Quetiapine XR for Cognitive and Functional Disability in Clinically Stable Patients With Bipolar Disorder
Condition: Bipolar Disorder; Cognitive Impairment
MeSH terms: Cognitive Dysfunction; Bipolar Disorder
Intervention: Quetiapine XR; Placebo
Intervention description: oral doses, 200 mg, 300 mg, 400 mg; 200mg, 300mg or 400mg
Intervention MeSH terms: Quetiapine Fumarate
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 32.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Cognition; attention; bipolar; disability

Summary:

      Quetiapine has been reported to have beneficial cognitive effects in several randomized
      controlled trials in schizophrenia. It has not yet been studied in bipolar disorder, but
      promising results from the use of extended release quetiapine for the maintenance treatment
      of bipolar disorder suggests that its cognitive benefits could be detected. Moreover,
      quetiapine has been shown to have direct beneficial effects on performance-based measures of
      social competence in schizophrenia and to improve quality of life (QoL) in bipolar
      depression. The investigators propose to study quetiapine augmentation of mood stabilizer
      monotherapy in clinically stable patients with bipolar disorder. This will be a randomized,
      placebo controlled trial, with attentional impairments as the primary outcome and other
      cognitive performance variables and measures of social and everyday living skills, as well as
      subjective QoL, as the secondary outcomes.
    

Eligibility criteria:

        Inclusion criteria:

          1. Provision of written informed consent

          2. A primary diagnosis of Bipolar disorder type 1 or 2, with a definite history of manic
             or hypomanic episodes by Diagnostic and Statistical Manual of Mental Disorders- Fourth
             Edition (DSM-IV).

          3. Females and/or males aged 18-65 years.

          4. Female patients of childbearing potential must be using a reliable method of
             contraception and have a negative urine human chorionic gonadotropin (HCG) test at
             enrolment.

          5. Able to understand and comply with the requirements of the study.

          6. YMDRS score <13.

          7. MADRS score <19.

          8. Currently receiving medication therapy with lithium, valproate, or lamotrigine or any
             combination thereof. (preference given to lithium and/or valproate).

          9. Clinically stable for 4 weeks prior to study entry, confirmed at week 2.

        Exclusion criteria:

          1. Intolerance of quetiapine

          2. Change in mood stabilizer medication or dose in the last 4 weeks, change in
             antidepressant medication or dose in the last two months.

          3. Current treatment with carbamazepine, stimulants, atomoxetine, or another
             antipsychotic

          4. Current treatment with norepinephrine reuptake inhibiting antidepressants
             (Milnacipran, bupropion, paroxetine, duloxetine, venlafaxine, all MAOI's, all TCAs)

          5. Current pregnancy or lactation

          6. Active Anorexia nervosa or Bulimia nervosa in the past six months

          7. History of non-affective psychotic disorders (including schizoaffective disorder)

          8. Patients who, in the opinion of the investigator, pose an imminent risk of suicide or
             a danger to self or others

          9. Use of any of the following cytochrome P450 3A4 inhibitors in the 14 days preceding
             enrolment including but not limited to: ketoconazole, itraconazole, fluconazole,
             erythromycin, clarithromycin, troleandomycin, indinavir, nelfinavir, ritonavir,
             fluvoxamine and saquinavir

         10. Use of any of the following cytochrome P450 inducers in the 14 days preceding
             enrollment including but not limited to: phenytoin, carbamazepine, barbiturates,
             rifampin, St. John's Wort, and glucocorticoids

         11. Administration of a depot antipsychotic injection within one dosing interval (for the
             depot) before randomisation

         12. Active Substance/ alcohol abuse or dependence in the past three months before
             enrollment ( except for caffeine or nicotine dependence), as defined by DSM-IV
             criteria Medical conditions that would affect absorption, distribution, metabolism, or
             excretion of study treatment

         13. Unstable or inadequately treated medical illness (e.g. diabetes, angina pectoris,
             hyperlipidemia, hypertension) as judged by the investigator

         14. Involvement in the planning and conduct of the study

         15. Previous enrolment or randomisation of treatment in the present study.

         16. Participation in another drug trial within 4 weeks prior enrolment into this study or
             longer in accordance with local requirements

         17. A patient with Diabetes Mellitus (DM) fulfilling one of the following criteria:

               -  Unstable DM defined as enrollment glycosylated hemoglobin (HbA1c) >8.5%.

               -  Admitted to hospital for treatment of DM or DM related illness in past 12 weeks.

               -  Not under physician care for DM

               -  Physician responsible for patient's DM care has not indicated that patient's DM
                  is controlled.

               -  Physician responsible for patient's DM care has not approved patient's
                  participation in the study

               -  Has not been on the same dose of oral hypoglycaemic drug(s) and/or diet for the 4
                  weeks prior to randomization. For thiazolidinediones (glitazones) this period
                  should not be less than 8 Weeks.

               -  Taking insulin whose daily dose on one occasion in the past 4 weeks has been more
                  than 10% above or below their mean dose in the preceding 4 weeks Note: If a
                  diabetic patient meets one of these criteria, the patient is to be excluded even
                  if the treating physician believes that the patient is stable and can participate
                  in the study.

         18. An absolute neutrophil count (ANC) of < 1.5 x 10^9 per liter