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We investigated the effects of the atypical antipsychotics risperidone, olanzapine, and aripiprazole on the cognitive functions of Japanese patients with schizophrenia with respect to dosage amounts and dosing schedules. We performed a cross-sectional survey using the Brief Assessment of Cognition in Schizophrenia - Japanese Language Version (BACS-J) to evaluate the neurocognitive functions of 101 schizophrenic patients who took the same dose of one of the three aforementioned antipsychotics for at least 3 months. The BACS-J composite score correlated negatively with the prescribed dosages of risperidone and olanzapine. In contrast, we did not find a correlation between the BACS-J composite score and the prescribed dosage of aripiprazole. Moreover, the primary scores for verbal learning, motor function, and attention and processing speed were significantly lower among the patients who were taking the prescribed dosage of risperidone. The scores for verbal learning and motor function were also significantly lower when correlated with the prescribed dosage of olanzapine. We did not find a correlation between any of the primary scores on the BACS-J and the prescribed dosage of aripiprazole. In fact, the results suggest there is no linear relationship between the dose of aripiprazole and cognitive impairment, which may be due to its unique pharmacological profile., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Objective: We hypothesized that an excessive dose of antipsychotic drug and/or a larger number of antipsychotic drug worsens cognitive functions in schizophrenia patients. To confirm the hypothesis, we compared several cognitive functions in the patients taking a second-generation antipsychotic drug (SGA) only (SGA monotherapy group) with those in patients taking more than two kinds of antipsychotic drugs (polypharmacy group)., Methods: The cognitive functions of 136 chronic schizophrenia patients were evaluated using the Brief Assessment of Cognition in Schizophrenia, Japanese-language version (BACS-J)., Results: A significantly negative correlation was found between the composite score in the BACS-J and the chlorpromazine equivalence of doses of antipsychotic drugs in whole patients (r = -0.43, P < 0.001). Schizophrenia patients in the polypharmacy group had lower composite scores than those in the SGA monotherapy group in the BACS-J. No difference was observed in the composite score and the primary score in each item in the BACS-J between patients with first- plus second-generation antipsychotic drug (FGA + SGA group) and those with two kinds of SGA (SGA + SGA group)., Conclusion: These results suggest that an excessive dose of antipsychotic drugs regardless of FGA and SGA might cause the deterioration of cognitive functions in chronic Japanese schizophrenia patients.

Objective: We investigated the effects of aripiprazole on plasma levels of brain-derived neurotrophic factor (BDNF) and catecholamine metabolites in first-episode untreated schizophrenia patients., Methods: The subjects were 50 Japanese first-episode untreated schizophrenia patients who met the Diagnostic and Statistical Manual of Mental Disorders Text Revision criteria and were treated with aripiprazole monotherapy. Twenty-nine were males, and 21 were females. The age ranged from 21 to 42 years (mean ± SD; 30.8 ± 5.3 years). Plasma BDNF and catecholamine metabolites were measured by ELISA and HPLC, respectively. Psychiatric symptoms were evaluated using by Positive and Negative Syndrome Scale., Results: Treatment with aripiprazole for 8 weeks significantly increased plasma BDNF levels. It also changed plasma levels of homovanillic acid and 3-methoxy-4-hydroxyphenylglycol. A negative correlation was also observed between duration of psychosis and plasma BDNF levels. No correlation was observed however between plasma BDNF levels and the dose of aripiprazole., Conclusions: To the best of our knowledge, this is the first report showing that aripiprazole increases plasma BDNF levels in first-episode untreated schizophrenia patients. Furthermore, the BDNF Val66Met polymorphism was independent of the response to aripiprazole., (Copyright © 2011 John Wiley & Sons, Ltd.)

We investigated the effects of atypical antipsychotic drugs on GABA concentrations in early-stage, first-episode schizophrenia patients. Sixteen (8 males, 8 females; age, 30±11 years old) patients were followed up for six months. We also included 18 sex- and age-matched healthy control subjects. All patients were treated with atypical antipsychotic drugs (5 patients with risperidone, 5 patients with olanzapine, 4 patients with aripiprazole, and 2 patients with quetiapine). In all three regions measured (frontal lobe, left basal ganglia, and parieto-occipital lobe), no differences in GABA concentrations were observed in a comparison of pre-treatment levels and those six months after treatment. These results suggest that relatively short-term treatment with atypical antipsychotic drugs may not affect GABAergic neurotransmission; however, it is also possible that such treatment prevents further reductions in brain GABA levels in people with early-stage, first-episode schizophrenia., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Only two-thirds of depressive patients respond to antidepressant treatment. Recently, addition of an atypical antipsychotic drug to ongoing treatment with an antidepressant has been considered effective and well-tolerated. In the present study, we examined the effects of various atypical antipsychotic drugs as adjuvant to antidepressants, including selective serotonin reuptake inhibitors (SSRIs), serotonin noradrenaline reuptake inhibitors, tricyclic antidepressants and mood stabilizers, on plasma BDNF levels in refractory depressed patients. Forty-five patients who met the DSM-IV criteria for major depressive disorder (n=31) or bipolar disorder (10 with bipolar I, 4 with bipolar II) were enrolled in the study. Twenty-one were male and 24 were female, and their ages ranged from 28 to 71 (mean+/-SD=49+/-12) years. Plasma BDNF levels were measured using a sandwich ELISA. The plasma BDNF levels in responders (those showing a decline in HAM-D scores of 50% or more) were significantly increased 4weeks after the administration of each atypical antipsychotic drug, while the levels in non-responders were not changed. Furthermore, there was a significant correlation between the changes in HAM-D scores and the changes in plasma BDNF levels. These results suggest that adding an atypical antipsychotic drug to ongoing treatment with an antidepressant or mood stabilizer is useful and well-tolerated for refractory depressed patients, and the efficacy of atypical antipsychotics as an adjuvant might involve an increase of plasma BDNF levels., (Copyright 2009 Elsevier Inc. All rights reserved.)

We reported a case with late-onset Tourette's disorder (TD) in whom motor tics and emotional instability improved with 18 mg/day of aripiprazole treatment. Plasma HVA levels, but not MHPG levels, were altered during the treatment. In contrast, serum BDNF levels remained consistently low during the treatment course. The present case suggests that aripiprazole might ameliorate tics and emotional instability via influencing dopaminergic neurons in late-onset TD.