Low-Dose Adjunctive Aripiprazole in the Treatment of Bipolar Depression: Double-Blind Placebo-Controlled Pilot Study

NCT ID: NCT01520350

Last Updated: 2014-07-29

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 2 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-02-29
• Study Completion Date: 2013-06-30

Brief Summary

Aripiprazole is a new antipsychotic agent which possesses unique capabilities compared to other antipsychotic agents, especially because of its partial dopaminergic agonistic activity. Moreover, like the other atypical agents, aripiprazole is an antagonist of the 5-HT2a receptor, and an agonist of the 5-HT1a receptor. These pharmacological properties should enable this molecule to provide antidepressant potentiating capabilities based on what has been observed with other compounds sharing similar pharmacological profiles.

Aripiprazole is now well recognized for its capacity to potentiate antidepressants in the treatment of unipolar depression. However, two randomized controlled trials of aripiprazole in the treatment of bipolar depression were negative. This surprising result may stem from the fact that the doses of aripiprazole used in these studies were rather high (17.6 ± 8.3 mg/d in study 1 and 15.5 ± 7.5 mg/d in study 2) and could have contributed to inhibit dopaminergic activity in key brain areas involved in the modulation of rewards, motivation and concentration. Bipolar depression is indeed heavily loaded with general symptoms of psychomotor retardation including poor concentration, low energy level, hypersomnolence, and hyperphagia. All these functions are modulated by dopamine and strategies aimed at improving dopaminergic function are used frequently to resolve residual symptoms of bipolar depression.

It is expected that aripiprazole used at a more adequate lower dose than in previous studies, should be efficacious in the treatment of bipolar type I depression.

Conditions

Bipolar Disorder; Depressive Episode

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Mood stabilizer + Aripiprazole

Group Type: EXPERIMENTAL

Low dose Adjunctive Aripiprazole

Intervention Type: DRUG

low-dose 2-5mg/d for 8 weeks

Mood stabilizer + placebo

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: DRUG

Placebo

Interventions

Low dose Adjunctive Aripiprazole

low-dose 2-5mg/d for 8 weeks

Intervention Type: DRUG

placebo

Placebo

Intervention Type: DRUG

Other Intervention Names

Abilify

Eligibility Criteria

Inclusion Criteria

• Age : 18-65
• Male or female
• Bipolar Disorder type I
• Current depressive episode (with MADRS ≥ 20 and item 2 (reported sadness) ≥ 3) for a minimum of 2 weeks but ≤ 52 weeks at screening visit and baseline visit)
• If female and of childbearing potential, is using an adequate method of contraception.
• Is treated with a mood stabilizer (lithium and/or valproate)
• Patient is able to give his consent

Exclusion Criteria

• Is at high risk of suicide as defined by a score of ≥ 3 to item 10 of MADRS and/or in the clinical opinion of the investigator
• Hypo(mania) episode with YMRS ≥ 8
• Psychotic symptoms as defined by a score of ≥ 4 to item 8 (content) of YMRS and/or in the opinion of the investigator
• Is treated with fluoxetine OR lamotrigine OR carbamazepine OR any antidepressants
• Is treated with risperidone OR olanzapine OR quetiapine OR ziprazidone OR any antipsychotics
• Is pregnant or lactating or absence of contraceptive treatment
• Drug abuse or dependence as per DSM-IV (MINI)
• Unstable medical condition
• Other psychiatric condition, organic brain disorder, unstable and/or untreated medical condition such as hypothyroidism, hyperthyroidism, diabetes, cardiac condition, hypertension
• Deficit in vitamin B12 or folate
• Alcohol or drug abuse
• Rapid cycling (more than 4 mood episodes per year)
• Active or history of difficulty to swallow
• Seizures not currently controlled with medications
• Orthostatic hypotension
• A history of clinically significant cardiovascular disorders and cardiac arrhythmias
• A low white blood cell count
• Known eye disease
• Involuntary, irregular muscle movements, especially in the face
• Known hypersensitivity to aripiprazole and any components of its formulation
• Known lactose intolerance or have hereditary galactose intolerance or glucose-galactose malabsorption, because ABILIFY tablets contain lactose

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bristol-Myers Squibb

INDUSTRY

Sponsor Role: collaborator

Serge Beaulieu

OTHER

Sponsor Role: lead

Responsible Party

Serge Beaulieu

Medical Chief, Bipolar Disorders Program

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Serge Beaulieu, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Douglas Institute

Locations

Douglas Mental Health University Institute

Montreal, Quebec, Canada

Countries

Canada

Other Identifiers

ARI_1109

Identifier Type: -

Identifier Source: org_study_id