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Treatment response and compliance are rarely absolute in schizophrenia.

NEW YORK -- In schizophrenia, black-and-white thinking fails to capture the reality of treatment response and compliance.

An appreciation of the wide middle ground can help clinicians understand relapse issues and the relative efficacy of antipsychotics, Jean-Pierre Lindenmayer, M.D., said at a meeting on psychopharmacology sponsored by New York University.

Even in ostensibly successful antipsychotic treatment, "it is rare for a patient to respond in all domains of pathology or function," which include excitement, affective symptoms, and cognitive deficits as well as positive and negative syndromes. "Partial response is the rule," said Dr. Lindenmayer, clinical director of the Manhattan Psychiatric Center, New York.

Although positive symptoms can be largely controlled by both conventional and atypical antipsychotics, cognitive deficits often remain troublesome. "They may be another core area in schizophrenia," he said.

Such deficits are independent of positive and negative symptoms and more highly correlated with work capacity, social adaptation, and community residency than either.

They are not iatrogenic but are present early in the disease.

Second-generation antipsychotics appear to have a more positive effect than older drugs on cognitive symptoms, particularly executive functions, and on verbal memory and learning.

Augmentation strategies have been disappointing. The best data are for ACE inhibitors, for which "the news is not too good," Dr. Lindenmayer said.

A large study involving atomoxetine for this application is currently underway, he said.

Psychosocial approaches, such as computer-assisted neurocognitive training, may be as effective as any drug treatment currently available for this aspect of schizophrenia, he said.

"Treatment for cognitive symptoms should be the center of development of new drugs, but it's not," Dr. Lindenmayer said.

Although second-generation agents appear more effective than their predecessors for negative and affective symptoms, these symptoms are still likely to remain after psychotic phenomena are under control.

Antidepressant augmentation may help, and there are some "encouraging data" for glutaminergic agents such as glycine and cycloserine, he said.

Atypical antipsychotics also appear to be more effective than conventional agents in preventing relapse.

A metaanalysis of studies including more than 1,700 patients found significantly fewer relapses in the course of a year with second-generation drugs (15%) than conventional drugs (23%) (Am. J. Psychiatry 2003;160:1209-22).

Difficulties in maintenance remain, however, and probably relate to continuing compliance problems.

It is well established that relapse rates are substantially higher with intermittent than with continuous antipsychotic therapy, and many patients are essentially opting for the former, Dr. Lindenmayer said at the conference.

"Both complete noncompliance and satisfactory compliance are rare," he said. "We see patients regularly and assume they are taking the antipsychotic, but most are partially compliant" and follow prescribed regimens erratically.

Although second-generation antipsychotics were expected to substantially ameliorate compliance problems, their advantage in this regard appears to diminish over the long run.

In one study of pharmacy refill records of outpatient veterans, investigators found that medication adherence rates were significantly higher with the newer atypical antipsychotics after 6 months.

However, adherence rates for typical and atypical antipsychotics were comparable after 1 year, Dr. Lindenmayer said (Am. J. Psychiatry 2002;159:103-8).

Depot formulations of older agents have been shown to reduce relapse rate, presumably through enhanced compliance, Dr. Lindenmayer observed, and data suggest this applies to depot risperidone as well.


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Title Annotation:Adult Psychiatry
Author:Sherman, Carl
Publication:Clinical Psychiatry News
Date:Aug 1, 2005
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