Biomedical subjects
Publications and source records attributed to Hisashi Higuchi.
This study investigated the effectiveness and tolerability of a switching strategy using quetiapine in 16 women with schizophrenia who were suffering from haloperidol- or risperidone-induced amenorrhea. Findings revealed that 10 patients (71.6%) resumed menstruation, without worsening of psychotic symptoms.
A high-performance liquid chromatographic (HPLC) method has been developed for the simultaneous determination of fluvoxamine and its major metabolite fluvoxamino acid in plasma. Fluvoxamine and fluvoxamino acid in plasma were extracted using a C18 bonded-solid phase cartridge, followed by C4 reversed-phase HPLC separation.Fluvoxamine, fluvoxamino acid and moperone as an internal standard were detected by ultraviolet absorbance at 254 nm. It was possible to determine both fluvoxamine and fluvoxamino acid in the concentration range of 25.0-200.0 ng/mL, respectively. The detection limits of both fluvoxamine and fluvoxamino acid were 10.0 ng/mL, respectively. The mean recoveries of fluvoxamine and fluvoxamino acid added to plasma were more than 94.0% and 96.5%, with a coefficient of variation of less than 7.6% and 8.2%, respectively. This method has been used for the simultaneous determination of steady-state plasma concentration (Css) of fluvoxamine and fluvoxamino acid in depressive patients treated with 200 mg of oral fluvoxamine dosed as 100 mg twice-daily. The Css values of fluvoxamine and fluvoxamino acid in twelve Japanese patients were showed individual variations, which were in the range of 48.3-532.9 ng/ml and 35.6-307.1 ng/ml, respectively.
The effect of nonadiabatic coupling due to breakdown of the Born-Oppenheimer approximation on chaos is investigated. A couple of measures (indicators) that detect the extent of chaos in wave-packet dynamics on coupled potential functions are devised. Using them, we show that chaos is indeed induced by a nonadiabatic coupling in individual time-dependent wave-packet dynamics. This chaos is genuinely of quantum nature, since it arises from bifurcation and merging of a wave packet at the quasicrossing region of two coupled potential functions.
Tardive dystonia is an uncommon but intractable and distressing complication of neuroleptic treatment. It is suggested that individual predisposing vulnerability plays a major role in the development of the side effect. This study aimed to investigate relationship tardive dystonia and several genetic factors such as polymorphism of cytochrome P4502D6, and receptor polymorphisms of dopamine D(2) (TaqI A and -141C Ins/Del polymorphisms) and D(3) (Ser(9)Gly polymorphism). Nine patients with tardive dystonia were genotyped for these genetic polymorphisms. No specific genotypes or alleles were overpresented in the patients. This study suggests that these polymorphisms are not related to the development of tardive dystonia.
We investigated the efficacy and safety of augmenting risperidone with fluvoxamine for the treatment of residual positive and negative symptoms in patients with chronic schizophrenia who had shown an incomplete response to risperidone. A total of 30 patients completed the open trial over a 12-week period during which fluvoxamine was added to risperidone. The result from the positive and negative syndrome scale (PANSS) and Simpson-Angus extrapyramidal effects (S-A) scale were examined at baseline, 1, 2, 4, 8 and 12 weeks of treatment. There were no significant differences in PANSS positive, negative and general psychopathology scores, or in S-A scale scores at any point during the treatment. These results suggest that fluvoxamine appears to be ineffective in augmenting the risperidone treatment response in chronic schizophrenic patients. Further controlled trials will be needed to confirm this observation.
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The presence of the long (l) variant of the serotonin (5-hydroxytryptamine: 5-HT) transporter gene-linked polymorphic region (5-HTTLPR) is reported to be associated with a more favorable and faster antidepressant effect of selective serotonin reuptake inhibitors in Caucasians. The frequency of the l allele is lower in Japanese than in Caucasians; therefore, the antidepressant effect of fluvoxamine can be not as good in Japanese as in Caucasians. The authors investigated whether 5-HTTLPR was associated with the antidepressant response to fluvoxamine in 66 Japanese patients with major depressive disorder in a protocolized-dosing 6-week study. The short (s) allele frequency was significantly higher in the responsive individuals than in the nonresponsive ones (P = .010). The present study suggests that fluvoxamine is not less effective in depressive patients carrying the s allele than in the ones carrying the l allele and it is not less effective in Japanese than in Caucasians.
Monoamine oxidase A (MAOA) and tryptophan hydroxylase (TPH) are the staple enzymes in the metabolism of serotonin (5-HT). The genetic polymorphisms of these two enzymes might individually alter the production, release, reuptake or degradation of 5-HT during the treatment of selective serotonin reuptake inhibitors (SSRIs), leading to the individual differences in the antidepressant effects of SSRIs. The authors investigated whether a functional polymorphism in the MAOA gene promoter (MAOA-VNTR) and a TPH gene polymorphism in intron 7 (TPH-A218C) were associated with the antidepressant response to fluvoxamine in 66 Japanese patients with major depressive disorder during a 6-week study with a specific dosage plan. Fifty-four patients completed the study. The present study fails to demonstrate that the genetic polymorphisms of MAOA-VNTR and TPH-A218C affect the antidepressant effect of fluvoxamine in Japanese patients with major depressive disorder.
We investigated the association between serotonergic polymorphisms and incidence of nausea, which is the most frequent side-effect of selective serotonin reuptake inhibiters (SSRIs), in 66 patients treated with fluvoxamine in a protocolized-dosing method. We focused on three polymorphisms of serotonin (5-HT) neuronal systems such as 5-HT transporter (5-HTT) gene-linked polymorphic region (5-HTTLPR), a variable number of tandem repeat (VNTR) polymorphism in the second intron of the 5-HTT gene (STin2) and tryptophan hydroxylase (TPH) gene polymorphism in intron 7 (TPH-A218C), which have been reported to possess positive association with treatment response to SSRIs. In addition to this, the relationship between development of nausea and treatment response was also analyzed. Results suggested that these three polymorphisms did not affect the development of fluvoxamine-induced nausea, and that incidence of nausea was not a phenomenon that predicts the treatment response to fluvoxamine.
Genetic polymorphism of the serotonin 5-HT(2A) receptor seems to be associated with therapeutic response to selective serotonin reuptake inhibitors (SSRIs). The present study investigated whether a novel -1438G/A polymorphism in the promoter region of the 5-HT(2A )receptor gene is associated with therapeutic response to fluvoxamine (an SSRI) in 66 Japanese patients with major depressive disorder. Fluvoxamine (50 to 200 mg) was administered twice daily for 6 weeks. Fifty-four patients completed this study. The genotype distribution and the allele frequencies showed no significant difference between responders and non-responders. The time-course of the Montgomery-Asberg Depression Rating Scale scores showed no significant difference among -1438G/G, -1438G/A, and -1438A/A genotype groups. The results demonstrated that the -1438G/A promoter polymorphism in the 5-HT(2A) receptor gene was unlikely to have a major role in therapeutic response to fluvoxamine in Japanese patients with major depressive disorder.
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We illustrate 2 patients with depression who attained dramatic improvement of energy loss and fatigue when treated with cabergoline, a dopamine agonist, and milnacipran, a serotonin-noradrenalin reuptake inhibitor. Although the biologic basis of energy, motivation, and fatigue in association with depression remains unknown, some reports suggest that the decrease of noradrenalin and dopamine in the brain are particularly related to these symptoms. Therefore, treatment strategy that enhances these two monoamine neurotransmissions may be appropriate for getting a boost in energy and eliminating fatigue in patients with depression. These cases suggest that further studies are warranted to confirm the potential benefit of this strategy in the treatment of patients with depression who failed to attain complete remission due to residual symptoms including energy loss and fatigue refractory to previous treatments.
Milnacipran--a new specific serotonin and noradrenaline reuptake inhibitor--is as effective as tricyclic antidepressants and exhibits a higher remission rate for major depressive patients than selective serotonin reuptake inhibitors. However, the effectiveness of milnacipran for severe major depressive patients had not been studied adequately. The study included 96 Japanese patients who fulfilled the DSM-IV criteria for the diagnosis of major depressive disorders and whose score on the Montgomery-Asberg Depression Rating Scale (MADRS) was 21 or higher. Of these, 16 patients were excluded because 10 did not complete the study, and 6 showed poor compliance. Finally, 80 patients were included. We defined patients with a baseline MADRS score of > or = 31 points as "severe" (n = 25). The remaining patients were classified as "moderate" (31 > MADRS score > or = 25, n = 30) and "mild" (MADRS score < 25, n = 25) using the median score of those patients as the cutoff. Milnacipran was administered twice daily for 6 weeks. The initial total dose was 50 mg/d; after a week it was increased to 100 mg/d. The response rates were 72%, 70%, and 44% in the "severe," "moderate," and "mild," respectively. No significant differences were found between "severe" and the "moderate"; however, significant differences were observed between "severe" and "mild" and "moderate" and "mild." These results demonstrated that milnacipran is almost equally effective in "severe" and "moderate." This study suggested that milnacipran has a reliable antidepressant effect in treating severe and moderate major depressive patients.
Milnacipran is a novel serotonin noradrenaline reuptake inhibitor. The authors describe the use of milnacipran for the treatment of chronic pain in a series of patients. There were 5 outpatients who suffered chronic pain for at least 3 months. None of these patients met the DSM-IV criteria for a major depressive disorder. Chronic pain was assessed clinically by means of a visual analog scale (VAS) before and 12 weeks after the start of the milnacipran treatment or at the time the drug was stopped. The duration of pain was 17.8 +/- 9.3 months (mean +/- SD), and the baseline VAS score was 88.2 +/- 6.3 points. Milnacipran was administered at 50 to 150 mg/day, and the dose at 12 weeks or at the time the drug was stopped was 85.0 +/- 31.3 mg/day. The mean +/- SD decrease in VAS at this time was 61.2 +/- 15.5%. Three patients showed marked improvement (decrease in VAS, >75%). Their decreases in VAS scores were 86.5%, 85.7%, and 77.6%. One patient showed mild improvement (42.0% decrease in VAS). These 4 patients tolerated the drug well. The fifth patient experienced nausea and discontinued treatment after 4 weeks. The VAS decrease for this patient was 14.3%. Results of this study show milnacipran to be beneficial in patients with chronic pain. This drug should be studied further for its effectiveness in the treatment of chronic pain.
A 34-year-old man presented with severe refractory depression. He had failed to respond to various antidepressants, augmentation therapy with lithium carbonate, and modified electroconvulsive therapy. Switching from amoxapine 150 mg/day to selegiline 7.5 mg/day, a selective monoamine oxidase type-B inhibitor, produced a dramatic reduction in hypobulia and lassitude, leading to a complete remission of all depressive symptoms. The patient reverted to his former position at work after an interval of approximately 3 years. Although the biologic basis of the antidepressant effect of selegiline in this patient is unknown, it is suggested that the enhancement of dopaminergic neurotransmission or elevation of brain-derived neurotrophic factor levels in the brain by administration of selegiline is involved in the recovery of this patient from severe refractory depression. This report indicates the antidepressant effect of selegiline in a refractory depressed patient.