Asenapine for Bipolar Depression

86 patients with an episode of major depression associated with bipolar disorder, type I
will be recruited by two sites for the study over fifteen months. Medication will be
administered in a double-blind manner. Patients will receive asenapine (or placebo)
beginning on day 0 at 5 mg bid. Dose may be increased to 10 mg bid and adjusted based on
clinical response. Patients will be evaluated by a blinded (to treatment status) rater.
Patients will be seen and ratings obtained at baseline (day 0) and on days 7, 14, 28, 42,
and 56 (or termination from the study). Adverse events will be evaluated as well.

Inclusion Criteria:

- Meet criteria for bipolar depression based on the MINI and confirmation of a previous
manic or mixed episode

- 18-55 years of age

- Female patients must be using a medically accepted means of contraception (e.g. oral
contraceptives, Depo-Provera, abstinence)

- Each patient must understand the nature of the study and must provide written
informed consent

- Patients must have a diagnosis of bipolar disorder, type I and currently display an
acute depressive episode as determined by M.I.N.I. (Sheehan et al, 1998)

- Patients must have a baseline (day 0) MADRS score ≥26

- Current episode of depression must have persisted for at least one month and no more
than six months at study entry

- Subjects should be fluent in English

Exclusion Criteria:

- Female patients who are either pregnant or lactating

- Clinically significant or unstable hepatic, renal, gastroenterologic, respiratory,
cardiovascular, endocrinologic, immunologic, hematologic or other systemic medical
conditions

- Any history of current or past diabetes that was treated with pharmacological
intervention

- Neurological disorders including epilepsy, stroke, or severe head trauma

- Clinically significant laboratory abnormalities, on any of the following tests: CBC
with differential, electrolytes, BUN, creatinine, hepatic transaminases, lipid
profile, fasting glucose, urinalysis, thyroid indices and EKG

- Depression due to a general medical condition or substance-induced depression
(DSM-IV)

- Mental retardation (IQ <70)

- Meeting criteria for a mixed episode, as defined by the Diagnostic and Statistical
Manual of Mental Disorders, Fourth Edition (DSM-IV)

- History of hypersensitivity to or intolerance of asenapine

- Prior history of asenapine non-response

- DSM-IV substance (except nicotine or caffeine) dependence within the past 3 months

- Judged clinically to be at suicidal risk (defined as having active suicidal ideation,
intent or plan, or a serious suicide attempt within 30 days, or a baseline MADRS
suicide score of >4)

- Participation in a clinical trial of another investigational drug within 1 month (30
days) prior to study entry

- Failure of the current depressive episode to respond to two or more pharmacological
interventions

- Treatment with an injectable depot neuroleptic within less than one dosing interval
between depot neuroleptic injections and day 0

- Schizophrenia or other psychotic disorders (including schizophreniform disorder,
schizoaffective disorder, delusional disorder, brief psychotic disorder, shared
psychotic disorder, psychotic disorder due to a general medical condition,
substance-induced psychotic disorder, psychotic disorder not otherwise specified) as
defined in the DSM-IV

- Major depressive disorder, dysthymic disorder, depressive disorder not otherwise
specified