High Dose Lurasidone for Patients With Treatment Resistant Schizophrenia

Inclusion Criteria:

- Patients diagnosed with schizophrenia or schizoaffective disorder according to DSM-IV
criteria

- All patients must be capable of giving written informed consent.

- The criteria for treatment resistance (TR) will be those of Kane et al, (1988) which
are:

- failure to respond adequately to two or more trials with typical or atypical
antipsychotic drugs, of adequate dose and duration (at least 6 weeks) lifetime
and at least one such trial within the last two years. No patient with a history
of a successful trial of this nature within the last two years will be eligible
for inclusion. The minimum doses of antipsychotic drugs permitted in these
unsuccessful trials are specified in Table 1.

- Patients must have scores of 4 (using a 1-7 scale) or more on at least two of the
following Positive and Negative Syndrome Scale (PANSS) items: delusions [P1],
hallucinations [P3] or unusual thought content [G9]

- Patients must have a total PANSS score of 70 or above

- Patients will have had no episodes of good functioning in the previous three
years (as defined by current CGI - Severity of moderate to severe, GAF below 60;

- Personal and Social Performance Scale of 60 or below.

- Requirement for previous exposure to antipsychotic treatment:

Patients who meet treatment resistance criteria must have had at least two trials with
approved antipsychotic drugs, typical or atypical, in the standard dose range. It is
recognized that some treatment resistant patients will have had good responses to
antipsychotic drugs before meeting treatment resistant criteria.

- All patients must have a Clinical Global Impression - Severity (CGI-S) scale score at
screening of at least moderate severity, and must have a PSP score of 60 or below.

- Patients may initially be inpatients or outpatients.

- Females of child bearing potential will be admitted only if they are on stable birth
control medication and understand that they should not get pregnant during the course
of the study. Pregnancy tests will be done at baseline and at approximately 2 month
intervals.

- All patients must have stable housing at the current time or will be discharged to a
stable outpatient setting for housing, if an inpatient.

- Patients must be willing to remain compliant on oral medication throughout the
duration of the trial.

Exclusion Criteria:

- Patients unable to provide written, informed consent

- Patients with a diagnosis other than schizophrenia or schizoaffective disorder.

- Patients currently taking clozapine or have failed an adequate trial of clozapine
which lasted at least 2 months.

- Patients who have already failed trials with high doses of other atypical
antipsychotic drugs such as risperidone or olanzapine..

- Pregnant females and females who are currently breastfeeding will be excluded.

- Patients with a diagnosis of substance dependence at screening or up to one year prior
to enrollment.

- Patients with a history of non-compliance to oral medication to a degree that would
interfere with the determination of treatment resistance or diminish likelihood of
complying with this protocol

- Patients > age 60

- Uncontrolled medical conditions or recent myocardial infarction or stroke

- BMI =/>45