Pioglitazone for the Treatment of Bipolar Depression
Condition: Bipolar Disorder; Insulin Resistance
MeSH terms: Insulin Resistance; Bipolar Disorder
Intervention: Pioglitazone; Placebo
Intervention description: Pioglitazone will be initiated at a starting daily dose of 15 mg. After 7 days, the dose may be increased to 30 mg and after 35 days may be increased to a maximum of 45 mg per day.; Placebo will be initiated at a starting daily dose of 15 mg. After 7 days, the dose may be increased to 30 mg and after 35 days may be increased to a maximum of 45 mg per day.
Intervention MeSH terms: Pioglitazone
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 37.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Bipolar Disorder; Insulin Resistance

Summary:

      The primary objective is to test the hypothesis that adjunctive pioglitazone is more
      effective than placebo for the relief of acute depressive symptoms resulting from bipolar
      disorder. The secondary objectives are to determine potential moderators and mediators of
      antidepressant efficacy.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Be male or female >= 18 years of age

          -  Diagnostic and Statistical Manual-IV (DSM-IV) diagnosis of bipolar disorder (type I,
             II, or NOS)

          -  Currently depressed as confirmed by the Mini-International Neuropsychiatric Interview
             (M.I.N.I.)-Plus at the screening visit

          -  Inventory of Depressive Symptoms total score > 25 or Quick Inventory of Depressive
             Symptomatology-Self-Report (QIDS-SR16) > 11 at study baseline

          -  Women of childbearing potential (not surgically sterile or 2 years postmenopausal),
             must use a medically accepted method of contraception and must agree to continue use
             of this method for the duration of the study and for 30 days after participation in
             the study. Acceptable methods of contraception include barrier method with spermicide,
             abstinence, intrauterine device (IUD), or steroidal contraceptive (oral, transdermal,
             implanted, and injected) in conjunction with a barrier method.

        Exclusion Criteria:

          -  Pregnant or breast feeding

          -  Unstable or inadequately treated medical illness as judged by the investigator

          -  Severe personality disorder

          -  Serious suicidal risk as judged by the investigator or having a score ≥ 4 on
             Montgomery Asberg Depression Rating Scale (MADRS) item number 10 (suicidal thoughts)
             at screening or baseline

          -  Known history of intolerance or hypersensitivity to pioglitazone

          -  Treatment with pioglitazone in the 3 months prior to randomization

          -  Dependence on alcohol or drugs (other than nicotine) in the 3 months prior to study
             entry

          -  Currently taking insulin or rosiglitazone.

          -  Diagnosed with dementia

          -  Acute Mania as defined by a Young Mania Rating Scale (YMRS) score > 15

          -  Diagnosed with heart failure

          -  Transaminase elevation >2.5 times the upper limit of normal

          -  Presence of renal impairment (eg. creatinine > 1.5)

          -  History of bladder carcinoma

          -  Fasting blood glucose >150 mg/dL and Hb A1c> 7%; participants meeting these criteria
             will be referred to an endocrinologist or their primary care physician for a diabetes
             evaluation and education.

          -  Receiving acute series of electroconvulsive therapy