013
city: Tokyo
country: Japan
facility: Site JP00014
city: Tokyo
country: Japan
facility: Site JP00015
city: Tokyo
country: Japan
facility: Site JP00016
city: Tokyo
country: Japan
facility: Site JP00017
city: Tokyo
country: Japan
facility: Site JP00018
city: Tokyo
country: Japan
facility: Site JP00019
city: Tokyo
country: Japan
facility: Site JP00020
city: Tokyo
country: Japan
facility: Site JP00045
city: Tokyo
country: Japan
facility: Site JP00048
city: Tokyo
country: Japan
facility: Site JP00051
city: Tokyo
country: Japan
facility: Site JP00057
city: Tokyo
country: Japan
facility: Site JP00060
city: Tokyo
country: Japan
facility: Site JP00064
city: Tokyo
country: Japan
facility: Site JP00065
city: Tokyo
country: Japan
facility: Site JP00066
city: Tokyo
country: Japan
facility: Site JP00070
city: Tokyo
country: Japan
facility: Site JP00071
city: Tokyo
country: Japan
facility: Site JP00078
city: Tokyo
country: Japan
facility: Site JP00081
city: Tokyo
country: Japan
facility: Site JP00085
city: Tokyo
country: Japan
facility: Site JP00086
city: Tokyo
country: Japan
facility: Site JP00087
city: Tokyo
country: Japan
facility: Site JP00088
city: Tokyo
country: Japan
facility: Site JP00089
city: Tokyo
country: Japan
facility: Site JP00090
city: Tokyo
country: Japan
facility: Site JP00093
city: Tokyo
country: Japan
facility: Site JP00099
city: Tottori
country: Japan
facility: Site JP00044
city: Toyama
country: Japan
facility: Site JP00026
Study officials:
affiliation: Astellas Pharma Inc
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Fukushi R, Nomura Y, Katashima M, Komatsu K, Sato Y, Takada A. Approach to Evaluating QT Prolongation of Quetiapine Fumarate in Late Stage of Clinical Development Using Concentration-QTc Modeling and Simulation in Japanese Patients With Bipolar Disorder. Clin Ther. 2020 Aug;42(8):1483-1493.e1. doi: 10.1016/j.clinthera.2020.06.002. Epub 2020 Aug 11.
citation: Fukushi R, Nomura Y, Katashima M, Komatsu K, Sato Y, Takada A. Population Pharmacokinetics Analysis of Quetiapine Extended-release Formulation in Japanese Patients with Bipolar Depression. Clin Ther. 2020 Jun;42(6):1067-1076.e2. doi: 10.1016/j.clinthera.2020.04.006. Epub 2020 Jun 6.
citation: Kanba S, Murasaki M, Koyama T, Takeuchi M, Shimizu Y, Arita E, Kuroishi K, Takeuchi M, Kamei S. Long-term mood/antidepressant effects of quetiapine extended-release formulation: an open-label, non-controlled extension study in Japanese patients with bipolar depression. BMC Psychiatry. 2019 Jun 26;19(1):198. doi: 10.1186/s12888-019-2181-9.