Pharmacological interventions for people with borderline personality disorder

Jutta M. Stoffers-Winterling, Ole Jakob Storebø*, Johanne Pereira Ribeiro, Mickey T. Kongerslev, Birgit A. Völlm, Jessica T. Mattivi, Erlend Faltinsen, Adnan Todorovac, Mie S. Jørgensen, Henriette E. Callesen, Christian P. Sales, Julie Perrine Schaug, Erik Simonsen, Klaus Lieb

*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskriftReviewForskningpeer review

7 Citationer (Scopus)
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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 We contacted researchers working in the field to ask for additional data from published and unpublished trials, and handsearched relevant journals.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.

OriginalsprogEngelsk
ArtikelnummerCD012956
TidsskriftCochrane Database of Systematic Reviews
Vol/bind2022
Udgave nummer11
ISSN1465-1858
DOI
StatusUdgivet - 2022

Bibliografisk note

Funding Information:
Quote: "Supported in part by grants from the National Institute of Mental Health (1 RO3 MH58168-01A1), Richville, Md. (Dr. Hollander); Abbott Laboratories, Abbott Park, Ill. (Dr. Hollander); the National Center for Research Resources, National Institutes of Health (5 MO1 RR00071), Rockville, Md., for the Mount Sinai General Clinical Research Center; and the Seaver Foundation and the PBO Foundation, New York, N.Y." (Hollander 2001, p. 199)

Funding Information:
Funding source: funded or partially funded by pharmaceutical industry

Funding Information:
For BPD severity, the intervention effect also varied according to subgroups of funding, with a seemingly higher effect of trials partially or fully funded by the pharmaceutical industry.

Funding Information:
1. Funding (funded or partially funded by pharmaceutical industry compared to no funding received compared to funded by universities or research foundations)

Funding Information:
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.

Funding Information:
Quote: "This study was supported by grants from the Fondo de Investigación Sanitaria (Ministry of Health, Spain), the REM-TAP Network, and Pfizer, Madrid, Spain. The authors report no additional financial or other relationships relevant to the subject of this article." (Pascual 2008, p. 603)

Funding Information:
Quote: "Funding for this trial was provided by the Health Technology Assessment programme of the National Institute for Health Research (NIHR) and will be published in full in Health Technology Assessment ;Vol. 22, No. 17. See the NIHR Journals Library website for further project information. The Imperial Biomedical Research Centre Facility, which is funded by NIHR, also provided support that has contributed to the research results reported within this paper. Part of Richard Morris’ salary during the project was paid by NIHR Collaboration for Leadership in Applied Health Research and Care East Midlands". (Crawford 2018, p. viii)

Funding Information:
Funding source: funded by grants from universities, authorities or research foundations

Funding Information:
Conflicts of interest: No conflicts of interest were reported besides from funding from the pharmaceutical industry.

Funding Information:
Comment: grant from the Stanley Medical Research Institute; grant from the National Health and Medical Research Council Australia; career development

Funding Information:
Conflicts of interest: No conflicts of interest were reported besides partial funding from the pharmaceutical industry.

Funding Information:
Funding source: Funded or partially funded by pharmaceutical industry

Funding Information:
Quote: "Supported by a grant from Eli Lilly and Co, Indianalpolis, Ind." (Bogen-schutz 2004, p. 104)

Funding Information:
Quote: "This study was supported by a grant from Lederle Laboratories, Pear River, New York." (Leone 1982, p. 148)

Funding Information:
Quote: "Supported by a grant from Abbott Laboratories, Chicago, Ill." (Frankenburg 2002, p. 442)

Funding Information:
Most trials (16 out of 45), were funded (full or partly) by the pharmaceutical industry. Ten were publicly funded, i.e. by grants from universities, authorities or research foundations, funding for 11 trials was unclear, and eight declared that no funding was received. For BPD severity, the intervention effect varied according to subgroups of funding with a seemingly higher effect of trials partially or fully funded by the pharmaceutical industry (SMD -0.34, 95% CI -0.61 to -0.08; I2 = 62%, 7 trials, 862 participants) compared to publicly funded trials (SMD 0.04, 95% CI -0.17 to 0.25; I2 = 0%, 4 trials, 348 participants) and trials with unclear funding (SMD 0.24, 95% CI -0.23 to 0.70; I2 = 0%, 2 trials, 73 participants). The test for subgroup differences indicated: Chi2 = 7.00, df = 2 (P = 0.03), I2 = 71.4%; Analysis 23.1. Intervention effects did not vary according to subgroups of funding sources for the outcome of psychosocial functioning (test for subgroup differences: Chi2 = 0.23, df = 2 (P = 0.89), I2 = 0%, Analysis 23.2).

Funding Information:
Quote: “This study was funded by an investigator initiated grant from Otsu-ka Pharmaceuticals. S.R.C.’s role in this study was funded by a Wellcome Trust Clinical Fellowship (110049/Z/15/Z and 110049/Z/15/A).” (Grant 2022 p. 63)

Funding Information:
Conflicts of interests: No conflicts of interest were reported besides partial funding from the pharmaceutical industry.

Publisher Copyright:
Copyright © 2022 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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