New approaches in treating schizophrenia
Address cognitive impairment, advises American expert
Recent advances in the management of schizophrenia and bipolar disorder have led to a shift in treatment approaches for these chronic conditions. From simply controlling positive symptoms and containing pathological excitement, new strategies have expanded the goals of treatment to include different but interlinked domains of psychotherapy in the "rehabilitation" of patients, according to Dr. Richard Petty, professor of medicine at the Georgia State University.
Speaking in a symposium on "Managing Schizophrenia and Bipolar Disorder: Beyond Efficacy to Effectiveness" last year, Petty said treatment strategies must consider not just the therapeutic efficacy of pharmacological agents used, but also the overall effectiveness and adequacy of treatment.
A 1999 report of the United States Surgeon General cited "minimal effects on negative symptoms and side effects--particularly extrapyramidal symptoms like acute dystonia, parkinsonism, dyskinesias, and akathisia--among the limitations of conventional neuroleptic medications. Poor patient compliance is also associated with these side effects.
Petty noted a steady rise in the use of the newer, atypical antipsychotics, especially in the US where they are prescribed for eight out of 10 patients. The reasons for the apparent success are not only medical, he said. Economic and ethical considerations are also a factor. Per tablet, they may be more expensive, but they have proven long-term benefits. Experts also believe that it is unethical to continue giving older conventional antipsychotics to patiebnts at high risk for suicide because of inadequate treatment.
Addressing cognitive impairment
Cognitive impairment remains the central problem in schizophrenia. "We lose between 20 to 40 percent of our vocabulary in the first two years. Cognition is the thing that determines the outcome," said Petty.
The prevalence of impairment is high at 85 percent, while specific delusions and hallucinations would be present in only 25 to 40 percent of patients (Palmer et al., 1997).
Explained Petty: "The illness actually attacks the association areas [of the brain]. You can see the importance of doing cognitive remediation and getting them back on their feet. You must break down the tasks. If you give too many things to do, they immediately flounder… they feel they are drowning and become demoralized."
Conventional antipsychotics, unfortunately, are not effective for cognitive impairment. They practically made everything, except attention, worse, Petty noted.
Recent studies on atypicals, however, have shown considerable promise. Meltzer and McGurk (1999) showed that risperidone improved working memory, executive function, and attention, though inconsistent for verbal learning and memory. Purdon et al. (2000), comparing various cognitive domains including executive functions, found olanzapine consistently superior to risperidone and haloperidol. In chronic treatment of schizophrenia, the most improvement in cognition was noted with olanzapine followed by risperidone, clozapine, and haloperidol.
Can newer antipsychotics then improve the treatment outcome?
Lieberman et al. compared olanzapine and haloperidol for first-episode psychotic disorder. Results showed significantly higher neurocognitive improvement in the major domains among patients in the olanzapine group compared with those in the haloperidol group. Interestingly, imaging showed decreases in the gray-matter-fluid volumes, greater among patients taking haloperidol than olanzapine. Conversely, the olanzapine group even showed increases in the fluid volume over time.
Observed Petty: "There are several potential reasons for these findings to be protective, to be neurotropic. But we think that olanzapine is actually neurotropic and neurogenetic. The idea that [the brain can be protected] and may even be restimulated is nothing short of extraordinary."
In bipolar disorder, treatment with first-generation antipsychotics proved to be comparable in efficacy with and sometimes faster in onset than lithium, divalproex, carbamazepine, olanzapine, and quetiapine. But significant limitations are posed by extrapyramidal symptoms (EPS), tardive dyskinesia, elevated prolactin, and cognitive side effects. Newer atypical antipsychotics possess potential advantages over the conventional agents because they offer a reduced risk of these side effects and fewer depressive symptoms (Nemeroff, 2000; McElroy and Keck, 2000).
Side effects can adversely affect a patient's willingness to continue treatment, said Petty. The advent of newer antipsychotic medications "has markedly lowered the burden of side effects, apparently leading to improved compliance, and has been shown to be associated with fewer episodes of relapse and hospitalization," he concluded.
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