Escitalopram in Bipolar Depression: a Placebo-controlled Study of Acute and Maintenance Treatment
Trial Snapshot
- Phase
- Phase 4
- Status
- Terminated
- Sponsor
- Enrollment
- 150
- Locations
- 2
- Primary Endpoint
- Phase 1:
Study Overview
Brief Summary
Funding: An investigator-initiated trial funded by H. Lundbeck AS.
Study design: Prospective, randomised, placebo-controlled parallel-group multicenter study.
Aim: To investigate efficacy and side effects (especially mood switches) of escitalopram,a selective serotonin reuptake inhibitor, in the acute and maintenance treatment of bipolar depression.
Hypotheses:
- Escitalopram, given in addition to mood stabilising medications, is significantly more efficacious, measured by response and remission rates than placebo in bipolar depression (the acute phase study).
- Continuation therapy with escitalopram gives significantly longer mean time to depressive relapse and fewer depressive relapses compared to placebo (the continuation study).
- The incidence of "mood switching" (defined as development of mixed episodes, mania, or hypomania according to DSM-IV criteria) do not differ significantly between escitalopram and placebo in either the acute or the continuation phases.
Patients: In- and outpatients receiving care in the specialised psychiatric services of Western Norway. The population is intended to be representative of the patients treated for bipolar depression in ordinary specialist care. Patients must have a MADRS score of at least 20 at baseline. Patients with ongoing substance abuse or dependence, organic mental illness, and non-affective psychotic symptoms are excluded.
Medication: Escitalopram 10-20 mg daily or placebo in addition to mood stabilisers. The dose of mood stabilisers must have been constant for the last six weeks prior to randomisation.
Method: Phase 1 is a eight-week acute treatment trial with six clinical assessments. Patients treated with escitalopram who have not responded after eight weeks (defined by at least 50% reduction of MADRS score compared to baseline) leave the study. Placebo non-responders are treated openly with escitalopram and repeat phase 1. Responders are re-randomised to 32 weeks of maintenance treatment (phase 2). Phase 2 has nine clinical assessments. Patients who develop hypomania, mania or depressive episodes (defined as episodes meeting DSM-IV criteria for Major Depressive Episode with MADRS scores of at least 20 points) leave the study in this phase. Patients leaving the study prematurely will be offered alternative treatment.
Detailed Description
Aims
The study has two main aims:
- To compare the efficacy and the risk of "mood switching" of escitalopram and placebo in the acute phase treatment of bipolar depression in patients already taking mood stabilising medication.
- To compare the efficacy of escitalopram and placebo in continuation phase therapy for bipolar depression using a placebo-controlled discontinuation design. The study will compare the occurrence of syndromal and subsyndromal relapses, mixed states, mania, hypomania, and "rapid cycling" in a seven months' maintenance study following response to acute phase treatment.
Hypotheses
- Escitalopram, given in addition to mood stabilising medications, is significantly more efficacious, measured by response and remission rates than placebo in bipolar depression (the acute phase study).
- Continuation therapy with escitalopram gives significantly longer mean time to depressive relapse and fewer depressive relapses compared to placebo (the continuation study).
- The incidence of "mood switching" (defined as development of mixed episodes, mania, or hypomania according to DSM-IV criteria do not differ significantly between escitalopram and placebo in either the acute or the continuation phases.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Double
Eligibility Criteria
- Ages
- 18 Years to 70 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Patients with bipolar disorder in major depressive episode according to DSM-IV
- •MADRS score of at least 20 points at screening and baseline
- •18-70 years of age
- •Unchanged dose of mood stabilising medication for at least six weeks prior to inclusion
- •Voluntary, informed and written consent
Exclusion Criteria
- •Non-affective psychotic symptoms at screening
- •Pregnancy or breast-feeding
- •Fertile women without appropriate contraception (the pill, IUD, or contraceptive injection)
- •Substance dependence during the last three months prior to baseline
- •Mental retardation and organic brain disorders
- •Suicide risk that mandates specific measures
- •Novel (within three months) or unstable medical conditions
- •Clinically significant abnormal results on medical examination or blood samples
- •Exposure to escitalopram during the last three months
- •Allergic reactions to citalopram or escitalopram
- •Anorexia nervosa with body mass index below 18
- •Formal psychotherapy started within six weeks of screening
- •Electroconvulsive therapy (ECT) during the current episode of depression
- •Patients who are unlikely to be reliable and compliant with study procedures
- •Patients who are not fluent in Norwegian
Outcomes
Primary Outcomes
Phase 1:
response rates
remission rates
Phase 2:
emergence of major depressive episodes
emergence of mania, hypomania, and mixed states.
Secondary Outcomes
- Phase 1:
- CGI-Improvement
- change on the IDS-SR
- Phase 2:
- Time spent at different depressive symptom levels as assessed by the DSM-IV diagnostic criteria.