Prize for Encouragement of the Society (EN) |
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
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.
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
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.
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
Objective: To compare outcomes between increasing versus maintaining the dose of mirtazapine in patients with depression without initial improvement.
|