Efficacy of Quetiapine XR Versus Placebo as Concomitant Treatment to Mood Stabilizers in the Control of Subsyndromal Symptoms of Bipolar Disorder

Bipolar Disorder Clinical Trial

Official title:

Efficacy of Quetiapine XR vs. Placebo as Concomitant Treatment to Mood Stabilizers in the Control of Subsyndromal Symptoms of Bipolar Disorder

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01197846
• Other study ID #: D1443L00079
• Status: Completed
• Phase: Phase 3
• First received: September 2, 2010
• Last updated: September 18, 2012
• Start date: September 2010
• Est. completion date: July 2012

Study information

• Verified date: September 2012
• Source: Centro de Investigación Biomédica en Red de Salud Mental
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Agencia Española de Medicamentos y Productos SanitariosSpain: Comité Ético de Investigación Clínica
• Study type: Interventional

Clinical Trial Summary

Pilot multicentric, prospective, placebo controlled, randomized double blinded, study of 12 weeks follow-up Adult patients diagnosed of bipolar disorder I or II, in previous treatment with no more than two concomitant mood stabilizers at stable doses and current subsyndromal symptoms, defined as YMRS ≤14 and/ or MADRS≥8 and ≤14 would be included Sub-acute phases would be excluded (at least 8 weeks from last exacerbation would be required for inclusion).

Description:

Remission of acute episodes usually doesn't correlate with symptomatic or functional recovery in occupational and social domains after (McQueen et al, 2001; Tohen et al, 2000) Ongoing depressive symptoms are the strongest predictor of functional deficits in persons with bipolar disorder (Bauer et al, 2001; Judd et al, 2005). Depressive subsyndromal symptoms are associated to functional impairment in bipolar disorder (Vojta et al, 2001; Altshuler et al, 2002; Yatham et al, 2004) The addition of olanzapine to valproate or lithium provided superior efficacy to valproate or lithium plus placebo in non completely remitted manic and mixed bipolar episodes, mainly through a control of depressive symptoms (Tohen et al, 2002) Quetiapine has demonstrated to be efficacious in the control of depressive symptoms in Bipolar Disorder (BOLDER, EMBOLDEN studies) and in the prevention of recurrences, maintaining the patient in YMRS and MADRS scores under the cut-off point between asymptomatic and subsyndromal states (Studies 126, 127 and 144) Thus it's expectable that adding quetiapine to previous mood stabilizers in bipolar patients with subsyndromal symptoms probably would improve their symptoms, mainly depressive, to levels not only of syndromic but of symptomatic remission, driving to a better functional status Quetiapine extended release would be used because its advantages on quetiapine immediate release regarding an easier and comfortable posology and potential better adherence

Recruitment information / eligibility

• Status: Completed
• Enrollment: 28
• Est. completion date: July 2012
• Est. primary completion date: February 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

1. Informed Consent signature

2. At least 18 years old

3. Diagnoses of bipolar disorder I or II (as DSM-IV-TR 4ª Ed codes)

4. Previous treatment with a mood stabilizer (lithium, valproate or lamotrigine) at stable and optimum doses for at least six weeks prior to the start of the trial (i.e., on the same dose and serum levels within the therapeutic ranges: 0.6-1.2 mEq/l of lithium or 50-100 ug/ml of valproate)

5. Presenting subsyndromal symptoms at enrolment and randomization point, defined as YMRS = 14 and/ or MADRS = 8 and =14

6. At least one manic, mixed, or depressed episode in the last 5 years

7. Being able to understand and meet the study requirements

Exclusion Criteria:

1. Pregnant or nursing women

2. Mental retardation.

3. Current active diagnoses of any axis I or II DSM-IV-TR diagnoses different from bipolar disorder I or II. This doesn't apply to nicotine nor caffeine abuse-dependence. Punctual alcohol and/or substances use not constitutive of a diagnoses of abuse or dependence following DSM-IV-TR criteria wouldn't suppose the exclusion of the patient from the study. Anxiety in levels not constitutive of any anxiety disorder within those codified in DSM-IV-TR wouldn't either suppose the exclusion of the patient from the study

4. Having suffered any acute episode (depressive, manic, or mixed) within the 8 weeks prior to enrolment, as defined in DSM-IV-TR

5. Patients that, in the investigator's opinion, are at a high risk of suicide or mean a risk of aggression to others.

6. Having been treated with any antidepressant at randomization.

7. Having been treated with any mood stabilizer other than lithium/valproate/lamotrigine at randomization.

8. Having been treated with any oral antipsychotic drug at randomization. Administration of a depot antipsychotic medication within one dosing interval prior to randomization (e.g. Long acting Risperidone 2 weeks; Zuclopenthixol 4 weeks; Pipotiazine 4 weeks; Flufenazine 6 weeks)

9. Having been treated with any of the following P450-3A4 cytochrome inhibitors in the 14 days prior to inclusion, including: ketoconazole, itraconazole, fluconazole, erythromycin, clarithromycin, fluvoxamine, indinavir, nelfinavir, ritonavir and saquinavir.

10. Having been treated with any of the following P450-3A4 cytochrome inducers in the 14 days prior to inclusion, including: phenytoin, carbamazepine, barbiturates, rifampicin, St. John's wart, and glucocorticoids.

11. Any contraindication to the use of quetiapine fumarate in the investigator's opinion (including lack of response to it in previous treatment attempts)

12. Suffering any medical condition that can effect the absorption, distribution, metabolism or excretion of the study treatment(s).

13. Suffering any medical condition in decompensation or not receiving inappropriate treatment for it in the investigator's opinion (e.g., hyperthyroidism, angina pectoris, hypertension...)

14. Suffering unstable diabetes at enrolment or randomization

15. Absolute neutrophil count = 1.5 x 109 per litre at randomization

16. Non-compliance with the study plan.

17. Participation in another clinical trial in the four weeks prior to randomization

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Bipolar Disorder

Intervention

Drug:
• Quetiapine
quetiapine 300 mg or 600 mg
• Placebo
Placebo

Locations

Country	Name	City	State
Spain	Hospital Clinic I Provincial	Barcelona
Spain	Hospital Santa Creu I Sant Pau	Barcelona
Spain	Hospital Universitari de Bellvitge	Barcelona
Spain	Hosptial Benito Menni	Barcelona
Spain	Parc Sanitari Sant Joan de Deu	Barcelona
Spain	Hospital General Universitario Gregorio Marañon	Madrid
Spain	Hospital Universitario Ramon Y Cajal	Madrid
Spain	Centro de Salud Menta II	Oviedo
Spain	Hosptial Clinico Valencia/ CSM Foios	Valencia
Spain	Hospital Santiago Apostol	Vitoria

Sponsors (1)

Lead Sponsor	Collaborator
Centro de Investigación Biomédica en Red de Salud Mental

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To assess the efficacy of quetiapine extended release (QTP XR) vs. placebo in the control of bipolar subsyndromal symptoms when added to previous mood stabilizer treatment (lithium/ valproate/lamotrigine)		Study of 12 weeks follow-up	Yes
Secondary	To assess the efficacy of QTP XR vs. placebo when added to previous mood stabilizer treatment (lithium/ valproate/lamotrigine) in functional level of bipolar patients with subsyndromal symptoms		Study of 12 weeks follow-up	Yes