Pharmacological interventions for people with borderline personality disorder.

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 We contacted researchers working in the field to ask for additional data from published and unpublished trials, and handsearched relevant journals.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

Narrative coherence of autobiographical memories in women with borderline personality disorder and associations with childhood adversity.

BACKGROUND: People suffering from Borderline Personality Disorder (BPD) seem to have incoherent autobiographical narratives. Tentative evidence suggests that reduced narrative coherence of autobiographical memories is associated with insecure attachment. However, it remains unknown whether incoherent autobiographical narratives in people with BPD are coupled to experiences of childhood trauma, which is highly prevalent in BPD. METHOD: We examined if written autobiographical memories in 26 female participants with BPD had reduced narrative coherence relative to 28 healthy female controls and whether more incoherent narratives were associated with childhood trauma. RESULTS: As hypothesized, results showed that compared to controls, the autobiographical memories in participants with BPD had reduced narrative coherence, specifically inadequate orientation about the narrative and lack of narrative structure. More self-reported childhood adversity was coupled to lower orientation across groups whereas increased childhood adversity showed a specific relationship to lowered narrative structure in BPD participants. CONCLUSION: Women with BPD had incoherent autobiographical narratives, and reduced narrative coherence was associated with more self-reported childhood adversity, which appeared to explain the group differences.

Psychological therapies for people with borderline personality disorder.

BACKGROUND: Over the decades, a variety of psychological interventions for borderline personality disorder (BPD) have been developed. This review updates and replaces an earlier review (Stoffers-Winterling 2012). OBJECTIVES: To assess the beneficial and harmful effects of psychological therapies for people with BPD. SEARCH METHODS: In March 2019, we searched CENTRAL, MEDLINE, Embase, 14 other databases and four trials registers. 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 different psychotherapeutic interventions with treatment-as-usual (TAU; which included various kinds of psychotherapy), waiting list, no treatment or active treatments in samples of all ages, in any setting, with a formal diagnosis of BPD. The primary outcomes were BPD symptom severity, self-harm, suicide-related outcomes, and psychosocial functioning. There were 11 secondary outcomes, including individual BPD symptoms, as well as attrition and adverse effects. 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 75 randomised controlled trials (4507 participants), predominantly involving females with mean ages ranging from 14.8 to 45.7 years. More than 16 different kinds of psychotherapy were included, mostly dialectical behaviour therapy (DBT) and mentalisation-based treatment (MBT). The comparator interventions included treatment-as-usual (TAU), waiting list, and other active treatments. Treatment duration ranged from one to 36 months. Psychotherapy versus TAU Psychotherapy reduced BPD symptom severity, compared to TAU; standardised mean difference (SMD) -0.52, 95% confidence interval (CI) -0.70 to -0.33; 22 trials, 1244 participants; moderate-quality evidence. This corresponds to a mean difference (MD) of -3.6 (95% CI -4.4 to -2.08) on the Zanarini Rating Scale for BPD (range 0 to 36), a clinically relevant reduction in BPD symptom severity (minimal clinical relevant difference (MIREDIF) on this scale is -3.0 points). Psychotherapy may be more effective at reducing self-harm compared to TAU (SMD -0.32, 95% CI -0.49 to -0.14; 13 trials, 616 participants; low-quality evidence), corresponding to a MD of -0.82 (95% CI -1.25 to 0.35) on the Deliberate Self-Harm Inventory Scale (range 0 to 34). The MIREDIF of -1.25 points was not reached. Suicide-related outcomes improved compared to TAU (SMD -0.34, 95% CI -0.57 to -0.11; 13 trials, 666 participants; low-quality evidence), corresponding to a MD of -0.11 (95% CI -0.19 to -0.034) on the Suicidal Attempt Self Injury Interview. The MIREDIF of -0.17 points was not reached. Compared to TAU, psychotherapy may result in an improvement in psychosocial functioning (SMD -0.45, 95% CI -0.68 to -0.22; 22 trials, 1314 participants; low-quality evidence), corresponding to a MD of -2.8 (95% CI -4.25 to -1.38), on the Global Assessment of Functioning Scale (range 0 to 100). The MIREDIF of -4.0 points was not reached. Our additional Trial Sequential Analysis on all primary outcomes reaching significance found that the required information size was reached in all cases. A subgroup analysis comparing the different types of psychotherapy compared to TAU showed no clear evidence of a difference for BPD severity and psychosocial functioning. Psychotherapy may reduce depressive symptoms compared to TAU but the evidence is very uncertain (SMD -0.39, 95% CI -0.61 to -0.17; 22 trials, 1568 participants; very low-quality evidence), corresponding to a MD of -2.45 points on the Hamilton Depression Scale (range 0 to 50). The MIREDIF of -3.0 points was not reached. BPD-specific psychotherapy did not reduce attrition compared with TAU. Adverse effects were unclear due to too few data. Psychotherapy versus waiting list or no treatment Greater improvements in BPD symptom severity (SMD -0.49, 95% CI -0.93 to -0.05; 3 trials, 161 participants), psychosocial functioning (SMD -0.56, 95% CI -1.01 to -0.11; 5 trials, 219 participants), and depression (SMD -1.28, 95% CI -2.21 to -0.34, 6 trials, 239 participants) were observed in participants receiving psychotherapy versus waiting list or no treatment (all low-quality evidence). No evidence of a difference was found for self-harm and suicide-related outcomes. Individual treatment approaches DBT and MBT have the highest numbers of primary trials, with DBT as subject of one-third of all included trials, followed by MBT with seven RCTs. Compared to TAU, DBT was more effective at reducing BPD severity (SMD -0.60, 95% CI -1.05 to -0.14; 3 trials, 149 participants), self-harm (SMD -0.28, 95% CI -0.48 to -0.07; 7 trials, 376 participants) and improving psychosocial functioning (SMD -0.36, 95% CI -0.69 to -0.03; 6 trials, 225 participants). MBT appears to be more effective than TAU at reducing self-harm (RR 0.62, 95% CI 0.49 to 0.80; 3 trials, 252 participants), suicidality (RR 0.10, 95% CI 0.04, 0.30, 3 trials, 218 participants) and depression (SMD -0.58, 95% CI -1.22 to 0.05, 4 trials, 333 participants). All findings are based on low-quality evidence. For secondary outcomes see review text. AUTHORS' CONCLUSIONS: Our assessments showed beneficial effects on all primary outcomes in favour of BPD-tailored psychotherapy compared with TAU. However, only the outcome of BPD severity reached the MIREDIF-defined cut-off for a clinically meaningful improvement. Subgroup analyses found no evidence of a difference in effect estimates between the different types of therapies (compared to TAU) . The pooled analysis of psychotherapy versus waiting list or no treatment found significant improvement on BPD severity, psychosocial functioning and depression at end of treatment, but these findings were based on low-quality evidence, and the true magnitude of these effects is uncertain. No clear evidence of difference was found for self-harm and suicide-related outcomes. However, compared to TAU, we observed effects in favour of DBT for BPD severity, self-harm and psychosocial functioning and, for MBT, on self-harm and suicidality at end of treatment, but these were all based on low-quality evidence. Therefore, we are unsure whether these effects would alter with the addition of more data.