Purpose/Background: In addition to clozapine, other atypical antipsychotic drugs pharmacologically similar to clozapine, for example, olanzapine, risperidone, and melperone, are also effective in a similar proportion of treatment-resistant schizophrenia (TRS) patients,~40%. The major goal of this study was to compare 2 doses of lurasidone, another atypical antipsychotic drug, and time to improvement in psychopathology and cognition during a 6-month trial in TRS patients.Methods/Procedures: The diagnosis of TRS was based on clinical history and lack of improvement in psychopathology during a 6-week open trial of lurasidone 80 mg/d (phase 1). This was followed by a randomized, doubleblind, 24-week trial of lurasidone, comparing 80-and 240-mg/d doses (phase 2).Findings/Results: Significant non-dose-related improvement in the Positive and Negative Syndrome Scale-Total and subscales and in 2 of 7 cognitive domains, speed of processing and executive function, were noted. Twenty-eight (41.8%) of 67 patients in the combined sample improved ≥20% in the Positive and Negative Syndrome Scale-Total. Of the 28 responders, 19 (67.9%) first reached ≥20% improvement between weeks 6 and 24 during phase 2, including some who had previously failed to respond to clozapine.Implications/Conclusions: Improvement with lurasidone is comparable with those previously reported for clozapine, melperone, olanzapine, and risperidone in TRS patients. In addition, this study demonstrated that 80 mg/d lurasidone, an effective and tolerable dose for non-TRS patients, was also effective in TRS patients but required longer duration of treatment. Direct comparison of lurasidone with clozapine in TRS patients is indicated.
The 3 discrete periods of psychopathology support the diagnosis of PSD. The unusual course and outcome, including remarkable improvement, in executive function and enhanced cortical gray matter in selective brain regions may have been the result of unique endogenous genetic and epigenetic factors and effect of medication.
A pattern of performance on the WAIS-R presumably related to temporal lobe abnormalities associated with Alzheimer's Disease was examined in patients with focal temporal lobe EEG abnormalities to determine if the profile was related to other forms of temporal lobe disease. Among 120 patients with unilateral or bilateral temporal lobe EEG abnormalities, only 4(3%) demonstrated the profile. The presence of the profile was unrelated to laterality of EEG abnormality. These findings were discussed in regard to previous studies and the utility of the so-called Fuld profile.
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