Pilot Study of Atomoxetine To Enhance COgnition In Patients With Schizophrenia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00488163
Recruitment Status : Completed
First Posted : June 20, 2007
Last Update Posted : October 5, 2017
Eli Lilly and Company
Information provided by (Responsible Party):
Joseph Friedman, Research Foundation for Mental Hygiene, Inc.

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Schizophrenia Drug: Atomoxetine Phase 4

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  (Clinical Trial)
Actual Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Pilot Study of Atomoxetine To Enhance COgnition In Patients With Schizophrenia
Study Start Date : January 2005
Primary Completion Date : April 2007
Study Completion Date : June 2007

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Schizophrenia
U.S. FDA Resources

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 Name: 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 Name: Strattera®

Primary Outcome Measures :
  1. Composite score on the Brief Assessment of Cognition in Schizophrenia [ Time Frame: 8 weeks ]
    Cognitive performance as measured by the BACS

Secondary Outcome Measures :
  1. Brain activation measured by functional magnetic resonance imaging [ Time Frame: 8 weeks ]
    Differences between changes in brain oxygenation level dependent imaging measures between placebo and Atomoxetine

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00488163

United States, New York
Pilgrim Psychiatric Center
Brentwood, New York, United States, 11717
Mount Sinai Hospital
New York, New York, United States, 10029
Sponsors and Collaborators
Research Foundation for Mental Hygiene, Inc.
Eli Lilly and Company
Principal Investigator: Joseph I Friedman, MD Pilgrim Psychiatric Center

Responsible Party: Joseph Friedman, Principal Investigator, Research Foundation for Mental Hygiene, Inc. Identifier: NCT00488163     History of Changes
Other Study ID Numbers: 00131-03-1284
First Posted: June 20, 2007    Key Record Dates
Last Update Posted: October 5, 2017
Last Verified: October 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Joseph Friedman, Research Foundation for Mental Hygiene, Inc.:

Additional relevant MeSH terms:
Schizophrenia Spectrum and Other Psychotic Disorders
Mental Disorders
Atomoxetine Hydrochloride
Adrenergic Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Adrenergic Agents
Neurotransmitter Agents
Physiological Effects of Drugs