Rovera Chiara, Mauri Massimo C, Di Pace Chiara, Paletta Silvia, Reggiori Alessandra, Ciappolino Valentina, Cattaneo Dario, Baldelli Sara, Clementi Emilio, Altamura Alfredo C
*Department of Neuroscience and Mental Health, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milano, Italy; †Unit of Clinical Pharmacology, ASST Fatebenefratelli Sacco University Hospital, Milano, Italy; ‡Department of Biomedical and Clinical Sciences, Consiglio Nazionale delle Ricerche Institute of Neuroscience, University Hospital, Luigi Sacco, Università di Milano, Milan, Italy; and §Scientific Institute IRCCS E. Medea, Bosisio Parini (LC), Italy.
Ther Drug Monit. 2017 Aug;39(4):441-445. doi: 10.1097/FTD.0000000000000413.
The aim of this study was to analyze the relationships between quetiapine and N-desalkylquetiapine plasma levels and clinical improvement, particularly, in regard to depressive and anxious symptoms and to hostility.
This was a prospective observational study that involved 37 outpatients diagnosed as having bipolar disorder I or II. All the patients were observed during a clinical acute and postacute phase. Patients were prescribed 50-800 mg of quetiapine. Patients were evaluated at baseline, after 15 days and after 3 months using the Brief Psychiatry Rating Scale with particular reference to the dimensions of depression, anxiety, and hostility. The plasma concentrations of quetiapine and N-desalkylquetiapine were determined after 3 months using blood samples taken at steady state.
There was a significant relationship between the N-desalkylquetiapine/quetiapine ratio and the improvement in the depression dimension, and there was not a significant relationship between the N-desalkylquetiapine/quetiapine ratio and anxiety and hostility improvement. Quetiapine treatment was well tolerated, and there were no extrapyramidal, anticholinergic, or other side effects to note. There was no relationship between plasma quetiapine or N-desalkylquetiapine concentrations and side effects.
Our findings confirm the efficacy of quetiapine on depressive symptoms, and the available data support that quetiapine's antidepressant activity is mediated by the active metabolite norquetiapine, and it exemplifies the case of an active metabolite that can make a drug like quetiapine originally introduced as an antipsychotic a useful antidepressant agent.
本研究旨在分析喹硫平与N-去烷基喹硫平血浆水平之间的关系以及临床改善情况，尤其是在抑郁、焦虑症状和敌意方面。
这是一项前瞻性观察性研究，纳入了37名被诊断为I型或II型双相情感障碍的门诊患者。所有患者在临床急性期和急性后期均接受观察。患者服用50 - 800毫克喹硫平。在基线、15天后和3个月后使用简明精神病评定量表对患者进行评估，特别关注抑郁、焦虑和敌意维度。3个月后使用稳态采集的血样测定喹硫平和N-去烷基喹硫平的血浆浓度。
N-去烷基喹硫平/喹硫平比值与抑郁维度的改善之间存在显著关系，而N-去烷基喹硫平/喹硫平比值与焦虑及敌意改善之间不存在显著关系。喹硫平治疗耐受性良好，未观察到锥体外系、抗胆碱能或其他副作用。血浆喹硫平或N-去烷基喹硫平浓度与副作用之间无相关性。
我们的研究结果证实了喹硫平对抑郁症状的疗效，现有数据支持喹硫平的抗抑郁活性由活性代谢物去甲喹硫平介导，这例证了一种活性代谢物可使原本作为抗精神病药物引入的喹硫平成为一种有效的抗抑郁药的情况。
