Department of Psychiatry and Psychotherapy, University Medical Center Mainz, Mainz, Germany.
Psychiatric Research Unit, Psychiatry Region Zealand, Slagelse, Denmark.
Cochrane Database Syst Rev. 2022 Nov 14;11(11):CD012956. doi: 10.1002/14651858.CD012956.pub2.
Among people with a diagnosis of borderline personality disorder (BPD) who are engaged in clinical care, prescription rates of psychotropic medications are high, despite the fact that medication use is off-label as a treatment for BPD. Nevertheless, people with BPD often receive several psychotropic drugs at a time for sustained periods.
To assess the effects of pharmacological treatment for people with BPD.
For this update, we searched CENTRAL, MEDLINE, Embase, 14 other databases and four trials registers up to February 2022. We contacted researchers working in the field to ask for additional data from published and unpublished trials, and handsearched relevant journals. We did not restrict the search by year of publication, language or type of publication.
Randomised controlled trials comparing pharmacological treatment to placebo, other pharmacologic treatments or a combination of pharmacologic treatments in people of all ages with a formal diagnosis of BPD. The primary outcomes were BPD symptom severity, self-harm, suicide-related outcomes, and psychosocial functioning. Secondary outcomes were individual BPD symptoms, depression, attrition and adverse events.
At least two review authors independently selected trials, extracted data, assessed risk of bias using Cochrane's risk of bias tool and assessed the certainty of the evidence using the GRADE approach. We performed data analysis using Review Manager 5 and quantified the statistical reliability of the data using Trial Sequential Analysis.
We included 46 randomised controlled trials (2769 participants) in this review, 45 of which were eligible for quantitative analysis and comprised 2752 participants with BPD in total. This is 18 more trials than the 2010 review on this topic. Participants were predominantly female except for one trial that included men only. The mean age ranged from 16.2 to 39.7 years across the included trials. Twenty-nine different types of medications compared to placebo or other medications were included in the analyses. Seventeen trials were funded or partially funded by the pharmaceutical industry, 10 were funded by universities or research foundations, eight received no funding, and 11 had unclear funding. For all reported effect sizes, negative effect estimates indicate beneficial effects by active medication. Compared with placebo, no difference in effects were observed on any of the primary outcomes at the end of treatment for any medication. Compared with placebo, medication may have little to no effect on BPD symptom severity, although the evidence is of very low certainty (antipsychotics: SMD -0.18, 95% confidence interval (CI) -0.45 to 0.08; 8 trials, 951 participants; antidepressants: SMD -0.27, 95% CI -0.65 to 1.18; 2 trials, 87 participants; mood stabilisers: SMD -0.07, 95% CI -0.43 to 0.57; 4 trials, 265 participants). The evidence is very uncertain about the effect of medication compared with placebo on self-harm, indicating little to no effect (antipsychotics: RR 0.66, 95% CI 0.15 to 2.84; 2 trials, 76 participants; antidepressants: MD 0.45 points on the Overt Aggression Scale-Modified-Self-Injury item (0-5 points), 95% CI -10.55 to 11.45; 1 trial, 20 participants; mood stabilisers: RR 1.08, 95% CI 0.79 to 1.48; 1 trial, 276 participants). The evidence is also very uncertain about the effect of medication compared with placebo on suicide-related outcomes, with little to no effect (antipsychotics: SMD 0.05, 95 % CI -0.18 to 0.29; 7 trials, 854 participants; antidepressants: SMD -0.26, 95% CI -1.62 to 1.09; 2 trials, 45 participants; mood stabilisers: SMD -0.36, 95% CI -1.96 to 1.25; 2 trials, 44 participants). Very low-certainty evidence shows little to no difference between medication and placebo on psychosocial functioning (antipsychotics: SMD -0.16, 95% CI -0.33 to 0.00; 7 trials, 904 participants; antidepressants: SMD -0.25, 95% CI -0.57 to 0.06; 4 trials, 161 participants; mood stabilisers: SMD -0.01, 95% CI -0.28 to 0.26; 2 trials, 214 participants). Low-certainty evidence suggests that antipsychotics may slightly reduce interpersonal problems (SMD -0.21, 95% CI -0.34 to -0.08; 8 trials, 907 participants), and that mood stabilisers may result in a reduction in this outcome (SMD -0.58, 95% CI -1.14 to -0.02; 4 trials, 300 participants). Antidepressants may have little to no effect on interpersonal problems, but the corresponding evidence is very uncertain (SMD -0.07, 95% CI -0.69 to 0.55; 2 trials, 119 participants). The evidence is very uncertain about dropout rates compared with placebo by antipsychotics (RR 1.11, 95% CI 0.89 to 1.38; 13 trials, 1216 participants). Low-certainty evidence suggests there may be no difference in dropout rates between antidepressants (RR 1.07, 95% CI 0.65 to 1.76; 6 trials, 289 participants) and mood stabilisers (RR 0.89, 95% CI 0.69 to 1.15; 9 trials, 530 participants), compared to placebo. Reporting on adverse events was poor and mostly non-standardised. The available evidence on non-serious adverse events was of very low certainty for antipsychotics (RR 1.07, 95% CI 0.90 to 1.29; 5 trials, 814 participants) and mood stabilisers (RR 0.84, 95% CI 0.70 to 1.01; 1 trial, 276 participants). For antidepressants, no data on adverse events were identified.
AUTHORS' CONCLUSIONS: This review included 18 more trials than the 2010 version, so larger meta-analyses with more statistical power were feasible. We found mostly very low-certainty evidence that medication may result in no difference in any primary outcome. The rest of the secondary outcomes were inconclusive. Very limited data were available for serious adverse events. The review supports the continued understanding that no pharmacological therapy seems effective in specifically treating BPD pathology. More research is needed to understand the underlying pathophysiologic mechanisms of BPD better. Also, more trials including comorbidities such as trauma-related disorders, major depression, substance use disorders, or eating disorders are needed. Additionally, more focus should be put on male and adolescent samples.
在接受临床护理的边缘型人格障碍（BPD）患者中，尽管药物治疗 BPD 并不对症，精神类药物的处方率仍然很高。然而，BPD 患者经常同时服用几种精神类药物，持续一段时间。
评估 BPD 患者药物治疗的效果。
为了更新本次综述，我们检索了 CENTRAL、MEDLINE、Embase 等 14 个数据库和 4 个试验注册库，检索时间截至 2022 年 2 月。我们联系了该领域的研究人员，要求他们提供已发表和未发表的试验的额外数据，并对相关期刊进行了手工检索。我们没有限制搜索的出版年份、语言或类型。
比较药物治疗与安慰剂、其他药物治疗或药物联合治疗的随机对照试验，所有参与者均被正式诊断为 BPD。主要结局为 BPD 症状严重程度、自伤、自杀相关结局和心理社会功能。次要结局为个体 BPD 症状、抑郁、脱落和不良事件。
至少两名综述作者独立选择试验、提取数据、使用 Cochrane 的偏倚风险工具评估风险偏倚，并使用 GRADE 方法评估证据的确定性。我们使用 Review Manager 5 进行数据分析，并使用试验序贯分析量化数据的统计可靠性。
我们纳入了 46 项随机对照试验（2769 名参与者），其中 45 项符合定量分析标准，总共包括 2752 名 BPD 患者。与 2010 年关于该主题的综述相比，这增加了 18 项试验。参与者主要为女性，除了一项仅纳入男性的试验外。纳入试验的平均年龄为 16.2 至 39.7 岁。纳入的分析包括 29 种不同类型的药物与安慰剂或其他药物相比。17 项试验的资金或部分资金来自制药业，10 项试验的资金来自大学或研究基金会，8 项试验没有资金，11 项试验的资金来源不明。对于所有报告的效应量，负效应估计表明活性药物有有益的效果。与安慰剂相比，在治疗结束时，任何药物对任何主要结局均无差异。与安慰剂相比，药物可能对 BPD 症状严重程度几乎没有影响，尽管证据的确定性非常低（抗精神病药：SMD -0.18，95%置信区间（CI）-0.45 至 0.08；8 项试验，951 名参与者；抗抑郁药：SMD -0.27，95%CI -0.65 至 1.18；2 项试验，87 名参与者；心境稳定剂：SMD -0.07，95%CI -0.43 至 0.57；4 项试验，265 名参与者）。与安慰剂相比，药物对自伤的影响的证据非常不确定，表明几乎没有影响（抗精神病药：RR 0.66，95%CI 0.15 至 2.84；2 项试验，76 名参与者；抗抑郁药：Overt Aggression Scale-Modified-Self-Injury 项目上的 MD 为 0.45 分（0 至 5 分），95%CI -10.55 至 11.45；1 项试验，20 名参与者；心境稳定剂：RR 1.08，95%CI 0.79 至 1.48；1 项试验，276 名参与者）。与安慰剂相比，药物对自杀相关结局的影响的证据也非常不确定，几乎没有影响（抗精神病药：SMD 0.05，95%CI -0.18 至 0.29；7 项试验，854 名参与者；抗抑郁药：SMD -0.26，95%CI -1.62 至 1.09；2 项试验，45 名参与者；心境稳定剂：SMD -0.36，95%CI -1.96 至 1.25；2 项试验，44 名参与者）。非常低确定性证据表明，药物与安慰剂在心理社会功能方面几乎没有差异（抗精神病药：SMD -0.16，95%CI -0.33 至 0.00；7 项试验，904 名参与者；抗抑郁药：SMD -0.25，95%CI -0.57 至 0.06；4 项试验，161 名参与者；心境稳定剂：SMD -0.01，95%CI -0.28 至 0.26；2 项试验，214 名参与者）。低确定性证据表明，抗精神病药可能会略微减少人际关系问题（SMD -0.21，95%CI -0.34 至 -0.08；8 项试验，907 名参与者），心境稳定剂可能会导致这种结果减少（SMD -0.58，95%CI -1.14 至 -0.02；4 项试验，300 名参与者）。抗抑郁药可能对人际关系问题几乎没有影响，但相应的证据非常不确定（SMD -0.07，95%CI -0.69 至 0.55；2 项试验，119 名参与者）。与安慰剂相比，抗精神病药的辍学率的证据非常不确定（RR 1.11，95%CI 0.89 至 1.38；13 项试验，1216 名参与者）。低确定性证据表明，抗抑郁药（RR 1.07，95%CI 0.65 至 1.76；6 项试验，289 名参与者）和心境稳定剂（RR 0.89，95%CI 0.69 至 1.15；9 项试验，530 名参与者）的辍学率可能没有差异，与安慰剂相比。不良事件的报告很差，且大多不规范。关于非严重不良事件的现有证据，抗精神病药的确定性非常低（RR 1.07，95%CI 0.90 至 1.29；5 项试验，814 名参与者）和心境稳定剂（RR 0.84，95%CI 0.70 至 1.01；1 项试验，276 名参与者）。对于抗抑郁药，没有发现不良事件的数据。
本次综述包括了 2010 年版本的 18 项试验，因此有更大的统计效力进行荟萃分析。我们发现，药物治疗可能在任何主要结局方面都没有差异的证据大多非常低。其他次要结局的结果也不确定。关于严重不良事件的有限数据。综述支持继续了解到，似乎没有任何一种药物疗法对 BPD 病理有特别的疗效。需要更多的研究来更好地了解 BPD 的潜在病理生理机制。还需要更多包括创伤相关障碍、重度抑郁症、物质使用障碍或饮食障碍等共病的试验。此外，应该更多地关注男性和青少年样本。
