Pharmacological interventions for borderline personality disorder

 

Abstract

Background

Drugs are widely used in borderline personality disorder (BPD) treatment, chosen because of properties known from other psychiatric disorders ("off-label use"), mostly targeting affective or impulsive symptom clusters.

Objectives

To assess the effects of drug treatment in BPD patients.

Search methods

We searched bibliographic databases according to the Cochrane Developmental, Psychosocial and Learning Problems Group strategy up to September 2009, reference lists of articles, and contacted researchers in the field.

Selection criteria

Randomised studies comparing drug versus placebo, or drug versus drug(s) in BPD patients. Outcomes included total BPD severity, distinct BPD symptom facets according to DSM-IV criteria, associated psychopathology not specific to BPD, attrition and adverse effects.

Data collection and analysis

Two authors selected trials, assessed quality and extracted data, independently.

Main results

Twenty-eight trials involving a total of 1742 trial participants were included. First-generation antipsychotics (flupenthixol decanoate, haloperidol, thiothixene); second-generation antipsychotics (aripirazole, olanzapine, ziprasidone), mood stabilisers (carbamazepine, valproate semisodium, lamotrigine, topiramate), antidepressants (amitriptyline, fluoxetine, fluvoxamine, phenelzine sulfate, mianserin), and dietary supplementation (omega-3 fatty acid) were tested. First-generation antipsychotics were subject to older trials, whereas recent studies focussed on second-generation antipsychotics and mood stabilisers. Data were sparse for individual comparisons, indicating marginal effects for first-generation antipsychotics and antidepressants.

The findings were suggestive in supporting the use of second-generation antipsychotics, mood stabilisers, and omega-3 fatty acids, but require replication, since most effect estimates were based on single studies. The long-term use of these drugs has not been assessed.

Adverse event data were scarce, except for olanzapine. There was a possible increase in self-harming behaviour, significant weight gain, sedation and changes in haemogram parameters with olanzapine. A significant decrease in body weight was observed with topiramate treatment. All drugs were well tolerated in terms of attrition.

Direct drug comparisons comprised two first-generation antipsychotics (loxapine versus chlorpromazine), first-generation antipsychotic against antidepressant (haloperidol versus amitriptyline; haloperidol versus phenelzine sulfate), and second-generation antipsychotic against antidepressant (olanzapine versus fluoxetine). Data indicated better outcomes for phenelzine sulfate but no significant differences in the other comparisons, except olanzapine which showed more weight gain and sedation than fluoxetine. The only trial testing single versus combined drug treatment (olanzapine versus olanzapine plus fluoxetine; fluoxetine versus fluoxetine plus olanzapine) yielded no significant differences in outcomes.

Authors' conclusions

The available evidence indicates some beneficial effects with second-generation antipsychotics, mood stabilisers, and dietary supplementation by omega-3 fatty acids. However, these are mostly based on single study effect estimates. Antidepressants are not widely supported for BPD treatment, but may be helpful in the presence of comorbid conditions. Total BPD severity was not significantly influenced by any drug. No promising results are available for the core BPD symptoms of chronic feelings of emptiness, identity disturbance and abandonment. Conclusions have to be drawn carefully in the light of several limitations of the RCT evidence that constrain applicability to everyday clinical settings (among others, patients' characteristics and duration of interventions and observation periods).

 

Plain language summary

Drug treatment for borderline personality disorder

Many people with borderline personality disorder (BPD) receive medical treatment. However, there are no drugs available for BPD treatment specifically. A certain drug is most often chosen because of its known properties in the treatment of associated disorders, or BPD symptoms that are also known to be present in other conditions, such as depressive, psychotic, or anxious disorders. BPD itself is characterised by a pervasive pattern of instability in affect regulation (with symptoms such as inappropriate anger, chronic feelings of emptiness, and affective instability), impulse control (symptoms: self-mutilating or suicidal behaviour, ideation, or suicidal threats to others), interpersonal problems (symptoms: frantic efforts to avoid abandonment, patterns of unstable relationships with idealization and depreciation of others), and cognitive-perceptual problems (symptoms: identity disturbance in terms of self perception, transient paranoid thoughts or feelings of dissociation in stressful situations). This review aimed to summarise the current evidence of drug treatment effects in BPD from high-quality randomised trials.

Available studies tested the effects of antipsychotic, antidepressant and mood stabiliser treatment in BPD. In addition, the dietary supplement omega-3 fatty acid (commonly derived from fish) which is supposed to have mood stabilising effects was tested. Twenty-eight studies covering 1742 study participants were included.

The findings tended to suggest a benefit from using second-generation antipsychotics, mood stabilisers, and omega-3 fatty acids, but most effect estimates were based on single study effects so repeat studies would be useful. Moreover, the long-term use of these drugs has not been assessed. The small amount of available information for individual comparisons indicated marginal effects for first-generation antipsychotics and antidepressants.

The data also indicated that there may be an increase in self-harming behaviour in patients treated with olanzapine. In general, attention must be paid to adverse effects. Most trials did not provide detailed data of adverse effects and thus could not be considered within this review. We assumed their effects were similar to those experienced by patients with other conditions. Available data of the studies included here suggested adverse effects included weight gain, sedation and change of haemogram parameters with olanzapine treatment, and weight loss with topiramate. Very few beneficial effects were identified for first-generation antipsychotics and antidepressants. However, they may be helpful in the presence of comorbid problems that are not part of BPD core pathology, but can often be found in BPD patients.

There are only few study results per drug comparison, with small numbers of included participants. Thus, current findings of trials and this review are not robust and can easily be changed by future research endeavours. In addition, the studies may not adequately reflect several characteristics of clinical settings (among others, patients' characteristics and duration of interventions and observation periods).

 

摘要

背景

對邊緣性人格異常的藥物介入

邊緣性人格異常 (borderline personality disorder, BPD) 是普遍的 (在一般人口中盛行率2% ，在精神科住院病人中盛行率20%) ，而且常以危機的方式呈現，對照護機構形成重大的影響，但是對於所提供的幫助卻又缺乏動機善加利用。

目標

評估藥物介入對於邊緣性人格異常的效果。

搜尋策略

在2002年10月，我們以系統化的搜尋包括26個專門及一般書目的資料庫，還搜尋了相關文獻引用的參考文獻，以得到更進一步的試驗資料。

選擇標準

我們蒐納了針對邊緣性人格異常病患的精神藥物和其他治療方式的臨床隨機試驗。

資料收集與分析

我們獨立進行選擇、評估品質及萃取所需研究。針對二元性的結果，我們計算標準化風險比 (risk ratio, RR) ，95% 信賴區間 (95% confidence interval, CI) ，以及益一需治數/害一需治數 (number need to help/harm, NNT/H) 。針對連續性的結果，先選用有最終結果的數據，其次才考慮介入前後結果改便的數據。從具效度量測所得到的非偏差資料，則利用加權平均差異 (weighted mean difference, WMD) 來合成。

主要結論

我們找到10個小型 (總樣本數554) ，短期的隨機試驗，其中8個可萃取出可用以比較的資料比較。比較抗憂鬱劑和安慰劑的試驗雖是小型的 (總樣本數79，2個隨機對照試驗) ，但是對於評比憤怒的部份，相對於安慰劑，fluoxetine也許可以提供某種程度的改善 (總樣本數22，一個對照試驗，憤怒無改善的RR為0.3，C1 0.1 – 0.85；NNT = 2，C1 2 – 9) 。另一研究自殺企圖此重要結果的小型研究顯示，mianserin和安慰劑沒有差異存在 (總樣本數38，一個隨機對照試驗，RR = 0.82，C1 0.44 – 1.54) 。Haloperidol與抗憂鬱劑比起來，也許對於敵意和精神病症狀，治療效果較好。關於MAOI和安慰劑的比較，沒有明顯差別，除了接受MAOI的有較少的敵意 (總樣本數62，一個隨機對照試驗，平均差異 −9.19，信賴區間 −16.12至 −2.26) 。雖然某些評比有顯著的意義，但MAOI與其他抗精神病用藥並沒有令人信服的差異。抗精神病用藥和安慰劑比起來，也許對某些心智狀況症狀有效，但是目前的結果，很難有恰當的臨床詮釋，而且哪一種抗精神病用藥較為有益，也還缺乏證據。最後，情緒穩定劑，例如divalporex，也許可以幫忙心智狀態 (總樣本數16，一個隨機對照試驗，在沒有改善心智方面的風險比為0.58，信賴區間0.36至0.94，NNT為3，信賴區間2至17) ，但是資料並不足以做結論。

作者結論

藥物治療對於邊緣性人格異常的效果，並沒有良好的證據作為基礎，而且單憑這些隨機的試驗結果來做進一步的藥物使用也是令人爭議的。目前的試驗結果建議，抗憂鬱劑的正面治療效果，讓其使用特別值得考慮。良好設計、進行和報告有臨床意義的試驗是有可能的，而且也許需要首先著重抗憂鬱劑和安慰劑的比較。

翻譯人

本摘要由成功大學附設醫院紀美宏翻譯。

此翻譯計畫由臺灣國家衛生研究院 (National Health Research Institutes, Taiwan) 統籌。

總結

有邊緣性人格異常的人，有著對自我不穩定感覺的傾向，並且有人際關係困難、衝動性，和不穩定的情緒。此疾患相對來說是常見的，在一般人口中約有2% ，在精神科住院病人中約有20% 。自我傷害行為在此族群是常見的，而且邊緣性人格在健康機構方面有著重大的影響，因為那些被困擾的個案常以危機的方式呈現，但是對於接下來所提供的介入幫助卻又無法善加利用。對於常開立的藥物效果之證據是不夠的，但在某些方面並不是沒有希望。抗憂鬱劑常在一般的照護中被使用，而且試驗結果也提供了證據，支持其某些正向的效果。這是一個重要且急需進一步研究的領域。