This research is being done because people with schizophrenia often have problems with thinking including learning, remembering, paying attention, and problem solving. During this study, we will test if cognitive remediation (computer games made to improve thinking), used along with a drug called atomoxetine, may help the problems in thinking as well as some of the symptoms of schizophrenia.

Persons with schizophrenia in a stable and residual antipsychotic- treated clinical condition for at least 8 weeks will be recruited from several public mental health treatment settings into the UTSW Schizophrenia Research Clinic. Each volunteer will receive information about the protocol and its risks and benefits. If they give their informed consent after a full opportunity to learn about the details of the study, they will be allowed to proceed. All recruits will have been treated with optimal dosing of any 2nd generation antipsychotic drug (APD-2) and will have been clinically stable with respect to psychotic symptoms for at least 6 weeks prior to randomization, and on a stable dose of the medication for at least 2 weeks. All eligible volunteers will receive a routine medical assessment and psychiatric diagnostic work-up including the SCID and a consensus diagnosis by two experienced clinicians based on all available data, prior to the randomization. Just prior to randomization, the following sets of assessments will be performed: (1) Medical: Physical Examination, Clinical Chemistries, EKG, urinalysis, weight, and vital signs; (2) Symptomatic: general psychiatric symptom assessment, including the scores on the PANSS, Psychosis Change Scale, and CGI; (3) Cognitive: standard neuropsychometric test battery and surrogate psychosocial tests; all of the assessment batteries will be repeated at the end of the 12-week treatment period, and repeated again at the end of the three month follow-up period (at 6 months from study start). Clinical symptom scales, weight, and vital signs will be repeated at weeks 4, 8, 12, 16 , and 24 during the study.

The schizophrenia volunteers will be randomized into four treatment groups: (1) atomoxetine plus cognitive remediation; (2) atomoxetine plus remediation control; (3) placebo plus cognitive remediation; and (4) placebo plus remediation control. Atomoxetine or matching placebo will be administered at a dose of 40mg bid (80mg/day) or the placebo equivalent. The remediation sequence will last for 60 minutes and will be administered three times weekly; the remediation control will be administered on the same schedule and for the same duration. Because the volunteers attend the clinic so regularly, we will have an opportunity to track their progress, monitor medication adherence, and optimize study participation.

Then, each volunteer will be followed up while taking their blinded study medications, but without any more remediation/control sessions, for the next 3 months. Psychiatric rating scales will be completed the following times, relative to the blinded randomization: baseline, 1, 2, 3, 4, 5, 6 months, whereas the neuropsychological battery will be completed at baseline and at 3 and 6 months.

Inclusion Criteria:

• DSM-IV diagnosis of schizophrenia or schizoaffective disorder.
• Males and females.
• Ages 18-60 years old.
• All races and ethnicities.

Exclusion Criteria:

• Diagnosis of an organic brain disease.

• Diagnosis of DSM-IV alcohol or substance abuse within the last month or DSM-IV alcohol or substance dependence within the last 3 months.

• Meet criteria for primary negative symptoms, established by clinical judgment.

• Current or past history of clozapine treatment for antipsychotic non-response.

• Patients hospitalized in a psychiatric hospital within the previous 30 days.

• Patients with an unstable medical condition, as determined by the Investigator

• Colorblindness

• Concurrent treatment with electroconvulsive therapy or psychotherapy.

• Pregnant women.

• Must be able to read, speak, and understand English.

  • We do not have the resources necessary to properly study non-English speaking patients in this study. The computer software used for cognitive remediation and some clinical assessments are only available in English. The need to provide such resources in foreign languages would be prohibitive to the successful completion of the study.