TC-5619 as Augmentation Therapy to Improve Cognition in Outpatients With Cognitive Dysfunction in Schizophrenia
Status:
Completed
Trial end date:
2010-12-01
Target enrollment:
Participant gender:
Summary
Schizophrenia affects approximately 1% of the population worldwide, and in about 80% of
cases, it is a lifelong, disabling illness. It is a multi-dimensional disease that is
associated with symptoms that have been characterized as positive, negative, and cognitive.
CDS is a core feature of schizophrenia, and most individuals with schizophrenia exhibit
cognitive impairment. Attention disorders, slow information processing, working memory
disorders, and lack of flexibility for adaptive strategies are symptoms of cognitive
impairment that have a devastating impact on the function, employment, and social status of
patients with schizophrenia.
Older typical neuroleptic medications (e.g., haloperidol, fluphenazine) do not improve
cognition. In fact, haloperidol has been shown to induce cognitive impairment in
schizophrenic patients.
Novel atypical antipsychotics, such as risperidone, clozapine, and olanzapine, seem to
produce gains in cognition. This improvement may reflect a diminution of extrapyramidal side
effects of the typical high potency neuroleptics. Alternatively, it might reflect more
effective symptom reduction by the novel antipsychotics, or direct cognitive enhancement
through the effects of the newer agents on a variety of neurotransmitters, their receptors,
and gene expression. Even when the newer antipsychotic medications improve cognition, they do
not normalize it.
Presently, there are no approved therapies for CDS. However, in schizophrenic patients,
nicotine improves multiple cognitive domains, including working memory and attention.
Furthermore, based on a strong body of evidence ranging from genetic mapping to clinical
trials, the alpha7 NNR subtype has emerged as a primary therapeutic target relevant to CDS
and other core symptoms of schizophrenia