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Rx Resources: Cognitive enhancers for schizophrenia?

March 16, 2011
by William M. Glazer, MD
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Researchers explore a variety of interventions and agents

Since the coining of the term “dementia praecox” by the German psychiatrist Emil Kraepelin in 1896, we have been keenly aware of the role that cognitive dysfunction plays in the illness we now call schizophrenia. Yet, until the 1990s, we paid far more attention to symptoms like hallucinations and delusions than we did to signs of cognitive dysfunction, like remembering meetings, the house keys and where you left your lunch.

“Persistent cognitive deficits have a profound impact on schizophrenia patients’ ability to recover socially and vocationally. They interfere with work, school and activities of daily living,” says Alice Medalia, PhD, an expert in cognition in schizophrenia and a neuropsychologist in Columbia University’s Department of Psychiatry.

Perhaps the reason that cognitive dysfunction was overshadowed by symptoms like hallucinations and delusions was that antipsychotic medications worked better for the latter than the former. Nonetheless, cognitive deficits have emerged as a significant clinical target for research and treatment. Attempts to treat cognitive dysfunction in schizophrenia have involved both medication and non-medication approaches.

Non-Medication Approaches to Cognitive Dysfunction in Schizophrenia

ABOUT the author william m. glazer, md, is president of glazer medical solutions (www.glazmedsol.com) of key west, fla., and menemsha, mass. he is a clinician, researcher, lecturer, and consultant, and has been a member of faculty of the departments of psychiatry at the yale and harvard schools of medicine.
William M. Glazer, MD, is President of Glazer Medical Solutions of Key West, Fla., and Menemsha, Mass. He is a clinician, researcher, lecturer, and consultant, and has been a member of faculty of the departments of psychiatry at the Yale and Harvard schools of medicine.

Dr. Medalia and colleagues have co-authored a book describing “cognitive remediation” strategies1. Cognitive remediation therapy is an umbrella term for a number of interventions defined by their procedural characteristics such as use of a therapist, use of a computer and the method of training. Her group has developed the Neuropsychological Educational Approach to Cognitive Remediation (NEAR) Model-an evidence-based approach to cognitive remediation that utilizes a set of carefully crafted instructional techniques that reflect an understanding of how people learn best. NEAR provides a therapist guide that offers a step-by-step instruction for implementing techniques with patients to improve their cognitive functioning and quality of life.
Currently, the means through which cognitive change leads to change in functioning remains elusive, but hopefully the development of approaches like cognitive remediation will establish behavioral changes that signify improved functioning.

NIMH MATRICS program promotes new drug development

Recognizing the role that cognitive dysfunction plays in schizophrenia, the National Institute of Mental Health has launched the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) program.
Its purpose is to promote the development of pharmacologic agents that act on cognition and may become potential treatments for schizophrenia ( http://www.matrics.ucla.edu/). Considerable research is emanating out of the MATRICS project, including creation of standardized tests to assess cognition in schizophrenic persons, identification of psychopharmacologic targets for investigation and development of new drugs.
Currently, there is no medication that consistently treats cognitive dysfunction in schizophrenic patients. But neurobiological studies of animals have identified some promising treatments aimed at molecular targets such as dopamine-1 (D1) receptors, the serotonin system, the glutamatergic system, the nicotinic receptors, the cholinergic system, and the brain γ-aminobutyric acid (GABA) system 2. Other potential targets of interest include α2-adrenergic receptor antagonists and “wakefulness promoting agents 3.”
While we wait for research solutions, are there any available medications that might help?