Prize for Encouragement of the Society (EN)

  1. Special Lecture(SL)
  2. Symposium (S)
  3. CNP Paul Janssen Awards(PJ)
  4. Prize for Encouragement of the society(EN)
  5. Luncheon Seminar(LS)
  6. Oral Presentations(O)
  7. Poster Presentations(P)

EN-1

Challenging the need for sustained blockade of dopamine D2 receptor estimated from antipsychotic plasma levels in the maintenance treatment of schizophrenia: A Single-blind, randomized, controlled study

TAKASHI TSUBOI1, TAKEFUMI SUZUKI2,3, Robert R. Bies4, Gary Remington5, Bruce G. Pollock5, MASARU MIMURA2, HIROYUKI UCHIDA2

  1. Department of Neuropsychiatry, Kyorin University School of Medicine, Tokyo, Japan
  2. Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan
  3. Department of Psychiatry, Inokashira Hospital, Tokyo, Japan
  4. Division of Clinical Pharmacology, Indiana University School of Medicine, Indianapolis, IN, USA
  5. Department of Psychiatry, University of Toronto, Toronto, ON, Canada

OBJECTIVE: Blockade of dopamine D2 receptors with antipsychotics above 65% is associated with optimal chance of clinical response although recent data suggest a lower threshold for the maintenance treatment of schizophrenia. The objective of this study was to prospectively examine whether such continuous high blockade would be necessary for maintenance treatment. METHOD: In this single-blind, 52-week, randomized controlled trial, clinically stable patients with schizophrenia receiving risperidone or olanzapine were randomly assigned to the continuous D2 blockade (i.e. an estimated trough D2 blockade of > 65%) or non-continuous blockade group (i.e. an estimated peak level of > 65% with an estimated trough level of < 65%). Oral doses corresponding to the assigned blockade levels were estimated from random plasma drug concentrations, using the models we developed; antipsychotic doses were then adjusted accordingly. Psychopathology and side effects were assessed at baseline and one year with the Positive and Negative Syndrome Scale (PANSS), Simpson-Angus Scale (SAS), and Abnormal Involuntary Movement Scale (AIMS). The study was approved by the institutional review board at each participating site, and prior to study entry subjects provided written informed consent after receiving detailed information about the protocol. RESULTS: Sixty-eight subjects (34 in each group) were enrolled. Twenty-six (76.5%) and thirty-one (91.2%) subjects completed the study in the continuous and non-continuous blockade groups, respectively, without any significant group difference. A survival analysis also failed to show any significant difference in the completion rates between the two groups. No significant differences were found on any of the assessment scales between the two groups. The degree of dosage change was small in both groups. CONCLUSION: The findings from this pilot study suggest that sustained dopamine D2 receptor blockade above 65% may not be necessary in the maintenance treatment of schizophrenia. Going forward, these preliminary findings must be confirmed in future studies using actual measurement of dopamine D2 receptor occupancy levels with brain imaging. Moreover, they have to be confirmed through double-blind, larger scale trials with longer follow-up periods.

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EN-2

The Influence of 5-HTTLPR genotype on the association between the plasma concentration and therapeutic effect of paroxetine in patients with major depressive disorder

TETSU TOMITA, NORIO YASUI-FURUKORI, TAKU NAKAGAMI, SHOKO TSUCHIMINE, MASAMICHI ISHIOKA, AYAKO KANEDA, NORIO SUGAWARA, SUNAO KANEKO

  • Department of Neuropsychiatry, Hirosaki University, Graduate School of Medicine

Introduction: The efficacy of treatment with selective serotonin reuptake inhibitors in patients with major depressive disorder (MDD) can differ depending on the patient's serotonin transporter-linked polymorphic region (5-HTTLPR) genotype, and the effects of varying plasma concentrations of drugs can also vary. We investigated the association between the paroxetine plasma concentration and clinical response in patients with different 5-HTTLPR genotypes. Methods: Fifty-one patients were enrolled in this study. The Montgomery-Asberg Depression Rating Scale (MADRS) was used to evaluate patients at 0, 1, 2, 4, and 6 weeks. The patients' paroxetine plasma concentrations at week 6 were measured using high-performance liquid chromatography. Additionally, their 5-HTTLPR polymorphisms (alleles S and L) were analyzed using a polymerase chain reaction with specific primers. We divided the participants into two groups based on their L haplotype: the SS group and the SL and LL group. We performed single and multiple regression analyses to investigate the associations between MADRS improvement and paroxetine plasma concentrations or other covariates for each group. This study was approved by the Ethics Committee of Hirosaki University Hospital, and the patients provided written, informed consent prior to participating. Results: There were no significant differences between the two groups with regard to demographic or clinical data. In the SS group, the paroxetine plasma concentration was significantly negatively correlated with improvement in MADRS at week 6. In the SL and LL group, the paroxetine plasma concentration was significantly positively correlated with improvement in MADRS at week 6 according to the results of the single regression analysis; however, it was not significantly correlated with improvement in MADRS at week 6 according to the results of the multiple regression analysis. Conclusion: Among patients with MDD who do not respond to paroxetine, a lower plasma concentration or a lower oral dose of paroxetine might be more effective in those with the SS genotype, and a higher plasma concentration might be more effective in those with the SL or LL genotype.

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EN-3

Whether to increase or maintain dosage of mirtazapine in early nonimprovers with depression

FUMIHIKO UENO1,2, SHINICHIRO NAKAJIMA2,3, TAKEFUMI SUZUKI2,4, TAKAYUKI ABE5, YUJI SATO5, MASARU MIMURA2, HIROYUKI UCHIDA2

  1. Department of Psychiatry, National Hospital Organization Kurihama Medical and Addiction Center, Kanagawa, Japan
  2. Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan
  3. Geriatric Psychiatry Division, Centre for Addiction and Mental Health, Toronto, ON, Canada
  4. Department of Psychiatry, Inokashira Hospital
  5. Center for Clinical Research, Keio University School of Medicine

Objective: To compare outcomes between increasing versus maintaining the dose of mirtazapine in patients with depression without initial improvement.
Methods: Data from a six-week double-blind randomized controlled trial of mirtazapine in major depressive disorder (DSM-IV) conducted from November, 2004 to December, 2005 were used. Percentages of remitters (i.e. a score of ≤7 in the 17- item Hamilton Rating Scale for Depression (HAM-D17)) and HAM-D17 score changes from baseline to at week 6 were compared in the following two pairs, using Fisher's exact test or mixed-effects model for repeated measures: subjects who failed to show a ≥20% decrease in the HAM-D17 total scores at week 1 but were assigned to continue 15 mg/d (stay15 group) versus those who were assigned to increase the dose to 30 mg/d (increase30 group); and subjects who failed to show a ≥20% decrease with 30 mg/d at week 2 but were assigned to continue 30 mg/d (stay30 group) versus those who were assigned to increase the dose to 45 mg/d (increase45 group). The trial was approved by institutional review boards of all participating sites, and all participants provided informed consent after full explanation of the study. Moreover, the data were anonymized.
Results: The increase30 group showed a numerically but not significant higher remission rate and a significantly greater decrease in the HAM-D17 total score at week 6 than the stay15 group (34.7% [8/23] vs. 14.3% [3/21], p=0.2; least squares mean, -15.8 vs. -10.9, p=0.003). No significant differences were found between the increase45 and stay30 groups.
Conclusion: Dose increase of mirtazapine from 15 mg/d to 30 mg/d may be effective for patients with depression without initial improvement. However, this may not be the case beyond 30mg/d.

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  1. Special Lecture(SL)
  2. Symposium (S)
  3. CNP Paul Janssen Awards(PJ)
  4. Prize for Encouragement of the society(EN)
  5. Luncheon Seminar(LS)
  6. Oral Presentations(O)
  7. Poster Presentations(P)