Centre for Suicide Research, Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, UK.
Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK.
BMC Psychiatry. 2018 Dec 27;18(1):399. doi: 10.1186/s12888-018-1993-3.
Bipolar and other psychiatric disorders are associated with considerably increased risk of suicidal behaviour, which may include self-poisoning with medication used to treat the disorder. Therefore, choice of medication for treatment should include consideration of toxicity, especially for patients at risk. The aim of this study was to estimate the relative toxicity of specific drugs within two drug categories, antipsychotics and mood stabilizers, using large-scale databases to provide evidence that could assist clinicians in making decisions about prescribing, especially for patients at risk of suicidal behaviour.
Two indices were used to assess relative toxicity of mood stabilisers and antipsychotics: case fatality (the ratio between rates of fatal and non-fatal self-poisoning) and fatal toxicity (the ratio between rates of fatal self-poisoning and prescription). Mood stabilisers assessed included lithium [reference], sodium valproate, carbamazepine, and lamotrigine, while antipsychotics included chlorpromazine [reference], clozapine, olanzapine, quetiapine and risperidone. Fatal self-poisoning (suicide) data were provided by the Office for National Statistics (ONS), non-fatal self-poisoning data by the Multicentre Study of Self-harm in England, and information on prescriptions by the Clinical Practice Research Datalink. The primary analysis focussed on deaths due to a single drug. Cases where the drug of interest was listed as the likely primary toxic agent in multiple drug overdoses were also analysed. The study period was 2005-2012.
There appeared to be little difference in toxicity between the mood stabilisers, except that based on case fatality where multiple drug poisonings were considered, carbamazepine was over twice as likely to result in death relative to lithium (OR 2.37 95% CI 1.16-4.85). Of the antipsychotics, clozapine was approximately18 times more likely to result in death when taken in overdose than chlorpromazine (single drug case fatality: OR 18.53 95% CI 8.69-39.52). Otherwise, only risperidone differed from chlorpromazine, being less toxic (OR 0.06 95% CI 0.01-0.47).
There was little difference in toxicity of the individual mood stabilisers. Clozapine was far more toxic than the other antipsychotics. The findings are relevant to prescribing policy, especially for patients at particular risk of suicidal behaviour.
双相情感障碍和其他精神障碍与自杀行为的风险显著增加有关，自杀行为可能包括用治疗该疾病的药物进行自我中毒。因此，治疗药物的选择应考虑毒性，特别是对于有风险的患者。本研究的目的是使用大规模数据库来估计两种药物类别（抗精神病药和心境稳定剂）中特定药物的相对毒性，为临床医生在处方决策方面提供证据，特别是对于有自杀行为风险的患者。
使用两种指标评估心境稳定剂和抗精神病药的相对毒性：病死率（致命性和非致命性自我中毒之间的比率）和致命毒性（致命性自我中毒与处方之间的比率）。评估的心境稳定剂包括锂[参照]、丙戊酸钠、卡马西平、拉莫三嗪，而抗精神病药包括氯丙嗪[参照]、氯氮平、奥氮平、喹硫平和利培酮。致命性自我中毒（自杀）数据由国家统计局（ONS）提供，非致命性自我中毒数据由英格兰多中心自我伤害研究提供，处方信息由临床实践研究数据链提供。主要分析集中在单一药物引起的死亡上。还分析了在多个药物过量中毒中，感兴趣的药物被列为主要有毒物质的情况。研究期间为 2005-2012 年。
心境稳定剂之间的毒性似乎差异不大，除了基于病死率，在考虑多药中毒的情况下，卡马西平导致死亡的可能性是锂的两倍多（OR 2.37 95%CI 1.16-4.85）。在抗精神病药中，氯氮平在过量服用时导致死亡的可能性是氯丙嗪的 18 倍左右（单一药物病死率：OR 18.53 95%CI 8.69-39.52）。否则，只有利培酮与氯丙嗪不同，毒性较小（OR 0.06 95%CI 0.01-0.47）。
个别心境稳定剂的毒性差异不大。氯氮平比其他抗精神病药毒性大得多。这些发现与处方政策有关，特别是对有自杀行为特别风险的患者。
