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

This is an interventional treatment trial for Bipolar Disorder Read More

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