Key messages
This review is an update of a previous review on the same topic published in 2010. Although this review includes an additional 18 studies, the conclusions remain the same: there are probably no benefits and risks of medications for borderline personality disorder (BDP), but the evidence is unclear.
Better and larger studies comparing the effects of medication with placebo are needed. Such studies should focus on men, adolescents and those with additional psychiatric diagnoses.
What is BPD?
BPD affects how a person interacts with others and understands one's self. Although its exact causes are unclear, it is thought to result from a combination of genetic and environmental factors (e.g. stressful or traumatic life events when growing up). Approximately 2% of adults and 3% of adolescents are affected.
The symptoms of BPD can be grouped into four categories.
Instability in mood: People with BPD may experience intense feelings that change rapidly and are difficult to control. They may also feel empty and abandoned much of the time.
Cognitive distortions (disturbed patterns of thinking): People with BPD often have upsetting thoughts (e.g. they may think that they are a terrible person). They can have brief episodes of strange experiences (e.g. paranoid ideations or stress-induced dissociative experiences (i.e. feeling detached from the world around them).
Impulsive behaviour: People with BPD may act impulsively and do things that could harm themselves (e.g. when sad and depressed, they may self-harm or have suicidal feelings). They might also engage in reckless behaviour (e.g. drug misuse).
Intense but unstable relationships: People with BPD may find it difficult to keep stable relationships (e.g. they may feel very worried about being abandoned and might constantly text or call, or make threats to harm or kill themselves if the person leaves them).
A person only needs to experience five out of nine criteria across these categories to be given a diagnosis of BPD.
How is BPD treated?
No medication has been approved for the treatment of BPD. Nonetheless, a large proportion of people with BPD are given medications for sustained periods of time to alleviate their symptoms. The type of medication given is chosen based on its known effects on other disorders with similar symptoms.
Review question
We wanted to find out whether medications to treat BPD work better or worse than placebo; whether one medication works better than another; or whether one combination of medications work better than another combination of medications.
We wanted to look at how well medications worked on BPD severity, self-harm, suicide-related outcomes, and functioning (how well a person performs in everyday life).
We also wanted to find out if medications are associated with any unwanted side effects.
What did we do?
We searched for studies that compared the effects of different medications with placebo, another medication, or a combination of medications, in people diagnosed with BPD.
We compared and summarised the results and rated our confidence in the evidence based on factors such as sample size and methods used. Below, we present the findings from our key comparison: medication versus placebo.
What did we find?
We found 46 studies that involved 2769 people with BPD. The smallest study had 13 participants and the largest 451 participants. There were four studies with more than 100 participants. Except for one study that included men only, all studies included women. The average age of the participants ranged from 16 years to 39 years. Most studies were conducted in outpatient settings (31 studies) in Europe (20 studies) and lasted between four and 52 weeks. Pharmaceutical companies fully or partially funded 16 studies.
The studies looked at the effects of 27 different medications, mostly classified as: 1) antipsychotics (drugs to treat psychosis where a person’s thoughts and mood are so impaired that the person has lost contact with reality); 2) antidepressants (drugs to treat depression); or 3) mood stabilisers (drugs to control and even out mood swings, reducing both high moods (mania) and low moods (depression)).
Compared with placebo, medications seem to make little to no difference to BPD severity, self-harm, suicide-related outcomes, and psychosocial functioning. They may make little to no difference as to whether a person continues in a study or drops out. Compared to placebo, antipsychotics and mood stabilisers may make little to no difference to the occurrence of unwanted or harmful effects. No study reported on the side effects of antidepressants.
What are the limitations of the evidence?
Our confidence in the evidence varied between very low and low. The results of future research could differ from the results of this review. Four main factors reduced our confidence in the evidence. First, not all of the studies provided data about everything that we were interested in. Second, the results were very inconsistent across the different studies. Third, there were not enough studies to be certain about the results of our outcomes. Fourth, many studies did not clearly report how they were conducted.
How up-to-date is this evidence?
The evidence is up-to-date to February 2022.
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.
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.