Naturalistic Study, Comparison of Divalproex Extended Release (ER) and Quetiapine for Adults With Acute Mania or Mixed Episodes
Condition: Bipolar Disorder
MeSH terms: Bipolar Disorder
Intervention: divalproex ER; quetiapine
Intervention description: Dose: 30mg per kg, rounded to nearest 500mg, dosed PO QHS. Adjustments made through trial to obtain serum valproic acid levels of 85-125 mcg/ml; Dose: 200mg PO QHS, titrated up to therapeutic dose of 600-800mg.
Intervention MeSH terms: Valproic Acid; Quetiapine Fumarate
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Enrollment: 30.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: quetiapine; divalproex

Summary:

      The primary objective of this study is to compare the efficacy and tolerability of quetiapine
      versus divalproex extended-release administered in a rapid oral loading fashion in the
      treatment of acute episodes of mania or mixed mania in bipolar disorder. Three hypotheses
      will be tested:

      Hypothesis 1: treatment ( 3 weeks) of divalproex extended-release is similar to quetiapine in
      the symptomatic control of mania or mixed mania

      Hypothesis 2: divalproex extended-release orally loaded may produce significant improvements
      in symptoms of mania sooner than quetiapine

      Hypothesis 3: divalproex extended-release may produce significantly less sedation
    

Eligibility criteria:

        Inclusion Criteria:

        For inclusion, patients must fulfill all of the following criteria at enrollment:

          1. Provide written informed consent before initiation of any study-related procedures

          2. A diagnosis of Bipolar I Disorder, Most Recent Episode Manic (296.4x), or Bipolar I
             Disorder, Most Recent Episode Mixed (296.5x), with or without psychotic features, as
             defined by Diagnostic and Statistical Manual of Mental Disorders- Fourth Edition
             (DSMIV)

          3. Male or female, at least 18 years old

          4. YMRS score equal to or greater than 17 and a CGI of 4 (moderate) or greater.

          5. Female patients of childbearing potential must be using a reliable method of
             contraception. Reliable methods of contraception include hormonal contraceptives
             (e.g., oral contraceptive or long-term injectable or implantable hormonal
             contraceptive), double-barrier methods (e.g., condom and diaphragm, condom and foam,
             condom and sponge), intrauterine devices, and tubal ligation.

        Exclusion Criteria:

          1. Known intolerance or lack of response to quetiapine fumarate or Divalproex ER as
             judged by the investigator.

          2. Unwilling or not able to provide informed consent

          3. Positive urine toxicology result on screening for cocaine, phencyclidine (PCP),
             opiates or amphetamines that confirms the current manic/mixed episode is better
             accounted by a substance intoxication or withdrawal as judged by PI.

          4. History of schizophrenia or schizoaffective disorder

          5. Treatment with a depot antipsychotic within 1 treatment cycle

          6. Unstable medical condition including hepatic, renal, gastroenterologic, neurologic,
             immunologic, or hematologic diseases that is deemed by the principle investigator to
             likely to result in hospitalization in 6 months or death within one year

          7. A female subject who is pregnant or lactating

          8. Lorazepam will be provided for agitation and insomnia as needed for rescue only. Not
             to exceed 6 mg in the first 7 days; Not to exceed 4 mg for the next 3 days and note to
             exceed 2 mg/day for the remainder of the study. Those that require a greater amount of
             Lorazepam will be excluded.

          9. Hospitalized for more than 1 week for current episode at the screen

         10. Substance or alcohol dependence at enrollment and within the three months prior to
             enrollment (except dependence in full remission, and except for caffeine or nicotine
             dependence), as defined by DSM-IV criteria.

         11. Known diagnosis of dementia or MCI