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

Serge Beaulieu

Status and phase

Terminated

Phase 3

Conditions

Bipolar Disorder

Depressive Episode

Treatments

Drug: placebo

Drug: Low dose Adjunctive Aripiprazole

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT01520350

ARI_1109

Details and patient eligibility

About

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.

Enrollment

2 patients

Sex

All

Ages

18 to 65 years old

Volunteers

No Healthy Volunteers

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