blah

Borderline Personality Disorder A Review Falk Leichsenring, DSc; Nikolas Heim, MA, MSc; Frank Leweke, MD; Carsten Spitzer, MD; Christiane Steinert, PhD; Otto F. Kernberg, MD

B orderline personality disorder (BPD) is characterized by alterations in self-image and interpersonal relation- ships marked by sudden shifts between extremes of

idealization (extremely positive views about the self or others) and devaluation (extremely negative views about the self or others).1,2 People with BPD typically experience intense anxiety, irritability, or dysphoria as well as impulsive behavior with regard to spending, sexual activity, substance misuse, or binge eating.1

Borderline personality disorder affects approximately 0.7% to 2.7% of adults.3,4

This Review summarizes current evidence regarding the epi- demiology, pathophysiology, diagnosis, and treatment of BPD in adults. Questions about BPD typically asked by a generalist and their answers are listed in Box 1.

Methods

PubMed and PsycINFO were searched for English- and German- language articles on epidemiology, pathophysiology, diagnosis, and treatment of adult patients with BPD published between January 1, 2010, and November 10, 2022. Reference lists of included stud- ies were searched manually for relevant studies. For electronic searches, the title key word (borderline personality disorder [ti]) was combined with several search terms, ie, epidemiology, prevalence, diagnosis, treatment, therapy, psychotherapy, pharmacotherapy, neuroimaging, and neurobiology. The most recent studies and clini- cal trials as well as meta-analyses, systematic reviews, and clinical practice guidelines were prioritized for inclusion. The Cochrane

IMPORTANCE Borderline personality disorder (BPD) affects approximately 0.7% to 2.7% of adults in the US. The disorder is associated with considerable social and vocational impairments and greater use of medical services.

OBSERVATIONS Borderline personality disorder is characterized by sudden shifts in identity, interpersonal relationships, and affect, as well as by impulsive behavior, periodic intense anger, feelings of emptiness, suicidal behavior, self-mutilation, transient, stress-related paranoid ideation, and severe dissociative symptoms (eg, experience of unreality of one’s self or surroundings). Borderline personality disorder is typically diagnosed by a mental health specialist using semistructured interviews. Most people with BPD have coexisting mental disorders such as mood disorders (ie, major depression or bipolar disorder) (83%), anxiety disorders (85%), or substance use disorders (78%). The etiology of BPD is related to both genetic factors and adverse childhood experiences, such as sexual and physical abuse. Psychotherapy is the treatment of choice for BPD. Psychotherapy such as dialectical behavior therapy and psychodynamic therapy reduce symptom severity more than usual care, with medium effect sizes (standardized mean difference) between −0.60 and −0.65. There is no evidence that any psychoactive medication consistently improves core symptoms of BPD. For discrete and severe comorbid mental disorders, eg, major depression, pharmacotherapy such as the selective serotonin reuptake inhibitors escitalopram, sertraline, or fluoxetine may be prescribed. For short-term treatment of acute crisis in BPD, consisting of suicidal behavior or ideation, extreme anxiety, psychotic episodes, or other extreme behavior likely to endanger a patient or others, crisis management is required, which may include prescription of low-potency antipsychotics (eg, quetiapine) or off-label use of sedative antihistamines (eg, promethazine). These drugs are preferred over benzodiazepines such as diazepam or lorazepam.

CONCLUSIONS AND RELEVANCE Borderline personality disorder affects approximately 0.7% to 2.7% of adults and is associated with functional impairment and greater use of medical services. Psychotherapy with dialectical behavior therapy and psychodynamic therapy are first-line therapies for BPD, while psychoactive medications do not improve the primary symptoms of BPD.

JAMA. 2023;329(8):670-679. doi:10.1001/jama.2023.0589

JAMA Patient Page page 692

Supplemental content

Author Affiliations: Department of Psychosomatics and Psychotherapy, University of Giessen, Giessen, Germany (Leichsenring, Leweke, Steinert); Department of Psychosomatics and Psychotherapy, University of Rostock, Rostock, Germany (Leichsenring, Spitzer); International Psychoanalytic University, Berlin, Germany (Heim, Steinert); Weill Cornell Medical College, Personality Disorders Institute, New York, New York (Kernberg).

Corresponding Author: Falk Leichsenring, DSc, Department of Psychosomatics and Psychotherapy, University of Giessen, Ludwigstrasse 76, 35392 Giessen, Germany ([email protected]. uni-giessen.de).

Section Editor: Mary McGrae McDermott, MD, Deputy Editor.

Clinical Review & Education

JAMA | Review

670 JAMA February 28, 2023 Volume 329, Number 8 (Reprinted) jama.com

© 2023 American Medical Association. All rights reserved.

database was also searched between January 1, 2018, and Novem- ber 10, 2022, for meta-analyses of treatments for BPD. Four au- thors (F. Leichsenring, N. Heim, F. Leweke, C. Steinert) indepen- dently selected the most recent studies that were relevant to clinical practice. Of 2605 articles identified, 83 were included, consisting of 11 systematic reviews, 22 narrative reviews, 9 meta-analyses, 5 clinical practice guidelines, 7 articles on diagnostic assessment, 24 articles on epidemiology, 4 articles on neurobiology, and 1 article on family treatment.

Epidemiology Although BPD affects approximately 0.7% to 2.7% of adults in the general population,3,4 higher prevalence rates were reported in pri- mary care (6%), patients using outpatient psychiatric services (11%-12%), and patients treated in psychiatric hospitals (22%).4,5

In a US community sample of 34 481 adults, 2.7% had been diag- nosed with BPD in their lifetime. In this study, only slightly higher rates were observed in women compared with men (3% vs 2.4%),6

while among 3800 patients treated in a psychiatric outpatient setting, considerably higher rates of BPD were found in women compared with men (72% vs 28%).5 The age of onset varies, but symptoms are usually manifest in early adulthood.1 Borderline per- sonality disorder is associated with severe social and vocational impairments, such as inability to hold a job, high rates of comorbid mental disorders and somatic diseases, more frequent use of out- patient and inpatient medical services, high rates of suicide, and high direct medical and indirect costs (eg, sick-leave days). These factors are more common in patients with BPD compared with patients with anxiety and depressive disorders, diabetes, epilepsy, or Parkinson disease.7-12 Only approximately 16% of people with BPD were reported to be married or living with a partner and only about 35% had good work or school performance.13 People with BPD had worse global social functioning than people with other personality disorders (avoidant and obsessive-compulsive personality disorders) and higher rates of comorbid major depres- sive disorder.14

More patients with BPD than patients with other personality disorders die by suicide. A 24-year prospective follow-up study including 290 patients with BPD and 72 patients with other per- sonality disorders reported that 5.9% of patients with BPD died by suicide compared with 1.4% of patients with other personality disorders.12 While the sample size of the comparison group was relatively small, the results reported by this study were consistent with those of a recent meta-analysis that reported suicide rates of 2% to 5% (mean rate of 4%) over follow-up periods of 5 years to 14 years among people with BPD.11 Suicide attempts occurred in more than 75% of individuals with BPD.15 Patients with BPD have a higher prevalence of comorbidities such as endocrine, metabolic, respiratory, cardiovascular, and infectious (eg, HIV, hepatitis) dis- eases than persons without BPD.9,16 Mortality due to causes other than suicide is also higher. For example, in the 24-year longitudinal study by Temes et al,12 14% of patients with BPD and 5.5% of patients with personality disorders other than BPD died of non– suicide-related causes. Borderline personality disorder was associ- ated with a 2.3-fold increase in mortality rate during 2-year follow-up compared with patients without BPD who had other

mental disorders or medical conditions (absolute rates were not provided).9 Similar to people with other serious mental disorders, patients with BPD died approximately 14 to 32 years earlier than individuals in the general population,12 with some studies reporting loss of life expectancy of approximately 6 to 7 years.9 Discrepan- cies in results may be due to methodological differences between the study by Temes et al12 and the study by Schneider et al.9 While the study by Temes et al12 followed up 290 patients with BPD in the US for 24 years whose diagnoses were made using the Revised Diagnostic Interview for Borderlines,17 the study by Schneider et al9

was carried out in Germany and examined 2-year mortality in a ran- domly selected sample of 203 378 patients followed up for 2 years who were diagnosed with BPD via public health insurance data using the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10)18 by medical ser- vice providers for whom reliability of assessment was unclear. Compared with individuals without BPD, men with BPD had a poorer life expectancy than women (odds ratio, 2.40 [95% CI, 1.93- 2.54] vs 2.21 [95% CI, 2.08-2.77]).9

Borderline personality disorder is associated with significantly higher prevalences of other mental disorders.16 In the US study of 34 481 community-dwelling adults, people with BPD had higher rates of the following mental disorders in their lifetime: mood disor- ders such as major depression or bipolar disorder (83%), anxiety disorders (85%), substance use disorders (78%), posttraumatic stress disorder (PTSD) (30%), and other personality disorders (53%).6 In the general population, including approximately 12% of individuals with personality disorders including BPD,19 lifetime prevalence rates of mood disorders, anxiety disorders, PTSD, sub- stance use disorders, and personality disorders were 21%, 34%, 8%, 3%, and 12%, respectively.19-21 Of patients with BPD, approxi- mately 10% had bipolar I disorder (depressive and manic episodes) and an additional 10% had bipolar II disorder (depressive and hypomanic episodes).22,23 Among people with attention-deficit/ hyperactivity disorder, the lifetime rate of BPD was 37.7%.24

Box 1. Common Questions About BPD Typically Asked by Generalist Clinicians

How Should BPD Be Treated? Psychotherapy is an effective treatment for BPD. Dialectical behavior therapy and psychodynamic therapy are the types of psychotherapy that are most effective.

Can BPD Be Effectively Treated With Pharmacotherapy? There is no evidence that pharmacotherapy improves core symptoms of BPD. The first-line treatment is psychotherapy. Pharmacotherapy should be prescribed for discrete comorbid disorders only (eg, depressive or anxiety disorders) or in times of crisis.

Is There Any Indication for Prescribing Medications for BPD? Patients with BPD who have suicidal behavior, psychotic symptoms, severe depression, or extreme anxiety may be treated with medications. For the short-term treatment of crises, antipsychotic medications may be used, but should not be used for longer than 1 week.

Abbreviation: BPD, borderline personality disorder.

Review of Borderline Personality Disorder Review Clinical Review & Education

jama.com (Reprinted) JAMA February 28, 2023 Volume 329, Number 8 671

© 2023 American Medical Association. All rights reserved.

In older compared with younger patients with BPD, a shift in symp- toms toward more depression, feelings of emptiness, and somatic problems has been described.25-27 As people with BPD become older, emotional dysregulation, unstable interpersonal relation- ships, anger, and attachment insecurity typically persist, whereas impulsivity and identity disturbances tend to decrease.25,26 In older people with BPD, self-harm may manifest as nonadherence to medications or misuse of medication.26

Clinical Presentation of BPD In general, personality disorders are characterized by symptoms in 2 or more of the following domains: cognition (eg, perceiving and interpreting self, other people, and events), affectivity (eg, inten- sity, lability, and appropriateness of emotional responses), interper- sonal functioning (ways of responding to interpersonal situations), and impulse control. The symptom patterns are enduring and inflexible, that is, these symptoms are not adaptable to specific situations.1 This pattern of behavior differs from the expectations of an individual’s culture and leads to clinically significant distress or impairment in social, occupational, or other important areas of functioning, such as recreation or global adjustment.1 The pattern is not typically explained by another mental disorder or by the physi-

ological effects of a substance (eg, a drug or medication) or another medical condition (eg, head trauma).1 Borderline personality disor- der as a specific personality disorder is characterized by a pervasive pattern of abrupt changes in self-image, interpersonal relation- ships, and affects, including sudden shifts between all-good or all- bad images of the self and others.1 For example, a patient may describe a parent as abusive, then several minutes later describe them as their best friend. Individuals with BPD experience such extreme views of the self and of others as unrelated to each other.2,28 Borderline personality disorder is also characterized by marked impulsivity and by moods shifting between intense anxiety, irritability, and dysphoria, each lasting a few hours to a few days (Box 2).1 In contrast to dissociative identity disorder, which is char- acterized by a longitudinal variability in personality style (due to inconsistency among identities), BPD is characterized by a persis- tent and pervasive dysfunction in affect and interpersonal regulation.1 Because of this persistent and pervasive dysfunction, individuals with BPD can be distinguished from individuals with mood disorders, anxiety disorders, PTSD, substance-related disor- ders, or bipolar I and II disorders. In bipolar I and II disorders, for example, symptoms are restricted to a distinct episode and are separated by periods when the individual does not display signs of the mood disorder.1 Additional symptoms of BPD include intense anger, chronic feelings of emptiness, recurrent suicidal behavior or

Box 2. DSM-5 and ICD-11 Criteria for BPD

DSM-5 Criteria According to the categorical model of personality disorders, the DSM-5 characterizes BPD by a pervasive pattern of instability of interpersonal relationships, self-image, and affects, and marked impulsivity, beginning in early adulthood and present in a variety of contexts, as indicated by 5 or more of the following criteria1: • Frantic efforts to avoid real or imagined abandonment • A pattern of unstable and intense interpersonal relationships

characterized by alternating between extremes of idealization and devaluation

• Identity disturbance: markedly and persistently unstable self-image and sense of self

• Impulsivity in at least 2 areas that are potentially self-damaging, eg, spending, sex, substance abuse, reckless driving, binge eating

• Recurrent suicidal behavior, gestures, or threats, or self-mutilating behavior

• Affective instability due to a marked reactivity of mood, eg, intense episodic dysphoria, irritability, or anxiety, usually lasting a few hours and rarely more than a few days

• Chronic feelings of emptiness • Inappropriate intense anger or difficulty controlling anger,

eg, frequent displays of temper, constant anger, recurrent physical fights

• Transient, stress-related paranoid ideation or severe dissociative symptoms

DSM-5 Proposed Alternative Dimensional Model of Personality Disorders The proposed alternative dimensional model of personality disorders (AMPD) included in the DSM-5 assesses (1) the level of personality functioning and (2) pathological personality traits.1

Criterion A For BPD, criterion A requires moderate or severe impairments in at least 2 of the following areas: (1) unstable self-image (identity); (2) unstable goals and values (self-direction); (3) compromised ability to recognize the feelings and needs of others (empathy); and (4) intense, unstable, and conflicted relationships (intimacy).

With regard to personality functioning, the AMPD draws on psychodynamic concepts such as personality organization and mentalization.2,29

Criterion B Criterion B requires 4 or more of the following 7 personality traits for a diagnosis of BPD: emotional lability, anxiousness, separation insecurity (eg, fear of rejection or separation or fear of dependency and loss of autonomy), depressivity, impulsivity, risk taking, or hostility.1

Criteria C and D Impairments in personality functioning and pathological personality traits are required to be relatively pervasive and stable.

ICD-11 Criteria In the dimensional ICD-11 model of personality disorders, the diagnostician rates the severity of personality (dys)function on 3 levels: mild, moderate, or severe.30 While in the clinical setting most patients with BPD can be expected to be classified as having a severe personality disorder, the ICD-11 allows the rating of patients with BPD in whom some areas of personality functioning are relatively less affected, as with a moderate personality disorder.31 Of the former 10 discrete personality disorders, only BPD will remain a distinct diagnosis by use of a “borderline pattern qualifier,” that is, the additional diagnosis of BPD according to the categorical model of the DSM-5.30

Abbreviations: BPD, borderline personality disorder; DSM-5, Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition); ICD-11, International Classification of Diseases, 11th Revision.

Clinical Review & Education Review Review of Borderline Personality Disorder

672 JAMA February 28, 2023 Volume 329, Number 8 (Reprinted) jama.com

© 2023 American Medical Association. All rights reserved.

self-mutilation, extreme efforts to avoid abandonment, and tran- sient stress-related paranoid ideation or severe dissociative symp- toms (ie, disintegration of usually integrated mental functions such as consciousness, perception, memory, or identity leading to amnesia or experiencing self or surroundings as unreal).1 Although the symptoms are not listed in the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) (DSM-5), BPD is characterized by non–age-appropriate emotions or behaviors in unstructured situa- tions, which can complicate treatment of BPD.32 Susceptibility to behaving in a manner that is not age-appropriate in unstructured settings has been empirically demonstrated with unstructured psy- chological tests such as the Rorschach test or the Thematic Apper- ception Test.33-36 In these unstructured conditions, people with BPD show bizarre-idiosyncratic thinking (eg, “This is a man with the face of a snake and the paws of a tiger”).33-36

Adverse Childhood Experiences and Development of BPD Genetic factors and adverse childhood experiences may interact to influence brain development through altered hormones and neuro- peptides, increasing the risk of BPD.7,37-40 Adverse childhood expe- riences may modulate gene expression and lead to stable personal- ity traits.7,38,41 Borderline personality disorder is more common in people with a family history of BPD.7,42 For example, a population- based Swedish study including 1 851 755 participants, of whom 11 665 (0.6%) had a diagnosis of BPD according to the ICD-10, esti- mated heritability of BPD at 46%; the remaining 54% of variance was explained by nonshared environmental factors.43 The hazard ratio was highest in identical twins (11.5; 95% CI, 1.6-83.3). The risk of receiving a BPD diagnosis was increased 4.7-fold for full siblings.43 However, no single-nucleotide variants have been iden- tified for BPD.44 Adverse childhood experiences including physical, sexual, or emotional abuse and neglect are more common in people with BPD.16,45,46 However, not all people diagnosed with BPD have a history of adverse childhood experiences.45 An empiri- cally supported model of the neurobiology of BPD does not exist, as meta-analyses on neuroendocrinological processes47-49 and brain functioning50,51 found only a few differences in these vari- ables among people with BPD compared with healthy controls. The most consistent finding was hyperactivity of the amygdala,50,51 but its role remains unclear.52

Assessment and Diagnosis In the categorical model of personality disorders, which uses abso- lute (yes/no) categories of diagnostic criteria, 5 or more of 9 crite- ria listed in Box 2 are required for a diagnosis of BPD.1 The pro- posed alternative dimensional model of personality disorders of the DSM-5 defines personality disorders by the level of personality func- tioning (criterion A),1 which is rated on a continuum ranging from 0 (little or no impairment) to 4 (extreme impairment).1 For the di- agnosis of BPD, a moderate (score of 2) or greater (score of �3) impairment is required.1 Additionally required criteria are listed in Box 2. In the World Health Organization’s upcoming 11th revision of the ICD, the categorical system of personality disorders will be al-

most entirely replaced by a dimensional system similar to the pro- posed alternative DSM-5 model previously described (Box 2).53

In the initial assessment, primary care clinicians may use the screening questions shown in Table 1.

To identify patients with BPD, primary care clinicians should evaluate patients for recurrent suicidal behavior, gestures, or threats; self-mutilating behavior; and impulsive potentially self- damaging behavior (eg, massive spending, unprotected sex, substance abuse, reckless driving, binge eating), as well as for inap- propriate anger (frequent displays of temper, constant anger, recurrent physical fights). In addition, clinicians should look for marked reactivity of mood (eg, short-lived intense episodic dys- phoria, irritability, or anxiety) or chronic feelings of emptiness and fear of being abandoned. Inquiring about interpersonal relation- ships is helpful because these relationships are typically unstable and intense and characterized by alternating between extremes of idealization and devaluation.1

Borderline personality disorder can be reliably diagnosed by trained interviewers/clinicians using semistructured inter- views. Several reliable and validated interview methods exist.7,65

In addition, self-report questionnaires are helpful in diagnosis, as well as unstructured tests such as the Rorschach test or the Thematic Apperception Test, which facilitate assessment of per- sonality functioning.7,32,33,35,36 Sensitivity of these different diag- nostic instruments ranges between 83% and 89% and specificity between 78% and 93%.17,59,66

Treatment Clinical Management Patients with BPD should be informed of their diagnosis, the ex- pected course of the disorder, etiology, and treatment options.54 Cli- nicians should set clear boundaries, avoid responding to provoca- tive behavior, avoid polypharmacotherapy, and facilitate open communication and agreement on a consistent approach with all treating clinicians to prevent a situation in which some clinicians are regarded as “good” and others as “bad” (Table 1).54,55,67 The pa- tient should be informed that effective methods of psychotherapy exist and that medications are appropriate only for treating dis- crete comorbid mental disorders or in situations of crisis, such as sui- cidal behavior, extreme anxiety, or psychotic episodes. This educa- tion of patients facilitates an alliance between patients and clinicians and may encourage patients to take part in psychotherapy.7 Typi- cal crises in BPD consist of suicidal behavior or ideation, extreme anxi- ety, psychotic episodes, or other extreme behavior likely to endan- ger the patient or others, usually caused by interpersonal problems such as real or imagined abandonment or by shifts from idealiza- tion to devaluation. Life-threatening behaviors (eg, suicidal, self- mutilating, or high-risk behaviors, as well as attacks against others) should be identified and promptly treated (see Pharmacotherapy section and Table 1). With regard to comorbid mental disorders, ex- perts suggest that comorbid bipolar I disorder, early-onset com- plex PTSD, severe substance misuse, and anorexia should be treated before BPD, since these disorders need to be well controlled be- fore BPD can be treated successfully.7 In contrast, for patients who have comorbid depressive disorder, panic disorder, adult-onset PTSD, intermittent substance use disorder, or bulimia, treating BPD should

Review of Borderline Personality Disorder Review Clinical Review & Education

jama.com (Reprinted) JAMA February 28, 2023 Volume 329, Number 8 673

© 2023 American Medical Association. All rights reserved.

Table 1. Recommended Approaches for Treating Patients With BPD in Primary Care Settings

Approach Patient-clinician relationship

General clinical approach Set clear boundaries while maintaining empathy (eg, in case of excessive wishes for contact or treatment), avoid response to provocative behavior, and avoid polypharmacotherapy.54,55

Establishing a productive patient-clinician relationship Establish a helpful alliance by an attitude of understanding, acceptance, and empathy and by setting goals, communicating realistic hope, and explaining the disorder and possible treatments.56,57

Avoiding stigmatization Avoid preconceptions such as viewing patients with BPD as intentionally difficult or untreatable.58

Collaboration among all treating clinicians Open communication and agreement on a consistent approach with all clinicians to avoid splitting (eg, one clinician is “all good,” another “all bad”).54,55

Recognizing, managing, and using one’s own feelings to understand the patient

Patients with BPD typically have difficulty regulating interpersonal relationships and emotions, which may lead to behaviors that provoke strong and unusual reactions from clinicians (a phenomenon called countertransference), eg, feelings of being powerless or hopeless or of extreme anger or commitment.55

These feelings may inform clinicians of patients’ own feelings.55

Using biographical information such as sexual or physical maltreatment

Understanding patients’ biographical experiences may help clinicians to understand patients’ strong reactions, eg, of (inappropriate) anger, and prevent clinicians from taking them personally, as they may be a projection of other experiences.

Diagnostic assessment

Preliminary assessment of BPD In primary care, BPD can be identified based on unstable identity, interpersonal relationships, and affect.7 Helpful questions may include, for example59: • Do you often wonder who you really are? • Do you sometimes feel that another person appears in you that does not fit you? • Do your feelings toward other people quickly change into opposite extremes (eg, from love

and admiration to hate and disappointment)? • Do you often feel angry? • Do you often feel empty? • Have you been extremely moody? • Have you ever deliberately hurt yourself (eg, cut or burned yourself)?

Conveying the presumptive diagnosis of BPD Summarizing DSM-5 or screening criteria that seem to be present in a patient, a primary care clinician may say to the patient that these symptoms suggest BPD and that referral to a psychotherapist is recommended, since psychotherapy is first-line treatment for BPD. A primary care clinician may also ask a patient whether they have already been given the diagnosis of a (borderline) personality disorder.

Management in general practice and recommended treatment options

Long-term management Refer to a mental health expert.

Psychotherapy treatment recommendations Psychotherapy is first-line treatment. No differences in efficacy were found between empirically supported psychotherapies such as dialectical behavior therapy, cognitive behavior therapy, or psychodynamic therapy.60

Pharmacotherapy treatment recommendations Pharmacotherapy is not recommended for core features of BPD, only as adjunctive and targeted treatment of discrete comorbid disorders.61,62 In addition, pharmacotherapy may be applied in a mental health crisis, but for not longer than 1 week, using a single drug and a minimum effective dose.61,62

Risk management (suicidal behavior or intentions, self-harm, extreme anxiety, psychotic symptoms, uncontrolled behavior likely to endanger the patient or others)

Priority must be given to addressing life-threatening behaviors (eg, suicidal, self-mutilating, or high-risk behaviors, attacks against others). Verbal interventions include a calm attitude, understanding the crisis from a patient’s point of view, empathetic open questions, and stimulating reflections about solutions.61 Use antipsychotic or sedative medications to treat crises for no longer than 1 week.62

Understanding the meaning of self-harm (eg, cutting, burning)

Self-harm may serve different functions, eg, avoiding feelings of emptiness or dissociation, dampening painful emotions, or regulation of relationships by producing more closeness or distance.55 Therapists may conclude an agreement with a patient about self-harm, implying, eg, that the patient should attend a clinician who treats the wound before the next session.

Understanding and managing suicidality28,63 • Clarify the acute danger of attempting suicide (eg, has a patient already developed a plan how to attempt suicide, has the patient previously made a suicide attempt, is impulse control severely impaired [eg, by substance misuse], is there a lack of social support system, or is the patient trustful with regard to agreements?).

• Clarify whether there may be a discrete major depressive disorder, possibly requiring pharmacotherapy or inpatient treatment.

• If not, clarify the trigger of the present suicidality (eg, interpersonal loss, shift from “all good” to “all bad”).

• Suicide may be viewed by a patient as a solution of a problem (eg, stopping anxiety, despair, loneliness, emptiness, or anger). Discussing what makes life intolerable moves the focus from suicide to life’s distresses. Other solutions may emerge.

• Focus on “black-and-white” images of the self or of others related to the triggering situation (eg, “My mother again forgot my birthday. For me, she is no longer my mother!”) Present alternative, more integrated, less sharply divided views.

• Suicidal threats may be used by a patient to try to force a clinician not to “abandon” them (as others may have done). As a result, the clinician may also experience feelings of helplessness or anger. Clinicians are recommended not to counteract aggressively or emotionally in a way that might confirm the patient’s experiences and expectations or imply responsibility for a patient’s suicide attempts.

• Make a contract that commits a patient not to act on suicidal impulses, but to discuss them in sessions or to go to emergency psychiatric services if they feel that suicidal impulses cannot be controlled.

• Evidence-based psychotherapies for BPD include detailed recommendations how to treat suicidality.28,29,64

Referral to inpatient services If acute crises cannot be managed by outpatient services, inpatient treatment may be required.

Abbreviations: BPD, borderline personality disorder; DSM-5, Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition).

Clinical Review & Education Review Review of Borderline Personality Disorder

674 JAMA February 28, 2023 Volume 329, Number 8 (Reprinted) jama.com

© 2023 American Medical Association. All rights reserved.

take priority since these disorders will likely improve once BPD is con- trolled. In a randomized trial of 68 family members of patients with BPD, group psychoeducation about the disorder along with self- care and peer support skills reduced the emotional stress associ- ated with BPD in family members compared with a wait-list control condition.68 If specialized methods of psychotherapy are not avail- able, experienced mental health professionals may apply psycho- education (informing a patient about the disorder and its treat- ments) or manage acute crises using pharmacotherapy and clinical management as described in the Pharmacotherapy section.69 Ben- efit for this generalist model of treating patients with BPD has emerged from several randomized clinical trials.70-72 This type of care can be carried out by experienced clinicians without training in the specialized methods of psychotherapy discussed below.69

Pharmacotherapy Although the 2001 American Psychiatric Association practice guide- lines for BPD recommended antidepressants such as fluoxetine, ser- traline, or venlafaxine; mood stabilizers such as lithium carbonate, carbamazepine, or valproate; antipsychotics such as haloperidol; monoamine oxidase inhibitors such as phenelzine or tranylcypro- mine; or benzodiazepines such as alprazolam or clonazepam for af- fective dysregulation and impulsive behavior dyscontrol, new evi- dence has accumulated since these guidelines were published.73

No class of psychoactive medication has been consistently effec- tive in treating BPD in randomized clinical trials, and therefore no medications have been approved by the US Food and Drug Admin- istration or licensed for use in BPD in the UK.7,74-76 For these rea- sons, the UK National Institute for Health and Care Excellence (NICE) guideline does not recommend pharmacotherapy to treat any core symptom of BPD (eg, marked emotional instability, transient stress- related paranoid ideation).61,62 This is consistent with reviews of functional magnetic resonance imaging studies showing that phar- macotherapy does not induce changes in brain activity or brain connectivity,77 whereas psychotherapy appears to alter neural ac- tivities and connectivity of regions subserving executive control and emotion regulation.78 The NICE guideline recommends pharmaco- therapy in BPD only for discrete and severe comorbid disorders such as severe depressive disorders, including suicidal ideation or se- vere anxiety disorders. For these types of comorbid disorders in BPD, selective serotonin reuptake inhibitors such as escitalopram, ser- traline, or fluoxetine may be used. Antipsychotic drugs are not rec- ommended by the NICE guideline for medium- or long-term treat- ment of BPD. For specific recommendations regarding the treatment of comorbid conditions in BPD, NICE recommends consulting the NICE clinical guidelines for the respective disorders. Few random- ized clinical trials have focused on BPD with distinct comorbidities.76

Most randomized clinical trials of pharmacotherapy excluded pa- tients with comorbid major depressive disorder, bipolar disorder, psychotic disorders, or substance-related disorders, limiting avail- able evidence for patients with BPD and these comorbidities.76

For the management of crises in BPD as defined above, NICE recommends verbal intervention (eg, trying to understand a crisis from a patient’s view) (Table 1) and short-term pharmacotherapy using a single drug, with the minimum effective dose or prescribing fewer tablets more frequently if there is a risk of overdose.61 For treat- ment of acute crises in BPD, sedative antihistamines (eg, prometha- zine) or low-potency antipsychotics (eg, quetiapine), but not

benzodiazepines (eg, diazepam, lorazepam), may be used as part of an overall treatment plan agreed on by all participating clinical prac- titioners (Table 2).62 The duration of pharmacological treatment should be agreed on with the patient and is not recommended for longer than 1 week.61,62 Sedative antihistamines such as prometha- zine, however, are not licensed in either the US or in the UK for BPD; therefore, informed consent should be obtained and documented.61

This includes informing patients that promethazine is associated with abuse80 and should be used with caution in a disorder in which pa- tients have higher rates of substance abuse. For insomnia in BPD, general advice about sleep hygiene without medication prescrip- tion is recommended. For short-term management of insomnia, “Z-drugs” (eg, zolpidem or eszopiclone) may be prescribed.61 Due to concerns about dependency, use of Z-drugs is recommended only for severe insomnia, with the lowest dose possible and for no lon- ger than 4 weeks.81 Short-term symptoms of depression or anxiety that are part of BPD emotional instability and that can be related to specific triggering situations such as interpersonal problems should not be misinterpreted as comorbid disorders and should be treated solely with psychotherapy.

Psychotherapy Psychotherapy is first-line treatment for BPD and should be recom- mended to all patients with BPD.7,61,82 Several meta-analyses of

Table 2. Epidemiology, Impairment, and Treatment of Borderline Personality Disorder

Prevalence rate, duration, or type of treatment

Lifetime prevalence79 2.7%

Female vs male

Community samples, lifetime prevalence6

4% vs 3.4%

Outpatient clinical settings5 72% vs 28%

Social and vocational impairment13

Married or living with partner 16%

Good work or school performance

34%

Life expectancy

Reduction of life expectancy9 6-7 Years

Mortality by suicide12 2%-5% (Mean, 4%)

Lifetime high comorbidity with other mental disorders6

Anxiety disorders 84.8%

Mood disorder 82.7%

Substance use disorder 78.2%

Treatment

First-line treatment: evidence-based psychotherapy

Dialectical behavior therapy, psychodynamic therapy

Pharmacotherapy for discrete and severe comorbid disorders (eg, depressive disorders, anxiety disorders)

Selective serotonin reuptake inhibitors such as escitalopram, sertraline, or fluoxetine

Pharmacotherapy or for short-term treatment of acute crisis

Antihistamines or low-potency antipsychotics (ie, promethazine, quetiapine) rather than benzodiazepines (eg, diazepam, lorazepam)

Treatment of borderline personality disorder–associated insomnia

Sleep hygiene and short-term use of Z-drugs (eg, zolpidem) for severe insomnia, with the lowest dose possible and for no longer than 4 weeks

Review of Borderline Personality Disorder Review Clinical Review & Education

jama.com (Reprinted) JAMA February 28, 2023 Volume 329, Number 8 675

© 2023 American Medical Association. All rights reserved.

randomized clinical trials have shown that psychotherapy is asso- ciated with benefit for patients with BPD (Table 3). A Cochrane series of meta-analyses that included a total of 75 randomized clinical trials with 4507 patients provided evidence regarding effi- cacious therapies for BPD.60 For example, in a meta-analysis of 22 randomized clinical trials with 1244 patients comparing psycho- therapy with usual care, psychotherapy was associated with sig- nificant improvement in symptom severity compared with usual care, with a medium effect size (standardized mean difference [SMD], −0.52) (Table 3).60 This effect size exceeded the minimum clinically relevant difference for BPD symptom severity (SMD, 0.43) and represented a clinically relevant reduction.60 Psycho- therapy was not associated with higher rates of adverse effects compared with usual care (risk ratio, 0.86; 95% CI, 0.14-5.09; P = .86 [4 trials; n = 571]).60 Several types of psychotherapy for BPD exist (eTable in the Supplement). A subgroup analysis from the Cochrane meta-analysis60 compared dialectical behavior therapy, psychodynamic therapy, cognitive behavior therapy, and eclectic therapy in data from 17 randomized clinical trials and 1045 patients. There were no significant differences between these treatments for the outcome of symptom severity or psychosocial functioning (P = .88). Dialectical behavior therapy, a form of cognitive behavior therapy specifically developed for treatment of BPD, focuses on increasing a patient’s motivation to engage in treatment and problem-solving strategies, and uses group skills training to help regulate emotions and interpersonal relationships and telephone coaching in times of crises between regular ses- sions (eTable in the Supplement). Compared with usual care, dia- lectical behavior therapy was associated with a medium between- group effect size (SMD) of −0.60 for improving BPD severity (Table 3) and small between-group effect sizes for self-harm (SMD, −0.28) and psychosocial functioning (SMD, −0.36), with low to moderate heterogeneity (I2 = 42%, 0%, and 31%, respectively).60 Psychodynamic therapy proved to be efficacious in treatment of BPD as well.83 Psychodynamic therapy includes

a family of psychotherapeutic approaches that focus on identifica- tion of recurring patterns of behavior related to the self and oth- ers, including the therapeutic relationship, expression of emotion, exploration of defensive (avoidance) patterns, and discussion of past experiences that have an effect on a patient’s present experiences.85 Specific forms of psychodynamic therapy have been developed that tailor treatment specifically to BPD, such as transference-focused psychotherapy and mentalization-based therapy (eTable in the Supplement). In a meta-analysis that included 16 randomized clinical trials and 1081 participants, psy- chodynamic therapy was associated with medium between-group effect sizes compared with usual care (Table 3) for the outcomes of core BPD symptoms (SMD, −0.65), suicide-related outcomes (SMD, −0.67), and psychosocial functioning (SMD, −0.57), with low or moderate heterogeneity (I2 = 15%, 40%, and 60%, respec- tively) (John R. Keefe, written communication of data for compari- son of psychodynamic therapy with usual care for the meta- analysis by Barber et al,83 November 3, 2021).

However, many studies of psychotherapy for BPD had a high risk of bias assessed by the Cochrane risk-of-bias tool, and the qual- ity of evidence, assessed by the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system,86 was moderate.60 High risk of bias as well as publication bias found in some meta-analyses may have increased the observed effect sizes.60,87 Furthermore, most observed treatment benefits were not durable and were no longer present 6 months or more after the end of treatment.60,87 A meta-analysis of 28 randomized clinical trials and 2436 participants reported that psychotherapy was asso- ciated with a treatment nonresponse rate of 48.8%,88 suggesting that approximately half of the patients did not benefit from the treatments. However, the studies included in this meta-analysis defined treatment response differently, for example, as a reduction of 25% or 50% of symptoms or as no longer meeting criteria for BPD.88 As a limitation, the nonresponse rate of 48.8% was com- bined from studies that defined nonresponse differently.

Table 3. Summary of Meta-analyses of Psychotherapy for BPD: Forms and Efficacy

No. of patients No. of RCTs Form of psychotherapy Comparator Outcome

Effect size SMD (95% CI)a

Storebø et al,60 2020

1244 22 Major forms of psychotherapyb

Usual care Severity of BPD symptoms

−0.52 (−0.70 to −0.33)

616 13 Major forms of psychotherapyb

Usual care Self-harm −0.32 (−0.49 to −0.14)

666 13 Major forms of psychotherapyb

Usual care Suicide-related outcomes

−0.34 (−0.57 to −0.11)

1314 22 Major forms of psychotherapyb

Usual care Psychosocial functioning

−0.45 (−0.68 to −0.22)

149 3 Dialectical behavior therapy

Usual care Severity of BPD symptoms

−0.60 (−1.05 to −0.14)

376 7 Dialectical behavior therapy

Usual care Self-harm −0.28 (−0.48 to −0.07)

225 6 Dialectical behavior therapy

Usual care Psychosocial functioning

−0.36 (−0.69 to −0.03)

Barber et al,83 2021c

213 4 Psychodynamic therapy

Usual care Severity of BPD symptoms

−0.65 (−0.99 to −0.32)

354 5 Psychodynamic therapy

Usual care Suicide-related outcomes

−0.67 (−1.13 to −0.20)

392 5 Psychodynamic therapy

Usual care Psychosocial functioning

−0.57 (−1.04 to −0.10)

Abbreviations: BPD, borderline personality disorder; RCT, randomized clinical trial; SMD, standardized mean difference. a The SMD was calculated as the

difference between the means of the treatment group and the comparator group after treatment, divided by the pooled standard deviation (Mt − Mc/SD); SMDs of 0.20, 0.50, and 0.80 are regarded as small, medium, or large effect sizes.84

b Major forms of psychotherapy include dialectical behavior therapy, psychodynamic therapy, cognitive behavior therapy, schema-focused therapy, and acceptance and commitment therapy.

c John R. Keefe, written communication of data for comparison of psychodynamic therapy with usual care for the meta-analysis by Barber et al,83

November 3, 2021.

Clinical Review & Education Review Review of Borderline Personality Disorder

676 JAMA February 28, 2023 Volume 329, Number 8 (Reprinted) jama.com

© 2023 American Medical Association. All rights reserved.

Prognosis

An observational study of 290 patients with BPD reported that over a 10-year period, 50% recovered, defined as symptomatic remission and good social and vocational functioning over a 2-year period.89

Among the patients who recovered, 34% lost their recovery and 30% had a recurrence of BPD symptoms and diagnosis after a 2-year long remission.89 (In these studies, recovery was defined as sympto- matic recovery in combination with excellent social and vocational functioning over 2 years. Recurrence was defined as recurrence of classic BPD symptoms.) In contrast, 93% of BPD patients attained re- mission from BPD lasting 2 years and 86% attained remission lasting 4 years.89 Excellent recovery, defined as remission of BPD or other personality disorders and good social and full-time vocational func- tioning, occurred in 39% of patients with BPD compared with 73% of patients with other personality disorders.90 However, most indi- viduals with BPD in these longitudinal studies received pharmaco- therapy or psychotherapy. Therefore, these remission rates may be better than the natural history of untreated BPD over time and might be related to these therapies.91 A meta-analysis of 837 patients from 11 studies who were followed up for at least 5 years reported remis- sion rates between 50% and 70%, with a mean remission rate of 60%.11 However, the meta-analysis had high heterogeneity be- tween studies (I2 = 80.9%).11 In addition, this meta-analysis re- portedimprovementindepressionandfunctioning.Meansuiciderates ranged from 2% to 5%.11 Social functioning varied over time and was highly associated with symptomatic status.13,91 While some patients attained good social functioning for the first time, others lost their gains.92 Changes in personality traits (defined by the 5-factor model, including neuroticism, extraversion, openness, conscientiousness,

and agreeableness) were followed by changes in BPD personality dis- order criteria; however, the reverse did not occur.93 Traits of neuroti- cism and conscientiousness were more unstable over time, showing more variation in BPD than in patients with other personality disor- ders, indicating a “stable instability.”94,95

Early intervention consists of identification and treatment of BPD in adolescents and individuals with subthreshold BPD fea- tures or improving parenting behavior in parents with BPD.96 How- ever, currently there is no high-quality evidence that early interven- tion or prevention programs improve outcomes in patients with BPD.

Limitations This Review has several limitations. First, the literature search was restricted to English and German languages. Second, a formal as- sessment of literature quality was not performed. Third, some rel- evant articles may have been missed. Fourth, some recommenda- tions are based on relatively poor-quality evidence or expert opinion. Fifth, clinical practice guidelines were included, which are often based in part on expert opinion.

Conclusions Borderline personality disorder affects approximately 0.7% to 2.7% of adults and is associated with functional impairment and greater use of medical services. Psychotherapy with dialectical behavior therapy and psychodynamic therapy are first-line therapies for BPD, while psychoactive medications do not improve the primary symp- toms of BPD.

ARTICLE INFORMATION

Accepted for Publication: January 16, 2023.

Conflict of Interest Disclosures: None reported.

Submissions: We encourage authors to submit papers for consideration as a Review. Please contact Mary McGrae McDermott, MD, at [email protected].

REFERENCES

1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th ed. American Psychiatric Association; 2013.

2. Kernberg OF. Severe Personality Disorders: Psychotherapeutic Strategies. Yale University Press; 1984.

3. Eaton NR, Greene AL. Personality disorders: community prevalence and socio-demographic correlates. Curr Opin Psychol. 2018;21:28-32. doi:10. 1016/j.copsyc.2017.09.001

4. Ellison WD, Rosenstein LK, Morgan TA, Zimmerman M. Community and clinical epidemiology of borderline personality disorder. Psychiatr Clin North Am. 2018;41(4):561-573. doi:10. 1016/j.psc.2018.07.008

5. Zimmerman M, Becker L. The hidden borderline patient: patients with borderline personality disorder who do not engage in recurrent suicidal or self-injurious behavior. Psychol Med. Published online July 29, 2022. doi:10.1017/S0033291722002197

6. Tomko RL, Trull TJ, Wood PK, Sher KJ. Characteristics of borderline personality disorder in a community sample: comorbidity, treatment utilization, and general functioning. J Pers Disord. 2014;28(5):734-750. doi:10.1521/pedi_2012_26_093

7. Gunderson JG, Herpertz SC, Skodol AE, et al. Borderline personality disorder. Nat Rev Dis Primers. 2018;4:18029. doi:10.1038/nrdp.2018.29

8. Hastrup LH, Kongerslev MT, Simonsen E. Low vocational outcome among people diagnosed with borderline personality disorder during first admission to mental health services in Denmark: a nationwide 9-year register-based study. J Pers Disord. 2019;33(3):326-340. doi:10.1521/pedi_2018_ 32_344

9. Schneider F, Erhart M, Hewer W, et al. Mortality and medical comorbidity in the severely mentally ill. Dtsch Arztebl Int. 2019;116(23-24):405-411. doi:10. 3238/arztebl.2019.0405

10. Wagner T, Assmann N, Köhne S, et al. The societal cost of treatment-seeking patients with borderline personality disorder in Germany. Eur Arch Psychiatry Clin Neurosci. 2022;272(4):741-752. doi:10.1007/s00406-021-01332-1

11. Álvarez-Tomás I, Ruiz J, et al. Long-term clinical and functional course of borderline personality disorder: a meta-analysis of prospective studies. Eur Psychiatry. 2019;56:75-83. doi:10.1016/j.eurpsy. 2018.10.010

12. Temes CM, Frankenburg FR, Fitzmaurice GM, Zanarini MC. Deaths by suicide and other causes among patients with borderline personality disorder and personality-disordered comparison subjects over 24 years of prospective follow-up. J Clin Psychiatry. 2019;80(1):18m12436. doi:10. 4088/JCP.18m12436

13. Zanarini MC, Frankenburg FR, Hennen J, et al. Psychosocial functioning of borderline patients and axis II comparison subjects followed prospectively for six years. J Pers Disord. 2005;19(1):19-29. doi:10. 1521/pedi.19.1.19.62178

14. Skodol AE, Pagano ME, Bender DS, et al. Stability of functional impairment in patients with schizotypal, borderline, avoidant, or obsessive-compulsive personality disorder over two years. Psychol Med. 2005;35(3):443-451. doi: 10.1017/S003329170400354X

15. Black DW, Blum N, Pfohl B, Hale N. Suicidal behavior in borderline personality disorder: prevalence, risk factors, prediction, and prevention. J Pers Disord. 2004;18(3):226-239. doi:10.1521/ pedi.18.3.226.35445

16. Tate AE, Sahlin H, Liu S, et al. Borderline personality disorder: associations with psychiatric disorders, somatic illnesses, trauma, and adverse behaviors. Mol Psychiatry. 2022;27(5):2514-2521. doi:10.1038/s41380-022-01503-z

17. Zanarini MC, Gunderson JG, Frankenburg FR, Chauncey DL. The Revised Diagnostic Interview for

Review of Borderline Personality Disorder Review Clinical Review & Education

jama.com (Reprinted) JAMA February 28, 2023 Volume 329, Number 8 677

© 2023 American Medical Association. All rights reserved.

Borderlines: discriminating BPD from other Axis II disorders. J Pers Disord. 1989;3:10-18. doi:10.1521/ pedi.1989.3.1.10

18. World Health Organization. International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10). World Health Organization; 1992.

19. Volkert J, Gablonski TC, Rabung S. Prevalence of personality disorders in the general adult population in Western countries: systematic review and meta-analysis. Br J Psychiatry. 2018;213(6): 709-715. doi:10.1192/bjp.2018.202

20. Kessler RC, Petukhova M, Sampson NA, et al. Twelve-month and lifetime prevalence and lifetime morbid risk of anxiety and mood disorders in the United States. Int J Methods Psychiatr Res. 2012;21 (3):169-184. doi:10.1002/mpr.1359

21. Steel Z, Marnane C, Iranpour C, et al. The global prevalence of common mental disorders: a systematic review and meta-analysis 1980-2013. Int J Epidemiol. 2014;43(2):476-493. doi:10.1093/ ije/dyu038

22. Zimmerman M, Morgan TA. Problematic boundaries in the diagnosis of bipolar disorder: the interface with borderline personality disorder. Curr Psychiatry Rep. 2013;15(12):422. doi:10.1007/ s11920-013-0422-z

23. Pagura J, Stein MB, Bolton JM, et al. Comorbidity of borderline personality disorder and posttraumatic stress disorder in the US population. J Psychiatr Res. 2010;44(16):1190-1198. doi:10. 1016/j.jpsychires.2010.04.016

24. Bernardi S, Faraone SV, Cortese S, et al. The lifetime impact of attention deficit hyperactivity disorder: results from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). Psychol Med. 2012;42(4):875-887. doi: 10.1017/S003329171100153X

25. Winsper C. Borderline personality disorder: course and outcomes across the lifespan. Curr Opin Psychol. 2021;37:94-97. doi:10.1016/j.copsyc. 2020.09.010

26. Beatson J, Broadbear JH, Sivakumaran H, et al. Missed diagnosis: the emerging crisis of borderline personality disorder in older people. Aust N Z J Psychiatry. 2016;50(12):1139-1145. doi:10.1177/ 0004867416640100

27. D’Agostino A, Pepi R, Starcevic V. Borderline personality disorder and ageing: myths and realities. Curr Opin Psychiatry. 2022;35(1):68-72. doi:10.1097/YCO.0000000000000764

28. Yeomans FE, Clarkin JF, Kernberg OF. Transference-Focused Psychotherapy for Borderline Personality Disorder: A Clinical Guide. American Psychiatric Association; 2015.

29. Bateman A, Fonagy P. Mentalization-Based Treatment for Personality Disorders: A Practical Guide. Oxford University Press; 2016. doi:10.1093/med: psych/9780199680375.001.0001

30. Bach B, Kerber A, Aluja A, et al. International assessment of DSM-5 and ICD-11 personality disorder traits: toward a common nosology in DSM-5.1. Psychopathology. 2020;53(3-4):179-188. doi:10.1159/000507589

31. Bach B, First MB. Application of the ICD-11 classification of personality disorders. BMC Psychiatry. 2018;18(1):351. doi:10.1186/s12888-018-1908-3

32. Skodol AE, Gunderson JG, Pfohl B, et al. The borderline diagnosis I: psychopathology, comorbidity, and personality structure. Biol Psychiatry. 2002;51(12):936-950. doi:10.1016/ S0006-3223(02)01324-0

33. Singer MT, Larson DG. Borderline personality and the Rorschach test. Arch Gen Psychiatry. 1981; 38(6):693-698. doi:10.1001/archpsyc.1981. 01780310093010

34. Leichsenring F. Discriminating borderline from neurotic patients: a study with the Holtzman inkblot technique. Psychopathology. 1990;23(1):21- 26. doi:10.1159/000284633

35. Leichsenring F. Primary process thinking, primitive defensive operations and object relationships in borderline and neurotic patients. Psychopathology. 1991;24(1):39-44. doi:10.1159/ 000284695

36. Ackerman SJ, Clemence AJ, Weatherill R, Hilsenroth MJ. Use of the TAT in the assessment of DSM-IV cluster B personality disorders. J Pers Assess. 1999;73(3):422-448. doi:10.1207/ S15327752JPA7303_9

37. Torgersen S, Czajkowski N, Jacobson K, et al. Dimensional representations of DSM-IV cluster B personality disorders in a population-based sample of Norwegian twins: a multivariate study. Psychol Med. 2008;38(11):1617-1625. doi:10.1017/ S0033291708002924

38. Cattane N, Rossi R, Lanfredi M, Cattaneo A. Borderline personality disorder and childhood trauma: exploring the affected biological systems and mechanisms. BMC Psychiatry. 2017;17(1):221. doi:10.1186/s12888-017-1383-2

39. Perez-Rodriguez MM, Bulbena-Cabré A, Bassir Nia A, et al. The neurobiology of borderline personality disorder. Psychiatr Clin North Am. 2018; 41(4):633-650. doi:10.1016/j.psc.2018.07.012

40. Anderson G. Pathoetiology and pathophysiology of borderline personality: role of prenatal factors, gut microbiome, mu- and kappa-opioid receptors in amygdala-PFC interactions. Prog Neuropsychopharmacol Biol Psychiatry. 2020;98:109782. doi:10.1016/j.pnpbp. 2019.109782

41. Distel MA, Middeldorp CM, Trull TJ, et al. Life events and borderline personality features: the influence of gene-environment interaction and gene-environment correlation. Psychol Med. 2011; 41(4):849-860. doi:10.1017/S0033291710001297

42. Belsky DW, Caspi A, Arseneault L, et al. Etiological features of borderline personality related characteristics in a birth cohort of 12-year-old children. Dev Psychopathol. 2012;24(1): 251-265. doi:10.1017/S0954579411000812

43. Skoglund C, Tiger A, Rück C, et al. Familial risk and heritability of diagnosed borderline personality disorder: a register study of the Swedish population. Mol Psychiatry. 2021;26(3):999-1008. doi:10.1038/s41380-019-0442-0

44. Witt SH, Streit F, Jungkunz M, et al. Genome-wide association study of borderline personality disorder reveals genetic overlap with bipolar disorder, major depression and schizophrenia. Transl Psychiatry. 2017;7(6):e1155. doi:10.1038/tp.2017.115

45. Stepp SD, Lazarus SA, Byrd AL. A systematic review of risk factors prospectively associated with borderline personality disorder: taking stock and

moving forward. Personal Disord. 2016;7(4):316-323. doi:10.1037/per0000186

46. Porter C, Palmier-Claus J, Branitsky A, et al. Childhood adversity and borderline personality disorder: a meta-analysis. Acta Psychiatr Scand. 2020;141(1):6-20. doi:10.1111/acps.13118

47. Thomas N, Gurvich C, Hudaib AR, et al. Systematic review and meta-analysis of basal cortisol levels in borderline personality disorder compared to non-psychiatric controls. Psychoneuroendocrinology. 2019;102:149-157. doi:10. 1016/j.psyneuen.2018.12.009

48. Drews E, Fertuck EA, Koenig J, et al. Hypothalamic-pituitary-adrenal axis functioning in borderline personality disorder: a meta-analysis. Neurosci Biobehav Rev. 2019;96:316-334. doi:10. 1016/j.neubiorev.2018.11.008

49. Peled-Avron L, Abu-Akel A, Shamay-Tsoory S. Exogenous effects of oxytocin in five psychiatric disorders: a systematic review, meta-analyses and a personalized approach through the lens of the social salience hypothesis. Neurosci Biobehav Rev. 2020;114:70-95. doi:10.1016/j.neubiorev.2020.04. 023

50. Schulze L, Schulze A, Renneberg B, et al. Neural correlates of affective disturbances: a comparative meta-analysis of negative affect processing in borderline personality disorder, major depressive disorder, and posttraumatic stress disorder. Biol Psychiatry Cogn Neurosci Neuroimaging. 2019;4(3):220-232. doi:10.1016/j.bpsc.2018.11.004

51. Degasperi G, Cristea IA, Di Rosa E, et al. Parsing variability in borderline personality disorder: a meta-analysis of neuroimaging studies. Transl Psychiatry. 2021;11(1):314. doi:10.1038/s41398-021- 01446-z

52. Sicorello M, Schmahl C. Emotion dysregulation in borderline personality disorder: a fronto-limbic imbalance? Curr Opin Psychol. 2021;37:114-120. doi: 10.1016/j.copsyc.2020.12.002

53. Tyrer P, Mulder R, Kim YR, Crawford MJ. The development of the ICD-11 classification of personality disorders: an amalgam of science, pragmatism, and politics. Annu Rev Clin Psychol. 2019;15:481-502. doi:10.1146/annurev-clinpsy- 050718-095736

54. Dubovsky AN, Kiefer MM. Borderline personality disorder in the primary care setting. Med Clin North Am. 2014;98(5):1049-1064. doi:10. 1016/j.mcna.2014.06.005

55. Hall K, Moran P. Borderline personality disorder: an update for neurologists. Pract Neurol. 2019;19(6):483-491. doi:10.1136/practneurol-2019- 002292

56. Luborsky L. Principles of Psychoanalytic Psychotherapy: Manual for Supportive-Expressive Treatment. Basic Books; 1984.

57. Wnuk S, McMain S, Links PS, et al. Factors related to dropout from treatment in two outpatient treatments for borderline personality disorder. J Pers Disord. 2013;27(6):716-726. doi:10. 1521/pedi_2013_27_106

58. Ring D, Lawn S. Stigma perpetuation at the interface of mental health care: a review to compare patient and clinician perspectives of stigma and borderline personality disorder. J Ment Health. Published online March 12, 2019. doi:10. 1080/09638237.2019.1581337

Clinical Review & Education Review Review of Borderline Personality Disorder

678 JAMA February 28, 2023 Volume 329, Number 8 (Reprinted) jama.com

© 2023 American Medical Association. All rights reserved.

59. Leichsenring F. Development and first results of the Borderline Personality Inventory: a self-report instrument for assessing borderline personality organization. J Pers Assess. 1999;73(1): 45-63. doi:10.1207/S15327752JPA730104

60. Storebø OJ, Stoffers-Winterling JM, Völlm BA, et al. Psychological therapies for people with borderline personality disorder. Cochrane Database Syst Rev. 2020;5(5):CD012955. doi:10.1002/ 14651858.CD012955.pub2

61. National Institute for Health and Care Excellence. Borderline personality disorder: recognition and management—clinical guideline. Published January 28, 2009. Accessed December 25, 2022. http://www.nice.org.uk/guidance/cg78

62. National Institute for Health and Care Excellence. Personality disorders: borderline and antisocial—quality standard. Published June 11, 2015. Accessed December 25, 2022. http://nice.org. uk/guidance/qs88

63. Giernalczyk T, Petersen GK. Crisis intervention of borderline personality disorder. Psychotherapie. 2007;12:288-296.

64. Linehan MM. Dialectical behavior therapy for borderline personality disorder: theory and method. Bull Menninger Clin. 1987;51(3):261-276.

65. First MB, Williams JBW, Benjamin LS, Spitzer RL. User’s Guide for the SCID-5-PD (Structured Clinical Interview for DSM-5 Personality Disorder). American Psychiatric Association; 2016.

66. Leichsenring F. Discriminating schizophrenics from borderline patients: study with the Holtzman inkblot technique. Psychopathology. 1991;24(4): 225-231. doi:10.1159/000284718

67. Mendez-Miller M, Naccarato J, Radico JA. Borderline personality disorder. Am Fam Physician. 2022;105(2):156-161.

68. Grenyer BFS, Bailey RC, Lewis KL, et al. A randomized controlled trial of group psychoeducation for carers of persons with borderline personality disorder. J Pers Disord. 2019; 33(2):214-228. doi:10.1521/pedi_2018_32_340

69. Gunderson JG. The emergence of a generalist model to meet public health needs for patients with borderline personality disorder. Am J Psychiatry. 2016;173(5):452-458. doi:10.1176/appi.ajp.2015. 15070885

70. Clarkin JF, Levy KN, Lenzenweger MF, Kernberg OF. Evaluating three treatments for borderline personality disorder: a multiwave study. Am J Psychiatry. 2007;164(6):922-928. doi:10.1176/ ajp.2007.164.6.922

71. McMain SF, Links PS, Gnam WH, et al. A randomized trial of dialectical behavior therapy versus general psychiatric management for borderline personality disorder. Am J Psychiatry. 2009;166(12):1365-1374. doi:10.1176/appi.ajp.2009. 09010039

72. Bateman A, Fonagy P. Randomized controlled trial of outpatient mentalization-based treatment versus structured clinical management for borderline personality disorder. Am J Psychiatry. 2009;166(12):1355-1364. doi:10.1176/appi.ajp.2009. 09040539

73. American Psychiatric Association. Practice guideline for the treatment of patients with borderline personality disorder. Am J Psychiatry. 2001;158(10)(suppl):1-52.

74. Gartlehner G, Crotty K, Kennedy S, et al. Pharmacological treatments for borderline personality disorder: a systematic review and meta-analysis. CNS Drugs. 2021;35(10):1053-1067. doi:10.1007/s40263-021-00855-4

75. Bohus M, Stoffers-Winterling J, Sharp C, et al. Borderline personality disorder. Lancet. 2021;398 (10310):1528-1540. doi:10.1016/S0140-6736(21) 00476-1

76. Stoffers-Winterling JM, Storebø OJ, Pereira Ribeiro J, et al. Pharmacological interventions for people with borderline personality disorder. Cochrane Database Syst Rev. 2022;11(11):CD012956. doi:10.1002/14651858.CD012956.pub2

77. Cattarinussi G, Delvecchio G, Prunas C, et al. Effects of pharmacological treatments on emotional tasks in borderline personality disorder: a review of functional magnetic resonance imaging studies. J Affect Disord. 2021;288:50-57. doi:10. 1016/j.jad.2021.03.088

78. Marceau EM, Meuldijk D, Townsend ML, et al. Biomarker correlates of psychotherapy outcomes in borderline personality disorder: a systematic review. Neurosci Biobehav Rev. 2018;94:166-178. doi:10.1016/j.neubiorev.2018.09.001

79. Trull TJ, Jahng S, Tomko RL, et al. Revised NESARC personality disorder diagnoses: gender, prevalence, and comorbidity with substance dependence disorders. J Pers Disord. 2010;24(4): 412-426. doi:10.1521/pedi.2010.24.4.412

80. Chiappini S, Schifano F, Corkery JM, Guirguis A. Beyond the “purple drank”: study of promethazine abuse according to the European Medicines Agency adverse drug reaction reports. J Psychopharmacol. 2021;35(6):681-692. doi:10.1177/0269881120959615

81. National Institute for Health and Care Excellence. Guidance on the use of zaleplon, zolpidem and zopiclone for the short-term management of insomnia. Published 2004. Accessed December 26, 2022. https://www.nice. org/uk/guidance/ta77

82. Bateman AW, Gunderson J, Mulder R. Treatment of personality disorder. Lancet. 2015;385(9969): 735-743. doi:10.1016/S0140-6736(14)61394-5

83. Barber JP, Muran JC, McCarthy KS, Keefe JR, Zilcha-Mano S. Research on dynamic therapies. In: Barkham M, Castonguay LG, Lutz W, eds. Bergin and Garfield’s Handbook of Psychotherapy and Behavior Change. 7th ed. Wiley; 2021:387-419.

84. Cohen J. Statistical Power Analysis for the Behavioral Sciences. Lawrence Erlbaum; 1988.

85. Gabbard GO. Long-term Psychodynamic Psychotherapy. American Psychiatric Publishing; 2004.

86. Guyatt GH, Oxman AD, Vist GE, et al. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ. 2008;336(7650):924-926. doi:10.1136/bmj.39489. 470347.AD

87. Cristea IA, Gentili C, Cotet CD, et al. Efficacy of psychotherapies for borderline personality disorder: a systematic review and meta-analysis. JAMA Psychiatry. 2017;74(4):319-328. doi:10.1001/ jamapsychiatry.2016.4287

88. Woodbridge J, Townsend M, Reis S, et al. Non-response to psychotherapy for borderline personality disorder: a systematic review. Aust N Z J Psychiatry. 2022;56(7):771-787. doi:10.1177/ 00048674211046893

89. Zanarini MC, Frankenburg FR, Reich DB, Fitzmaurice G. Time to attainment of recovery from borderline personality disorder and stability of recovery: a 10-year prospective follow-up study. Am J Psychiatry. 2010;167(6):663-667. doi:10.1176/ appi.ajp.2009.09081130

90. Zanarini MC, Temes CM, Frankenburg FR, et al. Description and prediction of time-to-attainment of excellent recovery for borderline patients followed prospectively for 20 years. Psychiatry Res. 2018; 262:40-45. doi:10.1016/j.psychres.2018.01.034

91. Zanarini MC, Hörz S, Frankenburg FR, et al. The 10-year course of PTSD in borderline patients and Axis II comparison subjects. Acta Psychiatr Scand. 2011;124(5):349-356. doi:10.1111/j.1600-0447.2011. 01717.x

92. Zanarini MC, Frankenburg FR, Reich DB, Fitzmaurice G. The 10-year course of psychosocial functioning among patients with borderline personality disorder and Axis II comparison subjects. Acta Psychiatr Scand. 2010;122(2):103-109. doi:10.1111/j.1600-0447.2010.01543.x

93. Warner MB, Morey LC, Finch JF, et al. The longitudinal relationship of personality traits and disorders. J Abnorm Psychol. 2004;113(2):217-227. doi:10.1037/0021-843X.113.2.217

94. Hopwood CJ, Newman DA, Donnellan MB, et al. The stability of personality traits in individuals with borderline personality disorder. J Abnorm Psychol. 2009;118(4):806-815. doi:10.1037/a0016954

95. Schmideberg M. The borderline patient. In: Aruety S, ed. American Handbook of Psychiatry. Basic Books; 1959:398-416.

96. Florange JG, Herpertz SC. Parenting in patients with borderline personality disorder, sequelae for the offspring and approaches to treatment and prevention. Curr Psychiatry Rep. 2019;21(2):9. doi: 10.1007/s11920-019-0996-1

Review of Borderline Personality Disorder Review Clinical Review & Education

jama.com (Reprinted) JAMA February 28, 2023 Volume 329, Number 8 679

© 2023 American Medical Association. All rights reserved.

Copyright of JAMA: Journal of the American Medical Association is the property of American Medical Association and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.