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