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

• ClinicalTrials.gov Identifier: NCT01520350
• Recruitment Status: Terminated
• First Posted: January 27, 2012
• Last Update Posted: July 29, 2014
• Sponsor: Serge Beaulieu
• Collaborator: Bristol-Myers Squibb
• Information provided by (Responsible Party): Serge Beaulieu, Douglas Mental Health University Institute

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Bipolar Disorder; Depressive Episode	Drug: Low dose Adjunctive Aripiprazole; Drug: placebo	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 2 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Low-Dose Adjunctive Aripiprazole in the Treatment of Bipolar Depression: Double-Blind Placebo-Controlled Pilot Study
• Study Start Date: February 2012
• Actual Primary Completion Date: June 2013
• Actual Study Completion Date: June 2013

Arms and Interventions

Arm	Intervention/treatment
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

Outcome Measures

Primary Outcome Measures :

1. Response rate [ Time Frame: 8 weeks ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• 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

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

• Responsible Party: Serge Beaulieu, Medical Chief, Bipolar Disorders Program, Douglas Mental Health University Institute
• ClinicalTrials.gov Identifier: NCT01520350
• Other Study ID Numbers: ARI_1109
• First Posted: January 27, 2012
• Last Update Posted: July 29, 2014
• Last Verified: July 2014

Additional relevant MeSH terms:

Depression; Bipolar Disorder; Behavioral Symptoms; Bipolar and Related Disorders; Mental Disorders; Aripiprazole; Antidepressive Agents; Psychotropic Drugs; Antipsychotic Agents; Tranquilizing Agents; Central Nervous System Depressants; Physiological Effects of Drugs; Dopamine Agonists; Dopamine Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Serotonin 5-HT1 Receptor Agonists; Serotonin Receptor Agonists; Serotonin Agents; Serotonin 5-HT2 Receptor Antagonists; Serotonin Antagonists; Dopamine D2 Receptor Antagonists; Dopamine Antagonists