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

This study has been terminated.
(recruitment issues)
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
Serge Beaulieu, Douglas Mental Health University Institute
ClinicalTrials.gov Identifier:
NCT01520350
First received: January 25, 2012
Last updated: July 28, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention Phase
Bipolar Disorder
Depressive Episode
Drug: Low dose Adjunctive Aripiprazole
Drug: placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Low-Dose Adjunctive Aripiprazole in the Treatment of Bipolar Depression: Double-Blind Placebo-Controlled Pilot Study

Resource links provided by NLM:


Further study details as provided by Douglas Mental Health University Institute:

Primary Outcome Measures:
  • Response rate [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    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.


Enrollment: 2
Study Start Date: February 2012
Study Completion Date: June 2013
Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Mood stabilizer + Aripiprazole Drug: Low dose Adjunctive Aripiprazole
low-dose 2-5mg/d for 8 weeks
Other Name: Abilify
Placebo Comparator: Mood stabilizer + placebo Drug: placebo
Placebo

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01520350

Locations
Canada, Quebec
Douglas Mental Health University Institute
Montréal, Quebec, Canada, H4H 1R3
Sponsors and Collaborators
Serge Beaulieu
Bristol-Myers Squibb
Investigators
Principal Investigator: Serge Beaulieu, MD, PhD Douglas Institute
  More Information

No publications provided

Responsible Party: Serge Beaulieu, Medical Chief, Bipolar Disorders Program, Douglas Mental Health University Institute
ClinicalTrials.gov Identifier: NCT01520350     History of Changes
Other Study ID Numbers: ARI_1109
Study First Received: January 25, 2012
Last Updated: July 28, 2014
Health Authority: Canada: Health Canada

Additional relevant MeSH terms:
Depression
Bipolar Disorder
Depressive Disorder
Behavioral Symptoms
Affective Disorders, Psychotic
Mood Disorders
Mental Disorders
Aripiprazole
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Psychotropic Drugs

ClinicalTrials.gov processed this record on October 19, 2014