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CompletedNCT00931723Updated Apr 19, 2012Results posted

Adult Bipolar Mania

A Phase 4 interventional study of Quetiapine fumarate XR and Lithium in Acute Mania, sponsored by AstraZeneca. Completed at 65 sites in 9 countries. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2012-04-19.

Sponsored by AstraZeneca · Phase 4, Interventional, and Treatment

Phase
Phase 4
Study type
Interventional
Enrollment
356
Allocation
Randomized
Ages
18 Years to 65 Years
Sex
All
01

Study summary

The purpose of this study is to determine if lithium 600-1800 mg/day is effective when added to quetiapine fumarate extended release (quetiapine XR or SEROQUEL® XR) 400-800 mg/day in treating acute mania and if so, how it compares with placebo (a non-active capsule, like a sugar pill, that looks like lithium).

02

Conditions studied

  • Acute Mania

Keywords

  • Acute Mania
  • Mania, Adults
  • Seroquel
  • Acute Mania in Adult Patients
03

In context

Mania

97 studies on the registry are indexed under Mania; 10 are open to participants now.

This study's enrollment of 356 is above the median of 86 across 86 interventional studies indexed under Mania.

Browse Mania studies →

Lead sponsor

AstraZeneca is the lead sponsor of 3,429 studies on the registry; 270 are open to participants now.

Of its 357 completed or terminated interventional studies of FDA-regulated products, 173 (48%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 65 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Provision of informed consent before any study procedures are performed.
  • The patient must have a documented clinical diagnosis for bipolar I disorder, including recent episode manic or mixed, and being male of females age 18-65 years, inclusive.
  • Patients may be outpatients or inpatients at enrollment visit, but all patients must be inpatients when randomized and remain inpatients until discharged at the discretion of the investigator.

Exclusion criteria

Exclusion Criteria:

  • The patient can not have had up to 8 mood episodes during the past 12 months and not been continuously hospitalized for acute bipolar for up to 3 weeks immediately before participating in the study.
  • The patient can not have a past diagnosis of stroke or medically documented transient ischemic attacks (TIA) or a history of seizure disorder, except for febrile convulsions.
  • The patient must not have received electroconvulsive treatment (ECT) within 90 days before participating in the study and in the doctors judgement pose a current suicidal or homicidal risk.
05

Study design

Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
356 participants (actual)

Study arms

  • Active comparator
    1

    Seroquel XR and Lithium

    Drug: Quetiapine fumarate XR · Drug: Lithium

  • Placebo comparator
    2

    Seroquel XR and placebo

    Drug: Quetiapine fumarate XR · Drug: Placebo

Interventions

  • DrugQuetiapine fumarate XR

    Oral treatment, once daily, Day 1 = 300 mg, Day 2 and thereafter 600 mg. Dose might be adjusted as from Day 3 by the discretion of the investigator.

    Also known as: Seroquel XR

  • DrugLithium

    Oral treatment, twice daily, Days 1 and 2 = 600 mg/day, Days 3-8 = 900 mg/day. Dose adjustment from day 9 to end of study will be at the discretion of the investigator.

  • DrugPlacebo

    Oral treatment twice daily.

06

What researchers measure

Primary outcomes

  1. Change in the Young Mania Rating Scale (YMRS) Total Score From Baseline to Final Assessment (Day 43)

    The YMRS total score ranges from 0 to 60 where higher scores indicate more severe mania, thus, a negative change (or decrease) from baseline indicates a reduction (or improvement) in manic symptoms. Total score ≤12 indicates remission (13-19=minimal symptoms; 20-25=mild mania, 26-37=moderate mania, 38-60=severe mania).

    Time frame: Change in YMRS total score from baseline to Day 43.

Secondary outcomes

  1. The Number of Patients With Clinically Significant Response.

    The number of patients with clinically significant response (defined as ≥50% reduction from baseline to Day 43 in the YMRS total score) was calculated. The YMRS total score ranges from 0 to 60 where higher scores indicate more severe mania, thus, a negative change (or 50% reduction) from baseline indicates a reduction (or improvement) in manic symptoms.

    Time frame: 43 days (from baseline to Day 43)

  2. Remission

    The number of patients with clinically significant remission (defined as YMRS total score ≤12) from Days 8 to 43) was calculated. The Young Mania Rating Scale total score ranges from 0 to 60 where higher scores indicate more severe mania, thus, a negative change (or 50% reduction) from baseline indicates a reduction (or improvement) in manic symptoms. Total score ≤12 indicates remission (13-19=minimal symptoms; 20-25=mild mania, 26-37=moderate mania, 38-60=severe mania).

    Time frame: Days 8 to 43

  3. Change From Baseline to Day 43 in CGI-BP-S (Clinical Global Impressions for Bipolar Disorder-Severity of Illness)

    The CGI-BP-S scale rates the severity of the patient's illness at the time of assessment and is scored from 1 to 7 (1=normal, not ill to 7=very severely ill). Higher CGI-BP-S scores indicate greater illness severity.

    Time frame: Change from baseline to Day 43.

  4. Change From Baseline to Day 43 in CGI-BP-C (Clinical Global Impressions for Bipolar Disorder-Change From Preceding Phase)

    The CGI-BP-C scale rates how much the patient's illness has improved or worsened compared to the phase immediately preceding treatment and is scored on a scale from 1 to 8 (1=very much improved to 7=very much worse; 8=not applicable). A missing score will be used when a scale scored as 8 (not applicable). CGI-BP-C scores \>4 indicate worsening, while scores \<4 indicate improvement.

    Time frame: Change from baseline to Day 43

  5. Improvement of Overall Bipolar Illness

    The number of patients with a CGI-BP-C of "Much" or "Very much" improved in overall bipolar illness assessment at Day 43 was calculated. The CGI-BP-C scale rates how much the patient's illness has improved or worsened compared to the phase immediately preceding treatment and is scored on a scale from 1 to 8 (1=very much improved to 7=very much worse; 8=not applicable). A missing score will be used when a scale scored as 8 (not applicable). CGI-BP-C scores \>4 indicate worsening, while scores \<4 indicate improvement.

    Time frame: Day 43.

  6. Change From Baseline to Day 43 in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score

    The MADRS is a 10-item scale that evaluates depressive symptoms. Each MADRS item is rated on a 0 to 6 scale. Higher MADRS scores indicate higher levels of depressive symptoms.

    Time frame: Change from baseline to Day 43.

  7. Change From Baseline to Day 43 in Positive and Negative Syndrome Scale (PANSS) Total Score

    The PANSS is a 30-item scale designed to assess various symptoms of schizophrenia and are rated on a 7-point scale that ranges from 1 (absent) to 7 (extreme psychopathology). The PANSS total score is the sum of all 30 individual-item scores and ranges from 30 to 210.A negative change (or decrease) from baseline indicates a reduction (or improvement) in symptoms.

    Time frame: Change from baseline to Day 43

  8. Change From Baseline to Day 43 in PANSS Activation Subscale Score

    The PANSS is a 30-item scale designed to assess various symptoms of schizophrenia and are rated on a 7-point scale that ranges from 1 (absent) to 7 (extreme psychopathology). The PANSS activation subscale score for effect on agitation and aggression is the sum of 6 PANSS individual items (ie, hostility, poor impulse control, excitement, uncooperativeness, poor rapport and tension) and ranges from 6 to 42. A negative change (or decrease) from baseline indicates a reduction (or improvement) in symptoms.

    Time frame: Change from baseline to Day 43

  9. Change From Baseline to Day 43 in PANSS Positive Subscale Score

    The PANSS is a 30-item scale designed to assess various symptoms of schizophrenia and are rated on a 7-point scale that ranges from 1 (absent) to 7 (extreme psychopathology). The PANSS positive subscale score is the sum of the 7 positive item scores (ie, delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/persecution and hostility) and ranges from 7 to 49. A negative change (or decrease) from baseline indicates a reduction (or improvement) in symptoms.

    Time frame: Change from baseline to Day 43

  10. Change From Baseline to Day 43 in Each YMRS Item Score No. 1

    The YMRS assesses severity of mania in bipolar disorder. It rates 4 core items from 0 to 8 (0=normal); the other 7 items are rated from 0 to 4 (0=normal). This analysis is for Item 1 (Elevated mood) which ranges from 0 to 4 where higher scores indicate more severe symptoms, thus, a negative change (or decrease) from baseline indicates a reduction (or improvement) in symptoms.

    Time frame: Change from baseline to Day 43

  11. Change From Baseline to Day 43 in Each YMRS Item Score No. 2

    The YMRS assesses severity of mania in bipolar disorder. It rates 4 core items from 0 to 8 (0=normal); the other 7 items are rated from 0 to 4 (0=normal). This analysis is for Item 2 (increased motor activity-energy) which ranges from 0 to 4 where higher scores indicate more severe symptoms, thus, a negative change (or decrease) from baseline indicates a reduction (or improvement) in symptoms.

    Time frame: Change from baseline to Day 43

  12. Change From Baseline to Day 43 in Each YMRS Item Score No. 3

    The YMRS assesses severity of mania in bipolar disorder. It rates 4 core items from 0 to 8 (0=normal); the other 7 items are rated from 0 to 4 (0=normal). This analysis is for Item 3 (sexual interest) which ranges from 0 to 4 where higher scores indicate more severe symptoms, thus, a negative change (or decrease) from baseline indicates a reduction (or improvement) in symptoms.

    Time frame: Change from baseline to Day 43

  13. Change From Baseline to Day 43 in Each YMRS Item Score No. 4

    The YMRS assesses severity of mania in bipolar disorder. It rates 4 core items from 0 to 8 (0=normal); the other 7 items are rated from 0 to 4 (0=normal). This analysis is for Item 4 (sleep) which ranges from 0 to 4 where higher scores indicate more severe symptoms, thus, a negative change (or decrease) from baseline indicates a reduction (or improvement) in symptoms.

    Time frame: Change from baseline to Day 43

  14. Change From Baseline to Day 43 in Each YMRS Item Score No. 5

    The YMRS assesses severity of mania in bipolar disorder. It rates 4 core items from 0 to 8 (0=normal); the other 7 items are rated from 0 to 4 (0=normal). This analysis is for Item 5 (Irritability) which ranges from 0 to 8 where higher scores indicate more severe symptoms, thus, a negative change (or decrease) from baseline indicates a reduction (or improvement) in symptoms.

    Time frame: Change from baseline to Day 43

  15. Change From Baseline to Day 43 in Each YMRS Item Score No. 6

    The YMRS assesses severity of mania in bipolar disorder. It rates 4 core items from 0 to 8 (0=normal); the other 7 items are rated from 0 to 4 (0=normal). This analysis is for Item 6 (speech-rate and amount) which ranges from 0 to 8 where higher scores indicate more severe symptoms, thus, a negative change (or decrease) from baseline indicates a reduction (or improvement) in symptoms.

    Time frame: Change from baseline to Day 43

  16. Change From Baseline to Day 43 in Each YMRS Item Score No. 7

    The YMRS assesses severity of mania in bipolar disorder. It rates 4 core items from 0 to 8 (0=normal); the other 7 items are rated from 0 to 4. This analysis is for Item 7 (language-thought disorder) which ranges from 0 to 4 where higher scores indicate more severe symptoms, thus, a negative change (or decrease) from baseline indicates a reduction (or improvement) in symptoms.

    Time frame: Change from baseline to Day 43

  17. Change From Baseline to Day 43 in Each YMRS Item Score No. 8

    The YMRS assesses severity of mania in bipolar disorder. It rates 4 core items from 0 to 8 (0=normal); the other 7 items are rated from 0 to 4. This analysis is for Item 8 (content) which ranges from 0 to 8 where higher scores indicate more severe symptoms, thus, a negative change (or decrease) from baseline indicates a reduction (or improvement) in symptoms.

    Time frame: Change from baseline to Day 43

  18. Change From Baseline to Day 43 in Each YMRS Item Score No. 9

    The YMRS assesses severity of mania in bipolar disorder. It rates 4 core items from 0 to 8 (0=normal); the other 7 items are rated from 0 to 4. . This analysis is for Item 9 (disruptive-aggressive behavior) which ranges from 0 to 8 where higher scores indicate more severe symptoms, thus, a negative change (or decrease) from baseline indicates a reduction (or improvement) in symptoms.

    Time frame: Change from baseline to Day 43

  19. Change From Baseline to Day 43 in Each YMRS Item Score No. 10

    The YMRS assesses severity of mania in bipolar disorder. It rates 4 core items from 0 to 8 (0=normal); the other 7 items are rated from 0 to 4. This analysis is for Item 10 (appearance) which ranges from 0 to 4 where higher scores indicate more severe symptoms, thus, a negative change (or decrease) from baseline indicates a reduction (or improvement) in symptoms.

    Time frame: Change from baseline to Day 43

  20. Change From Baseline to Day 43 in Each YMRS Item Score No. 11

    The YMRS assesses severity of mania in bipolar disorder. It rates 4 core items from 0 to 8 (0=normal); the other 7 items are rated from 0 to 4. This analysis is for Item 11 (insight) which ranges from 0 to 4 where higher scores indicate more severe symptoms, thus, a negative change (or decrease) from baseline indicates a reduction (or improvement) in symptoms.

    Time frame: Change from baseline to Day 43

07

Results

Posted Apr 19, 2012

Participant flow

This multicenter study was conducted between 24 June 2009 and 22 November 2010.

Participant flow — Overall Study
MilestoneLithium+Quetiapine XRPlacebo+Quetiapine XR
Started173183
Completed147144
Not completed2639
Withdrew: Withdrawal by subject1113
Withdrew: Adverse event613
Withdrew: Lithium found in blood01
Withdrew: Condition under investigation worsened12
Withdrew: Lost to follow-up12
Withdrew: Study-specific discontinuation criteria11
Withdrew: Severe non-compliance to protocol20
Withdrew: Safety reasons01
Withdrew: Took prohibited concomitant medication01
Withdrew: Lack or insufficient theraputic response25
Withdrew: Sponsor decision10
Withdrew: Late hospital discharge10

Outcome measures

PrimaryChange in the Young Mania Rating Scale (YMRS) Total Score From Baseline to Final Assessment (Day 43)

The YMRS total score ranges from 0 to 60 where higher scores indicate more severe mania, thus, a negative change (or decrease) from baseline indicates a reduction (or improvement) in manic symptoms. Total score ≤12 indicates remission (13-19=minimal symptoms; 20-25=mild mania, 26-37=moderate mania, 38-60=severe mania).

Time frame:
Change in YMRS total score from baseline to Day 43.
Reported as:
Least squares mean · Scores on a scale
Change in the Young Mania Rating Scale (YMRS) Total Score From Baseline to Final Assessment (Day 43)
Scores on a scaleLithium+Quetiapine XRPlacebo+Quetiapine XR
Change in the Young Mania Rating Scale (YMRS) Total Score From Baseline to Final Assessment (Day 43)-22.8 ± 0.706-20.1 ± 0.711
SecondaryThe Number of Patients With Clinically Significant Response.

The number of patients with clinically significant response (defined as ≥50% reduction from baseline to Day 43 in the YMRS total score) was calculated. The YMRS total score ranges from 0 to 60 where higher scores indicate more severe mania, thus, a negative change (or 50% reduction) from baseline indicates a reduction (or improvement) in manic symptoms.

Time frame:
43 days (from baseline to Day 43)
Reported as:
Number · Participants
The Number of Patients With Clinically Significant Response.
ParticipantsLithium+Quetiapine XRPlacebo+Quetiapine XR
The Number of Patients With Clinically Significant Response.137120
SecondaryRemission

The number of patients with clinically significant remission (defined as YMRS total score ≤12) from Days 8 to 43) was calculated. The Young Mania Rating Scale total score ranges from 0 to 60 where higher scores indicate more severe mania, thus, a negative change (or 50% reduction) from baseline indicates a reduction (or improvement) in manic symptoms. Total score ≤12 indicates remission (13-19=minimal symptoms; 20-25=mild mania, 26-37=moderate mania, 38-60=severe mania).

Time frame:
Days 8 to 43
Reported as:
Number · Participants
Remission
ParticipantsLithium+Quetiapine XRPlacebo+Quetiapine XR
Remission125105
SecondaryChange From Baseline to Day 43 in CGI-BP-S (Clinical Global Impressions for Bipolar Disorder-Severity of Illness)

The CGI-BP-S scale rates the severity of the patient's illness at the time of assessment and is scored from 1 to 7 (1=normal, not ill to 7=very severely ill). Higher CGI-BP-S scores indicate greater illness severity.

Time frame:
Change from baseline to Day 43.
Reported as:
Least squares mean · Scores on a scale
Change From Baseline to Day 43 in CGI-BP-S (Clinical Global Impressions for Bipolar Disorder-Severity of Illness)
Scores on a scaleLithium+Quetiapine XRPlacebo+Quetiapine XR
Change From Baseline to Day 43 in CGI-BP-S (Clinical Global Impressions for Bipolar Disorder-Severity of Illness)-2.5 ± 0.079-2.2 ± 0.080
SecondaryChange From Baseline to Day 43 in CGI-BP-C (Clinical Global Impressions for Bipolar Disorder-Change From Preceding Phase)

The CGI-BP-C scale rates how much the patient's illness has improved or worsened compared to the phase immediately preceding treatment and is scored on a scale from 1 to 8 (1=very much improved to 7=very much worse; 8=not applicable). A missing score will be used when a scale scored as 8 (not applicable). CGI-BP-C scores \>4 indicate worsening, while scores \<4 indicate improvement.

Time frame:
Change from baseline to Day 43
Reported as:
Least squares mean · Scores on a scale
Change From Baseline to Day 43 in CGI-BP-C (Clinical Global Impressions for Bipolar Disorder-Change From Preceding Phase)
Scores on a scaleLithium+Quetiapine XRPlacebo+Quetiapine XR
Change From Baseline to Day 43 in CGI-BP-C (Clinical Global Impressions for Bipolar Disorder-Change From Preceding Phase)1.7 ± 0.0851.9 ± 0.086
SecondaryImprovement of Overall Bipolar Illness

The number of patients with a CGI-BP-C of "Much" or "Very much" improved in overall bipolar illness assessment at Day 43 was calculated. The CGI-BP-C scale rates how much the patient's illness has improved or worsened compared to the phase immediately preceding treatment and is scored on a scale from 1 to 8 (1=very much improved to 7=very much worse; 8=not applicable). A missing score will be used when a scale scored as 8 (not applicable). CGI-BP-C scores \>4 indicate worsening, while scores \<4 indicate improvement.

Time frame:
Day 43.
Reported as:
Number · Participants
Improvement of Overall Bipolar Illness
ParticipantsLithium+Quetiapine XRPlacebo+Quetiapine XR
Improvement of Overall Bipolar Illness134125
SecondaryChange From Baseline to Day 43 in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score

The MADRS is a 10-item scale that evaluates depressive symptoms. Each MADRS item is rated on a 0 to 6 scale. Higher MADRS scores indicate higher levels of depressive symptoms.

Time frame:
Change from baseline to Day 43.
Reported as:
Least squares mean · Scores on a scale
Change From Baseline to Day 43 in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score
Scores on a scaleLithium+Quetiapine XRPlacebo+Quetiapine XR
Change From Baseline to Day 43 in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score-4.8 ± 0.366-4.1 ± 0.368
SecondaryChange From Baseline to Day 43 in Positive and Negative Syndrome Scale (PANSS) Total Score

The PANSS is a 30-item scale designed to assess various symptoms of schizophrenia and are rated on a 7-point scale that ranges from 1 (absent) to 7 (extreme psychopathology). The PANSS total score is the sum of all 30 individual-item scores and ranges from 30 to 210.A negative change (or decrease) from baseline indicates a reduction (or improvement) in symptoms.

Time frame:
Change from baseline to Day 43
Reported as:
Least squares mean · Scores on a scale
Change From Baseline to Day 43 in Positive and Negative Syndrome Scale (PANSS) Total Score
Scores on a scaleLithium+Quetiapine XRPlacebo+Quetiapine XR
Change From Baseline to Day 43 in Positive and Negative Syndrome Scale (PANSS) Total Score-19.2 ± 0.914-15.6 ± 0.914
SecondaryChange From Baseline to Day 43 in PANSS Activation Subscale Score

The PANSS is a 30-item scale designed to assess various symptoms of schizophrenia and are rated on a 7-point scale that ranges from 1 (absent) to 7 (extreme psychopathology). The PANSS activation subscale score for effect on agitation and aggression is the sum of 6 PANSS individual items (ie, hostility, poor impulse control, excitement, uncooperativeness, poor rapport and tension) and ranges from 6 to 42. A negative change (or decrease) from baseline indicates a reduction (or improvement) in symptoms.

Time frame:
Change from baseline to Day 43
Reported as:
Least squares mean · Scores on a scale
Change From Baseline to Day 43 in PANSS Activation Subscale Score
Scores on a scaleLithium+Quetiapine XRPlacebo+Quetiapine XR
Change From Baseline to Day 43 in PANSS Activation Subscale Score-7.1 ± 0.281-5.9 ± 0.283
SecondaryChange From Baseline to Day 43 in PANSS Positive Subscale Score

The PANSS is a 30-item scale designed to assess various symptoms of schizophrenia and are rated on a 7-point scale that ranges from 1 (absent) to 7 (extreme psychopathology). The PANSS positive subscale score is the sum of the 7 positive item scores (ie, delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/persecution and hostility) and ranges from 7 to 49. A negative change (or decrease) from baseline indicates a reduction (or improvement) in symptoms.

Time frame:
Change from baseline to Day 43
Reported as:
Least squares mean · Scores on a scale
Change From Baseline to Day 43 in PANSS Positive Subscale Score
Scores on a scaleLithium+Quetiapine XRPlacebo+Quetiapine XR
Change From Baseline to Day 43 in PANSS Positive Subscale Score-8.1 ± 0.316-7.0 ± 0.316
SecondaryChange From Baseline to Day 43 in Each YMRS Item Score No. 1

The YMRS assesses severity of mania in bipolar disorder. It rates 4 core items from 0 to 8 (0=normal); the other 7 items are rated from 0 to 4 (0=normal). This analysis is for Item 1 (Elevated mood) which ranges from 0 to 4 where higher scores indicate more severe symptoms, thus, a negative change (or decrease) from baseline indicates a reduction (or improvement) in symptoms.

Time frame:
Change from baseline to Day 43
Reported as:
Least squares mean · Scores on a scale
Change From Baseline to Day 43 in Each YMRS Item Score No. 1
Scores on a scaleLithium+Quetiapine XRPlacebo+Quetiapine XR
Change From Baseline to Day 43 in Each YMRS Item Score No. 1-1.8 ± 0.079-1.6 ± 0.080
SecondaryChange From Baseline to Day 43 in Each YMRS Item Score No. 2

The YMRS assesses severity of mania in bipolar disorder. It rates 4 core items from 0 to 8 (0=normal); the other 7 items are rated from 0 to 4 (0=normal). This analysis is for Item 2 (increased motor activity-energy) which ranges from 0 to 4 where higher scores indicate more severe symptoms, thus, a negative change (or decrease) from baseline indicates a reduction (or improvement) in symptoms.

Time frame:
Change from baseline to Day 43
Reported as:
Least squares mean · Scores on a scale
Change From Baseline to Day 43 in Each YMRS Item Score No. 2
Scores on a scaleLithium+Quetiapine XRPlacebo+Quetiapine XR
Change From Baseline to Day 43 in Each YMRS Item Score No. 2-1.9 ± 0.071-1.7 ± 0.072
SecondaryChange From Baseline to Day 43 in Each YMRS Item Score No. 3

The YMRS assesses severity of mania in bipolar disorder. It rates 4 core items from 0 to 8 (0=normal); the other 7 items are rated from 0 to 4 (0=normal). This analysis is for Item 3 (sexual interest) which ranges from 0 to 4 where higher scores indicate more severe symptoms, thus, a negative change (or decrease) from baseline indicates a reduction (or improvement) in symptoms.

Time frame:
Change from baseline to Day 43
Reported as:
Least squares mean · Scores on a scale
Change From Baseline to Day 43 in Each YMRS Item Score No. 3
Scores on a scaleLithium+Quetiapine XRPlacebo+Quetiapine XR
Change From Baseline to Day 43 in Each YMRS Item Score No. 3-1.3 ± 0.063-1.1 ± 0.064
SecondaryChange From Baseline to Day 43 in Each YMRS Item Score No. 4

The YMRS assesses severity of mania in bipolar disorder. It rates 4 core items from 0 to 8 (0=normal); the other 7 items are rated from 0 to 4 (0=normal). This analysis is for Item 4 (sleep) which ranges from 0 to 4 where higher scores indicate more severe symptoms, thus, a negative change (or decrease) from baseline indicates a reduction (or improvement) in symptoms.

Time frame:
Change from baseline to Day 43
Reported as:
Least squares mean · Scores on a scale
Change From Baseline to Day 43 in Each YMRS Item Score No. 4
Scores on a scaleLithium+Quetiapine XRPlacebo+Quetiapine XR
Change From Baseline to Day 43 in Each YMRS Item Score No. 4-2.0 ± 0.085-1.8 ± 0.086
SecondaryChange From Baseline to Day 43 in Each YMRS Item Score No. 5

The YMRS assesses severity of mania in bipolar disorder. It rates 4 core items from 0 to 8 (0=normal); the other 7 items are rated from 0 to 4 (0=normal). This analysis is for Item 5 (Irritability) which ranges from 0 to 8 where higher scores indicate more severe symptoms, thus, a negative change (or decrease) from baseline indicates a reduction (or improvement) in symptoms.

Time frame:
Change from baseline to Day 43
Reported as:
Least squares mean · Scores on a scale
Change From Baseline to Day 43 in Each YMRS Item Score No. 5
Scores on a scaleLithium+Quetiapine XRPlacebo+Quetiapine XR
Change From Baseline to Day 43 in Each YMRS Item Score No. 5-3.1 ± 0.109-2.8 ± 0.110
SecondaryChange From Baseline to Day 43 in Each YMRS Item Score No. 6

The YMRS assesses severity of mania in bipolar disorder. It rates 4 core items from 0 to 8 (0=normal); the other 7 items are rated from 0 to 4 (0=normal). This analysis is for Item 6 (speech-rate and amount) which ranges from 0 to 8 where higher scores indicate more severe symptoms, thus, a negative change (or decrease) from baseline indicates a reduction (or improvement) in symptoms.

Time frame:
Change from baseline to Day 43
Reported as:
Least squares mean · Scores on a scale
Change From Baseline to Day 43 in Each YMRS Item Score No. 6
Scores on a scaleLithium+Quetiapine XRPlacebo+Quetiapine XR
Change From Baseline to Day 43 in Each YMRS Item Score No. 6-3.1 ± 0.116-2.9 ± 0.118
SecondaryChange From Baseline to Day 43 in Each YMRS Item Score No. 7

The YMRS assesses severity of mania in bipolar disorder. It rates 4 core items from 0 to 8 (0=normal); the other 7 items are rated from 0 to 4. This analysis is for Item 7 (language-thought disorder) which ranges from 0 to 4 where higher scores indicate more severe symptoms, thus, a negative change (or decrease) from baseline indicates a reduction (or improvement) in symptoms.

Time frame:
Change from baseline to Day 43
Reported as:
Least squares mean · Scores on a scale
Change From Baseline to Day 43 in Each YMRS Item Score No. 7
Scores on a scaleLithium+Quetiapine XRPlacebo+Quetiapine XR
Change From Baseline to Day 43 in Each YMRS Item Score No. 7-1.5 ± 0.071-1.4 ± 0.072
SecondaryChange From Baseline to Day 43 in Each YMRS Item Score No. 8

The YMRS assesses severity of mania in bipolar disorder. It rates 4 core items from 0 to 8 (0=normal); the other 7 items are rated from 0 to 4. This analysis is for Item 8 (content) which ranges from 0 to 8 where higher scores indicate more severe symptoms, thus, a negative change (or decrease) from baseline indicates a reduction (or improvement) in symptoms.

Time frame:
Change from baseline to Day 43
Reported as:
Least squares mean · Scores on a scale
Change From Baseline to Day 43 in Each YMRS Item Score No. 8
Scores on a scaleLithium+Quetiapine XRPlacebo+Quetiapine XR
Change From Baseline to Day 43 in Each YMRS Item Score No. 8-3.1 ± 0.132-2.9 ± 0.133
SecondaryChange From Baseline to Day 43 in Each YMRS Item Score No. 9

The YMRS assesses severity of mania in bipolar disorder. It rates 4 core items from 0 to 8 (0=normal); the other 7 items are rated from 0 to 4. . This analysis is for Item 9 (disruptive-aggressive behavior) which ranges from 0 to 8 where higher scores indicate more severe symptoms, thus, a negative change (or decrease) from baseline indicates a reduction (or improvement) in symptoms.

Time frame:
Change from baseline to Day 43
Reported as:
Least squares mean · Scores on a scale
Change From Baseline to Day 43 in Each YMRS Item Score No. 9
Scores on a scaleLithium+Quetiapine XRPlacebo+Quetiapine XR
Change From Baseline to Day 43 in Each YMRS Item Score No. 9-2.5 ± 0.088-2.1 ± 0.089
SecondaryChange From Baseline to Day 43 in Each YMRS Item Score No. 10

The YMRS assesses severity of mania in bipolar disorder. It rates 4 core items from 0 to 8 (0=normal); the other 7 items are rated from 0 to 4. This analysis is for Item 10 (appearance) which ranges from 0 to 4 where higher scores indicate more severe symptoms, thus, a negative change (or decrease) from baseline indicates a reduction (or improvement) in symptoms.

Time frame:
Change from baseline to Day 43
Reported as:
Least squares mean · Scores on a scale
Change From Baseline to Day 43 in Each YMRS Item Score No. 10
Scores on a scaleLithium+Quetiapine XRPlacebo+Quetiapine XR
Change From Baseline to Day 43 in Each YMRS Item Score No. 10-1.1 ± 0.057-1.0 ± 0.057
SecondaryChange From Baseline to Day 43 in Each YMRS Item Score No. 11

The YMRS assesses severity of mania in bipolar disorder. It rates 4 core items from 0 to 8 (0=normal); the other 7 items are rated from 0 to 4. This analysis is for Item 11 (insight) which ranges from 0 to 4 where higher scores indicate more severe symptoms, thus, a negative change (or decrease) from baseline indicates a reduction (or improvement) in symptoms.

Time frame:
Change from baseline to Day 43
Reported as:
Least squares mean · Scores on a scale
Change From Baseline to Day 43 in Each YMRS Item Score No. 11
Scores on a scaleLithium+Quetiapine XRPlacebo+Quetiapine XR
Change From Baseline to Day 43 in Each YMRS Item Score No. 11-1.4 ± 0.069-1.2 ± 0.070

Adverse events

Non-serious events are listed at a 2% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Lithium+Quetiapine XR—4/173 (2.3%)106/173 (61.3%)
Placebo+Quetiapine XR—8/183 (4.4%)83/183 (45.4%)
Most frequent serious events
Most frequent serious events
EventLithium+Quetiapine XRPlacebo+Quetiapine XR
ManiaPsychiatric disorders3/1736/183
GastroenteritisInfections and infestations1/1730/183
Aggression; HostilityPsychiatric disorders0/1731/183
No Therapeutic ResponseInvestigations0/1731/183
Most frequent other events
Showing 10 of 15
Most frequent other events
EventLithium+Quetiapine XRPlacebo+Quetiapine XR
TremorNervous system disorders27/1739/183
SomnolenceNervous system disorders22/17310/183
ConstipationGastrointestinal disorders16/17316/183
Dry MouthGastrointestinal disorders14/17314/183
InsomniaPsychiatric disorders11/17312/183
DizzinessNervous system disorders11/1738/183
HeadacheNervous system disorders9/17311/183
PyrexiaGeneral disorders10/1739/183
DiarrhoeaGastrointestinal disorders8/1732/183
VomitingGastrointestinal disorders8/1730/183

Baseline characteristics

Age Continuous
Age Continuous(Years)Lithium+Quetiapine XRPlacebo+Quetiapine XRTotal
Mean37.9 ± 12.7138.8 ± 12.0938.3 ± 12.39
Sex: Female, Male
Sex: Female, Male(Participants)Lithium+Quetiapine XRPlacebo+Quetiapine XRTotal
Female7262134
Male101121222
08

Study locations

65 sites
  • Research Site
    Cedex, Belgium
  • Research Site
    Dendermonde, Belgium
  • Research Site
    Montignies-sur-sambre, Belgium
  • Research Site
    Overpelt, Belgium
  • Research Site
    Tournai, Belgium
  • Research Site
    Burgas, Bulgaria
  • Research Site
    Cedex, Bulgaria
  • Research Site
    Kazanlak, Bulgaria
  • Research Site
    Pazardjik, Bulgaria
  • Research Site
    Plovdiv, Bulgaria
  • Research Site
    Radnevo, Bulgaria
  • Research Site
    Sofia, Bulgaria
  • Research Site
    Berlin, BE, Germany
  • Research Site
    Koln, NW, Germany
  • Research Site
    Berlin, Germany
  • Research Site
    Cedex, Germany
  • Research Site
    Mannheim, Germany
  • Research Site
    Munchen, Germany
  • Research Site
    Nurnberg, Germany
  • Research Site
    Visakhapatnam, Andh Prad, India
  • Research Site
    Ahmedabad, Gujarat, India
  • Research Site
    Bangalore, Karna, India
  • Research Site
    Mangalore, Karna, India
  • Research Site
    Manipal, Karna, India
  • Research Site
    Nashik, Mahara, India
  • Research Site
    Jaipur, Rajasthan, India
  • Research Site
    Kanpur, Uttar Prad, India
  • Research Site
    Cedex, India
  • Research Site
    Bat Yam, Israel
  • Research Site
    Beer Ya'acov, Israel
  • Research Site
    Cedex, Israel
  • Research Site
    Haifa, Israel
  • Research Site
    Petach-tikva, Israel
  • Research Site
    Tel-hashomer, Israel
  • Research Site
    Bydgoszcz, Poland
  • Research Site
    Cedex, Poland
  • Research Site
    Choroszcz, Poland
  • Research Site
    Gorlice, Poland
  • Research Site
    Katowice, Poland
  • Research Site
    Krakow, Poland
  • Research Site
    Lublin, Poland
  • Research Site
    Poznan, Poland
  • Research Site
    Arkhangelsk, Russian Federation
  • Research Site
    Cedex, Russian Federation
  • Research Site
    Chita, Russian Federation
  • Research Site
    Kazan, Russian Federation
  • Research Site
    Moscow, Russian Federation
  • Research Site
    Saratov, Russian Federation
  • Research Site
    St Petersburg, Russian Federation
  • Research Site
    St. Petersburg, Russian Federation
  • Research Site
    Voronezh, Russian Federation
  • Research Site
    Bloemfontein, Free State, South Africa
  • Research Site
    Vereeniging, Free State, South Africa
  • Research Site
    Worcester, W Cape, South Africa
  • Research Site
    Cape Town, South Africa
  • Research Site
    Cedex, South Africa
  • Research Site
    Johannesburg, South Africa
  • Research Site
    Port Elizabeth, South Africa
  • Research Site
    Cedex, Ukraine
  • Research Site
    Dnipropetrovsk, Ukraine
  • Research Site
    Donetsk, Ukraine
  • Research Site
    Kharkov, Ukraine
  • Research Site
    Kiev, Ukraine
  • Research Site
    Odessa, Ukraine
  • Research Site
    Vinnitsia, Ukraine
09

References and documents

Publications

  • Bourin MS, Severus E, Schronen JP, Gass P, Szamosi J, Eriksson H, Chandrashekar H. Lithium as add-on to quetiapine XR in adult patients with acute mania: a 6-week, multicenter, double-blind, randomized, placebo-controlled study. Int J Bipolar Disord. 2014 Nov 8;2:14. doi: 10.1186/s40345-014-0014-9. eCollection 2014. PubMed 25505693 ↗
10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Apr 19, 2012, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT00931723
Lead sponsor
AstraZeneca
Collaborators
Quintiles, Inc.
Responsible party
Sponsor
First posted
Jul 2, 2009
Start date
Jun 2009
Primary completion
Nov 2010
Completion
Nov 2010
Results posted
Apr 19, 2012
Last update
Apr 19, 2012

Study contacts

Michael Castiglione
study director · AstraZeneca
Michel Bourin, Professeur
principal investigator · Neurobiologie de l'anxiété et de la dépression Faculté de Médecine

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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