Atomoxetine as an Adjunct to Novel Antipsychotic Medication in the Treatment of Cognitive Deficits of Schizophrenia

Participants with schizophrenia or schizoaffective disorder who are competent to participate in the informed consent process and provide written informed consent will be enrolled into the study. Participants will undergo a psychiatric evaluation, which will include the ascertainment of demographic information, past psychiatric and treatment history, and Structured Clinical Interview for DSM-IV (SCID; First et al, 1997) diagnostic interviews. A best estimate diagnostic approach will be utilized in which information from the SCID is supplemented by information from family informants, previous psychiatrists, and medical records to generate a diagnosis.

Clinical Assessments: The symptom assessments will include the Brief Psychiatric Rating Scale (BPRS; Overall and Gorham, 1961); Scale for the Assessment of Negative Symptoms (SANS; Andreasen, 1982); and Clinical Global Impression Scale (CGI; Guy, 1976). i) BPRS: the four positive symptom items - conceptual disorganization, suspiciousness, hallucinatory behavior, and unusual thought content - will be used to measure positive psychotic symptoms. These four items have been have been used to assess positive symptoms in previous studies (Kane et al, 1988; Buchanan et al, 1998). The BPRS Anxiety/Depression Factor, consisting of the somatic concern, anxiety, guilt feelings, and depression items, will be used to assess dysphoria (Guy, 1976). The BPRS hostility and uncooperativeness items will be used to assess hostility. We are not including the suspiciousness item, which is traditionally part of the BPRS Hostility Factor (Guy, 1976), because we have included this item with the other positive symptom items. ii) SANS: the SANS total score, minus the global items, inappropriate affect, poverty of content of speech, and attention items, will be used to measure negative symptoms. The inappropriate affect, poverty of content of speech, and attention items are excluded as lacking construct validity and because factor analytic study results suggest that these items are not closely related to negative symptoms (Buchanan and Carpenter, 1994). iii) CGI: the CGI severity of illness item will be used to assess global changes.

Safety Assessments: The safety assessments will include the Simpson-Angus Extrapyramidal Symptom Rating Scale (SAS; Simpson and Angus, 1970); Abnormal Involuntary Movement Scale (AIMS) (Guy, 1976); Barnes Akathisia Scale (BAS; Barnes, 1989) and Side Effect Checklist (SEC). i) SAS: a modified 11-item version of the SAS will be used to assess EPS. ii) AIMS: is a 12-item scale, with 7 items designed to assess abnormal facial, oral, extremity, and trunk movements; 3 global judgement items; and 2 current dental status items. iii) BAS : is a 4 item scale assessing objective and subjective symptoms of akathisia. iv) SEC: is designed to assess vital signs and commonly occurring antipsychotic side effects. v) Changes in total body weight, body mass index, lipid profile, and serum glucose.

Neurocognitive Assessments: The following neuropsychological tests will be administered: (1) reaction time, processing speed and efficiency, working memory-Digit Symbol, Number Sequencing, Letter Number Sequencing, Mental Arithmetic, Grooved Pegboard, Simple Reaction Time, Complex Reaction Time, Delayed Match to Sample from the Automated Neuropsychological Assessment Metric; (2) sustained attention and resistance to distractibility-Gordon's Continuous Performance Test; (3) learning and memory-California Verbal Learning Test and Brief Visual Memory Test; (4) executive functioning- Planning Test and Phonemic Fluency.

2-Week Stabilization Phase: In the 2-week stabilization phase, participants will undergo baseline symptom, medical, safety, and neurocognitive assessments. The participants will undergo a physical examination; an EKG; and laboratory tests of major organ functions (i.e., CBC, liver function tests, electrolytes, glucose, BUN/Creatinine, Urinanalysis (UA), and thyroid functions). A baseline antipsychotic level will be collected. All women will have a pregnancy test.