Psychiatric Annals

CME Article 

Treatment Advances in Borderline Personality Disorder

Katharine J. Nelson, MD; S. Charles Schulz, MD

Abstract

Katharine J. Nelson, MD, is Assistant Professor of Psychiatry; and Medical Director, Borderline Personality Disorder Program, Department of Psychiatry, University of Minnesota, Minneapolis. S. Charles Schulz, MD, is Professor, Head, and Donald W. Hastings Endowed Chair, Department of Psychiatry, University of Minnesota.

Dr. Nelson has disclosed no relevant financial relationships. Dr. Schulz has disclosed the following relevant financial relationships: consulting fees, Eli Lilly; contracted research, AstraZeneca, Otsuka, and Rules-Based Medicine (RBM).

Address correspondence to: Katharine J. Nelson, MD, F282/2A West, 2450 Riverside Ave., Minneapolis, MN 55454; fax: 612-273-9779; email: nels2286@umn.edu.

Over the past 20 years, the field of psychiatry has been met with important advances in the understanding of the etiology, pathophysiology, and treatment of borderline personality disorder.1 Far from the classic assumptions, closer examination has revealed borderline personality disorder directly affects 2% to 6% of the population,2,3 is equally prevalent in men and women,3 and is heritable.4 The natural course of the disorder is remission over several years to decades.5,6 Similar to other mood disorders, the condition arises from biological and developmental underpinnings; is associated with significant disability and comorbidity;3 and (unlike personality disorders) is egodystonic.

Functional imaging studies have demonstrated a significant advantage to understanding the pathophysiology of borderline personality disorder (BPD) compared with earlier structural imaging studies. Functional MRI (fMRI) has shown decreased white matter integrity and decreased connectivity in the frontal lobe in BPD.7 New and colleagues have utilized positron emission tomography (PET) imaging to demonstrate a decrease in orbitofrontal cortex and amygdala coupling in 24 impulsive and aggressive patients with BPD.8 These imaging studies support the clinical observation that patients with BPD experience interpersonal interactions as threatening, with deficits in prefrontal cortex connectivity, limiting their ability to think ahead, predict consequences, imagine the viewpoint of others, or problem-solve using adaptive behaviors.

Accurate conceptualization of BPD as a treatable, good prognosis disorder, with neurophysiological correlates implicating specific deficits in brain functioning, contributes to the clinician’s ability to guide rational treatment. Rather than allowing decades of slow suffering to pass, treatment has the potential to accelerate the pace at which the functional connectivity and neurodevelopmental deficits recover.

Several evidence-based interventions for the treatment of BPD exist, including pharmacotherapy, psychotherapy, or a combination of both with various intensities of service levels. Successful treatments have common elements. These include accurate, patient-centered diagnosis of BPD symptoms and comorbidities; psychoeducation; nonjudgmental patient interactions; referral to supportive and educational resources; and patient advocacy.

Screening for BPD symptoms and thoughtfully determining the chronicity and pattern of symptoms over time, in partnership with the patient, is superior to the approach of diagnosis using a brief clinical impression. Symptom screening can also assist in determining symptom domains that would benefit from a targeted treatment approach. High placebo response in clinical trials points to the positive effect of structured, nonjudgmental interactions with staff who respond to symptoms seriously.9

General psychiatric management (GPM) is an effective treatment approach10 based on the manualization of the APA Practice Guideline for the Treatment of Patients with Borderline Personality Disorder11 and highlights the benefit of psychiatric care provided by clinicians experienced with BPD. GPM was compared with dialectical behavioral therapy in a 1-year single blind study of 180 outpatients. Both treatments produced improvement in the primary outcome measures of suicidality, nonsuicidal self-injury, and most secondary outcome measures. There were no significant differences noted between groups, suggesting that both treatments were equally effective in this study.10

Current pharmacologic research has yet to result in FDA approval for use of specific medications in BPD, although there has been little engagement from the pharmaceutical industry in the FDA approval process for obtaining an approved…

Katharine J. Nelson, MD, is Assistant Professor of Psychiatry; and Medical Director, Borderline Personality Disorder Program, Department of Psychiatry, University of Minnesota, Minneapolis. S. Charles Schulz, MD, is Professor, Head, and Donald W. Hastings Endowed Chair, Department of Psychiatry, University of Minnesota.

Dr. Nelson has disclosed no relevant financial relationships. Dr. Schulz has disclosed the following relevant financial relationships: consulting fees, Eli Lilly; contracted research, AstraZeneca, Otsuka, and Rules-Based Medicine (RBM).

Address correspondence to: Katharine J. Nelson, MD, F282/2A West, 2450 Riverside Ave., Minneapolis, MN 55454; fax: 612-273-9779; email: nels2286@umn.edu.

Over the past 20 years, the field of psychiatry has been met with important advances in the understanding of the etiology, pathophysiology, and treatment of borderline personality disorder.1 Far from the classic assumptions, closer examination has revealed borderline personality disorder directly affects 2% to 6% of the population,2,3 is equally prevalent in men and women,3 and is heritable.4 The natural course of the disorder is remission over several years to decades.5,6 Similar to other mood disorders, the condition arises from biological and developmental underpinnings; is associated with significant disability and comorbidity;3 and (unlike personality disorders) is egodystonic.

Functional imaging studies have demonstrated a significant advantage to understanding the pathophysiology of borderline personality disorder (BPD) compared with earlier structural imaging studies. Functional MRI (fMRI) has shown decreased white matter integrity and decreased connectivity in the frontal lobe in BPD.7 New and colleagues have utilized positron emission tomography (PET) imaging to demonstrate a decrease in orbitofrontal cortex and amygdala coupling in 24 impulsive and aggressive patients with BPD.8 These imaging studies support the clinical observation that patients with BPD experience interpersonal interactions as threatening, with deficits in prefrontal cortex connectivity, limiting their ability to think ahead, predict consequences, imagine the viewpoint of others, or problem-solve using adaptive behaviors.

Accurate conceptualization of BPD as a treatable, good prognosis disorder, with neurophysiological correlates implicating specific deficits in brain functioning, contributes to the clinician’s ability to guide rational treatment. Rather than allowing decades of slow suffering to pass, treatment has the potential to accelerate the pace at which the functional connectivity and neurodevelopmental deficits recover.

Commonalities in Treatment Approaches

Several evidence-based interventions for the treatment of BPD exist, including pharmacotherapy, psychotherapy, or a combination of both with various intensities of service levels. Successful treatments have common elements. These include accurate, patient-centered diagnosis of BPD symptoms and comorbidities; psychoeducation; nonjudgmental patient interactions; referral to supportive and educational resources; and patient advocacy.

Screening for BPD symptoms and thoughtfully determining the chronicity and pattern of symptoms over time, in partnership with the patient, is superior to the approach of diagnosis using a brief clinical impression. Symptom screening can also assist in determining symptom domains that would benefit from a targeted treatment approach. High placebo response in clinical trials points to the positive effect of structured, nonjudgmental interactions with staff who respond to symptoms seriously.9

General psychiatric management (GPM) is an effective treatment approach10 based on the manualization of the APA Practice Guideline for the Treatment of Patients with Borderline Personality Disorder11 and highlights the benefit of psychiatric care provided by clinicians experienced with BPD. GPM was compared with dialectical behavioral therapy in a 1-year single blind study of 180 outpatients. Both treatments produced improvement in the primary outcome measures of suicidality, nonsuicidal self-injury, and most secondary outcome measures. There were no significant differences noted between groups, suggesting that both treatments were equally effective in this study.10

Pharmacologic Strategies for BPD

Current pharmacologic research has yet to result in FDA approval for use of specific medications in BPD, although there has been little engagement from the pharmaceutical industry in the FDA approval process for obtaining an approved indication for medication treatment of BPD. The United Kingdom’s provider of guidelines for patient care, the National Institute for Clinical Excellence (NICE), evaluated the existing evidence and deemed it insufficient to incorporate pharmacotherapy into the national care guidelines for BPD.12

Most clinical trials have been small and somewhat imprecise. Current pharmacologic management appropriately seeks to identify Axis I comorbidities, such as bipolar disorder, post-traumatic stress disorder, depression, or schizophrenia, and uses appropriate medication treatment strategies to address these disorders. However, BPD symptoms, not just comorbidities, need to be recognized and directly addressed due to the risk of treatment resistance, decreased functioning, added disability, and suicide.

Practical opportunities result from the clinical neuroscience findings and conceptualization of the pathophysiology in BPD. Treatment approaches have also borrowed from our understanding of other disorders with some symptom overlap, such as mood instability in bipolar disorder type II. Although the evidence base is not definitively established, specific symptom domains benefit from pharmacologic treatment facilitating the neurodevelopmental tasks of interpersonal skill acquirement and emotion regulation.

The heterogeneous presentation of the illness lends itself well to a symptom-targeted approach that has been upheld in recent meta-analytic studies examining early evidence.13,14 These studies may actually have shed light on the limitations of designing studies, whereby the entry criteria are for those with heterogeneous presentations of BPD, rather than by examining subgroups with similar symptom domains.

Ingenhoven and colleagues performed a meta-analysis that included 21 studies examining the classes of medication and the effect on the following symptom domains: cognitive perceptual symptoms; impulsive-behavioral dyscontrol; and affective dysregulation (with subdomains including depressed mood, anxiety, anger, and mood lability).13

This analysis noted a moderate effect of antipsychotics on cognitive-perceptual symptoms and a moderate to large effect on anger. Antidepressants had a small effect on anxiety and anger, but no other domains. Mood stabilizers resulted in a very large effect on impulsive-behavioral control as well as anger; a large effect on anxiety; and a moderate effect on depressed mood. Mood stabilizers had a greater effect on global functioning than antipsychotics.13

Stoffers and colleagues conducted a Cochrane Review of 28 studies and noted that current evidence for use of medications is sparse due to the state of research in this area. However, findings support the use of second-generation antipsychotics, mood stabilizers, and omega-3 fatty acids (see Table). The study author also noted that polypharmacy is not supported by evidence and should be avoided.14

Results of the Cochrane Systematic Review of Randomized Trials (2010)14

Table. Results of the Cochrane Systematic Review of Randomized Trials (2010)14

Of note, evidence suggests that medications that inhibit learning, promote impulsivity, and interfere with skill acquirement, such as benzodiazepines, should be avoided in this population.15 Also, medications that bear a high risk of toxicity in overdose (tricyclic antidepressants) may pose additional risks, including death due to fatal arrhythmia.16 In most trials, antipsychotic medications were typically dosed at about one-third to one-half of the dose utilized for primary psychotic disorders. Mood stabilizer dosing was similar to the dose used for the treatment of bipolar disorder, and antidepressant dosing tended to be higher than the dose used for the treatment of major depression.

Because medications are theorized to be effective in reducing intensity of symptoms that inhibit learning, such as impulsivity, perceptual disturbances, and emotionality, an interesting area of research has focused on combining medication plus psychotherapy. For example, Linehan, the developer of dialectical behavioral therapy (DBT), conducted a study combining DBT and olanzapine.18 In this study, 24 women with BPD and high levels of irritability and anger were assigned to 6 months of DBT alone or DBT plus olanzapine. Both groups experienced significant improvement in irritability, depression, aggression, and self-injury, but the irritability and aggression scores decreased more quickly for the olanzapine group.

A similar double blind, placebo-controlled trial conducted by Soler and colleagues treated 60 patients with BPD with DBT for 4 months, randomly assigning patients to olanzapine or placebo. The combined approach appeared to lower drop-out rates, as well as improve most symptoms overall. These types of studies represent an area of research that is likely to yield important findings in the field of comprehensive treatment for BPD.19

Psychotherapeutic Treatment

Psychotherapy can facilitate the development of healthy emotional experience by theoretically activating the prefrontal cortex through reflection, mindfulness, mentalization, and emotion reappraisal. Although medications can be helpful in mediating this process, pharmacotherapy is not uniformly necessary. Several recent psychotherapeutic treatments have been described and have produced evidence of efficacy; however, limitations in treatment availability and reimbursement pose significant care access issues.

Dialectical Behavioral Therapy

Linehan’s DBT is both manualized and principle-based treatment. The term “dialectical” refers to the philosophical principle of opposite truths. Therapists are trained to approach patients nonjudgmentally, a process that is facilitated by examining and synthesizing the “opposite truths” inherently present in all realities.

Adherent DBT consists of individual therapy with a therapist trained in DBT who uses dialectical principles of acceptance and change, employing cognitive-behavioral treatment techniques, including symptom tracking through use of a diary card and behavioral chain analyses for understanding and problem-solving target behaviors such as suicidality and self-injury. This is balanced with validation and radical acceptance techniques. Behavioral targets are organized hierarchically: Life-threatening behaviors are addressed first, followed by therapy-interfering behaviors, and then quality-of-life–interfering behaviors. Therapists must participate in a weekly consultation group to ensure adherence to treatment principles and procedures and to provide therapist support.

Patients attend a weekly skills training group with an evidence-based, manualized curriculum that encompasses training in mindfulness, interpersonal, emotion regulation, and distress tolerance skills. Individual DBT phone coaching is a required element to provide patients with skills generalization and support, especially in the midst of crisis.20

DBT is the most widely available of the current evidence-based psychotherapeutic treatments. Linehan’s group has developed national credentialing procedures, which will soon be implemented, to ensure fidelity to the evidence-based treatment model. DBT has been shown to be an effective treatment21–23 and is being applied to patient groups with comorbid substance abuse,24 eating disorders, depression, and forensic populations.

Mentalization-Based Therapy

Mentalization-based therapy (MBT), developed by Peter Fonegy, PhD, FBA, and Anthony Bateman, MA, FRCPsych, is a principle-based psychodynamic therapy rooted in attachment and cognitive theory. MBT acknowledges the patient’s difficulty with accurately imagining the mental states of others and seeks to “strengthen a patient’s capacity to understand their own and other’s mental states in attachment contexts in order to address difficulties with affect, impulse regulation, and interpersonal functioning, which act as triggers for suicide and self-harm.”25

MBT has been compared with structured clinical management and treatment as usual. An 8-year follow-up of the MBT vs treatment-as-usual study indicated that patients who received MBT remained better than the treatment-as-usual group with regard to several outcome measures, including suicidality, diagnostic status, service use, use of medication, global function, and vocational status, although social functioning remained impaired.26

STEPPS

Systems training for emotional predictability and problem-solving systems training for emotional predictability and problem-solving (STEPPS), developed by Nancee Blum, MSW, and colleagues at the University of Iowa, is a manual-based treatment that serves as a supplement to existing psychiatric treatment. Weekly, 2-hour seminars occur over 20 weeks, facilitated by two therapists who provide patients with an agenda, packet materials, and homework. A detailed lesson plan is followed.

The program’s three main components are: psychoeducation about BPD; emotion management skills training; and behavior management skills training. The systems component seeks to educate relatives, friends, or other care providers about how to best interact with the patient. This approach has been shown effective when compared to treatment-as-usual with at least 1-year follow-up.27

Transference-Focused Psychotherapy

Transference-focused psychotherapy (TFP) is a principle-based psychodynamic psychotherapy developed by Otto Kernberg, MD, based on his conceptualization of BPD.28 Treatment takes place during two 50-minute sessions per week. The treatment seeks to integrate internalized experiences of dysfunctional early relationships. The transference relationship is heavily utilized in this process. A hierarchy of thematic priorities is used in each session. TFP was shown to be superior when compared with treatment by an experienced community psychotherapist in a study of 104 female outpatients with BPD.29

Schema-Focused Therapy

Schema-focused therapy, developed by Jeffery Young, PhD, is a principle-based psychotherapy utilizing cognitive theory. Treatment is provided in two 50-minute weekly sessions. Schema modes, or pervasive patterns of thinking, feeling, and behaving, are distinguished in BPD and include the detached protector, punitive parent, abandoned/abused child, and the angry, impulsive child.

The therapeutic techniques used include the therapeutic alliance, “outside life” (content associated with activities of daily living, including social and occupations settings), homework, and prior experiences, including trauma.

A randomized trial assigning 88 patients with BPD to schema-focused therapy vs transference-focused therapy resulted in a statistical advantage for schema-focused therapy using the Borderline Personality Disorder Severity Index (BP-DSI) as the main outcome measure.30

Family Involvement

The involvement of family members is increasingly recognized as important to caring for patients with BPD. The development of family psychoeducation curricula has addressed an important psychosocial need compared with the historical practice of either blaming or ignoring patients’ families. The National Educational Alliance for Borderline Personality Disorder (NEA-BPD), a patient advocacy organization, has developed a family support and education program called “Family Connections.”

Groups are facilitated by trained family members of patients with BPD and take place locally or via teleconferencing. This resource is free and available through accessing the organization’s website.31 Another patient advocacy organization, Treatment and Research Advancements Association for Personality Disorder (TARA APD) organizes educational workshops for family members.32

The next frontier in comprehensive treatment of BPD would be the development of centers of excellence to further advance patient care and provide needed data for enhanced understanding of this disorder.

The ideal care system would include multiple integrated levels of care, including case management, inpatient hospitalization, intensive residential treatment, partial hospitalization, day treatment and outpatient psychiatry, and psychotherapy.33 For complex cases, having multiple, unified team members, and family education and involvement can provide necessary support to patients, and minimize the potential for clinician burnout.34 Psychiatry trainees should be trained in best-practices using model curricula that accounts for our rapidly evolving conceptualization of the disorder and treatment practices.

There is sufficient justification for the reclassification of BPD as an Axis I disorder based on the scientific knowledge that has accumulated since DSM-IV.1 The categorical model for BPD has been validated, and although there are limitations, they are similar to other categorical Axis I diagnoses (heterogeneous presentations and issues related to comorbidity). Patient advocacy groups, including NEA-BPD and TARA APD, have argued for reclassification of the disorder, and have suggested that the name of the disorder be revised to decrease associated stigma.

Conclusion

Psychiatry’s understanding of BPD is rapidly evolving. Early evidence suggests a hopeful prognosis for patients struggling with symptoms of this disorder, with several medication and psychotherapeutic strategies now available to decrease the disability and mortality related to this illness. Best practices involve a system of care that meets patients’ diverse therapeutic needs, including options for level of care, multiple skilled treatment team members, family involvement, and medical education.

References

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  14. Stoffers J, Völlm BA, Rücker G, Timmer A, Huband N, Lieb K. Pharmacological interventions for borderline personality disorder: Cochrane Database of Syst Rev. 2010;(6): CD005653.
  15. Cowdry RW, Gardner DL. Pharmacotherapy of borderline personality disorder. Alprazolam, carbamazepine, trifluoperazine, and tranylcypromine. Arch Gen Psychiatry. 1988;45(2):111–9. doi:10.1001/archpsyc.1988.01800260015002 [CrossRef]
  16. Soloff PH, George A, Nathan RS, Schulz PM, Perel JM. Behavioral dyscontrol in borderline patients treated with amitriptyline. Psychopharmacol Bull. 1987;23(1):177–181.
  17. Nelson KJ, Schulz SC. Pharmacologic Treatment of Borderline Personality Disorder. Curr Psychiatr. 2011;10(8):30–40.
  18. Linehan MM, McDavid JD, Brown MZ, Sayrs JH, Gallop RJ. Olanzapine plus dialectical behavior therapy for women with high irritability who meet criteria for borderline personality disorder: a double-blind, placebo-controlled pilot study. J Clin Psychiatry. 2008;69(6):999–1005. doi:10.4088/JCP.v69n0617 [CrossRef]
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Results of the Cochrane Systematic Review of Randomized Trials (2010)14

ClassMedication
Cognitive perceptual symptoms
AntipsychoticsOlanzapine, aripiprazole
Impulsive behavioral dyscontrol
Mood stabilizersTopiramate, lamotrigine
AntipsychoticsAripiprazole
Affective dysregulation
AntidepressantsAmitriptyline (depressed mood)
Mood stabilizersTopiramate, lamotrigine (anger), valproate (depressed mood)
AntipsychoticsHaloperidol (anger), olanzapine, aripiprazole
Omega-3 fatty acidsFish oil (depression)
Suicidal behavior/suicidality
AntipsychoticsFlupenthixol decanoate
Omega-3 fatty acidsFish oil
Interpersonal problems
AntipsychoticsAripiprazole
Mood stabilizersValproate, topiramate

CME Educational Objectives

  1. Conceptualize borderline personality disorder (BPD) as a treatable, good prognosis disorder with neurophysiological correlates which guide rational treatment.

  2. Describe the rationale for prescribing medications for patients with BPD using a symptom-targeted approach.

  3. List the evidence-based psychotherapeutic interventions for the treatment of BPD.

Authors

Katharine J. Nelson, MD, is Assistant Professor of Psychiatry; and Medical Director, Borderline Personality Disorder Program, Department of Psychiatry, University of Minnesota, Minneapolis. S. Charles Schulz, MD, is Professor, Head, and Donald W. Hastings Endowed Chair, Department of Psychiatry, University of Minnesota.

Dr. Nelson has disclosed no relevant financial relationships. Dr. Schulz has disclosed the following relevant financial relationships: consulting fees, Eli Lilly; contracted research, AstraZeneca, Otsuka, and Rules-Based Medicine (RBM).

Address correspondence to: Katharine J. Nelson, MD, F282/2A West, 2450 Riverside Ave., Minneapolis, MN 55454; fax: 612-273-9779; email: .nels2286@umn.edu

10.3928/00485713-20120124-06

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