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

NCT01520350 | Terminated Phase 3

• 1 other identifier: ARI_1109
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• Response rate

  The primary outcome measure will be the response rate as defined by a differential reduction of 5 points on the Montgomery Asberg rating Scale (MADRS) between the active treatment group and the placebo group at 8 weeks of treatment.

  8 weeks

Study Arms (2)

Mood stabilizer + Aripiprazole

EXPERIMENTAL

Drug: Low dose Adjunctive Aripiprazole

Mood stabilizer + placebo

PLACEBO COMPARATOR

Drug: placebo

Interventions

Low dose Adjunctive Aripiprazole DRUG

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

Also known as: Abilify

Mood stabilizer + Aripiprazole

placebo DRUG

Placebo

Mood stabilizer + placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Serge Beaulieu: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

Douglas Mental Health University Institute

Montreal, Quebec, H4H 1R3, Canada

Location

MeSH Terms

Conditions

Bipolar Disorder

Interventions

Aripiprazole

Condition Hierarchy (Ancestors)

Bipolar and Related Disorders; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Serge Beaulieu, MD, PhD

  Douglas Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Medical Chief, Bipolar Disorders Program

Study Record Dates

• First Submitted: January 25, 2012
• First Posted: January 27, 2012
• Study Start: February 1, 2012
• Primary Completion: June 1, 2013
• Study Completion: June 1, 2013
• Last Updated: July 29, 2014

Record last verified: 2014-07

Locations

CA (1)