The aim of the protocol is to study the effects of 320 mg/day of ziprasidone (Geodon) on glucose and lipid metabolism of patients with both Diabetes Type II (DM) and schizophrenia or schizoaffective disorder, after switching their antipsychotic medication/s from typical and/or atypical to ziprasidone monotherapy.

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.