論文 - 内田　裕之

Reducing the dose of antipsychotic agents ameliorates visual hypersensitivity attack

Uchida Hiroyuki, Suzuki Takefumi, Yamazawa Ryoko, Tomita Masayuki, Nemoto Takahiro, Kimura Yoshie, Watanabe Koichiro, Imasaka Yasushi, Kashima Haruo

Journal of Clinical Psychopharmacology 26 （ 1 ） 50 - 55 2006年02月

ISSN  0271-0749

　概要を見る

<p>There are sporadic reports of antipsychotic-induced visual hypersensitivity attack (VHA). VHA is characterized by hypersensitivity of perception mainly in the visual modality and sometimes accompanied by an oculogyric crisis. However, some researchers regard VHA as a schizophrenia symptom. To determine whether VHA is an adverse effect of antipsychotic agents, we examined the effect of dose reduction on VHA. This was an open-label 36-week study. We randomized 34 patients with VHA to a reduced-dose group and a fixed-dose group. Primary outcome measures were the frequency and duration of VHA, assessed with patients' self-reports, and the Clinical Global Impressions (CGI). Assessment also included the Drug-induced Extrapyramidal Symptoms Scale for extrapyramidal symptoms, the Positive and Negative Syndrome Scale (PANSS) for schizophrenia, and the CGI for other diagnoses. Data were collected from August 2000 to April 2005 at 4 psychiatric hospitals in Tokyo. VHA diminished in 16 patients (94.1%) in the reduced-dose group in the CGI score, the frequency (number of episodes per week), and the duration of the episodes (from 4.06 to 1.77, P &lt; 0.001; from 2.59 to 0.82, P = 0.001; and from 1.92 to 0.66 hours, P = 0.007, respectively), but there were no changes in the fixed-dose group. There were no changes in the underlying illness as measured by the PANSS in both groups. Reducing the dose of antipsychotic agents ameliorates VHA and represents the ideal treatment option for patients with VHA.</p>

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Reducing the dose of antipsychotic agents ameliorates visual hypersensitivity attack: An ideal treatment option in terms of the adverse effect

Uchida H., Suzuki T., Yamazawa R., Tomita M., Nemoto T., Kimura Y., Watanabe K., Imasaka Y., Kashima H.

Journal of Clinical Psychopharmacology （Journal of Clinical Psychopharmacology）  26 （ 1 ） 50 - 55 2006年02月

ISSN  02710749

　概要を見る

There are sporadic reports of antipsychotic-induced visual hypersensitivity attack (VHA). VHA is characterized by hypersensitivity of perception mainly in the visual modality and sometimes accompanied by an oculogyric crisis. However, some researchers regard VHA as a schizophrenia symptom. To determine whether VHA is an adverse effect of antipsychotic agents, we examined the effect of dose reduction on VHA. This was an open-label 36-week study. We randomized 34 patients with VHA to a reduced-dose group and a fixed-dose group. Primary outcome measures were the frequency and duration of VHA, assessed with patients' self-reports, and the Clinical Global Impressions (CGI). Assessment also included the Drug-induced Extrapyramidal Symptoms Scale for extrapyramidal symptoms, the Positive and Negative Syndrome Scale (PANSS) for schizophrenia, and the CGI for other diagnoses. Data were collected from August 2000 to April 2005 at 4 psychiatric hospitals in Tokyo. VHA diminished in 16 patients (94.1%) in the reduced-dose group in the CGI score, the frequency (number of episodes per week), and the duration of the episodes (from 4.06 to 1.77, P < 0.001; from 2.59 to 0.82, P = 0.001; and from 1.92 to 0.66 hours, P = 0.007, respectively), but there were no changes in the fixed-dose group. There were no changes in the underlying illness as measured by the PANSS in both groups. Reducing the dose of antipsychotic agents ameliorates VHA and represents the ideal treatment option for patients with VHA. Copyright © 2006 by Lippincott Williams & Wilkins.

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Combined treatment with sulpiride and paroxetine for accelerated response in patients with major depressive disorder

Uchida H., Takeuchi H., Suzuki T., Nomura K., Watanabe K., Kashima H.

Journal of Clinical Psychopharmacology （Journal of Clinical Psychopharmacology）  25 （ 6 ） 545 - 551 2005年12月

ISSN  0271-0749

　概要を見る

Although serotonin reuptake inhibitors are recommended as first-line agents for major depressive disorder, delayed onset of action is problematic, and faster effective treatment is needed. Sulpiride, a dopamine-mediated agent, has been reported to show faster antidepressant efficacy, and we examined the efficacy of adjunctive sulpiride in combination with paroxetine (PAX), compared with PAX alone, to clarify whether the combined treatment exerts faster effect. Forty-one major depressive disorder patients were enrolled in this 12-week open-label trial and were randomly assigned to a PAX (10-40 mg/d) or a PAX (10-40 mg/d) plus sulpiride (100 mg/d) group. Assessments included the Montgomery-Asberg Depression Rating Scale, the 17-item Hamilton Rating Scale for Depression, and the Zung Self-rating Depression Scale on an intent-to-treat basis, and safety was also monitored. Thirty-three patients completed the study. Both PAX + sulpiride and PAX treatments showed a mean reduction in the total Montgomery-Asberg Depression Rating Scale score of 34.4 to 5.6 and 32.2 to 10.4, respectively (P < 0.001). The combined treatment group had a significantly superior outcome in terms of the change in the total Montgomery-Asberg Depression Rating Scale, Hamilton Rating Scale for Depression, and Zung Self-rating Depression Scale scores between week 1 and the study end point (P < 0.05). Median times to response among responders alone for the combined treatment and monotherapy were 2 and 6 weeks, respectively. Both treatments were well tolerated, with no clinically significant differences in safety measures except for an elevation of prolactin in the combined treatment group. The combination treatment may be a safe and effective strategy for accelerating antidepressant response. Copyright © 2005 by Lippincott Williams & Wilkins.

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高機能広汎性発達障害のロールシャッハ反応(2)　反応様式の質的検討

明翫 光宜, 内田 裕之, 辻井 正次

ロールシャッハ法研究 （日本ロールシャッハ学会）  9   1 - 13 2005年11月

ISSN  1345-0743

　概要を見る

本研究では,高機能広汎性発達障害者(High-Functioning Pervasive Developmental Disorder以下HFPDDとする)におけるロールシャッハ反応様式の特徴について,主に思考言語カテゴリーや形式構造解析を用いて質的に検討した.研究協力者は,HFPDD群34名(17.65±3.17歳range12-26 男子26名,女子8名)と大学生群21名(男子8名:女子13名,年齢20.48±0.93歳range19-23)であった.HFPDD群の検査実施はNPO法人「アスペ・エルデの会」において個別法で,包括システムに準拠して施行した.各スコアの出現頻度についてχ2検定を用いて両群を比較した結果,把握の未熟さ,特徴的な反応態度が示された.今後はこれらの情報を基に発達支援に役立てることが望まれる(著者抄録)

Simplifying psychotropic medication regimen into a single night dosage and reducing the dose for patients with chronic schizophrenia

Suzuki T., Uchida H., Takeuchi H., Nomura K., Tanabe A., Watanabe K., Yagi G., Kashima H.

Psychopharmacology （Psychopharmacology）  181 （ 3 ） 566 - 575 2005年09月

ISSN  0033-3158

　概要を見る

Rationale: Taking psychotropic medications is frequently problematic from both consumers' and caregivers' perspective. Occasionally missed doses may lead to pervasive non-adherence with relapse a likely outcome. Objective: To evaluate the simple medication regimen, all psychotropics were given at night for patients with chronic schizophrenia, who had been taking them at least twice a day for more than 12 weeks before the entry. Methods: Switching of agents took place in two ways: converting only antipsychotic medications followed by other psychotropics, and changing all psychotropics simultaneously. Any psychotropics of little clinical significance were then cautiously minimized. Final evaluation was made 12 weeks after the competed dose consolidation. Patients finally rated their subjective impression on this intervention. Results: Twenty-five patients were recruited in each treatment arm (50 in total). After switching, 11 got better, 29 remained stable whereas seven got worse, according to the Global Improvement. Three were not assessable. Overall, there were no relevant changes in clinical ratings including adverse effects. However, the chlorpromazine equivalent dose of antipsychotics and the number of total psychotropics were significantly reduced from 957 to 722 mg/day (p<0.0001) and from 4.0 to 3.2 (p<0.0001), respectively. Dose deflation of psychotropics was feasible in 35 subjects (74.5%). Twenty-six (of 40 successful) patients indicated that they favored the night-time regimen mainly because it was less complicated. Sedation in the morning was identified as an important adverse event, which should be addressed by reducing the dose. Conclusions: The procedure may be of value to counteract a recent trend of psychotropic polypharmacy in schizophrenia. © Springer-Verlag 2005.

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Two case reports of successful prevention of overdosing in borderline patients

Uchida H., Watanabe K., Suzuki T., Goto A., Kashima H.

Psychiatry （Psychiatry）  68 （ 2 ） 179 - 182 2005年06月

ISSN  0033-2747

　概要を見る

Overdosing often occurs among patients with borderline personality disorder (BPD) and confronts physicians with the dilemma of whether to prescribe psychotropic agents for them or not. Prescribing psychotropic agents is often unavoidable in the real world, because psychotherapy alone is sometimes insufficient to control their labile emotions. We report two cases of BPD in which overdosing was successfully prevented by changing the dosage form from tablets to a powder and adding a bitter taste to make it difficult to swallow a large dose at one time. Prevention of overdosing by BPD patients definitely requires a comprehensive treatment approach in terms of its social, biological, psychological, and psychopathological aspects. Although no perfect method of preventing overdosing is currently available, our method provides an option when psychotropic agents are prescribed for BPD patients in clinical practice.

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治療抵抗性、治療不耐性症例への対応

内田裕之,渡邊衡一郎

臨床精神薬理 8   425-430 2005年

研究論文（学術雑誌）, 単著

Revising polypharmacy to a single antipsychotic regimen for patients with chronic schizophrenia

Suzuki T., Uchida H., Tanaka K., Nomura K., Takano H., Tanabe A., Watanabe K., Yagi G., Kashima H.

International Journal of Neuropsychopharmacology （International Journal of Neuropsychopharmacology）  7 （ 2 ） 133 - 142 2004年06月

ISSN  1461-1457

　概要を見る

Antipsychotic polypharmacy has been empirically used and a recent trend in favour of that mode of therapy has been suggested for the treatment of schizophrenia. The clinical efficacy, however, still remains to be clarified. In order to critically evaluate the usefulness of such kind of psychopharmacotherapy, antipsychotic combination regimen (polypharmacy) was switched to a treatment with the single main antipsychotic (monotherapy) in cross-tapered fashion, while approximately maintaining the total amount, for patients with chronic schizophrenia. Patients had been treated with an average of three antipsychotics and maintained with the same antipsychotic polypharmacy regimen for more than 6 months before the entry. They were followed up with an antipsychotic monopharmacy and evaluated at 24 wk after completion of switching. Forty-seven patients were recruited for this study. Of 44 patients for whom evaluation was possible, 24 (54.5%) remained stable, while 10 (22.7%) showed improvement and the same number of patients ended in a deleterious status. Twenty-two patients were converted to antipsychotic monotherapy, while another 12 needed minimal dosing of low-potency agents. Overall, social functioning, evaluated by the Global Assessment of Functioning and the Clinical Global Impression, remained unchanged. Eighteen of 34 successful patients showed adverse effects of the main antipsychotic medication, which necessitated a significant dose reduction. Nine out of 10 deteriorating patients had been treated with a combination of low- and high-potency antipsychotics. It is suggested that many instances of antipsychotic polypharmacy is avoidable. The result is compatible with the current treatment recommendations, which dictate the use of a single antipsychotic agent.

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A clinical case series of switching from antipsychotic polypharmacy to monotherapy with a second-generation agent on patients with chronic schizophrenia

Suzuki T., Uchida H., Watanabe K., Yagi G., Kashima H.

Progress in Neuro-Psychopharmacology and Biological Psychiatry （Progress in Neuro-Psychopharmacology and Biological Psychiatry）  28 （ 2 ） 361 - 369 2004年03月

ISSN  0278-5846

　概要を見る

Second-generation antipsychotic medications have become popular as a treatment for schizophrenia. The authors investigated 25 chronic subjects who had previously been treated with high-dose antipsychotic polypharmacy without amelioration. All patients had a history of having been treated with an antipsychotic polypharmacy regimen of the total daily chlorpromazine equivalent dose exceeding 1000 mg/day for more than 6 weeks. They were subsequently switched to a second-generation antipsychotic monotherapy. Other psychotropic medications were simplified at the same time. For successful patients whose symptoms showed at least minimal improvement, the medical chart was reviewed retrospectively. After completed switching, the patients were followed up for 12 weeks, when final evaluation was made. The Global Assessment of Functioning score improved from 32 to 47. The number of antipsychotic medications and total psychotropic medications were significantly reduced from 3.5 to 1.1 and 6.8 to 2.6, respectively. Also, the antipsychotic dose was significantly minimized from 2203 to 619 mg/day. Eleven of eighteen inpatients were discharged and the other four were better enough to be ready for discharge. By showing successful cases, the authors suggest a possibility of antipsychotic monotherapy with a second-generation agent even for those patients who had been treated with high-dose antipsychotic polypharmacy in vain. © 2003 Elsevier Inc. All rights reserved.

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薬物療法における精神障害の見方と治療姿勢

内田裕之,渡邊衡一郎,八木剛平

臨床精神薬理 4   359-363 2004年

研究論文（学術雑誌）, 共著

Reducing the dose of antipsychotic medications for those who had been treated with high-dose antipsychotic polypharmacy

Suzuki Takefumi, Uchida Hiroyuki, Tanaka Kenji F., Tomita Masayuki, Tsunoda Kenichi, Nomura Kensuke, Takano Harumasa, Tanabe Akira, Watanabe Koichiro, Yagi Gohei, Kashima Haruo

International Clinical Psychopharmacology 18 （ 6 ） 323 - 329 2003年11月

ISSN  0268-1315

　概要を見る

<p>Antipsychotic medications are often used at higher than the recommended dose and sometimes in a combination regimen to treat schizophrenia. However, in general, high-dose therapies have been abandoned in recent clinical studies. In this study, dose reduction of antipsychotic medication was implemented for patients with chronic schizophrenia, most of whom (81%) had been treated with an antipsychotic high-dose polypharmacy regimen consisting of more than 1000 mg/day in total amount. The results show that merely reducing the amount of antipsychotic led to favourable outcome in 23 out of 41 cases (56%), with another 13 cases (32%) showing no change. Dose reduction ended in failure in only five subjects (12%). Overall, the amount as well as the number of antipsychotic medications was significantly reduced from 1984 mg to 812 mg per day (reductions of 59% and from 3.6 to 2.2, respectively; both P&lt;0.0001). The Global Assessment of Functioning scale improved from 30.6 to 37.2, which reached significance (P&lt;0.001). Accordingly, the Severity of Illness improved from 4.7 to 4.2, and was also significant (P&lt;0.01). Dose reduction is an encouraging strategy to consider for those patients with schizophrenia who have chronically been treated with high-dose antipsychotic polypharmacy, even if judged unavoidable in the past.</p>

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Reducing the dose of antipsychotic medications for those who had been treated with high-dose antipsychotic polypharmacy: An open study of dose reduction for chronic schizophrenia

Suzuki T., Uchida H., Tanaka K., Tomita M., Tsunoda K., Nomura K., Takano H., Tanabe A., Watanabe K., Yagi G., Kashima H.

International Clinical Psychopharmacology （International Clinical Psychopharmacology）  18 （ 6 ） 323 - 329 2003年11月

ISSN  02681315

　概要を見る

Antipsychotic medications are often used at higher than the recommended dose and sometimes in a combination regimen to treat schizophrenia. However, in general, high-dose therapies have been abandoned in recent clinical studies. In this study, dose reduction of antipsychotic medication was implemented for patients with chronic schizophrenia, most of whom (81%) had been treated with an antipsychotic high-dose polypharmacy regimen consisting of more than 1000 mg/day in total amount. The results show that merely reducing the amount of antipsychotic led to favourable outcome in 23 out of 41 cases (56%), with another 13 cases (32%) showing no change. Dose reduction ended in failure in only five subjects (12%). Overall, the amount as well as the number of antipsychotic medications was significantly reduced from 1984 mg to 812 mg per day (reductions of 59% and from 3.6 to 2.2, respectively; both P<0.0001). The Global Assessment of Functioning scale improved from 30.6 to 37.2, which reached significance (P<0.001). Accordingly, the Severity of Illness improved from 4.7 to 4.2, and was also significant (P<0.01). Dose reduction is an encouraging strategy to consider for those patients with schizophrenia who have chronically been treated with high-dose antipsychotic polypharmacy, even if judged unavoidable in the past. © 2003 Lippincott Williams & Wilkins.

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Recurrent episodes of perceptual alteration in patients treated with antipsychotic agents

Uchida H., Suzuki T., Tanaka K., Watanabe K., Yagi G., Kashima H.

Journal of Clinical Psychopharmacology （Journal of Clinical Psychopharmacology）  23 （ 5 ） 496 - 499 2003年10月

ISSN  0271-0749

　概要を見る

Antipsychotics have been sporadically reported to induce the brief recurrent episodes characterized by hypersensitivity of the visual perception, which is known as paroxysmal perceptual alteration (PPA) mainly in Japan. PPA is characterized by hypersensitivity of perception mainly in visual modalities, which could occur in patients treated with antipsychotics. PPA is occasionally known to be accompanied by an oculogyric crisis (OGC). In this study, we examine the prevalence and the characteristics of patients with PPA. Three hundred thirty-eight patients who were treated with antipsychotics and diagnosed with schizophrenia, mood disorders, or neurotic disorders (International Classification of Disease, or ICD-10) were interviewed. We compared the characteristics between subjects with and without PPA. The mean overall prevalence of PPA was 3.25%, which was higher among patients treated with high-potency antipsychotics (3.91%) than in subjects treated with mid-potency or low-potency drugs (1.16%). PPA occurred simultaneously with OGC at the rate of 36.4%. We also found much similarity between PPA and OGC in terms of phenomenology. We suggest that PPA could manifest itself as an undesirable effect of antipsychotics, especially those of high potency. PPA and OGC may a share common underlying mechanism.

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精神科薬物療法におけるエビデンスの意義と限界

内田裕之,八木剛平

臨床精神薬理 6   983-989 2003年

研究論文（学術雑誌）, 共著

援助技術、統合失調症の薬物療法

内田 裕之

精神科臨床サービス 3   449-454 2003年

研究論文（学術雑誌）, 単著

抗精神病薬多剤併用療法に対する減量・減薬の試みー対応ガイドラインー

鈴木健文,内田裕之,渡邊衡一郎,八木剛平

精神科治療学 18   899-906 2003年

研究論文（学術雑誌）, 共著

治療抵抗性分裂病(統合失調症)への対処

八木剛平,稲垣中,内田裕之,渡邊衡一郎

Schizophrenia Frontier 4   215-219 2003年

研究論文（学術雑誌）, 共著

抗精神病薬の多種併用及び大量療法の有用性に関する研究

鈴木 健文, 渡邊 衡一郎, 高野 晴成, 角田 健一, 内田 裕之, 八木 剛平, 鹿島 晴男

精神薬療研究年報 （(公財)先進医薬研究振興財団）   （ 34 ） 84 - 92 2002年03月

ISSN  1346-1702

　概要を見る

有効性を支持するエビデンスに乏しいにも拘わらず,精神分裂病の治療に汎用されてきている抗精神病薬の多種併用及び大量療法を批判的に検証するため,慢性の精神分裂病に罹患し,半年間以上処方変更が行われず,病状の固定化した患者の抗精神病薬を,クロルプロマジン換算等価量をおおよそ維持しながら主剤の単独服用に移行(単剤化研究),或いは一日服薬量が1000mgを越える例で,用量の少ない薬剤より順に減薬(減量研究)し,病状を24週以上観察した.単剤化研究では,72.5%が成功し,総じて精神症状は不変,使用抗精神病薬数が3.0→1.5剤に削減できた.減量研究では,87.5%が成功し,使用抗精神病薬量が2018→815mg/日に削減され,GAF及びSOIは有意に改善し,GIは2.2と大幅に緩和された.よって,抗精神病薬の多種併用・大量療法の妥当性は多くの場合否定され,大量処方例においては,減量が積極的な治療方法となり得ることが示唆された

米国ロチェスター大学における急性精神病に対する救急薬物療法事情

内田裕之,渡邊衡一郎

精神科治療学 17   367-370 2002年

研究論文（学術雑誌）, 共著

オランザピン

内田裕之,八木剛平

臨床と薬物治療 21   314-315 2002年

研究論文（学術雑誌）, 共著