Effect of Ziprasidone on Glucose & Plasma Lipids in Diabetes (II) and Schizophrenia or Schizoaffective Disorder

Inpatients with DSM IV diagnosis of schizophrenia or schizoaffective disorder and DM II will
be enrolled after giving informed consent. Participants may stay on their original ward at
MPC, if their clinical care would be better served on their home ward because of patient
programs and/or continuity of care reasons. Patients recruited from other participating sites
will be transferred to MPC research ward.

There will be a screening phase (two weeks) on the prior antipsychotic regimen, a
cross-titration phase (three week) and a ziprasidone phase (eight weeks; four time points).

All medications, except for the antipsychotic agents, will be kept stable throughout the
protocol. These medications may include anticholinergics, mood stabilizers and
antidepressants. After the screening phase lasting two weeks, patients will enter the
cross-titration phase lasting three week. The cross titration schedule will be changed in
accordance with Deutschman & Deutschman's 2005 recommendations. The current antipsychotic
will be gradually decreased to zero and ziprasidone will be started at 40 mg bid po and
raised up to 160 mg po bid during the cross-titration phase, according to clinical response
and tolerance. After the cross-titration phase has concluded, the ziprasidone dose will range
from 80 mg bid p.o. to 160 mg bid p.o. daily according to clinical response during the eight
week treatment phase.

Inclusion Criteria:

1. Aged 18 to 65 years

2. DSM IV diagnosis of schizophrenia (all subtypes) or schizoaffective disorder

3. Diabetes Mellitus type II treated with oral antidiabetic drugs or insulin

4. Stable dose of antipsychotic regimen for previous one month.

5. Stable dose of antidepressant regimen for previous one month.

6. Stable dose of adjunctive mood stabilizer and/or anticholinergic regimen for previous
1 month

7. Signed informed consent

8. Absence of significant cardiovascular pathology as demonstrated by EKG (QTc < 450
millisec)

9. Absence of severe medical conditions (except for DM) requiring frequent changes in
medication.

Exclusion Criteria:

1. DSM IV diagnosis other than Schizophrenia or Schizoaffective disorder

2. Unstable epilepsy

3. Acute, unstable or significant medical condition

4. Suicidal or physically violent behavioral episodes in the previous month

5. Current DSM IV diagnosis of substance or alcohol abuse with positive urine toxicology
in the past two weeks.

6. Liver enzyme test values ≥ three times upper normal limit for AST, ALT, GGT, and
Alkaline Phosphatase; ≥ two times upper limit for LDH.