Bipolar I disorder depression Mental and Behavioural Disorders Bipolar affective disorder
Conditions
Interventions
Open label acute treatment phase:
1. Escitalopram will be initiated at a dose of 10 mg daily:
1.1. The dose may be increased in increments of 10 mg at the discretion of the study psychiatrist, until
Sponsors
University of British Columbia (Canada)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients meeting all of the following criteria will be eligible for inclusion in the open-label study phase: 1. Diagnosed with BD, current episode depressed, with a Montgomery Asberg Depression Rating Scale (MADRS) score greater than or equal to 20 at both the screening and baseline assessments 2. The duration of the current depressive episode is greater than or equal to 2 weeks but less than or equal to 52 weeks 3. Taking or initiating treatment with a mood stabilising medication at a therapeutic dose. Mood stabilising medications and therapeutic doses are: lithium, serum level 0.6 - 1.4 mEq/L; divalproex, serum level 350 - 700 mM; risperidone 1 - 6 mg/day; olanzapine 5 - 30 mg/day; quetiapine IR or XR 300 - 900 mg/day; aripiprazole 10 - 30 mg/day; and ziprasidone 80 - 160 mg/day. 4. If taking any other psychoactive medication (other than lorazepam less than or equal to 4 mg/day or equivalent), is agreeable to tapering and discontinuing it over a period of less than or equal to 4 weeks 5. If female and of childbearing potential, is using an adequate method of contraception. Adequate methods of contraception include abstinence; oral contraceptive pill or surgically implanted device; intra-uterine device; condom plus spermicidal foam or jelly; or tubal ligation. 6. Aged 18 - 70 years, inclusive, either sex 7. Fluent in English and capable of providing informed consent Patients meeting all of the following criteria will be eligible to be included in the double-blind study phase: 1. Taking escitalopram 10 - 30 mg/day or bupropion XL 150 - 450 mg/day, in addition to either a mood stabilising medication (lithium, serum level 0.8 - 1.2 mEq/L or divalproex, serum level 350 - 700 mM), an SGA (risperidone 1 - 6 mg/day; olanzapine 5 - 30 mg/day; quetiapine IR or XR 150 - 900 mg/day; aripiprazole 10 - 30 mg/day; or ziprasidone 80 - 160 mg/day), or a mood stabiliser plus a second-generation antipsychotic (SGA). 2. Has adequately tolerated the combination of antidepressant plus mood stabiliser, and is currently in remission for greater than or equal to 2 weeks and less than or equal to 8 weeks 3. If female and of childbearing potential, is using an adequate method of contraception
Exclusion criteria
Exclusion criteria: Patients meeting any of the following criteria will be excluded from the open-label study phase: 1. Has a history of rapid cycling, defined as greater than or equal to 4 mood episodes in the preceding 12 months 2. Has current manic, hypomanic, or subsyndromal hypomanic symptoms, defined as a Young Mania Rating Scale (YMRS) score greater than or equal to 8 at the screening or baseline visits 3. Has previously been refractory to treatment with both escitalopram and bupropion XL, or has been unable to tolerate both medications due to intolerable side effects or an allergic reaction 4. Has active substance dependence, other than caffeine or nicotine dependence, in the preceding 3 months. Otherwise, patients with comorbid substance abuse or other comorbid psychiatric illnesses will be eligible to participate in the study. 5. Is at high risk for suicide, as defined by a score of greater than or equal to 3 on the suicide item of the Hamilton Depression Rating Scale (HAM-D), or in the opinion of the investigator 6. Has an unstable medical illness, as defined by a change in medication or other treatment in the past 4 weeks, or in the opinion of the investigator 7. Is pregnant or lactating Patients meeting any of the following criteria will be excluded from the double-blind study phase: 1. Has a history of rapid cycling, defined as greater than or equal to 4 mood episodes in the preceding 12 months 2. Has current manic, hypomanic, or subsyndromal hypomanic symptoms, defined as a YMRS score greater than or equal to 8 at the screening or baseline visits 3. Has active substance dependence, other than caffeine or nicotine dependence, in the preceding 3 months. Otherwise, patients with comorbid substance abuse or other comorbid psychiatric illnesses will be eligible to participate in the study. 4. Is at high risk for suicide, as defined by a score of greater than or equal to 3 on the suicide item of the HAM-D, or in the opinion of the investigator 5. Has an unstable medical illness, as defined by a change in medication or other treatment in the past 4 weeks, or in the opinion of the investigator 6. Is pregnant or lactating 7. Has experienced an episode of mania, hypomania, or a mixed episode during antidepressant treatment of the acute depression, defined as a YMRS score of greater than or equal to 16 at any open-label study visit, or in the opinion of the study psychiatrist
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Open-Label Phase: The primary outcome for the open-label phase is mean improvement in Montgomery ?Asberg Depression Rating Scale (MADRS) score from baseline to endpoint. The MADRS will be completed at all study visits in the open label phase. Double-Blind Phase: 1. MADRS 2. Young Mania Rating Scale (YMRS) 3. Clinical Global Impression: Bipolar Severity Scale (CGI BP ?Severity) 4. Hospitalization 5. Requirement for additional treatment for mood episode. These measures will be completed at all visits in the double-blind phase. | — |
Secondary
| Measure | Time frame |
|---|---|
| Open-Label Phase: 1. MADRS 2. Inventory of Depressive Symptomatology (Clinician- Rated) Scale (IDS-CEnglish[1]) 3. Inventory of Depressive Symptomatology (Self-Rated ) Scale (IDS-SREnglish[1] 4. YMRS 5. CGI BP - Severity 6. Clinical Global mpression: Bipolar Change Scale (CGI BP ? Change) 7. Quality of Life scale (Q-LES-Q) 8. MDC Side Effect Scale (MDCSES). The MADRS, IDS-CEnglish[1], IDS-SREnglis[1], YMRS, CGI BP ?Severity and the MDCSES scales will be completed at all study visits. The CGI BP ? Change will be completed at every visit starting at Week 2 and the Q-LES-Q will be completed at Baseline and Week 16/ Termination. Double-Blind Phase: 1. Time to manic or hypomanic episode 2. Time to depressive episode 3. Time to study discontinuation for any reason (eg. onset of mood episode, intolerable side effects, patient or clinician decision) 4. Percentages of patients who experience any mood episode, a manic or hypomanic episode, or a depressive episode 5. Percentage of patients who experience subsyndromal symptoms and the percentage of time spent with subsyndromal symptoms 6. Rates of adverse events and serious adverse effects (SAEs) 7. Mean endpoint scores on the clinical rating scales. These will be assessed using the MADRS, IDS-CEnglish[1], IDS-SREnglish [1], YMRS, CGI BP ?Severity; CGI BP ? Change; MDCSES scales and will be completed at all visits in the double-blind phase. | — |
Countries
Canada
Outcome results
None listed