Pilot Study of Atomoxetine To Enhance COgnition In Patients With Schizophrenia

Relationships between altered prefrontal cortical dopamine, norepinephrine and some cognitive impairments of schizophrenia supports and approach for pharmacological remediation of cognitive symptoms through manipulations of prefrontal cortical dopamine and norepinephrine. Atomoxetine, a selective norepinephrine re-uptake inhibitor, produces a widespread increase in brain norepinephrine and a secondary and selective increase in prefrontal dopamine. Given this, we are evaluating atomoxetine's cognitive effects in a pilot placebo controlled trial in patients with schizophrenia. Moreover, an fMRI investigation was undertaken to assess the neural mechanisms underlying the cognitive effects of atomoxetine.

Study Overview

• Status: Completed
• Conditions: Schizophrenia
• Intervention / Treatment: Drug: Atomoxetine

Detailed Description

Participants carrying a diagnosis of schizophrenia and receiving treatment with one of the following antipsychotic medications are eleigible for participation: risperidone, olanzapine, quetiapine, aripirazole. Following consent, participants will be observed for 4 weeks to ensure stability of their symptoms. Following this, there will be baseline assessments of symptom severity, cognitive ability, functional ability and an fMRI scan. Following this, participants will be randomly assigned to receive treatment with 40 mg of atomoxetine or placebo daily during a double-blind parallel designed four week treatment period, following which the dose of atomoxetine will be increased to 40 mg twice day (or matching placebo) for an additional 4 weeks. The cognitive assessment battery and MRI will be repeated following 8 weeks of treatment.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • New York
    • Brentwood, New York, United States, 11717
      • Pilgrim Psychiatric Center
    • New York, New York, United States, 10029
      • Mount Sinai Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Subjects will be males and females between the ages of 18 and 65
2. In good general medical health
3. For patient subjects, a DSM-IV diagnosis of schizophrenia, any subtype
4. Currently in remission or with stable, unchanging residual symptoms
5. Receiving treatment with olanzapine, aripiprazole, risperidone, or quetiapine as their antipsychotic medication at a stable dose for a minimum of eight weeks.
6. Able to complete neurocognitive tests
7. Able to give informed consent. All subjects will be required to have at least an 8th grade reading level and/or a full-scale IQ of at least 85 as assessed by the Wide Range Achievement Test (WRAT).

Exclusion Criteria:

1. Recent history (within previous year) of serious suicide, homicide, or physical violence, or current suicidal or homicidal thoughts
2. Any axis I DSM-IV diagnosis in addition to schizophrenia or schizoaffective disorder except substance abuse in remission
3. History of severe head trauma, neurological disorder, or medical illness which may contribute to the subjects' psychiatric symptoms or cognitive impairment
4. Medical illness which requires taking any medication that has CNS activity which is known to impair cognition.
5. Untreated or unstable hypertension.
6. Coronary artery disease.
7. Receiving concomitant anticholinergic drugs, antidepressants or mood stabilizers. If patient subjects are receiving benzodiazepines, they must be short or intermediate acting (e.g. alprazolam, lorazepam) and must be held 48 hours prior to cognitive testing
8. Unable to give informed consent
9. History of developmental disorder or less than an eighth

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Atomoxetine; Atomoxetine 40 mg compounded into capsules.	Drug: Atomoxetine; Dose escalation from 40 mg to 50 mg of Atomoxetine active treatment.; Other Names: Strattera®
Placebo Comparator: Placebo; Inactive matching compounding of placebo capsules	Drug: Atomoxetine; Dose escalation from 40 mg to 50 mg of Atomoxetine active treatment.; Other Names: Strattera®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite score on the Brief Assessment of Cognition in Schizophrenia	Cognitive performance as measured by the BACS	8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Brain activation measured by functional magnetic resonance imaging	Differences between changes in brain oxygenation level dependent imaging measures between placebo and Atomoxetine	8 weeks

Collaborators and Investigators

• Sponsor: Research Foundation for Mental Hygiene, Inc.
• Collaborators: Eli Lilly and Company
• Investigators: Principal Investigator: Joseph I Friedman, MD, Pilgrim Psychiatric Center

Publications and helpful links

General Publications

• Bymaster FP, Katner JS, Nelson DL, Hemrick-Luecke SK, Threlkeld PG, Heiligenstein JH, Morin SM, Gehlert DR, Perry KW. Atomoxetine increases extracellular levels of norepinephrine and dopamine in prefrontal cortex of rat: a potential mechanism for efficacy in attention deficit/hyperactivity disorder. Neuropsychopharmacology. 2002 Nov;27(5):699-711. doi: 10.1016/S0893-133X(02)00346-9.

Study record dates

Study Major Dates

• Study Start: January 1, 2005
• Primary Completion (Actual): April 1, 2007
• Study Completion (Actual): June 1, 2007

Study Registration Dates

• First Submitted: June 18, 2007
• First Submitted That Met QC Criteria: June 18, 2007
• First Posted (Estimate): June 20, 2007

Study Record Updates

• Last Update Posted (Actual): October 5, 2017
• Last Update Submitted That Met QC Criteria: October 3, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Keywords: cognition; schizophrenia; atomoxetine; norepinephrine; dopamine
• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Adrenergic Uptake Inhibitors; Atomoxetine Hydrochloride
• Other Study ID Numbers: 00131-03-1284

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No