Study of Icariin for Bipolar Disorder and Co-Occurring Substance Use Disorders

Ten adults with current bipolar disorder (BPD) and current cocaine or alcohol use disorders,
based on a structured clinical interview (SCID), and a baseline Hamilton Rating Scale for
Depression (HAMD) score of ≥ 15, will be recruited through a patient database of a recently
completed study of bipolar disorder patients with cocaine dependence. Informed consent will
be obtained. The clinician version of the structured Clinical Interview for DSM-IV (SCID) is
a brief structured interview for major Axis I disorders in DSM-IV including major depressive
disorder, dysthymic disorder, bipolar disorders, psychotic disorders, anxiety disorders,
eating disorders, and alcohol and substance abuse/dependence. This will be given at baseline
to confirm bipolar disorder diagnosis. Blood draws and a physical examination by a physician
will be performed at baseline to general physical health. Participants will return to
receive icariin (100 mg/day)once their general health and diagnosis are confirmed.

Participants will be assessed at baseline and weekly with the HAMD and a urine drug screen,
for 8 consecutive weeks after initiating intervention (icariin). A dose titration from 100
mg/day to 200 mg/day will be allowed at week 3 for participants with less than a 30%
reduction in HAMD and/or still using cocaine or alcohol or have a positive urine drug
screen. An additional dose titration to 300 mg/day will be allowed at week 6 for
participants with less than a 50% reduction in HAMD scores and/or still using cocaine or
alcohol or have a positive urine drug screen.

Pill counts will be conducted, and a list of current medications and doses will be obtained
at each visit. Participants will be compensated and receive bus passes at each appointment.
Participants will be evaluated by both the research assistant (RA) and principal
investigator (PI) at each follow-up appointment.

The HAM-D will be the primary outcome measure. Other cognitive assessments will be performed
at these same visits as well.

Inclusion Criteria:

- Current BPD I, II or NOS and cocaine or alcohol use disorder with HAMD score of ≥ 15

- Cocaine or alcohol use with 5 days of initiating study drug

- Men and women

- Age 18-70 years

Exclusion Criteria:

- Psychotic features

- Non-English speakers

- Treatment resistant depression defined as failure of a trial of antidepressants (≥ 4
weeks at a therapeutic dose) in current episode

- Major medical condition including heart, lung, liver or renal disease, cancer,
neurological or immunological conditions

- Vulnerable populations including prisoners, cognitively impaired individuals, and
pregnant or nursing women

- Prior side effects or allergic reactions to icariin-containing preparations

- Change in psychotropic medications within 14 days of study entry

- Current suicidal ideation (plan and intent), a suicide attempt within the past 12
months or history of > 1 lifetime suicide attempt