Magazine article Clinical Psychiatry News

Practical Psychopharmacology: Cognitive Deficits and Schizophrenia

Magazine article Clinical Psychiatry News

Practical Psychopharmacology: Cognitive Deficits and Schizophrenia

Article excerpt

Cognitive deficits have long been recognized in the core definition of schizophrenia, but only in the past few years has their full impact become clear. They predict disability more powerfully than do positive or negative symptoms.

Overall progress in pharmacotherapy notwithstanding, "our current treatments don't appear to do very well in this area," said Dr. Wayne Fenton, associate director for clinical affairs at the National Institute of Mental Health (NIMH), Bethesda, Md.

Current research aims to rectify the situation. NIMH's ongoing Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) initiative is intended to facilitate development of novel drugs targeted to this symptom domain.

Two decades of neurobiologic research have progressed "to the point where ... a translational leap from lab to clinic" is eminently foreseeable, said Dr. Fenton, MATRICS project officer.

Meanwhile, how can contemporary clinicians best approach this aspect of schizophrenia?

First, do as little harm as possible. "Minimizing problematic side effects of the primary antipsychotic treatment is the best strategy," Dr. Fenton said. Second-generation antipsychotics may not impair cognition to the extent that conventional neuroleptics do. For maintenance treatment, all antipsychotics should be prescribed at the lowest dose needed to prevent symptom recurrence.

Dr. Robert Buchanan, professor of psychiatry at the University of Maryland, Baltimore, observed that the difference between old and new in this regard disappears when first-generation agents are used at low dosages. For a patient who remains on a conventional neuroleptic, "try to get the dosage down," Dr. Buchanan said.

Beyond that, consider the overall regimen with an eye toward simplification, Dr. Buchanan suggested.

Whether any antipsychotics actively ameliorate cognitive deficits is a matter of debate. "There was initially great enthusiasm that second-generation drugs would address cognition, but to a substantial extent they have fallen short," Dr. Fenton explained. "The relatively small improvements seen with these agents are likely due to better side effect profiles."

Dr. Herbert Y. Meltzer, professor of psychiatry and pharmacology at Vanderbilt University, Nashville, Tenn., is more hopeful.

He noted that in the contemporary version of the dopamine hypothesis, enhanced dopamine activity in the limbic system is putatively responsible for positive symptoms, but a diminution of the neurotransmitter in the prefrontal cortex is responsible for cognitive deficits. Research suggests that the atypicals enhance dopamine activity in that region, probably through 5-H[T.sub.2A] effects, Dr. Meltzer said.

Some cognitive improvements have been seen with atypicals, he said. Although differences probably exist between agents, the evidence is insufficient to choose among them on that basis.

"My advice to clinicians would be to assess cognition when starting an antipsychotic and consider switching to another or trying an augmentation strategy if there hasn't been a significant improvement after 3-6 months," Dr. Meltzer said.

The data for augmentation strategies are similarly less than overwhelming.

In "the world of blunt instruments" in which contemporary clinicians try to meet patients' needs, cholinesterase inhibitors are probably "as good an approach as we have," Dr. …

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