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. 2022 Nov 14;11(11):CD012956.
doi: 10.1002/14651858.CD012956.pub2.

Pharmacological interventions for people with borderline personality disorder

Jutta M Stoffers-Winterling  1 , Ole Jakob Storebø  2   3   4 , Johanne Pereira Ribeiro  2   4 , Mickey T Kongerslev  4   5 , Birgit A Völlm  6 , Jessica T Mattivi  1 , Erlend Faltinsen  2 , Adnan Todorovac  2 , Mie S Jørgensen  2 , Henriette E Callesen  2 , Christian P Sales  7   8 , Julie Perrine Schaug  9 , Erik Simonsen  10 , Klaus Lieb  1
Affiliations

Pharmacological interventions for people with borderline personality disorder

Jutta M Stoffers-Winterling et al. Cochrane Database Syst Rev. .

Abstract

Background: 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.

Objectives: To assess the effects of pharmacological treatment for people with BPD.

Search methods: 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 We contacted researchers working in the field to ask for additional data from published and unpublished trials, and handsearched relevant journals.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.

Selection criteria: 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.

Data collection and analysis: 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.

Main results: 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.

Trial registration: ClinicalTrials.gov NCT00254748 NCT00880919 NCT03418675 NCT02097706 NCT00222482 NCT00635921 NCT00634062 NCT01133301 NCT00124839 NCT00091650 NCT00088036 NCT00255554 NCT00463775 NCT00633802 NCT01103180 NCT00437099 NCT01912391 NCT03495375 NCT04100096 NCT04566601.

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Conflict of interest statement

Jutta M Stoffers‐Winterling (JSW) is a board‐certified clinical psychologist ('Psychologische Psychotherapeutin', cognitive behaviour therapy). She does not prescribe or administer medication in a clinical context.

Ole Jakob Storebø (OJS) is a clinical psychologist with the Psychiatric Research Unit, Region Zealand Psychiatry, Denmark, and does not prescribe or administer medication in a clinical context. He also reports being the trial coordinator for an ongoing study at Region Zealand investigating a new drug treatment for people with borderline personality disorder (NCT04566601), which is included in this review; the study is funded and designed by Boehringer Ingelheim. OJS did not assess the eligibility of this trial which was assessed by two independent reviewers (JPR and JSW). In addition, OJS is an editor for Cochrane Developmental, Psychosocial and Learning Problems (DPLP); however, he was not involved in the editorial process for this review. OJS is also Editor‐in‐Chief for the Scandinavian Journal of Child and Adolescent Psychiatry and Psychology.

Jessica T Mattivi (JTM) is currently working with Psychiatric Services in Meran, Italy. JTM has declared a grant from the German Federal Ministry of Education and Research, paid to University Medical Center Mainz, Germany. The grant was for a systematic review on psychosocial interventions for self‐harm in adolescents; the funder did not have any role in design, methods, data analysis and reporting of the study.

Mickey T Kongerlev is a clinical psychologist and does not prescribe or administer medication in a clinical context. He is employed as manager of a District Psychiatric Service in Region Zealand Mental Health Services, Roskilde, Denmark, and is President of the Institute of Personality Theory and Psychopathology.

Birgit A Völlm is a medical practitioner with the University of Rostock, with the authority to prescribe medication in a clinical context. She is affiliated to the Royal College of Psychiatrists and the DGPPN (Deutsche Gesellschaft für Psychiatrie, Psychotherapie, Psychosomatik und Nervenheilkunde; the German Association for Psychiatry, Psychotherapy and Psychosomatics, which is the largest scientific medical association focusing on mental health in Germany), who have declared an opinion or position on the topic.

Henriette E Callesen is a neuroscientist and does not prescribe or administer medication in a clinical context. She has declared that she has no conflicts of interest.

Adnan Todorovac is a clinical psychologist and does not prescribe or administer medication in a clinical context. He has declared that he has no conflicts of interest.

Christian P Sales is a clinical psychologist with Nottinghamshire Healthcare NHS Foundation Trust, UK, and does not prescribe or administer medication in a clinical context. He has declared that he has no conflicts of interest.

Erlend Faltinsen is a clinical psychologist and does not prescribe or administer medication in a clinical context.

Mie S Jørgensen is a clinical psychologist with Region Zealand Mental Health Services, Denmark, and does not prescribe or administer medication in a clinical context. She has declared that she has no conflicts of interest.

Johanne P Ribeiro is a registered nurse with the authority to administer prescribed medications; however, she is employed as a research assistant at Region Zealand and therefore does not administer medication in a clinical context. She has declared that she has no conflicts of interest.

Julie P Schaug is a psychologist and does not prescribe or administer medication in a clinical context. She has declared that she has no conflicts of interest.

Erik Simonsen (ES) is a psychiatrist with the authority to prescribe medication in a clinical context but does not exercise this authority as he is currently employed as a research director. ES reports that he is the Princpal Investigator of one site (Slagelse, Denmark) of an ongoing, international, multi‐site study investigating a new drug treatment for people with borderline personality disorder (NCT04566601), which is included in this review; the study is funded and designed by Boehringer Ingelheim. ES did not assess the eligibility of this trial, which was assessed by two independent reviewers (JPR and JSW). ES also reports travel and associated expenses (congress fees and accommodation) from Boehringer Ingelheim.

Klaus Lieb (KL) is a board‐certified cognitive behaviour therapist with a special interest in schema therapy. He is also a psychiatrist with the authority to prescribe medication (i.e. recommend treatments for personality disorders); however, he is employed as Director of the Department of Psychiatry and Psychotherapy, University Medical Centre Mainz, Germany and therefore does not prescribe or administer medication in a clinical context. KL is also an editor for DPLP but was not involved in the editorial process for this review.

Figures

1
1
PRISMA flow diagram of study selection
2
2
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies
3
3
Risk of bias summary: review authors' judgements about each risk of bias item for each included trial
4
4
TSA borderline severity: antipsychotics DARIS: Diversity‐adjusted required information size; MIREDIF: Minimal relevant difference; TSA: Trial Sequential Analysis
5
5
Funnel plot of comparison: 1 Medications compared with placebo, outcome: 1.11 Secondary: Anger at end of treatment (continuous outcomes, SMDs)
6
6
Funnel plot of comparison: 1 Medications compared with placebo, outcome: 1.16 Secondary: Impulsivity at end of treatment (continuous outcomes, SMDs)
7
7
TSA interpersonal problems: antipsychotics DARIS: Diversity‐adjusted required information size; MIREDIF: Minimal relevant difference; TSA: Trial Sequential Analysis
8
8
TSA attrition: antipsychotics DARIS: Diversity‐adjusted required information size; Pc: proportion with an outcome in the control group; RRR: Relative risk ratio; TSA: Trial Sequential Analysis
9
9
Funnel plot of comparison: 1 Pharmacotherapies compared with placebo, outcome: 1.19 Secondary: Attrition at end of treatment RR: Relative Risk; SE(log[RR]): Standard Error of the logarithmic Risk Ratio
10
10
TSA attrition: antidepressants DARIS: Diversity‐adjusted required information size;Pc: proportion with an outcome in the control group; RRR: Relative risk ratio; TSA: Trial Sequential Analysis
11
11
TSA attrition: mood stabilisers DARIS: Diversity‐adjusted required information size; Pc: proportion with an outcome in the control group; RRR: Relative risk ratio; TSA: Trial Sequential Analysis
12
12
TSA non‐serious adverse events: antipsychotics DARIS: Diversity‐adjusted required information size; Pc: proportion with an outcome in the control group; RRR: Relative risk ratio; TSA: Trial Sequential Analysis
13
13
Funnel plot of comparison: 26 Subgroup analyses: trial size, outcome: 26.2 Secondary: Anger at end of treatment SE(SMD): Standard error of the standardised mean difference; SMD: Standardised mean difference
14
14
Funnel plot of comparison: 26 Subgroup analyses: trial size, outcome: 26.1 Primary: Psychosocial functioning at end of treatment SE(SMD): Standard error of the standardised mean difference; SMD: Standardised mean difference
1.1
1.1. Analysis
Comparison 1: Medications compared with placebo, Outcome 1: Primary: BPD symptom severity at end of treatment (continuous outcomes, SMDs)
1.2
1.2. Analysis
Comparison 1: Medications compared with placebo, Outcome 2: Primary: BPD symptom severity at end of treatment (continuous outcomes, MDs)
1.3
1.3. Analysis
Comparison 1: Medications compared with placebo, Outcome 3: Primary: Self‐harm at end of treatment (continuous outcomes, MDs)
1.4
1.4. Analysis
Comparison 1: Medications compared with placebo, Outcome 4: Primary: Self‐harm at end of treatment (dichotomous outcomes, RRs)
1.5
1.5. Analysis
Comparison 1: Medications compared with placebo, Outcome 5: Primary: Suicide‐related outcomes at end of treatment (continuous outcomes, SMDs)
1.6
1.6. Analysis
Comparison 1: Medications compared with placebo, Outcome 6: Primary: Suicide‐related outcomes at end of treatment (continuous outcomes, MDs)
1.7
1.7. Analysis
Comparison 1: Medications compared with placebo, Outcome 7: Primary: Suicide‐related outcomes at end of treatment (dichotomous outcomes, RRs)
1.8
1.8. Analysis
Comparison 1: Medications compared with placebo, Outcome 8: Primary: Psychosocial functioning at end of treatment (continuous outcomes, SMDs)
1.9
1.9. Analysis
Comparison 1: Medications compared with placebo, Outcome 9: Primary: Psychosocial functioning at end of treatment (continuous outcomes, MDs)
1.10
1.10. Analysis
Comparison 1: Medications compared with placebo, Outcome 10: Primary: Psychosocial functioning at end of treatment (dichtotomous outcomes, RRs)
1.11
1.11. Analysis
Comparison 1: Medications compared with placebo, Outcome 11: Secondary: Anger at end of treatment (continuous outcomes, SMDs)
1.12
1.12. Analysis
Comparison 1: Medications compared with placebo, Outcome 12: Secondary: Anger at end of treatment (continuous outcomes, MDs)
1.13
1.13. Analysis
Comparison 1: Medications compared with placebo, Outcome 13: Secondary: Affective instability at end of treatment (continuous outcomes, SMDs)
1.14
1.14. Analysis
Comparison 1: Medications compared with placebo, Outcome 14: Secondary: Affective instability at end of treatment (continous outcomes, MDs)
1.15
1.15. Analysis
Comparison 1: Medications compared with placebo, Outcome 15: Secondary: Chronic feelings of emptiness at end of treatment (continuous outcomes, SMDs)
1.16
1.16. Analysis
Comparison 1: Medications compared with placebo, Outcome 16: Secondary: Impulsivity at end of treatment (continuous outcomes, SMDs)
1.17
1.17. Analysis
Comparison 1: Medications compared with placebo, Outcome 17: Secondary: Impulsivity at end of treatment (continuous outcomes, MDs)
1.18
1.18. Analysis
Comparison 1: Medications compared with placebo, Outcome 18: Secondary: Impulsivity at end of treatment (dichtotomous outcomes, RRs)
1.19
1.19. Analysis
Comparison 1: Medications compared with placebo, Outcome 19: Secondary: Interpersonal problems at end of treatment (continuous outcomes, SMDs)
1.20
1.20. Analysis
Comparison 1: Medications compared with placebo, Outcome 20: Secondary: Abandonment at end of treatment (continuous outcomes, SMDs)
1.21
1.21. Analysis
Comparison 1: Medications compared with placebo, Outcome 21: Secondary: Identity disturbance at end of treatment (continuous outcomes, SMDs)
1.22
1.22. Analysis
Comparison 1: Medications compared with placebo, Outcome 22: Secondary: Dissociation and psychotic‐like symptoms at end of treatment (continuous outcomes, SMDs)
1.23
1.23. Analysis
Comparison 1: Medications compared with placebo, Outcome 23: Secondary: Dissociation and psychotic‐like symptoms at end of treatment (continuous outcomes, MDs)
1.24
1.24. Analysis
Comparison 1: Medications compared with placebo, Outcome 24: Secondary: Depression at end of treatment (continuous outcomes, SMDs)
1.25
1.25. Analysis
Comparison 1: Medications compared with placebo, Outcome 25: Secondary: Depression at end of treatment (continuous outcomes, MDs)
1.26
1.26. Analysis
Comparison 1: Medications compared with placebo, Outcome 26: Secondary: Depression at end of treatment (dichotomous outcomes, RRs)
1.27
1.27. Analysis
Comparison 1: Medications compared with placebo, Outcome 27: Secondary: Attrition at end of treatment (dichotomous outcomes, RRs)
1.28
1.28. Analysis
Comparison 1: Medications compared with placebo, Outcome 28: Secondary: Non‐serious adverse events at end of treatment (dichotomous outcomes, RRs)
1.29
1.29. Analysis
Comparison 1: Medications compared with placebo, Outcome 29: Secondary: Serious adverse events at end of treatment (dichotomous outcomes, RRs)
2.1
2.1. Analysis
Comparison 2: Medications compared with placebo ‐ non‐serious adverse events ‐ central nervous system, Outcome 1: Antipsychotics
2.2
2.2. Analysis
Comparison 2: Medications compared with placebo ‐ non‐serious adverse events ‐ central nervous system, Outcome 2: Mood stabilisers
2.3
2.3. Analysis
Comparison 2: Medications compared with placebo ‐ non‐serious adverse events ‐ central nervous system, Outcome 3: Memantine hydrochloride
3.1
3.1. Analysis
Comparison 3: Medications compared with placebo ‐ non‐serious adverse events ‐ cardiovascular and respiratory system, Outcome 1: Antipsychotics
3.2
3.2. Analysis
Comparison 3: Medications compared with placebo ‐ non‐serious adverse events ‐ cardiovascular and respiratory system, Outcome 2: Antipsychotics
3.3
3.3. Analysis
Comparison 3: Medications compared with placebo ‐ non‐serious adverse events ‐ cardiovascular and respiratory system, Outcome 3: Mood stabilisers
4.1
4.1. Analysis
Comparison 4: Medications compared with placebo – non‐serious adverse events ‐ metabolic and gastro‐intestinal system, Outcome 1: Antipsychotics
4.2
4.2. Analysis
Comparison 4: Medications compared with placebo – non‐serious adverse events ‐ metabolic and gastro‐intestinal system, Outcome 2: Antipsychotics
4.3
4.3. Analysis
Comparison 4: Medications compared with placebo – non‐serious adverse events ‐ metabolic and gastro‐intestinal system, Outcome 3: Mood stabilisers
4.4
4.4. Analysis
Comparison 4: Medications compared with placebo – non‐serious adverse events ‐ metabolic and gastro‐intestinal system, Outcome 4: Memantine hydrochloride
5.1
5.1. Analysis
Comparison 5: Medications compared with placebo ‐ non‐serious adverse events ‐ musculoskeletal system, Outcome 1: Antipsychotics
5.2
5.2. Analysis
Comparison 5: Medications compared with placebo ‐ non‐serious adverse events ‐ musculoskeletal system, Outcome 2: Antipsychotics
5.3
5.3. Analysis
Comparison 5: Medications compared with placebo ‐ non‐serious adverse events ‐ musculoskeletal system, Outcome 3: Antidepressants
5.4
5.4. Analysis
Comparison 5: Medications compared with placebo ‐ non‐serious adverse events ‐ musculoskeletal system, Outcome 4: Mood stabilisers
5.5
5.5. Analysis
Comparison 5: Medications compared with placebo ‐ non‐serious adverse events ‐ musculoskeletal system, Outcome 5: Mood stabilisers
6.1
6.1. Analysis
Comparison 6: Medications compared with placebo ‐ non‐serious adverse events ‐ sensory system, Outcome 1: Mood stabilisers
7.1
7.1. Analysis
Comparison 7: Medications compared with placebo ‐ non‐serious adverse events ‐ reproductive system, Outcome 1: Mood stabilisers
8.1
8.1. Analysis
Comparison 8: Medications compared with placebo ‐ non‐serious adverse events ‐ other, Outcome 1: Mood stabilisers
9.1
9.1. Analysis
Comparison 9: Medications compared with placebo ‐ withdrew due to adverse events, Outcome 1: Memantine hydrochloride
10.1
10.1. Analysis
Comparison 10: Single medication compared with alternate single medication , Outcome 1: Primary: BPD symptom severity at end of treatment (continuous outcomes, MDs)
10.2
10.2. Analysis
Comparison 10: Single medication compared with alternate single medication , Outcome 2: Primary: Self‐harm at end of treatment (continuous outcomes, MDs)
10.3
10.3. Analysis
Comparison 10: Single medication compared with alternate single medication , Outcome 3: Primary: Suicide‐related outcomes at end of treatment (continuous outcomes, MDs)
10.4
10.4. Analysis
Comparison 10: Single medication compared with alternate single medication , Outcome 4: Primary: Psychosocial functioning (continuous outcomes, MDs)
10.5
10.5. Analysis
Comparison 10: Single medication compared with alternate single medication , Outcome 5: Secondary: Anger at end of treatment (continuous outcomes, MDs)
10.6
10.6. Analysis
Comparison 10: Single medication compared with alternate single medication , Outcome 6: Secondary: Affective instability at end of treatment (continuous outcomes, MDs)
10.7
10.7. Analysis
Comparison 10: Single medication compared with alternate single medication , Outcome 7: Secondary: Chronic feelings of emptiness at end of treatment (continuous outcomes, MDs)
10.8
10.8. Analysis
Comparison 10: Single medication compared with alternate single medication , Outcome 8: Secondary: Impulsivity at end of treatment (continuous outcomes, MDs)
10.9
10.9. Analysis
Comparison 10: Single medication compared with alternate single medication , Outcome 9: Secondary: Interpersonal problems at end of treatment (continuous outcomes, MDs)
10.10
10.10. Analysis
Comparison 10: Single medication compared with alternate single medication , Outcome 10: Secondary: Abandonment at end of treatment (continuous outcomes, MDs)
10.11
10.11. Analysis
Comparison 10: Single medication compared with alternate single medication , Outcome 11: Secondary: Identity disturbance at end of treatment (continuous outcomes, MDs)
10.12
10.12. Analysis
Comparison 10: Single medication compared with alternate single medication , Outcome 12: Secondary: Dissociation and psychotic‐like symptoms at end of treatment (continuous outcomes, MDs)
10.13
10.13. Analysis
Comparison 10: Single medication compared with alternate single medication , Outcome 13: Secondary: Depression at end of treatment (continuous outcomes, MDs)
10.14
10.14. Analysis
Comparison 10: Single medication compared with alternate single medication , Outcome 14: Secondary: Attrition at end of treatment (dichotomous outcomes, RRs)
10.15
10.15. Analysis
Comparison 10: Single medication compared with alternate single medication , Outcome 15: Secondary: Adverse events at end of treatment (dichotomous outcomes, RRs)
11.1
11.1. Analysis
Comparison 11: Single medication compared with alternate single medication ‐ withdrew due to adverse events (AE), Outcome 1: Withdrew due to AE
12.1
12.1. Analysis
Comparison 12: Single medication compared with alternate single medication ‐ non‐serious adverse events ‐ central nervous system, Outcome 1: Sedation
12.2
12.2. Analysis
Comparison 12: Single medication compared with alternate single medication ‐ non‐serious adverse events ‐ central nervous system, Outcome 2: Restlessness
12.3
12.3. Analysis
Comparison 12: Single medication compared with alternate single medication ‐ non‐serious adverse events ‐ central nervous system, Outcome 3: Restlessness/anxiety
12.4
12.4. Analysis
Comparison 12: Single medication compared with alternate single medication ‐ non‐serious adverse events ‐ central nervous system, Outcome 4: Sleepiness/drowsiness
12.5
12.5. Analysis
Comparison 12: Single medication compared with alternate single medication ‐ non‐serious adverse events ‐ central nervous system, Outcome 5: Fainting spells
12.6
12.6. Analysis
Comparison 12: Single medication compared with alternate single medication ‐ non‐serious adverse events ‐ central nervous system, Outcome 6: Akhatisia
12.7
12.7. Analysis
Comparison 12: Single medication compared with alternate single medication ‐ non‐serious adverse events ‐ central nervous system, Outcome 7: Moderate anxiety
12.8
12.8. Analysis
Comparison 12: Single medication compared with alternate single medication ‐ non‐serious adverse events ‐ central nervous system, Outcome 8: Fatigue
13.1
13.1. Analysis
Comparison 13: Single medication compared with alternate single medication ‐ cardiovascular and respiratory system, Outcome 1: Oral hypoaesthesia
14.1
14.1. Analysis
Comparison 14: Single medication compared with alternate single medication ‐ non‐serious adverse events ‐ musculoskeletal system, Outcome 1: Muscle spasm
14.2
14.2. Analysis
Comparison 14: Single medication compared with alternate single medication ‐ non‐serious adverse events ‐ musculoskeletal system, Outcome 2: Body weight change
14.3
14.3. Analysis
Comparison 14: Single medication compared with alternate single medication ‐ non‐serious adverse events ‐ musculoskeletal system, Outcome 3: Weight gain (3 or more kg within 4 weeks)
15.1
15.1. Analysis
Comparison 15: Single medication compared with combination of medications, Outcome 1: Primary: BPD symptom severity at end of treatment (continuous outcome, MDs)
15.2
15.2. Analysis
Comparison 15: Single medication compared with combination of medications, Outcome 2: Primary: Self‐harm at end of treatment (continuous outcome, MDs)
15.3
15.3. Analysis
Comparison 15: Single medication compared with combination of medications, Outcome 3: Primary: Suicide‐related outcomes at end of treatment (continuous outcome, MDs)
15.4
15.4. Analysis
Comparison 15: Single medication compared with combination of medications, Outcome 4: Primary: Psychosocial functioning at end of treatment (continuous outcome, MDs)
15.5
15.5. Analysis
Comparison 15: Single medication compared with combination of medications, Outcome 5: Secondary: Anger at end of treatment (continuous outcome, MDs)
15.6
15.6. Analysis
Comparison 15: Single medication compared with combination of medications, Outcome 6: Secondary: Affective instability at end of treatment (continuous outcome, MDs)
15.7
15.7. Analysis
Comparison 15: Single medication compared with combination of medications, Outcome 7: Secondary: Chronic feelings of emptiness at end of treatment (continuous outcome, MDs)
15.8
15.8. Analysis
Comparison 15: Single medication compared with combination of medications, Outcome 8: Secondary: Impulsivity at end of treatment (continuous outcome, MDs)
15.9
15.9. Analysis
Comparison 15: Single medication compared with combination of medications, Outcome 9: Secondary: Interpersonal problems at end of treatment (continuous outcome, MDs)
15.10
15.10. Analysis
Comparison 15: Single medication compared with combination of medications, Outcome 10: Secondary: Abandonment at end of treatment (continuous outcome, MDs)
15.11
15.11. Analysis
Comparison 15: Single medication compared with combination of medications, Outcome 11: Secondary: Identity disturbance at end of treatment (continuous outcome, MDs)
15.12
15.12. Analysis
Comparison 15: Single medication compared with combination of medications, Outcome 12: Secondary: Dissociation and psychotic‐like symptoms at end of treatment (continuous outcome, MDs)
15.13
15.13. Analysis
Comparison 15: Single medication compared with combination of medications, Outcome 13: Secondary: Depression at end of treatment (continuous outcome, MDs)
15.14
15.14. Analysis
Comparison 15: Single medication compared with combination of medications, Outcome 14: Secondary: Attrition at end of treatment (dichotomous outcomes, RRs)
16.1
16.1. Analysis
Comparison 16: Single medication compared with combination of medications ‐ non‐serious adverse events ‐ central nervous system, Outcome 1: Sedation
17.1
17.1. Analysis
Comparison 17: Single medication compared with combination of medications ‐ non‐serious adverse events ‐ gastro‐intestinal system, Outcome 1: Nausea
17.2
17.2. Analysis
Comparison 17: Single medication compared with combination of medications ‐ non‐serious adverse events ‐ gastro‐intestinal system, Outcome 2: Dyspepsia
18.1
18.1. Analysis
Comparison 18: Single medication compared with combination of medications ‐ musculoskeletal system, Outcome 1: Akathisia
18.2
18.2. Analysis
Comparison 18: Single medication compared with combination of medications ‐ musculoskeletal system, Outcome 2: Body weight change
18.3
18.3. Analysis
Comparison 18: Single medication compared with combination of medications ‐ musculoskeletal system, Outcome 3: Body weight change
19.1
19.1. Analysis
Comparison 19: Medication compared with placebo ‐ TSA sensitivity analyses, Outcome 1: BPD symptom severity at end of treatment
19.2
19.2. Analysis
Comparison 19: Medication compared with placebo ‐ TSA sensitivity analyses, Outcome 2: Secondary: interpersonal problems at end of treatment
19.3
19.3. Analysis
Comparison 19: Medication compared with placebo ‐ TSA sensitivity analyses, Outcome 3: Attrition at end of treatment
20.1
20.1. Analysis
Comparison 20: Subgroup analysis: types of medication, Outcome 1: BPD symptom severity ‐ antipsychotics vs placebo by class (1st vs 2nd generation)
20.2
20.2. Analysis
Comparison 20: Subgroup analysis: types of medication, Outcome 2: Suicide‐related outcomes ‐ antipsychotics vs placebo by class (1st vs 2nd generation)
20.3
20.3. Analysis
Comparison 20: Subgroup analysis: types of medication, Outcome 3: Psychosocial functioning ‐ antipsychotics vs placebo by class (1st vs 2nd generation)
20.4
20.4. Analysis
Comparison 20: Subgroup analysis: types of medication, Outcome 4: BPD symptom severity ‐ antipsychotics vs placebo by substance
20.5
20.5. Analysis
Comparison 20: Subgroup analysis: types of medication, Outcome 5: BPD symptom severity ‐ mood stabiliser vs placebo by substance
20.6
20.6. Analysis
Comparison 20: Subgroup analysis: types of medication, Outcome 6: Suicide‐related outcomes ‐ antipsychotics vs placebo by substance
20.7
20.7. Analysis
Comparison 20: Subgroup analysis: types of medication, Outcome 7: Psychosocial functioning ‐ antipsychotics vs placebo by substance
20.8
20.8. Analysis
Comparison 20: Subgroup analysis: types of medication, Outcome 8: Psychosocial functioning ‐ antidepressants vs placebo by class/substance
21.1
21.1. Analysis
Comparison 21: Subgroup analysis: psychosocial functioning at baseline, Outcome 1: Primary: BPD symptom severity by severity of impairment at baseline
21.2
21.2. Analysis
Comparison 21: Subgroup analysis: psychosocial functioning at baseline, Outcome 2: Primary: Suicide‐related outcomes by severity of impairment at baseline
21.3
21.3. Analysis
Comparison 21: Subgroup analysis: psychosocial functioning at baseline, Outcome 3: Primary: Psychosocial functioning by severity of impairment at baseline
22.1
22.1. Analysis
Comparison 22: Subgroup analysis: setting, Outcome 1: BPD symptom severity by setting
22.2
22.2. Analysis
Comparison 22: Subgroup analysis: setting, Outcome 2: Primary: Suicide‐related outcomes at end of treatment
22.3
22.3. Analysis
Comparison 22: Subgroup analysis: setting, Outcome 3: Primary: Psychosocial functioning at end of treatment
23.1
23.1. Analysis
Comparison 23: Subgroup analysis: funding, Outcome 1: BPD symptom severity by funding
23.2
23.2. Analysis
Comparison 23: Subgroup analysis: funding, Outcome 2: Primary: Psychosocial functioning at end of treatment
24.1
24.1. Analysis
Comparison 24: Subgroup analysis: trial size, Outcome 1: Primary: Psychosocial functioning at end of treatment
24.2
24.2. Analysis
Comparison 24: Subgroup analysis: trial size, Outcome 2: Secondary: Anger at end of treatment
25.1
25.1. Analysis
Comparison 25: Subgroup analysis: recruitment, Outcome 1: Antipsychotics ‐ anger at end of treatment
26.1
26.1. Analysis
Comparison 26: Sensitivity analysis: mood stabiliser trials outliers SMD > 1.5 included, Outcome 1: Secondary: Anger at end of treatment
See this image and copyright information in PMC

Update of

  • doi: 10.1002/14651858.CD012956

References

References to studies included in this review

Amminger 2013 {published data only}
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Bozzatello 2017 {published data only}ACTRN12614000551695
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De la Fuente 1994 {published data only}
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Frankenburg 2002 {published data only}
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Goldberg 1986 {published data only}
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Grant 2022 {published data only}
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Hollander 2001 {published data only}
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Jariani 2010 {published data only}
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Leone 1982 {published data only}
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Loew 2006 {published data only}
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Shafti 2010 {published data only}
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Tritt 2005 {published data only}
    1. Leiberich P, Nickel MK, Tritt K, Pedrosa Gil F. Lamotrigine treatment of aggression in female borderline patients, part II: an 18-month follow-up. Journal of Psychopharmacology 2008;22(7):805-8. [DOI: 10.1177/0269881107084004] [PMID: ] - DOI - PubMed
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Zanarini 2001 {published data only}
    1. Zanarini MC, Frankenburg FR. Olanzapine treatment of female borderline personality disorder patients: a double-blind, placebo-controlled pilot study. Journal of Clinical Psychiatry 2001;62(11):849-54. [DOI: 10.4088/jcp.v62n1103] [PMID: ] - DOI - PubMed
Zanarini 2003 {published data only}
    1. Zanarini MC, Frankenburg FR. Omega-3 fatty acid treatment of women with borderline personality disorder: a double-blind, placebo-controlled pilot study. American Journal of Psychiatry 2003;160(1):167-9. [DOI: 10.1176/appi.ajp.160.1.167] [PMID: ] - DOI - PubMed
Zanarini 2004 {published data only}
    1. Zanarini MC, Frankenburg FR, Parachini EA. A preliminary, randomized trial of fluoxetine, olanzapine, and the olanzapine-fluoxetine combination in women with borderline personality disorder. Journal of Clinical Psychiatry 2004;65(7):903-7. [DOI: 10.4088/jcp.v65n0704] [PMID: ] - DOI - PubMed
Zanarini 2007 {published data only}
    1. Eli Lilly and Company. Efficacy and safety of olanzapine in patients with borderline personality disorder: a randomized double-blind comparison with placebo [Summary ID # 6253. Clinical Study Summary: Study F1D-MC-HGKK]. www.lillytrials.com/results_files/zyprexa/zyprexa_summary_6523/ (accessed 14 February 2008).
    1. NCT00088036. Efficacy and safety of olanzapine in patients with borderline personality disorder [Efficacy and safety of olanzapine in patients with borderline personality disorder: a randomized double-blind comparison with placebo]. clinicaltrials.gov/ct2/show/NCT00088036 (first received 19 July 2004).
    1. Zanarini MC, Schulz SC, Detke HC, Tanaka Y, Zhao F, Lin D, et al. A dose comparison of olanzapine for the treatment of borderline personality disorder: a 12-week randomized, double-blind, placebo controlled study. European Psychiatry 2007;22(Suppl 1):S172-3. [DOI: 10.1016/j.eurpsy.2007.01.565] - DOI - PubMed
    1. Zanarini MC, Schulz SC, Detke HC, Tanaka Y, Zhao F, Lin D, et al. A dose comparison of olanzapine for the treatment of borderline personality disorder: a 12-week randomized, double-blind, placebo-controlled study. In: Association of European Psychiatrists. 15th European Congress of Psychiatry; 2007 Mar 17-21; Madrid, Spain. 2007.
    1. Zanarini MC, Schulz SC, Detke HC, Tanaka Y, Zhao F, Lin D, et al. P02.102 A dose comparison of olanzapine for the treatment of borderline personality disorder: a 12-week randomized double-blind placebo-controlled study. International Journal of Neuropsychopharmacology 2006;9(Suppl 1):S191. [DOI: 10.1017/S1461145706007450] - DOI - PubMed
Ziegenhorn 2009 {published data only}
    1. Ziegenhorn AA, Roepke S, Schommer NC, Merkl A, Danker-Hopfe H, Perschel FH, et al. Clonidine improves hyperarousal in borderline personality disorder with or without comorbid posttraumatic stress disorder: a randomized, double-blind, placebo-controlled trial. Journal of Clinical Psychopharmacology 2009;29(2):170-3. [DOI: 10.1097/JCP.0b013e31819a4bae] [PMID: ] - DOI - PubMed

References to studies excluded from this review

ACTRN12615000705583 {published data only}
    1. ACTRN12615000705583. Investigation of the benefits of using quetiapine as an adjunct treatment in addition to psychotherapy in patients diagnosed with severe Borderline Personality Disorder. www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=368589 (first received 8 July 2015).
Bellino 2006b {published data only}
    1. Bellino S, Zizza M, Rinaldi C, Bogetto F. Combined treatment of major depression in patients with borderline personality disorder: a comparison with pharmacotherapy. Canadian Journal of Psychiatry 2006;51(7):453-60. [DOI: 10.1177/070674370605100707] [PMID: ] - DOI - PubMed
Coccaro 1997 {published data only (unpublished sought but not used)}
    1. Coccaro EF, Kavoussi RJ. Fluoxetine and impulsive aggressive behavior in personality-disordered subjects. Archives of General Psychiatry 1997;54(12):1081-8. [DOI: 10.1001/archpsyc.1997.01830240035005] [PMID: ] - DOI - PubMed
Hollander 2005 {published data only}
    1. Hollander E, Swann AC, Coccaro EF, Jiang P, Smith TB. Impact of trait impulsivity and state aggression on divalproex versus placebo response in borderline personality disorder. American Journal of Psychiatry 2005;162(3):621-4. [DOI: 10.1176/appi.ajp.162.3.621] [PMID: ] - DOI - PubMed
    1. Hollander E, Tracy KA, Swann AC, Coccaro EF, McElroy SL, Wozniak P, et al. Divalproex in the treatment of impulsive aggression: efficacy in cluster B personality disorders. Neuropsychopharmacology 2003;28(6):1186-97. [DOI: 10.1038/sj.npp.1300153] [PMID: ] - DOI - PubMed
ISRCTN11135486 {published data only}11135486
    1. ISRCTN11135486. Quetiapine versus sertraline as the pharmacological component in a standardised psychopharmacological and psychotherapeutic treatment of borderline personality disorder: a randomised, rater-blinded study. www.isrctn.com/ISRCTN11135486 (first received 1 August 2006). [ISRCTN11135486]
    1. Malevani J. AW: Cochrane review: RCT zu Quetapin und Sertraline bei BPS [personal communication]. Email to: J Stoffers-Winterling 17 June 2020.
Koenigsberg 2003 {published data only}
    1. Koenigsberg HW, Reynolds D, Goodman M, New AS, Mitropoulou V, Trestman RL, et al. Risperidone in the treatment of schizotypal personality disorder. Journal of Clinical Psychiatry 2003;64(6):628-34. [DOI: 10.4088/jcp.v64n0602] [PMID: ] - DOI - PubMed
La Malfa 2003 {published data only}
    1. La Malfa G, Lampronti L, Bertelli M, Conte M, Cabras P. Aggressiveness and personality disorders: evaluation of efficacy and existence of predictors in the treatment with fluvoxamine and lithium [Aggressività e disturbi della personalità]. Minerva Psychiatrica 2003;44(2):75-82. [WEB PAGE: Available at www.minervamedica.it/en/journals/minerva-psychiatry/article.php?cod=R17Y...
Links 1990 {published data only}
    1. Links PS, Steiner M, Boiago I, Irwin D. Lithium therapy for borderline patients: preliminary findings. Journal of Personality Disorders 1990;4(2):173-81. [DOI: 10.1521/pedi.1990.4.2.173] - DOI
Marchesi 2006 {published data only}
    1. Marchesi C, De Panfilis C, Cantoni A, Fontò S, Giannelli MR, Maggini C. Personality disorders and response to medication treatment in panic disorder: a 1-year naturalistic study. Progress in Neuro-Psychopharmacology & Biological Psychiatry 2006;30(7):1240-5. [DOI: 10.1016/j.pnpbp.2006.03.010] [PMID: ] - DOI - PubMed
NCT00255554 {published data only}
    1. Goodman M, New AS, Koenigsberg HW, Hazlett E, Flory J, Siever L. Psychotherapy and combined treatment in BPD: possible effects. In: Psychosomatic Medicine. Integrating Psychiatry & Medicine. 158th Annual Meeting of the American Psychiatric Association; 2005 May 21-26; Atlanta (GA). 2005:126-7. [ABSTRACT #: No. 19F] [PDF: www.psychiatry.org/File%20Library/Psychiatrists/Directories/Library-and-...
    1. Goodman M. RE: [EXTERNAL] Cochrane Colllaboration review [personal communication]. Email to: J Stoffers-Winterling 16 June 2018.
    1. NCT00255554. DBT and escitalopram in borderline personality disorder [Effects of dialectical behavioral therapy and escitalopram on impulsive aggression, affective instability and cognitive processing in borderline personality disorder]. clinicaltrials.gov/ct2/show/NCT00255554 (first received 17 November 2005). [NCT00255554]
NCT00463775 {published data only}
    1. NCT00463775. Topiramate for treatment of patients with borderline personality disorder and alcohol dependence. clinicaltrials.gov/ct2/show/NCT00463775 (first received 18 April 2007).
NCT00633802 {published data only}
    1. Bloch M. Re: RCT of Risperidone in borderline PD [pers commun]. Email to: J. Stoffers-Winterling 15 August 2018.
    1. NCT00633802. Low-dose risperidone treatment for subjects suffering from borderline personality disorder. clinicaltrials.gov/ct2/show/NCT00633802 (first received 4 March 2008).
NCT01103180 {published data only}
    1. McCloskey M. Fwd: Cochrane Collaboration review - RCT of escitalopram in BPD. Email to: J Stoffers-Winterling 15 August 2018.
    1. NCT01103180. Selective serotonin reuptake inhibitors (SSRIs) in borderline personality disorder [SSRIs and self-harm in borderline personality disorder]. clinicaltrials.gov/ct2/show/NCT01103180 (first received 12 April 2010).
NCT03395314 {published data only}
    1. NCT03395314. Ketamine in borderline personality disorder [A randomized active placebo controlled trial of ketamine in borderline personality disorderKetamine in Borderline Personality Disorder]. clinicaltrials.gov/ct2/show/NCT03395314 (first received 10 January 2018). [NCT03395314]
Parsons 1989 {published data only}
    1. Parsons B, Quitkin FM, McGrath PJ, Stewart JW, Tricamo E, Ocepek-Welikson K, et al. Phenelzine, imipramine, and placebo in borderline patients meeting criteria for atypical depression. Psychopharmacology Bulletin 1989;25(4):524-34. [PMID: ] - PubMed
Rombold 2014 {published data only}
    1. Rombold F, Lauterbach E, Felber W, Mueller-Oerlinghausen B, Ahrens B, Bronisch T, et al. Adjunctive lithium treatment in the prevention of suicidal behavior in patients with depression and comorbid personality disorders. International Journal of Psychiatry in Clinical Practice 2014;18(4):300-3. [DOI: 10.3109/13651501.2014.940052] [PMID: ] - DOI - PubMed
Russell 2003 {published data only}
    1. Russell JM, Kornstein SG, Shea MT, McCullough JP, Harrison WM, Hirschfeld RM, et al. Chronic depression and comorbid personality disorders: response to sertraline versus imipramine. Journal of Clinical Psychiatry 2003;64(5):554-61. [DOI: 10.4088/jcp.v64n0510] [PMID: ] - DOI - PubMed
Serban 1984 {published data only}
    1. Serban G, Siegel S. Response of borderline and schizotypal patients to small doses of thiothixene and haloperidol. American Journal of Psychiatry 1984;141(11):1455-8. [DOI: 10.1176/ajp.141.11.1455] [PMID: ] - DOI - PubMed
Verkes 1998 {published data only}
    1. Verkes RJ, Van der Mast RC, Hengeveld MW, Tuyl JP, Zwinderman AH, Van Kempen GM. Reduction by paroxetine of suicidal behavior in patients with repeated suicide attempts but not major depression. American Journal of Psychiatry 1998;155(4):543-7. [DOI: 10.1176/ajp.155.4.543] [PMID: ] - DOI - PubMed
Wollmer 2022 {published data only}
    1. Wollmer MA, Neumann I, Jung S, Bechinie A, Herrmann J, Müller A, et al. Clinical effects of glabellar botulinum toxin injections on borderline personality disorder: a randomized controlled trial. Journal of Psychopharmacology 2022;36(2):159-69. [DOI: 10.1177/02698811211069108] [PMID: ] - DOI - PubMed

References to studies awaiting assessment

NCT00437099 {published data only}
    1. NCT00437009. Efficacy of omega-3 fatty acids on borderline personality disorder: a randomised, double blind clinical trial. clinicaltrials.gov/ct2/show/NCT00437099 (first received 16 February 2007).
NCT01912391 {published data only}
    1. NCT01912391. Clinical research study to evaluate selegiline in the treatment of borderline personality disorder [A phase III randomized double-blind, 12 week, placebo controlled trial of transdermal selegiline in borderline personality disorder (BPD) to evaluate efficacy and safety]. clinicaltrials.gov/ct2/show/NCT01912391 (first received 16 July 2013).

References to ongoing studies

ACTRN12617001317381 {published data only}ACTRN12617001317381
    1. ACTRN12617001317381. Estrogen for the treatment of borderline personality disorder [A randomised placebo controlled trial of estradiol for the treatment of women with borderline personality disorder]. anzctr.org.au/Trial/Registration/TrialReview.aspx?id=373455 (first received 10 August 2017).
Arteaga‐Henríquez 2020 {published data only}
    1. Arteaga-Henríquez G, Rosales-Ortiz SK, Arias-Vásquez A, Bitter I, Ginsberg Y, Ibañez-Jimenez P, et al. Treating impulsivity with probiotics in adults (PROBIA): study protocol of a multicenter, double-blind, randomized, placebo-controlled trial. Trials 2020;21(1):161. [DOI: 10.1186/s13063-019-4040-x] [PMCID: PMC7014653] [PMID: ] - DOI - PMC - PubMed
    1. NCT03495375. Treating impulsivity in adults with probiotics (PROBIA) [Randomized placebo-controlled treatment of impulsivity in adults with probiotics]. clinicaltrials.gov/ct2/show/NCT03495375 (first received 26 February 2018).
Chanen 2019 {published data only}ACTRN12616001192471
    1. ACTRN12616001192471. VERBATIM: a randomised controlled trial of aripiprazole for the treatment of auditory verbal hallucinations in borderline personality disorder [A randomised controlled trial of aripiprazole for the treatment of auditory verbal hallucinations in borderline personality disorder]. anzctr.org.au/Trial/Registration/TrialReview.aspx?id=371038 (first received 26 August 2016).
    1. Chanen AM, Betts J, Jackson H, McGorry P, Nelson B, Cotton SM, et al. Ripiprazole compared with placebo for auditory verbal hallucinations in youth with borderline personality disorder: protocol for the VERBATIM randomized controlled trial. Early Intervention in Psychiatry 2019;13(6):1373-81. [DOI: 10.1111/eip.12774] [PMID: ] - DOI - PubMed
DRKS00015817 {published data only}
    1. DRKS00015817. Stellate ganglion block in patients with borderline personality disorder and posttraumatic stress disorder. www.drks.de/DRKS00015817 (first received 31 October 2018).
EUCTR2020‐003469‐20‐ES {published data only}
    1. EUCTR2020-003469-20-ES. A phase IIb study to evaluate the safety and efficacy of vafidemstat in an adult borderline personality disorder population [A double blind, randomized, placebo-controlled, adaptive 14-week phase IIb trial to evaluate the efficacy and safety of vafidemstat in an adult borderline personality disorder (BPD) population (PORTICO)]. trialsearch.who.int/?TrialID=EUCTR2020-003469-20-ES (first received 19 November 2020). [EUCTR2020-003469-20-ES]
EudraCT 2018‐002471‐18‐GB {published data only}ISRCTN18352058
    1. EudraCT 2018-002471-18. Clozapine in the treatment of borderline personality disorder [The clinical effectiveness and cost effectiveness of clozapine for inpatients with borderline personality disorder: randomised controlled trial]. clinicaltrialsregister.eu/ctr-search/search?query=2018-002471-18/GB (first received 19 June 2019).
    1. ISRCTN18352058. Clozapine in the treatment of borderline personality disorder. The CALMED study [The clinical effectiveness and cost effectiveness of clozapine for inpatients with borderline personality disorder: randomised controlled trial]. www.isrctn.com/ISRCTN18352058 (first received 18 March 2019).
IRCT20210106049948N1 {published data only}IRCT20210106049948N1
    1. IRCT20210106049948N1. Memantine and borderline personality disorder [The effect of memantine on the symptoms of Borderline personality disorder in the Iranian population]. trialsearch.who.int/?TrialID=IRCT20210106049948N1 (first received 21 February 2021). [IRCT20210106049948N1]
IRCT20210531051453N1 {published data only}IRCT20210531051453N1
    1. IRCT20210531051453N1. Effect of omega 3 fatty acid in borderline personality disorder [Study the effectiveness of omega 3 fatty acid as adjuvant treatment on depression, aggression and poor impuls control in hospitalized patients of borderline personality disorder]. trialsearch.who.int/Trial2.aspx?TrialID=IRCT20210531051453N1 (first received 30 July 2021). [IRCT20210531051453N1]
NCT04100096 {published data only}
    1. NCT04100096. A trial of brexpiprazole in the treatment of borderline personality disorder [A multicenter, randomized, flexible-dose, double-blind trial of brexpiprazole versus placebo for the treatment of adults with borderline personality disorder]. clinicaltrials.gov/ct2/show/NCT04100096 (first received 20 September 2019).
NCT04566601 {published data only}
    1. NCT04566601. A study to test different doses of BI 1358894 and find out whether they reduce symptoms in people with borderline personality disorder [A phase II randomized, double-blinded, placebo-controlled parallel group trial to examine the efficacy and safety of 4 oral doses of BI 1358894 once daily over 12 week treatment period in patients with borderline personality disorder]. clinicaltrials.gov/ct2/show/NCT04566601 (first received 28 September 2020).
NCT05356013 {published data only}
    1. NCT05356013. Caplyta in borderline personality disorder. clinicaltrials.gov/ct2/show/NCT05356013 (first received 02 May 2022).

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