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Hisashi Higuchi

Publications and source records attributed to Hisashi Higuchi.

At least 19 recordsLinked to original sources
PubMed2006

The G196A polymorphism of the brain-derived neurotrophic factor gene and the antidepressant effect of milnacipran and fluvoxamine.

Prediction of the response to different classes of antidepressants has been an important matter of concern in the field of psychopharmacology. The purpose of the present study was to investigate whether the G196A polymorphism of the brain-derived neurotrophic factor (BDNF) gene is associated with the antidepressant effect of milnacipran, a serotonin norepinephrine reuptake inhibitor, and fluvoxamine, a selective serotonin reuptake inhibitor. The subjects of our previous study of milnacipran (n = 80) and fluvoxamine (n = 54) were included in the present study. Severity of depression was assessed with the Montgomery Asberg depression rating scale (MADRS). Assessments were carried out at baseline and at 1, 2, 4 and 6 weeks of treatment. Polymerase chain reaction was used to determine allelic variants. In all subjects receiving milnacipran or fluvoxamine, the G/A genotype of the BDNF G196A polymorphism was associated with a significantly better therapeutic effect in the MADRS scores during this study. When milnacipran and fluvoxamine-treated subjects were analysed independently, the G/A genotype group showed greater reduction of MADRS scores than other genotype groups, irrespective of which antidepressant was administered. These results suggest that the BDNF G196A polymorphism in part determines the antidepressant effect of both milnacipran and fluvoxamine.

Adult↗
PubMed2006

Switching to risperidone after unsuccessful treatment of olanzapine in the first-episode schizophrenia: an open trial.

The purpose of this study was to assess the effect of switching to risperidone in the treatment of first-episode schizophrenia who had failed to respond to an initial-prescribed antipsychotic, olanzapine. Fifty-one patients with first-episode schizophrenia after unsuccessful treatment of olanzapine (the mean (S.D.) dosage: 16.4 (4.4) mg/day) were included in this switching study. Of the 51 patients, 43 (84.3%) completed the full 12-week trial and 8 (15.7%) dropped out. The mean dosage of risperidone at the endpoint (last observation) was 3.1 (2.0) mg/day. The total scores of Brief Psychiatric Rating Scales (BPRS) were significantly reduced from baseline to endpoint, especially in the positive and excitement factors (p<0.001). Responder rate (at least 20% decrease in BPRS total score plus final Clinical Global Impression score of 3 or less) was 35.3%. These findings indicate that the switching to risperidone could be one of the useful treatment options in this population.

Adolescent↗
PubMed2006

Switching to olanzapine after unsuccessful treatment with risperidone during the first episode of schizophrenia: an open-label trial.

BACKGROUND: The efficacy and safety of switching to olanzapine were investigated in patients with first-episode schizophrenia who failed to attain an adequate clinical response to an initial therapeutic trial of risperidone (2-6 mg/day for 12 weeks). METHOD: A total of 58 first-episode patients with DSM-IV schizophrenia who had residual symptoms following treatment with risperidone were enrolled in an open-label, 12-week study of olanzapine. Dosing was determined by clinical judgment. The main efficacy measure was the Brief Psychiatric Rating Scale (BPRS). Patients with a 20% or greater decrease in BPRS total score plus a final Clinical Global Impressions-Severity of Illness scale score of or= 7%) from baseline. CONCLUSION: Although we cannot draw any conclusion from a study without a control group, favorable outcomes and good tolerance were observed after switching to olanzapine from risperidone in our population. In addition, factors that predicted a good overall response included a relative absence of positive symptoms at baseline and the percentage reduction in total BPRS score at 4 weeks of treatment. Double-blind, crossover trials are needed to confirm these observations.

Adolescent↗
PubMed2005

Genomewide high-density SNP linkage analysis of 236 Japanese families supports the existence of schizophrenia susceptibility loci on chromosomes 1p, 14q, and 20p.

The Japanese Schizophrenia Sib-Pair Linkage Group (JSSLG) is a multisite collaborative study group that was organized to create a national resource for affected sib pair (ASP) studies of schizophrenia in Japan. We used a high-density single-nucleotide-polymorphism (SNP) genotyping assay, the Illumina BeadArray linkage mapping panel (version 4) comprising 5,861 SNPs, to perform a genomewide linkage analysis of JSSLG samples comprising 236 Japanese families with 268 nonindependent ASPs with schizophrenia. All subjects were Japanese. Among these families, 122 families comprised the same subjects analyzed with short tandem repeat markers. All the probands and their siblings, with the exception of seven siblings with schizoaffective disorder, had schizophrenia. After excluding SNPs with high linkage disequilibrium, we found significant evidence of linkage of schizophrenia to chromosome 1p21.2-1p13.2 (LOD=3.39) and suggestive evidence of linkage to 14q11.2 (LOD=2.87), 14q11.2-q13.2 (LOD=2.33), and 20p12.1-p11.2 (LOD=2.33). Although linkage to these regions has received little attention, these regions are included in or partially overlap the 10 regions reported by Lewis et al. that passed the two aggregate criteria of a meta-analysis. Results of the present study--which, to our knowledge, is the first genomewide analysis of schizophrenia in ASPs of a single Asian ethnicity that is comparable to the analyses done of ASPs of European descent--indicate the existence of schizophrenia susceptibility loci that are common to different ethnic groups but that likely have different ethnicity-specific effects.

Chromosomes, Human, Pair 1↗
PubMed2005

A three-factor model of the MADRS in major depressive disorder.

Major Depressive Disorder (MDD) may be composed of some symptom clusters with distinct neurochemical disturbances, suggesting the importance of the factor analysis of depressive symptoms; however, the results of previous studies using the Montgomery-Asberg Depression Rating Scale (MADRS) have been inconsistent. In the present study, factor analysis of the MADRS was performed in 132 Japanese patients (range 23-74 years, mean 47.6 years) with MDD without any psychiatric comorbidity. The principal component analysis with Varimax rotation identified three factors, accounting for 61% of the total variance: The first factor, labeled dysphoria, included pessimistic thoughts, suicidal thoughts, and reported sadness; the second factor, labeled retardation, included lassitude, inability to feel, apparent sadness, and concentration difficulties; and the third factor, labeled vegetative symptoms, included reduced sleep, reduced appetite, and inner tension. The score of the vegetative factor showed a significant positive correlation with age and was significantly higher in females than in males. This study suggests that the symptoms of MDD, as assessed by the MADRS, cluster into three factors (dysphoria, retardation, and vegetative symptoms).

Adult↗
PubMed2004

Remarkable effect of milnacipran, a serotonin-noradrenalin reuptake inhibitor (SNRI), on depressive symptoms in patients with Parkinson's disease who have insufficient response to selective serotonin reuptake inhibitors (SSRIs): two case reports.

The authors present here two cases of Parkinson's disease with depression refractory to SSRIs treatment, who experienced a complete remission after replacing the ongoing SSRIs with a serotonin-noradrenalin reuptake inhibitor (SNRI), milnacipran. The case reports suggest that milnacipran may be one of the treatment options for depression in patients with Parkinson's disease who had inadequate response to SSRIs. Further studies are warranted to confirm this observation.

Adrenergic Uptake Inhibitors↗
PubMed2004

Prediction of antidepressant response to milnacipran by norepinephrine transporter gene polymorphisms.

OBJECTIVE: With a multitude of antidepressants available, predictors of response to different classes of antidepressants are of considerable interest. The purpose of the present study was to determine whether norepinephrine transporter gene (NET) and serotonin transporter gene (5-HTT) polymorphisms are associated with the antidepressant response to milnacipran, a dual serotonin/norepinephrine reuptake inhibitor. METHOD: Ninety-six Japanese patients with major depressive disorder were treated with milnacipran, 50-100 mg/day, for 6 weeks. Severity of depression was assessed with the Montgomery-Asberg Depression Rating Scale. Assessments were carried out at baseline and at 1, 2, 4, and 6 weeks of treatment. The method of polymerase chain reaction was used to determine allelic variants. RESULTS: Eighty patients completed the study. The presence of the T allele of the NET T-182C polymorphism was associated with a superior antidepressant response, whereas the A/A genotype of the NET G1287A polymorphism was associated with a slower onset of therapeutic response. In contrast, no influence of 5-HTT polymorphisms on the antidepressant response to milnacipran was detected. CONCLUSIONS: The results suggest that NET but not 5-HTT polymorphisms in part determine the antidepressant response to milnacipran.

Adrenergic Uptake Inhibitors↗
PubMed2003

Relationship between clinical effects of fluvoxamine and the steady-state plasma concentrations of fluvoxamine and its major metabolite fluvoxamino acid in Japanese depressed patients.

OBJECTIVES: The relationship between clinical effects of fluvoxamine (FLV) and the steady-state plasma concentrations (Css) of FLV and its major metabolite fluvoxamino acid (FLA) was studied. METHODS: The subjects were 49 Japanese patients with major depressive disorder receiving FLV 200 mg/day for 6 weeks. Depressive symptoms and side effects were evaluated by the Montgomery Asberg Depression Rating Scale (MADRS), and the UKU Side Effect Rating Scale, respectively. The Css of FLV and FLA were measured by HPLC, and the CYP2D6 genotyping was performed by PCR methods. RESULTS: The Css of FLV and FLV+FLA showed significant negative correlations with the final MADRS score. The Css of FLV, FLA and FLV+FLA were significantly higher in the responders (final MADRS score < or =10) than in non-responders. The proportion of responders was significantly higher in the patients with the Css of FLV, FLA and FLV+FLA above 150, 55 and 180 ng/ml, respectively. In the multiple regression, the Css of FLV+FLA showed a significant negative correlation with the final MADRS score. In the logistic regression, the Css of FLA had a significant effect on the differentiation of responders from non-responders. The incidence of side effects was low, and the development of nausea, the most frequent one, was not dependent on any Css. The number of mutated CYP2D6 alleles causing absent or decreased enzyme activity was not related to the therapeutic response or development of nausea. CONCLUSIONS: The present study suggests that there is a therapeutic threshold for the Css of FLV and probably also for the Css of FLA, and the Css of FLV+FLA above 180 ng/ml best predicts a good therapeutic response.

Adult↗
PubMed2003

Milnacipran plasma levels and antidepressant response in Japanese major depressive patients.

The relationship between antidepressant effects and plasma levels of milnacipran was studied in 49 cases of major depression without psychotic features during 6 weeks of milnacipran treatment. The daily dose of milnacipran was 50 mg/day for the first week, and up to 100 mg/day thereafter. Depressive symptoms were evaluated by the Montgomery and Asberg depression rating scale (MADRS) before treatment and at 1, 2, 4 and 6 weeks after the beginning of this study. Thirty-four patients (69.4%) were responders (defined as a 50% or greater decrease in the baseline MADRS score). Significant differences of MADRS scores were seen from 1 week after the beginning of this study (p=0.004, unpaired t-test) between responders and nonresponders. The mean plasma milnacipran level of responders, 82.0 +/- 29.4 ng/ml, was similar to that of non-responders, 78.6+/-23.1 ng/ml; there was no significant difference between responders and nonresponders. Neither a significant linear nor a curvilinear relationship was obtained between the final MADRS score and the plasma levels of milnacipran. Although there was no significant relationship between the plasma levels of milnacipran and the antidepressant response, milnacipran should be considered an efficacious agent in the treatment of major depressive patients.

Adrenergic Uptake Inhibitors↗
PubMed2003

Quetiapine treatment of psychotic symptoms and aggressive behavior in patients with dementia with Lewy bodies: a case series.

The authors describe here the clinical outcomes of quetiapine treatment in nine patients with dementia with Lewy bodies (DLB) who manifested psychotic symptoms and aggressive behavior. Patients who had a score of 3 or higher on any of the three items of the Neuropsychiatric Inventory (NPI), agitation/aggression, hallucinations, and delusions, were given quetiapine 25-75 mg/day. Each patient's clinical status was assessed at baseline and after 4 and 8 weeks of treatment by using the NPI, Mini-Mental State Examination (MMSE), and Simpson-Angus Scale (S-A). Five of nine patients had a positive response with a decline of more than 50% in the sum of scores for three items of the NPI. The other three patients withdrew from quetiapine treatment due to somnolence or orthostatic hypotension. The remaining patient exhibited no clinically significant change in the NPI score. The S-A scale was not affected by quetiapine treatment in any patient. These findings suggest that quetiapine may be effective in treating psychotic symptoms and disruptive behavior in some patients with DLB. Further placebo-controlled, randomized, double-blind trials with this drug are needed to confirm this observation.

Aged↗
PubMed2003

Effects of the CYP 2D6 genotype and cigarette smoking on the steady-state plasma concentrations of fluvoxamine and its major metabolite fluvoxamino acid in Japanese depressed patients.

The effects of the cytochrome P450 (CYP) 2D6 genotype and cigarette smoking on the steady-state plasma concentrations (C(ss)) of fluvoxamine (FLV) and its demethylated metabolite fluvoxamino acid (FLA) were studied in 49 Japanese depressed patients receiving FLV 200 mg/d. The C(ss) of FLV and FLA were measured by HPLC, and the wild-type allele (*1) and two mutated alleles causing absent (*5) or decreased (*10) CYP 2D6 activity were identified by PCR methods. The patients were divided into three genotype groups by the number of mutated alleles: 12 cases with no (*1/*1), 27 cases with one (*1/*5 and *1/*10), and 10 cases with two (*5/*10 and *10/*10) mutated alleles. The means +/- SD of the C(ss) of FLV and FLA and the FLA/FLV ratio of all patients were 169.1 +/- 147.5 ng/mL, 83.9 +/- 52.7 ng/mL, and 0.71 +/- 0.50, respectively. The C(ss) of FLV and FLA were not significantly different among the three genotype groups. However, the FLA/FLV ratio was significantly lower in the patients with one (P < 0.05) and two (P < 0.01) mutated alleles than in those with no mutated allele. There was no significant difference between nonsmokers (n = 34) and smokers (n = 15) in these values. In the stepwise multiple regression, the C(ss) of FLA (P < 0.05) and FLA/FLV ratio (P < 0.001) showed significant negative correlations with the number of mutated alleles, and the FLA/FLV ratio was significantly (P < 0.05) lower in women than in men. The present study suggests that the CYP 2D6 genotype and cigarette smoking have no major impact on the C(ss) of FLV and FLA, though CYP 2D6 is involved in the demethylation of FLV.

Adult↗
PubMed2003

Monoamine oxidase A gene polymorphism, 5-HT 2A receptor gene polymorphism and incidence of nausea induced by fluvoxamine.

Selective serotonin reuptake inhibitors cause a side effect of nausea with high frequency, but there have been no accurate methods to predict its incidence. The authors first investigated whether a functional polymorphism in the monoamine oxidase A (MAOA-VNTR) and a -1438G/A polymorphism in the promoter region of the 5-HT(2A) gene were associated with the incidence of nausea induced by fluvoxamine. Fluvoxamine was administered for 6 weeks with a specific dosage plan (50-200 mg/day) in 66 Japanese major depressive patients. The frequency of MAOA-VNTR allele 1 was significantly higher in the patients without nausea than in ones with nausea in the statistical analysis including the patients whose plasma levels were below the average and who were considered to be pharmacodynamically more sensitive to nausea. This study showed that the genetic polymorphism of MAOA-VNTR might affect the incidence of nausea induced by SSRIs. If this finding is replicated in other studies with more subjects, MAOA-VNTR polymorphism would be of great clinical use to predict the incidence of nausea induced by SSRIs.

Adult↗