Letters to the Editor
Gains in Speeded Information Processing Following Clozapine Treatment of Schizophrenia
Dear Editor:
Recent studies have focused on the impact of novel antipsychotics upon schizophrenia’s core cognitive deficits. Clozapine is one of the agents within this domain, and evidence is growing to support its positive impact upon cognitive functioning, including processing speed (1–5). Because cognitive functioning has predicted functional outcome (6,7), use of agents that may improve it is likely to become increasingly important. Further, clozapine should not be considered a treatment of last resort, as is often the case in Canada. We describe clozapine treatment of a male schizophrenia patient and the marked increase in cognitive as well as vocational functioning subsequently observed.
Case Report
A 35-year-old single man who was a full-time graduate student and living independently was admitted to the Prevention and Early Intervention Program for Psychoses (PEPP) with a first episode of paranoid schizophrenia. Over the first 2 years of treatment, he continued to suffer from florid psychosis, was non- compliant with medication, and was hospitalized on 2 occasions. Trials of oral risperidone and olanzapine and depot intramuscular risperidone were undertaken, with only temporary and partial symptom relief. The patient remained enrolled in his PhD program but kept putting off his dissertation. Twenty-seven months into PEPP, he began a trial of clozapine.
At baseline cognitive assessment following entry into PEPP, the patient scored at or above average on measures of intellectual functioning, working memory, immediate and delayed auditory memory, delayed visual memory, and mental flexibility. Weakness (that is, a score 1 or more standard deviations below average) was demonstrated in immediate visual memory, concept formation, attention, and processing speed. The patient was not willing or able to tolerate the demands of testing again until 41 months after entering the program. At that time, he had been taking clozapine 400 mg daily for approximately 14 months. He showed significant improvement in positive and negative symptoms of psychosis. Significant gains in concept formation and attention were seen. Most notably, the patient demonstrated an improvement in speeded information processing, rising from over 2 standard deviations below average to 0.5 standard deviations below average (a gain of 31 points). Although he did not complete his PhD, he is now employed full-time in his field of study.
Discussion
The gain in processing speed following clozapine treatment was far beyond that reported in other studies (1–5), significantly greater than gains in other areas (suggesting differential impact), and not explained by practice effects. There were no changes in other cognitive domains. Since persistent clinical improvement and medication adherence was noted only after he started taking clozapine, the likelihood of cognitive gains predating clozapine is minimal.
Cognitive data from our centre involving a large sample of first-episode psychosis patients treated with novel antipsychotics (primarily risperidone) do not demonstrate the same degree of improvement in processing speed. This domain, in fact, remains an area of relative weakness, despite gains in other areas (8). Symptom reduction is also not likely to explain this gain. Reports on the relation between cognition and symptoms have been inconsistent in the literature and are often weak, at best (9–11).
Our results confirm that clozapine treatment effectively enhances neuro- cognitive function and suggest that significant gains are possible, particularly in the area of processing speed. This effect was demonstrated after an extended period of unsuccessfully treated illness; the reported case supports this medication’s benefit in stabilizing not only psychotic symptoms but also cognitive difficulties—even more than 3 years after the emergence of what appeared to be a treatment-resistant psychosis. This case demonstrates the need to consider introducing clozapine early, as well as the benefits of not waiting until several trials of other antipsychotics have been undertaken.
References
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2. Galletly CA, Clark RC, McFarlane AC, Weber DL. The effect of clozapine on the speed and accuracy of information processing in schizophrenia. Progress in Neuropsychopharmacolgy and Biological Psychiatry 2000;24:1329–38.
3. Hagger C, Buckley P, Kenny JT, Friedman L, Ubogy D, Meltzer HY. Improvement in cognitive functions and psychiatric symptoms in treatment-refractory schizophrenic patients receiving clozapine. Biol Psychiatry 1993;34:702–12.
4. Lee MA, Jayathilake K, Meltzer HY A comparison of the effect of clozapine with typical neuroleptics on cognitive function in neuroleptic responsive schizophrenia. Schizophr Res 1999;37:1–11.
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6. Green MF. What are the functional consequences of neurocognitive deficits in schizophrenia? Am J Psychiatry 1996;153:321–30.
7. McGurk SR, Meltzer HY. The role of cognition in vocational functioning in schizophrenia. Schizophrenia Research 2000;45:175–84.
8. Townsend LA, Norman RMG, Malla AK, Rychlo A, Ahmed RR. Changes in cognitive functioning following comprehensive treatment for first episode patients with schizophrenia spectrum disorders. Psychiatry Res 2002;113:69–81.
9. Capleton RA Cognitive function in schizophrenia: association with negative and positive symptoms Psychol Rep 1996;78:123–8.
10. Banaschewski T, Schulz E, Martin M, Remschmidt H. Cognitive functions and psychopathological symptoms in early-onset schizophrenia. Eur Child Adolesc Psychiatry 2000;9:11–20.
11. Nieuwenstein MR, Aleman A, de Haan EH. Relationship between symptoms dimensions and neurocognitive functioning in schizophrenia: a meta-analysis of WCST and CPT studies. J Psychiatr Res 2001;35:119–25.
Laurel A Townsend, PhD
Rahul Manchanda, MD
London, Ontario
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