ArticleLiterature Review

Clinical psychopharmacology of borderline personality disorder: An update on the available evidence in light of the Diagnostic and Statistical Manual of Mental Disorders - 5

January 2012
Current Opinion in Psychiatry 25(1):52-8

Source
PubMed

Authors:

Icahn School of Medicine at Mount Sinai

Clinical considerations for evidence-based treatment of borderline personality disorder (BPD) are outlined in the context of the best available evidence, discussed with reference to BPD traits currently identified in the upcoming Diagnostic and Statistical Manual of Mental Disorders - 5 (DSM-5) revision. The DSM-5 will highlight refractory affective, interpersonal, and identity symptoms in BPD as potential treatment targets. In addition to providing a framework for clinical decision-making, future research strategies will also focus on neurotransmitter systems of greater relevance to understanding overall personality functioning. Although only a few randomized controlled trials of psychopharmacological treatments for BPD have been published recently, several meta-analyses and systematic reviews converge on the consensus effectiveness of lamotrigine, topiramate, valproate, aripiprazole, olanzapine, and omega-3 fatty acid supplementation. Stronger evidence exists for treating disinhibition and antagonism than negative affectivity, particularly interpersonal facets of such traits. In addition, basic research suggests a future role for modifying glutamatergic, opioid, and oxytocinergic neurotransmitter systems to treat BPD. Clinicians should utilize omega-3, anticonvulsants, and atypical antipsychotic agents in treating specific DSM-5 BPD traits, notably disinhibition, antagonism, and some aspects of negative affectivity. Future research will focus on normalizing opioid and oxytocin dysregulation, as an adjunct to evidence-based psychotherapy, in an effort to improve interpersonal functioning.

O paciente difícil: transtorno de personalidade borderline

Chapter

Jan 2017

Transtorno de personalidade borderline: o paciente difícil na prática médica

Article

Full-text available

Aug 2016

Transtornos de personalidade não diagnosticados po- dem ser a base para relações médico-paciente custosas, especialmente no caso do Transtorno de Personalidade Borderline (TPB). Este artigo tem como objetivo fazer uma revisão narrativa sobre o TPB, tendo em vista, particular- mente, o manejo do transtorno na atenção primária. O TPB é um transtorno grave, caracterizado por instabilidade emocional, impulsividade, dificuldade de relacionamento interpessoal e perturbação da autoimagem. É frequente na prática médica, porém subdiagnosticado e comumente não tratado. Problemas na relação médico-paciente são comuns. Pacientes com TPB são descritos pelos profissio- nais como exigentes, desafiadores e perturbadores. Esses pacientes apresentam prejuízos graves no funcionamento, tais como relações interpessoais tempestuosas, estresse familiar alto, dependência de outras pessoas, dificuldade em manter empregos e comportamento autoagressivo. Apresentam também preocupações somáticas excessivas e comportamentos de autossabotagem. Os pacientes com TPB apresentam taxas de suicídio maiores do que as encontradas na população em geral, morbidade e mortali- dade elevadas, além de utilização excessiva de serviços de saúde. O curso do TPB é caracterizado por altas taxas de remissão e taxas razoáveis de recuperação. Todavia, um número significativo de pacientes persiste com prejuízo importante do funcionamento social. O tratamento de escolha para o TPB é a psicoterapia. Os psicofármacos atuam de forma complementar. É essencial que o trata- mento seja fundamentado em aliança terapêutica sólida, psicoeducação do paciente, estabelecimento de limites e trabalho em equipe. Na prática clínica, a identificação e o tratamento do TPB podem melhorar a relação médico- -paciente, aumentar a aderência ao tratamento, reduzir as taxas de mobidade/mortalidade, além de refrear a utilização dos serviços de saúde.

The position statement of the Working Group of the Polish Psychiatric Association on the use of D2/D3 dopamine receptor partial agonists in the treatment of mental disorders

Article

Full-text available

Oct 2021

Aripiprazole, cariprazine and brexpiprazole are antipsychotic drugs (APD) whose action is associated with partial agonism at the dopamine D2/D3 receptors. They are increasingly more widely used in clinical practice, also off-label. The aim of this article is to present the current state of knowledge on the use of these drugs in the treatment of mental disorders. The position statement was developed by the panel of experts appointedby the Executive Board of the Polish Psychiatric Association, consisting of individuals with many years of experience in treating patients with mental disorders. The evaluation included the analysis of literature databases (Medline, Embase, Cochrane) and information obtained from metaanalyses and summaries of product characteristics. A key property of D2/D3 partial agonists is that they display diverse effects on dopamine pathways: (a) blockade of mesolimbic signalling that is overactive in the acute phase of schizophrenia and mania, (b) stimulation of mesocortical pathways with an improvement (or at least with no deterioration) of cognitive functions and negative symptoms, (c) no blockade of the tuberoinfundibular pathway and, consequently, low risk of increased prolactin secretion, (d) no blockade of nigrostriatal pathway and, consequently, low risk of extrapyramidal symptoms. Selective profile of action and intrinsic activity at dopamine D2 (aripiprazole > brexpiprazole) and D3 (cariprazine) receptors in combination with the lack of antihistamine and anticholinergic properties make aripiprazole, brexpiprazole and cariprazine different form other APD in terms of their safety and tolerability. This is the reason for the increasing use of these drugs in the treatment of schizophrenia and mood disorders, and in the case of aripiprazole also in obsessive-compulsive, autism-spectrum and tic disorders.

Fear Conditioning in Borderline Personality Disorder

Article

Full-text available

Mar 2016

Borderline Personality Disorder (BPD) is a severe mental disorder causing significant, persistent disability, and with a high lifetime risk of suicide. The limited knowledge about the neurobiological underpinnings of BPD is a critical obstacle for the development of new, more effective treatments. There is high comorbidity and overlap in symptoms and neurobiological findings between BPD, anxiety disorders, and post-traumatic stress disorder (PTSD). Moreover, a wealth of evidence suggests that there are abnormalities in fear processing and emotional learning in BPD. Given these findings, it is surprising that very few studies have used fear conditioning paradigms in BPD patients. What follows is a review of the evidence of symptomatic overlap and comorbidity between BPD, anxiety disorders, and PTSD, and the neurobiological findings that suggest abnormal fear processing in BPD. We also discuss fear conditioning and related paradigms that probe the brain systems involved in fear processing and will review studies using the same methodologies in BPD patients. Finally, we describe potential research and treatment implications, and future directions.

Gait Domains May Be Used as an Auxiliary Diagnostic Index for Alzheimer’s Disease

Article

Full-text available

Nov 2023
BSRCCS

Background: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder with cognitive dysfunction and behavioral impairment. We aimed to use principal components factor analysis to explore the association between gait domains and AD under single and dual-task gait assessments. Methods: A total of 41 AD participants and 41 healthy control (HC) participants were enrolled in our study. Gait parameters were measured using the JiBuEn® gait analysis system. The principal component method was used to conduct an orthogonal maximum variance rotation factor analysis of quantitative gait parameters. Multiple logistic regression was used to adjust for potential confounding or risk factors. Results: Based on the factor analysis, three domains of gait performance were identified both in the free walk and counting backward assessments: “rhythm” domain, “pace” domain and “variability” domain. Compared with HC, we found that the pace factor was independently associated with AD in two gait assessments; the variability factor was independently associated with AD only in the counting backwards assessment; and a statistical difference still remained after adjusting for age, sex and education levels. Conclusions: Our findings indicate that gait domains may be used as an auxiliary diagnostic index for Alzheimer’s disease.

Time trends in pharmacological treatment of major depressive disorder: Results from the AMSP Pharmacovigilance Program from 2001–2017

Article

Dec 2020
J AFFECT DISORDERS

Background: Currently available data on the prescription practice among patients with major depressive disorder (MDD) reflect the outpatient setting. This is the first study to provide information on time trends of psychotropic drug utilization in psychiatric inpatients. Method: Data stems from German-speaking psychiatric hospitals collected by the program “Drug Safety in Psychiatry” (Arzneimittelsicherheit in der Psychiatrie, AMSP) between 2001 and 2017. 44,418 psychiatric inpatients with MDD were included. Time trends in drug utilization were analyzed by comparing the first (2001–2003) and last time point (2015–2017) using risk ratios (RR). Results: Antidepressant drugs (ADD) were the most used psychotropic drug class with utilization decreasing slightly from 2001–2003 (89.7%) to 2015–2017 (85.5%). Use of tricyclic ADDs showed the greatest decline (RR 0.35), while use of selective serotonin-noradrenaline reuptake inhibitors (SSNRIs; RR 1.72) and “other ADDs” increased the most. Use of antipsychotic drugs (APD), especially second generation antipsychotic drugs (RR 1.46), increased. Use of tranquilizing (RR 0.71) and hypnotic drugs (RR 0.43) both decreased. Most patients were treated with more than one psychotropic drug, most often ADD + APD, which was utilized more often in 2015–2017 (51.1%) than in 2001–2003 (45.1%; RR 1.13). Combination of two ADDs gained popularity from 2001–2003 (24.5%) to 2015–2017 (33.0%; RR 1.35). Limitations: The cross-sectional design does not allow conclusions to be drawn about causal relationship of findings. Further, only certain clinical and sociodemographic data was available. Conclusion: Treatment of MDD has shown significant changes from 2001 to 2017.

Current and emerging medications for borderline personality disorder: is pharmacotherapy alone enough?

Article

Full-text available

Nov 2019

Introduction: The treatment of borderline personality disorder (BPD) remains an open question for clinicians. There is scarce evidence available and the guidelines’ conclusions diverge. Together with these factors, the complexity of BPD generates uncertainty in day-to-day practice. This narrative review aims to provide an overview of advances in BPD treatment and posit a critical opinion based on clinical evidence and practice. Areas covered: The authors review the clinical trials concerning the efficacy of the main classes of drugs in BPD: antidepressants, mood stabilizers, first-, second-, and third-generation antipsychotics, and other agents (opiate antagonists, clonidine, oxytocin, omega-3 fatty acids). They also include in this review studies on combinations of drugs and psychotherapies. Expert opinion: An individualized, tailored pharmacotherapy for BPD that targets the prominent symptom clusters can improve relevant aspects of the clinical picture. However, no medication is indicated to treat the global psychopathology of BPD. Polypharmacy should be avoided or strictly limited. To date, pharmacotherapy alone does not suffice to manage the complexity of BPD. Combining medication with psychotherapy may improve specific BPD symptom dimensions. In particular, it may help those aspects that respond slowly or not at all to monotherapy.

Zusammenhang zwischen pathologischen Entzündungsparametern und der Serumkonzentration von Antipsychotika

Thesis

Jan 2019

Anne Weidner

In einer Studie wurde der Zusammenhang pathologischer Werte von C-Reaktivem Protein (295 Fälle)- - sowie Leukozyten-Anzahlen (292 Fälle) einerseits und dosiskorrigierter Serumkonzentration der Antipsychotika Haloperidol, Risperidon, Olanzapin, Quetiapin und Aripiprazol andererseits mittels therapeutischem Drug Monitoring bestimmter Serumkonzentrationen sowie pathologische CRP (295 Fälle)- und Leukozyten (292 Fälle)-Werte ausgewertet. Zielsetzung der vorliegenden Arbeit war es, den Einfluss von Entzündung, gemessen durch CRP-Wert und Leukozyten, auf die dosiskorrigierten Antipsychotika-Serumkonzentrationen zu untersuchen. In der Quetiapin-Stichprobe konnte ein signifikanter Zusammenhang von pathologischen CRP-Werten und der dosiskorrigierten Serumkonzentration berechnet werden. In der Olanzapin-Stichprobe ergab sich ein trendmäßiger Zusammenhang von pathologischen CRP-Werten und der dosiskorrigierten Serumkonzentration. Dosiskorrigierte Serumkonzentrationen über der therapeutischen Obergrenze waren in der Quetiapin-Stichprobe mit pathologischen CRP-Werten assoziiert. In keiner Stichprobe konnte ein signifikanter Zusammenhang von Leukozyten-Anzahl und dosiskorrigierter Serumkonzentration aufgezeigt werden. Wir konnten damit erstmals einen signifikanten Zusammenhang von Entzündung und Serumkonzentration für Quetiapin (und partiell auch Olanzapin) zeigen. Klinische Konsequenz sollte - vor allem bei älteren Patienten - eine Quetiapin (und auch Olanzapin-)-Dosisanpassung unter inflammatorischen Bedingungen sein, um das Risiko verstärkter bzw. sogar toxischer Nebenwirkungen durch einen Anstieg der Serumkonzentration zu minimieren. Weitere Studien mit einer größeren Fallzahl für die anderen hier untersuchten und nicht signifikant assoziiert gefundenen Antipsychotika sind erforderlich, um das Risiko erhöhter Serumkonzentrationen unter inflammatorischen Bedingungen für diese ausschließen zu können. Darüber hinaus sind weitere Untersuchungen mit Berücksichtigung anderer auf CYP-Ebene interagierender Faktoren wie Komedikation, körperlichen Begleiterkrankungen, Raucherstatus oder Polymorphismen sinnvoll, um Risikogruppen noch genauer definieren zu können.

Арипризол – уникальный антипсихотик с широким спектром применения в психиатрии: факты и перспективы // Ariprizol, an unique antipsychotic with wide spectrum of therapeutic utility in psychiatry: facts and future perspectives

Article

Full-text available

Dec 2018

Арипризол (арипипразол) – уникальный антипсихотик III поколения с особым механизмом действия, парциальный агонист дофаминовых D2-рецепторов и серотониновых 5-HT1A-рецепторов. В спектр его фармакологической активности входят антипсихотическое, антиманиакальное, нормотимическое (тимостабилизирующее), антидепрессивное, противотревожное, антиобсессивное действие. Он обладает низким потенциалом экстрапирамидных побочных явлений и метаболических нарушений, не вызывает гиперпролактинемии, хорошо переносится. Арипризол проявляет высокую эффективность в коррекции не только продуктивных, но и негативных, когнитивных и аффективных симптомов шизофрении. Он эффективен также в купировании маниакальных фаз и в профилактике рецидивов аффективных психозов, при синдроме Туретта и других тикозных расстройствах, при коррекции поведения у детей с расстройствами аутистического спектра, в качестве потенцирующего агента к антидепрессантам при резистентных депрессиях, резистентном обсессивно-компульсивном расстройстве. Имеются предварительные данные об его эффективности при резистентных тревожных расстройствах и др. В настоящей статье мы подробно рассматриваем доказательную базу для его применения при различных психических патологиях и перспективы его дальнейшего изучения. Ключевые слова: арипипразол, Арипризол, антипсихотик III поколения, экстрапирамидные побочные явления, гиперпролактинемия, метаболический синдром, шизофрения, биполярное аффективное расстройство, резистентные депрессии, синдром Туретта, аутизм. Ariprizol (aripiprazole) is a unique third generation antipsychotic with a new and distinctive mechanism of action. It acts as a partial agonist at both dopamine D2 receptors and serotonin 5-HT1A receptors. Its pharmacological profile includes antipsychotic, antimanic, mood stabilizing, antidepressant, anxiolytic, and antiobsessive actions. Aripiprazole has a low potential for extrapyramidal side effects (excluding akathisia) and for metabolic disturbances. It does not cause hyperprolactinemia, and is generally well tolerated. Aripiprazole exhibits high efficacy in correcting not only positive, but also negative, cognitive and affective symptoms of schizophrenia. It is also effective in relieving mania, in the prevention of relapse in affective disorders, in Tourette’s syndrome and other tic disorders, for behavioral problems (irritability, hostility, aggression etc) in children with autism spectrum disorders, and as an augmenting agent for antidepressants in cases of refractory depression or refractory obsessive-compulsive disorder. There are also preliminary data on its efficacy in various refractory anxiety disorders and other conditions. In this article, we thoroughly describe the existing evidence base for its use in various mental disorders and possible further uses that need additional investigation in the future. Keywords: aripiprazole, Ariprizol, third generation antipsychotic, extrapyramidal side effects, hyperprolactinemia, metabolic syndrome, schizophrenia, bipolar affective disorder, treatment-resistant depression, Tourette’s syndrome, autism.

Diagnosis and Treatment of Borderline Personality Disorder in the College Mental Health Setting

Article

Full-text available

May 2018
Curr Psychiatr Rep

Claire M. Brickell

Purpose of review: The impact of borderline personality disorder (BPD) on college students is not well studied, and there is currently little data about its phenomenology or treatment in this population. We review the available literature regarding evidence-based treatment for BPD on college campuses, as well as best-practice guidelines for the treatment of mental illness in the college setting. Diagnostic disclosure and psychoeducation are proposed as practical first steps in improving the treatment landscape. Recent findings: Preliminary studies of targeted treatment for BPD on college campuses are promising. They suggest that even pared-down interventions have the potential to help students feel better and function better. Experts in college mental health treatment emphasize the importance of gathering data, intervening early, communicating across treatment environments, appropriately marshaling resources, and providing psycho-education. To bring the on-campus treatment of BPD in line with best-practice guidelines, improved diagnostic practices are needed. Disclosing the diagnosis of BPD and educating students about this disorder are simple yet powerful interventions that can set the stage for further treatment and provide symptom relief.

Borderline personality disorder and unmet needs

Article

Full-text available

Aug 2017
NEUROENDOCRINOL LETT

Background: Borderline personality disorder (BPD) is a disabling psychiatric condition with a chronic and challenging course. BPD is reflected as a disorder of self-regulation" and is associated with both psychological vulnerabilities and social relations that fail to support basic emotional needs. The objective of the paper is to provide the up-to-date data on the unmet needs of BPD patients and their families. Method: A computerized search of the literature printed between January 1990 and May 2017 was conducted in PubMed, and additional papers were extracted using keywords "borderline personality disorder,"needs," "pharmacotherapy," "psychotherapy," "CBT," and "family" in various combinations. According to the eligibility criteria, 57 articles were chosen. Secondary articles from the reference lists of primarily identified papers have been selected for the eligibility and added to the first list (N=151). Results: The results were divided into three categories: the needs connected with (1) the symptom control; (2) the treatment; (3) the quality of life. The needs connected with symptoms were described issues such as emotional needs, social interactions, self-harm, parasuicide, suicidality, comorbidity, mentalization, identity disturbance, moreover, barriers to treatment. The needs connected with the treatment described are focused on needs for early diagnosis, early intervention, holding environment, therapeutic relation, assertive community treatment, destigmatization, hospitalization, and primary care. The needs connected with the quality of life involve family needs, physical health, spiritual needs, advocacy needs, and needs for the separation-individuation. The part focused on implications for the treatment presented several treatment approaches, focusing mostly on the their basics and efficacy. Conclusion: Observing the patients' needs may be essential to the treatment of the individuals suffering from BPD. However, many needs remain unmet in the areas linked to medical, personal, and social factors. A bigger focus on the patients' needs could be beneficial and should be targeted in the treatment.

An update on pharmacotherapy for personality disorders

Article

Full-text available

Aug 2016

Increased Prevalence of Intermittent Rhythmic Delta or Theta Activity (IRDA/IRTA) in the Electroencephalograms (EEGs) of Patients with Borderline Personality Disorder

Article

Full-text available

Feb 2016

Introduction: An increased prevalence of pathological electroencephalography (EEG) signals has been reported in patients with borderline personality disorder (BPD). In an elaborative case description of such a patient with intermittent rhythmic delta and theta activity (IRDA/IRTA), the BPD symptoms where linked to the frequency of the IRDAs/IRTAs and vanished with the IRDAs/IRTAs following anticonvulsive therapy. This observation raised a question regarding the prevalence of such EEG abnormalities in BPD patients. The aim of this retrospective study was to identify the frequency of EEG abnormalities in a carefully analyzed psychiatric collective. Following earlier reports, we hypothesized an increased prevalence of EEG abnormalities in BPD patients. Participants and methods: We recruited 96 consecutive patients with BPD from the archive of a university clinic for psychiatry and psychotherapy, and compared the prevalence of EEG abnormalities to those of 76 healthy controls subjects. The EEGs were rated by three different blinded clinicians, including a consultant specializing in epilepsy from the local epilepsy center. Results: We found a significant increase in the prevalence of IRDAs and IRTAs in BPD patients (14.6%) compared to the control subjects (3.9%; p = 0.020). Discussion: In this blinded retrospective case-control study, we were able to confirm an increased prevalence of pathological EEG findings (IRDAs/IRTAs only) in BPD patients. The major limitation of this study is that the control group was not matched on age and gender. Therefore, the results should be regarded as preliminary findings of an open uncontrolled, retrospective study. Future research performing prospective, controlled studies is needed to verify our findings and answer the question of whether such EEG findings might predict a positive response to anticonvulsive pharmacological treatment.

Percorso per i disturbi di personalità gravi, dalle evidenze alle prassi possibili nei Servizi di Psichiatria e Neuropsichiatria infantile

Book

Full-text available

Nov 2015

Italian revision of scientific evidences in diagnosis and treatment of severe personality disorders, specifically in borderline spectrum of PD. The work-group, under the sponsorship of Istituto Lombardo di Farmacovigilanza, involved several experts in adult psychiatry, developmental psychiatry, psychology and psychotherapeutics, clinical pharmacology; the work-group, after a deep analysis of the most recent validated scientific evidences, summarized the emerging data with particular emphasis on the psychiatric work in community psychiatry

Emotional and Behavioral Dyscontrol After Traumatic Brain Injury

Article

Mar 2014

Emotional and behavioral dyscontrol are relatively common neuropsychiatric sequelae of traumatic brain injury and present substantial challenges to recovery and community participation. Among the most problematic and functionally disruptive of these types of behaviors are pathologic laughing and crying, affective lability, irritability, disinhibition, and aggression. Managing these problems effectively requires an understanding of their phenomenology, epidemiology, and clinical evaluation. This article reviews these issues and provides clinicians with brief and practical suggestions for the management of emotional and behavioral dyscontrol.

Changes in Cognitive Function From Pre-surgery to Four Months Post-surgery in Individuals Undergoing Dysvascular Amputation.

Article

Dec 2013

To describe cognition among individuals with new amputations at three time points: pre-surgical, 6 weeks and 4 months post-amputation. Design: Prospective cohort. Four medical centers. Referred sample of primarily male Veterans (N=80) experiencing their first lower extremity amputation (LEA) due to complications of Diabetes Mellitus or Peripheral Arterial Disease, screened for the absence of gross cognitive impairment using the Short Portable Mental Status Questionnaire (SPMSQ). Of those eligible, (87) 64% enrolled; 29 were enrolled pre-surgically, and have cognitive data for all three time points, and 58 were enrolled post-amputation. Eighty of the 87 enrolled by 6 weeks remained enrolled at 4 months. Not applicable. Demographic and general health information, general mental status (SPMSQ), and four brief, well-established neuropsychological measures. Most mean neuropsychological test scores fell in the Low Average or Average range. For a majority of participants, overall cognitive status improved from pre-to post-surgery and then remained stable between 6 weeks and 4 months. There were significant improvements between pre- and post-surgical test scores in verbal learning and memory, and these remained unchanged between 6 weeks and 4 months. Better 4 month cognitive performance was associated with higher perceived general health. Overall cognitive performance is poorest pre-surgically. Though there is improvement between pre- and post-amputation, cognition appears generally stable between 6 weeks and 4 months.

Therapeutic Drug Monitoring of Common Antipsychotics

Article

Dec 2012

The aim of this review is to provide information for interpreting outcome results from monitoring of antipsychotics in biological samples. A brief overview of the working mechanisms, pharmacological effects, drug interactions, and analytical methods of classical and atypical antipsychotics is given. Nineteen antipsychotics were selected based on their importance in the worldwide market as follows: amisulpride, aripiprazole, asenapine, bromperidol, clozapine, flupenthixol, haloperidol, iloperidone, lurasidone, olanzapine, paliperidone, perphenazine, pimozide, pipamperone, quetiapine, risperidone, sertindole, sulpiride, and zuclopenthixol. A straightforward relationship between administered dose, plasma or serum concentration, clinical outcome, or adverse effects is often lacking. Nowadays, focus lies on therapeutic drug monitoring and individualized therapy to find adequate treatment, to explain treatment failure or nonresponse, and to check patient compliance. However, extensive research in this field is still mandatory.

Dialectical Behavioral Therapy

Chapter

May 2023

Pharmacotherapy of Personality Disorders

Chapter

Nov 2022

Personality disorders (PD) represent a group of more than 10 disorders, depending on the diagnostic classification used, but most research on pharmacological treatments deals with borderline PD. International guidelines consider the evidence for the usefulness of psychopharmacotherapy for PD limited and therefore, their major recommendation is to center this therapeutic approach for the treatment of the frequent psychiatric comorbidities. Indeed, current evidence favors psychotherapy compared to psychopharmacotherapy in the treatment of personality disorders (PD). However, antipsychotic drugs, antidepressants, anti-convulsants, and other psychotropic drugs are widely used, very frequently as combination treatments, despite not any of them has been introduced by national drug authorities for this indication. Previous studies are based on the use of diagnostic systems which changed over the past decades, and this explains the difficulty to compare pharmacological studies. The present situation is characterized by a transition from a categorical to a more dimensional classification, and to a hybrid model. Future research in this field will have to consider the new classification of PD and hopefully, yield evidence for efficacity of both old and new drugs in development.

Olanzapine in the Treatment of Psychosis

Chapter

Nov 2022

Gerd Laux

Olanzapine is a second-generation (atypical) antipsychotic primarily used to treat schizophrenia and bipolar disorder. It is taken by mouth or by injection into a muscle. Olanzapine has a broad spectrum of receptor affinities with highest affinity for 5-HT2A serotonin receptors and dopamine receptors; it is also a potent antagonist of muscarinic, histamine, and α-adrenergic receptors. The efficacy in treatment of psychoses was established in numerous randomized, double-blind, placebo-controlled studies and maintenance studies. Common side effects include weight gain, sedation, dizziness, feeling tired, constipation, and movement disorders.

Olanzapine in the Treatment of Psychosis

Chapter

Jan 2022

Gerd Laux

Pharmacotherapy of Personality Disorders

Chapter

Jan 2022

მოსაზღვრე პიროვნული აშლილობის მკურნალობა და მართვა

Book

Full-text available

Mar 2017

Eka Chkonia

The Case of Monica Khuma: More than Borderline Difficulties: A Clinical Casebook

Chapter

Jan 2019

Anna H. Rosen

Borderline personality disorder (BPD) typically presents during late adolescence and can persist if untreated through adulthood. It can wreak havoc on an individual’s interpersonal and professional life and is frequently difficult to diagnose and subsequently difficult to treat. The hallmark feature of BPD is an unstable sense of self that manifests with impulsive, attention-seeking, and self-destructive behaviors. There is high comorbidity between BPD and mood and anxiety disorders as well as with substance use disorders. The ideal treatment involves a combination of pharmacology to address symptoms such as irritability, impulsivity, and anxiety and psychotherapy to create a more positive and cohesive sense of oneself. Central to work with patients with BPD is an awareness of transferential issues and bringing them to the patient’s awareness as part of the treatment.

Prescribing Practices for Patients With Borderline Personality Disorder During Psychiatric Hospitalizations

Article

Feb 2019
J PERS DISORD

This study aimed to understand prescribing practices during acute psychiatric hospitalization in a large cohort of patients (N = 569) with borderline personality disorder (BPD) at a tertiary care psychiatry unit from January 1, 2013, through January 1, 2015. The mean number of hospitalizations per patient was 1.5 (range, 1–7). The odds of being prescribed antidepressants, antipsychotics, mood stabilizers, hypnotics, or anxiolytics were higher at discharge than at admission. The rate of psychotropic prescriptions was also higher at discharge than at admission (incidence rate ratio, 1.9). This pattern was true for the combined psychotropic and nonpsychotropic (“medical”) prescriptions. Further guidelines are needed regarding optimal psychosocial, medical, and psychopharmacological care of patients with BPD during acute psychiatric hospitalizations.

The Bipolar Spectrum: Modelling, Measuring and Managing

Chapter

Jan 2019

Chris B. Aiken

Case Study Application for Psychopharmacology With Borderline Personality Disorder

Article

May 2018

Barbara J. Limandri

Using an evolving case study, the current article demonstrates the principles of working with a client who has borderline personality disorder in relation to medications. The case study poses questions for the reader to consider and answers at the end of the article. [Journal of Psychosocial Nursing and Mental Health Services, 56(5), 16-19.].

Psychopharmacology for Borderline Personality Disorder

Article

Apr 2018

Barbara J. Limandri

Treating individuals with borderline personality disorder (BPD) is a complex and challenging process fraught with clinician stigma and bias. Clinically, polypharmacy is the most common approach, even though it is more likely to produce greater drug-drug adverse effects and interactions than effective improvement in symptoms. Currently, there are no approved medications specific for the treatment of BPD. The current article reviews the extant literature on psychopharmacology and provides treatment recommendations. [Journal of Psychosocial Nursing and Mental Health Services, 56(4), 8-11.].

The Black Book of Psychotropic Dosing and Monitoring

Article

Jan 2018
Psychopharmacol Bull

Personality disorders

Article

Full-text available

Feb 2017

Os Transtornos da personalidade são padrões psicológicos de difícil diagnóstico que exigem uma avaliação criteriosa por parte do profissional da saúde mental. A relação médico-paciente também se configura como fator de extrema importância para o manejo destes quadros. Dentro deste contexto, é imprescindível orientar os alunos das áreas de graduação em saúde sobre a existência de tal categoria de transtornos. O presente artigo consiste em uma revisão descritiva, que busca elucidar a definição de transtornos da personalidade; além de discorrer sobre aspectos históricos, nosológicos e epidemiológicos. Nesta publicação ainda serão revisadas as particularidades referentes ao diagnóstico, as comorbidades, ao curso e tratamento destes transtornos. O enfoque maior será no manejo de indivíduos com transtorno da personalidade borderline, dada a maior procura destes por unidades de atendimento psiquiátrico

Tratamento da dependência química e psiquiatria forense

Chapter

Full-text available

Dec 2015

Valdir Ribeiro Campos

Psychopharmacological treatment of 2,195 in-patients with borderline personality disorder: A comparison with other psychiatric disorders

Article

Apr 2015
EUR NEUROPSYCHOPHARM

Patients with borderline personality disorder (BPD) are usually prescribed a variety of psychotropic drugs; however, none is recommended in the guidelines nor has any been approved for this indication. As data on drug prescriptions for BPD are sparse, cross-sectional data from the European Drug Safety Project AMSP were used to analyse drug prescriptions of 2195 in-patients with BPD between 2001 and 2011, and the mean values, confidence intervals and regression analyses were calculated. 70% of all BPD patients were medicated with antipsychotics and/or antidepressants, 33% with anticonvulsants, 30% with benzodiazepines, and 4% with lithium; 90% received at least one, 80%≥2, and 54%≥3 psychotropic drugs concomitantly (mean: 2.8). Prescription rates for quetiapine, the single drug most often used in BPD (22%), increased significantly over time. In view of the high percentage of young females with BPD, 18-40 year-old female patients with BPD were compared with patients of the same age but with depression (unipolar and bipolar) and schizophrenia. Typical sedative antipsychotics and anticonvulsants were prescribed more often in BPD than in the other diagnostic groups, with the exception of bipolar depression; this was true for the single substances quetiapine, levomepromazine, chlorprothixene, carbamazepine, and valproate. A limitation of the study was the use of clinical data without verifying the diagnoses by structured interviews. Contrary to the guidelines, about 90% of in-patients with BPD received psychotropic drugs. Polypharmacy was common, and antipsychotics with sedative profiles such as quetiapine and mood-stabilizing anticonvulsants such as valproate appear to be preferred. Copyright © 2015. Published by Elsevier B.V.

Biological Advances in Personality Disorders

Article

Jan 2013

Neurobiological studies have focused primarily on DSM-IV axis I disorders, as they display extensive, and often severe and episodic symptomatology. However, there is an emerging focus on the neurobiology of personality disorders, consisting largely of maladaptive traits that impair functioning and adaptation to the environment. These clusters of maladapative traits are partially heritable, associated with specific candidate genes that are beginning to be identified by preliminary genetic studies, and are grounded in specific neurocircuitry changes; borderline personality disorder (BPD), antisocial personality disorder (ASPD), and schizotypal personality disorder (STPD) have been the most studied and have the largest empirical evidence. Greater understanding of the neurobiological grounding of these disorders will in part inform the conceptualization of personality disorders in the new nonaxial diagnostic system in DSM−5.

Treatment of personality disorder

Article

Feb 2015

The evidence base for the effective treatment of personality disorders is insufficient. Most of the existing evidence on personality disorder is for the treatment of borderline personality disorder, but even this is limited by the small sample sizes and short follow-up in clinical trials, the wide range of core outcome measures used by studies, and poor control of coexisting psychopathology. Psychological or psychosocial intervention is recommended as the primary treatment for borderline personality disorder and pharmacotherapy is only advised as an adjunctive treatment. The amount of research about the underlying, abnormal, psychological or biological processes leading to the manifestation of a disordered personality is increasing, which could lead to more effective interventions. The synergistic or antagonistic interaction of psychotherapies and drugs for treating personality disorder should be studied in conjunction with their mechanisms of change throughout the development of each. Copyright © 2015 Elsevier Ltd. All rights reserved.

The Use of Oxytocin in Personality Disorders: Rationale and Current Status

Article

Oct 2014

Impaired interpersonal functioning is a core feature of borderline, schizotypal and avoidant personality disorders, characterized by abnormal social information processing; however, pharmacological treatments targeting social cognition are currently lacking. Oxytocin is a novel treatment for social cognitive abnormalities that has yielded promising preliminary results in the autism spectrum, social anxiety disorders and schizophrenia. Here, we describe the main components of social cognition, review the biology of the oxytocinergic system and the hypothesized models and mechanisms through which exogenous oxytocin modulates social cognition. We then review the studies on the effect of oxytocin administration on social cognition and their application to personality disorders treatment. We also review the preliminary evidence supporting the use of oxytocin as an adjunct to non pharmacological interventions. Finally, we describe the main challenges that need to be addressed in order to be able to use oxytocin effectively in clinical populations.

Empathic Accuracy and Borderline Personality Disorder

Article

Jan 2014

Luis H Ripoll

Borderline personality disorder (BPD) includes severe, refractory interpersonal dysfunction. One component of interpersonal dysfunction in BPD entails a distinct style of empathy (the ability to understand others’ mental states to guide subsequent interpersonal behavior), highlighted by clinical experience with such patients and associated phenomenology. Empathic processing involves two parallel neural networks: one involving implicit, relatively automatic mirroring and shared mental representations (SR); the other involving explicit, deliberate mental state attribution (MSA). One neurobiological model of BPD suggests that it involves hyperreactivity of SR networks and impairment in MSA processing, under the influence of dysregulated neuropeptide signaling. A complex interaction between genetics and development (particularly attachment stressors) contributes to the ontogeny of this neurobiological dysfunction. A neuropsychoanalytic approach provides the means by which future research can guide questions to test this model, further understand BPD etiology and psychopathology, and eventually improve treatment for this disorder.

Bartz JA, Zaki J, Bolger N, Ochsner KN. Social effects of oxytocin in humans context and person matter. Trends Cogn Sci 15: 301-309

Article

Full-text available

Jun 2011

Building on animal research, the past decade has witnessed a surge of interest in the effects of oxytocin on social cognition and prosocial behavior in humans. This work has generated considerable excitement about identifying the neurochemical underpinnings of sociality in humans, and discovering compounds to treat social functioning deficits. Inspection of the literature, however, reveals that the effects of oxytocin in the social domain are often weak and/or inconsistent. We propose that this literature can be informed by an interactionist approach in which the effects of oxytocin are constrained by features of situations and/or individuals. We show how this approach can improve understanding of extant research, suggest novel mechanisms through which oxytocin might operate, and refine predictions about oxytocin pharmacotherapy.

Ten-Year Course of Borderline Personality Disorder Psychopathology and Function From the Collaborative Longitudinal Personality Disorders Study

Article

Full-text available

Apr 2011

Borderline personality disorder (BPD) is traditionally considered chronic and intractable. To compare the course of BPD's psychopathology and social function with that of other personality disorders and with major depressive disorder (MDD) over 10 years. A collaborative study of treatment-seeking, 18- to 45-year-old patients followed up with standardized, reliable, and repeated measures of diagnostic remission and relapse and of both global social functioning and subtypes of social functioning. Nineteen clinical settings (hospital and outpatient) in 4 northeastern US cities. Three study groups, including 175 patients with BPD, 312 with cluster C personality disorders, and 95 with MDD but no personality disorder. The Diagnostic Interview for DSM-IV Personality Disorders and its follow-along version (the Diagnostic Interview for DSM-IV Personality Disorders-Follow-Along Version) were used to diagnose personality disorders and assess changes in them. The Structured Clinical Interview for DSM-IV Axis I Disorders and the Longitudinal Interval Follow-up Evaluation were used to diagnose MDD and assess changes in MDD and in social function. Eighty-five percent of patients with BPD remitted. Remission of BPD was slower than for MDD (P < .001) and minimally slower than for other personality disorders (P < .03). Twelve percent of patients with BPD relapsed, a rate less frequent and slower than for patients with MDD (P < .001) and other personality disorders (P = .008). All BPD criteria declined at similar rates. Social function scores showed severe impairment with only modest albeit statistically significant improvement; patients with BPD remained persistently more dysfunctional than the other 2 groups (P < .001). Reductions in criteria predicted subsequent improvements in DSM-IV Axis V Global Assessment of Functioning scores (P < .001). The 10-year course of BPD is characterized by high rates of remission, low rates of relapse, and severe and persistent impairment in social functioning. These results inform expectations of patients, families, and clinicians and document the severe public health burden of this disorder.

Oxytocin can hinder trust and cooperation in borderline personality disorder

Article

Full-text available

Nov 2010
SOC COGN AFFECT NEUR

We investigated the effects of intranasal oxytocin (OXT) on trust and cooperation in borderline personality disorder (BPD), a disorder marked by interpersonal instability and difficulties with cooperation. Although studies in healthy adults show that intranasal OXT increases trust, individuals with BPD may show an altered response to exogenous OXT because the effects of OXT on trust and pro-social behavior may vary depending on the relationship representations and expectations people possess and/or altered OXT system functioning in BPD. BPD and control participants received intranasal OXT and played a social dilemma game with a partner. Results showed that OXT produced divergent effects in BPD participants, decreasing trust and the likelihood of cooperative responses. Additional analyses focusing on individual differences in attachment anxiety and avoidance across BPD and control participants indicate that these divergent effects were driven by the anxiously attached, rejection-sensitive participants. These data suggest that OXT does not uniformly facilitate trust and pro-social behavior in humans; indeed, OXT may impede trust and pro-social behavior depending on chronic interpersonal insecurities, and/or possible neurochemical differences in the OXT system. Although popularly dubbed the 'hormone of love', these data suggest a more circumspect answer to the question of who will benefit from OXT.

A Longitudinal Study of the 10-Year Course of Interpersonal Features in Borderline Personality Disorder

Article

Full-text available

Jun 2010

The literature on borderline personality disorder (BPD) describes interpersonal disturbances as a core sector of psychopathology. The longitudinal course of these features remains poorly understood. Our aim is to describe the course of interpersonal features of BPD in a more detailed way than has been done previously. Twenty interpersonal aspects of borderline psychopathology were assessed using two reliable semi-structured diagnostic interviews at baseline and at five successive two-year follow-up waves in the ongoing McLean Study for Adult Development. Behaviorally-oriented features, such as recurrent breakups, sadism, demandingness, entitlement, regression in treatment, and boundary violations, remitted quickly and were rare at the end of follow-up. The interpersonal features slowest to remit were affective responses to being alone, active caretaking, discomfort with care, and dependency. The behavioral interpersonal features of BPD remit rapidly, while core affectively-oriented features related to intolerance of aloneness and conflicts over dependency are more persistent.

Dysregulation of Regional Endogenous Opioid Function in Borderline Personality Disorder

Article

Full-text available

May 2010
AM J PSYCHIAT

Borderline personality disorder is characterized by a lack of effective regulation of emotional responses. The authors investigated the role of the endogenous opioid system and mu-opioid receptors in emotion regulation in borderline personality disorder. Mu-opioid receptor availability in vivo (nondisplaceable binding potential, or BP(ND)) was measured with positron emission tomography and the selective radiotracer [(11)C]carfentanil during neutral and sustained sadness states in 18 unmedicated female patients with borderline personality disorder and 14 healthy female comparison subjects. Patients showed greater regional mu-opioid BP(ND) than did comparison subjects at baseline (neutral state) bilaterally in the orbitofrontal cortex, caudate, and nucleus accumbens and in the left amygdala, but lower BP(ND) in the posterior thalamus. Sadness induction was associated with greater reductions in BP(ND) (endogenous opioid system activation) in the patient group than in the comparison group in the pregenual anterior cingulate, left orbitofrontal cortex, left ventral pallidum, left amygdala, and left inferior temporal cortex. Patients showed evidence of endogenous opioid system deactivation in the left nucleus accumbens, the hypothalamus, and the right hippocampus/parahippocampus relative to comparison subjects. Correlations of baseline measures with the Dissociative Experiences Scale and endogenous opioid system activation with the Barratt Impulsiveness Scale did not remain significant after correction for multiple comparisons. Differences exist between patients with borderline personality disorder and comparison subjects in baseline in vivo mu-opioid receptor concentrations and in the endogenous opioid system response to a negative emotional challenge that can be related to some of the clinical characteristics of patients with borderline personality disorder. The regional network involved is implicated in the representation and regulation of emotion and stress responses.

Borderline Personality Disorder: A Dysregulation of the Endogenous Opioid System?

Article

Full-text available

Apr 2010

The neurobiology of borderline personality disorder (BPD) remains unclear. Dysfunctions of several neurobiological systems have been discussed, including serotoninergic, dopaminergic, and other neurotransmitter systems. Here we present a theory that alterations in the sensitivity of opioid receptors or the availability of endogenous opioids constitute part of the underlying pathophysiology of BPD. ¹ The alarming symptoms and self-destructive behaviors of the affected patients may be explained by uncontrollable and unconscious attempts to stimulate their endogenous opioid system (EOS) and the dopaminergic reward system, regardless of the possible harmful consequences. Neurobiological findings that support this hypothesis are reviewed: Frantic efforts to avoid abandonment, frequent and risky sexual contacts, and attention-seeking behavior may be explained by attempts to make use of the rewarding effects of human attachment mediated by the EOS. Anhedonia and feelings of emptiness may be an expression of reduced activity of the EOS. Patients with BPD tend to abuse substances that target μ-opioid receptors. Self-injury, food-restriction, aggressive behavior, and sensation-seeking may be interpreted as a desperate attempt to artificially set the body to “survival mode”, in order to mobilize the last reserves of the EOS. BPD-associated symptoms, such as substance abuse, anorexia, self-injury, depersonalization, and sexual overstimulation, can be treated successfully with μ-opioid receptor antagonists. An understanding of the neurobiology of BPD may help in developing new treatments for patients with this severe disorder.

An Attachment Perspective on Borderline Personality Disorder: Advances in Gene–Environment Considerations

Article

Full-text available

Feb 2010
Curr Psychiatr Rep

Accumulating evidence points to severe relationship dysfunction as the core epigenetic expression of borderline personality disorder (BPD). In adulthood, BPD is typified by disorganization within and across interpersonal domains of functioning. When interacting with their infants, mothers with BPD show marked withdrawal and frightening or frightened behavior, leading to disorganized infant-mother attachments. Linked to both infant disorganization and BPD is a maternal state of mind typified by unresolved mourning regarding past loss or trauma. Early risk factors for BPD in adulthood include maternal withdrawal in infancy and separation of 1 month or more from mother in the first 5 years of life. Likely contributing biological factors include genes linked to dopamine, serotonin, the hypothalamic-pituitary-adrenal axis, and neuropeptides. The complex gene-environment picture emerging confers risk or protection against BPD pathology in ways consistent with infants varying biological sensitivity to context. This line of research may refine early risk assessment and preventive mental health services.

Pharmacotherapy for borderline personality disorder: Cochrane systematic review of randomised trials

Article

Full-text available

Jan 2010
BRIT J PSYCHIAT

Many patients with borderline personality disorder receive pharmacological treatment, but there is uncertainty about the usefulness of such therapies. To evaluate the evidence of effectiveness of pharmacotherapy in treating different facets of the psychopathology of borderline personality disorder. A Cochrane Collaboration systematic review and meta-analysis of randomised comparisons of drug v. placebo, drug v. drug, or single drug v. combined drug treatment in adult patients with borderline personality disorder was conducted. Primary outcomes were overall disorder severity as well as specific core symptoms. Secondary outcomes comprised associated psychiatric pathology and drug tolerability. Twenty-seven trials were included in which first- and second-generation antipsychotics, mood stabilisers, antidepressants and omega-3 fatty acids were tested. Most beneficial effects were found for the mood stabilisers topiramate, lamotrigine and valproate semisodium, and the second-generation antipsychotics aripiprazole and olanzapine. However, the robustness of findings is low, since they are based mostly on single, small studies. Selective serotonin reuptake inhibitors so far lack high-level evidence of effectiveness. The current evidence from randomised controlled trials suggests that drug treatment, especially with mood stabilisers and second-generation antipsychotics, may be effective for treating a number of core symptoms and associated psychopathology, but the evidence does not currently support effectiveness for overall severity of borderline personality disorder. Pharmacotherapy should therefore be targeted at specific symptoms.

Effectiveness of Pharmacotherapy for Severe Personality Disorders: Meta-Analyses of Randomized Controlled Trials

Article

Full-text available

Sep 2009
J CLIN PSYCHIAT

There has been little systematic attempt to validate current pharmacologic treatment algorithms and guidelines for severe personality disorder. We evaluated studies on the effectiveness of psychoactive drugs on specific symptom domains for borderline and/or schizotypal personality disorder. The literature was searched for placebo-controlled randomized clinical trials (PC-RCTs) on the effectiveness of psychopharmacologic drugs in personality disorder patients. The PubMed, PsychINFO, PiCarta, Cochrane, and Web of Science databases were searched using the search terms borderline personality, schizotypal personality, personality disorder, cluster A, cluster B, treatment, drug, pharmacotherapy, antipsychotic, antidepressant, mood stabilizer, effect, outcome, review, and meta-analysis for studies published between 1980 and December 2007, and references were identified from bibliographies from articles and books. Placebo-controlled randomized clinical trials on the efficacy of antipsychotics, antidepressants, and mood stabilizers regarding cognitive-perceptual symptoms, impulsive-behavioral dyscontrol, and affective dysregulation (with subdomains depressed mood, anxiety, anger, and mood lability) were selected in patients with well defined borderline and/or schizotypal personality disorder. Studies whose primary emphasis was on the treatment of Axis I disorders were excluded. Meta-analyses were conducted using 21 retrieved studies. Antipsychotics have a moderate effect on cognitive-perceptual symptoms (5 PC-RCTs; standardized mean difference [SMD]=0.56) and a moderate to large effect on anger (4 PC-RCTs; SMD=0.69). Antidepressants have no significant effect on impulsive-behavioral dyscontrol and depressed mood. They have a small but significant effect on anxiety (5 PC-RCTs; SMD=0.30) and anger (4 PC-RCTs; SMD=0.34). Mood stabilizers have a very large effect on impulsive-behavioral dyscontrol (6 PC-RCTs; SMD=1.51) and anger (7 PC-RCTs; SMD=1.33), a large effect on anxiety (3 PC-RCTs; SMD=0.80), but a moderate effect on depressed mood (5 PC-RCTs; SMD=0.55). Mood lability as an outcome measure was seldomly assessed. Mood stabilizers have a more pronounced effect on global functioning (3 PC-RCTs; SMD=0.79) than have antipsychotics (5 PC-RCTs; SMD=0.37). The effect of antidepressants on global functioning is negligible. Drug therapy tailored to well-defined symptom domains can have a beneficial effect on patients with severe personality disorder. The findings from this study raise questions on current pharmacologic algorithms.

Clonidine Improves Hyperarousal in Borderline Personality Disorder With or Without Comorbid Posttraumatic Stress Disorder

Article

Full-text available

May 2009
J CLIN PSYCHOPHARM

The Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition borderline personality disorder (BPD) seems to constitute a very heterogeneous category. Therefore, pharmacological therapy is symptom-oriented or targets comorbid conditions. A high comorbidity exists between BPD and posttraumatic stress disorder (PTSD). In a double-blind, randomized, placebo-controlled crossover study, we sought to determine whether the antinoradrenergic agent clonidine was effective in reducing hyperarousal and measures of BPD-specific and general psychopathology in a sample of 18 patients with BPD, with or without comorbid PTSD, and with a prominent hyperarousal syndrome. Hyperarousal as measured by the Clinician Administered PTSD scale improved significantly compared with placebo (P = 0.003) irrespective of PTSD comorbidity. Improvements in general and BPD-typical psychopathology were mainly seen in the PTSD-positive subgroup, whereas the subjective sleep latency (P = 0.005) and the restorative qualities of the sleep (P = 0.014) improved in the whole sample. Improvements, despite the small sample size of this pilot study, lead us to conclude that clonidine might be a useful adjunct to pharmacotherapy in patients with BPD who have marked hyperarousal and/or sleep problems and, in particular, in patients with BPD who have a PTSD comorbidity.

Mentalization: Ontogeny, Assessment, and Application in the Treatment of Borderline Personality Disorder

Article

Full-text available

Oct 2008
AM J PSYCHIAT

This article aims to review the development of the concept of mentalization, its applications in the understanding and treatment of borderline personality disorder, and the issue of its assessment. While conceptually derivative of theory of mind, Fonagy's concept of mentalization concerns more affectively and interpersonally complex understandings of oneself and others, reflecting abilities that enable an individual not only to navigate the social world effectively but also to develop an enriched, stable sense of self. The components of mentalization can be organized around self-/other-oriented, implicit/explicit, and cognitive/affective dimensions. Concepts of mindfulness, psychological mindedness, empathy, and affect consciousness are shown to partially overlap with mentalization within these three dimensions. Mentalization is assessed by the measure of reflective function, a scale to be used adjunctively on semistructured narrative interviews such as the Adult Attachment Interview. Its validity has not been fully tested, and its usage has been hampered by the time and expense it requires. Although the concept of mentalization is a useful heuristic that enables clinicians to adopt a coherent treatment approach, it may be too broad and multifaceted to be operationalized as a marker for specific forms of psychopathology such as borderline personality disorder. Research elucidating the relationship between reflective function, overlapping concepts, and features of borderline psychopathology is needed.

Prolactin Response to Fenfluramine and Suicide Attempt Lethality in Major Depression

Article

Full-text available

Apr 1996

This study employed an alternative method for assessing serotonergic function to further evaluate our finding that cerebrospinal fluid (CSF) 5-hydroxyindole acetic acid (5-HIAA) in depressed suicide attempters with a lifetime history of higher lethality suicide attempts is significantly lower compared to depressed patients who have a history of low lethality suicide attempts. We used dl-fenfluramine (60 mg) as a neuroendocrine probe to examine the serotonin system in 41 in-patients with a DSM-III-R major depressive episode, divided into two groups on the basis of a lifetime history of high or low lethality suicide attempts. Fenfluramine challenge test outcome was defined as the maximum prolactin response in the five hours following fenfluramine. Patients with a history of a higher lethality suicide attempt had a significantly lower prolactin response to fenfluramine, even when controlling for cortisol, age, sex, weight, comorbid cluster B personality disorder, pharmacokinetic and menstrual cycle effects. The data provide further support for the hypothesis that serotonin dysfunction is associated with more lethal suicide attempts, and suggests that higher lethality suicide attempters or failed suicides resemble completed suicides both behaviourally and biochemically.

Dr. Siever and Colleagues Reply

Article

Aug 1991

Lithium Carbonate in Emotionally Unstable Character Disorder

Article

Oct 1972
ARCH GEN PSYCHIAT

Arthur Rifkin

Emotionally unstable character disorder (EUCD) is the diagnosis applied to those patients with chronic maladaptive behavior patterns, such as poor acceptance of reasonable authority, truancy, poor work history, manipulativeness, but with a core psychopathological disturbance of depressive and hypomanic mood swings that last hours to days. Their lability is not usually reactive to environmental or interpersonal events. We examined 21 such patients in a six-week, double-blind random assignment cross-over study comparing lithium carbonate to placebo. Using a global measure of mood swings, lithium carbonate was statistically significantly superior to placebo. This was also true for a week's rating of the mean of the daily range of mood swings. We interpret these findings to mean that EUCD is closely related to affective illness and that lithium carbonate joins chlorpromazine as a valuable, and perhaps a superior, therapy for EUCD.

Serotonergic Studies in Patients With Affective and Personality Disorders

Article

Jul 1989
ARCH GEN PSYCHIAT

Emil Coccaro

• Dysfunction of the central serotonergic system has been variously associated with depression and with suicidal and/or impulsive aggressive behavior. To evaluate central serotonergic function in relation to these variables, prolactin responses to a singledose challenge with fenfluramine hydrochloride (60 mg orally), a serotonin releasing/uptake-inhibiting agent, were examined in 45 male patients with clearly defined major affective (n = 25) and/or personality disorder (n 20) and in 18 normal male control patients. Prolactin responses to fenfluramine among all patients were reduced compared with responses of controls. Reduced prolactin responses to fenfluramine were correlated with history of suicide attempt in all patients but with clinician and selfreported ratings of impulsive aggression in patients with personality disorder only; there was no correlation with depression. These results suggest that reduced central serotonergic function is present in a subgroup of patients with major affective and/or personality disorder and is associated with history of suicide attempt in patients with either disorder, but with impulsive aggression in patients with personality disorder only.

Lithium Therapy for Borderline Patients: Preliminary Findings

Article

Jun 1990
J PERS DISORD

This preliminary report of a double-blind random-order placebo control cross-over trial of lithium carbonate and desipramine in borderline personality disorder (BPD) addresses two questions. (1) Is desipramine or lithium more effective than placebo in reducing the affective symptoms in BPD? (2) What are the perceptions of the patients and therapist regarding the usefulness of desipramine or lithium versus placebo? The patients received, in random order, either placebo, lithium, or desipramine for 6-week intervals with a 2-week washout between each arm. Seventeen consenting patients have completed involvement with the trial, 2 (11.8%) dropped out prior to receiving medication, 5 (29.4%) dropped out after completion of one arm, and 10 (58. 8%) completed two or more arms. Responses based on the Hamilton Depression Scale and the Carroll Scale for Depression indicated no significant differences between lithium versus placebo and desipramine versus placebo. Regarding anger and suicidal symptoms, 8/11 patients on lithium versus 4/11 patients on desipramine improved (x2 = 2.93, df = 1, p = .09). Therapists' perceptions rated lithium significantly superior to placebo (x2 = 4.54, df = 1, p = .03). These initial results suggest that the improvement noted on lithium may be related to its effects on the impulsive aspects of BPD.

Borderline Personality, Opioids, and Naltroxone

Article

Dec 2001
HEADACHE

Joel R. Saper

Serotonin function and self-injurious behavior in personality disorder patients

Article

Apr 1997
PSYCHIAT RES

Self-directed aggression, whether in the form of non-suicidal self-mutilation or suicidal behavior, is a prominent feature of personality disorders. We hypothesized that self-injurious behavior, like suicidal behavior, represents a form of self-directed aggression, and may, like suicidal behavior and impulsive aggression, be associated with a decrease in central serotonin function in personality disorder patients. Ninety-seven patients with DSM-III personal ity disorder underwent d,l-fenfluramine challenge as an assessment of serotonergic activity. Patients with a history of self-mutilation or suicide had blunted prolactin and cortisol responses to d,l-fenfluramine compared to those with neither, and those with both had the most blunted responses to fenfluramine. These data raise the possibility that the central 5-HT abnormality, previously associated with suicidal behavior, may be associated with self-directed violence and not necessarily specifically with suicidal intent.

Recent Advances in the Biological Study of Personality Disorders

Article

Sep 2008

While it is premature to provide a simple model for the vulnerability to the development of either borderline (BPD) or schizotypal (SPD) personality disorder, it is clear that these heritable disorders lend themselves to fruitful neurobiological exploration. The most promising findings in BPD suggest that a diminished top-down control of affective responses, which is likely to relate to deceased responsiveness of specific midline regions of prefrontal cortex, may underlie the affective hyperresponsiveness in this disorder. In addition, genetic and neuroendocrine and molecular neuroimaging findings point to a role for serotonin in this affective disinhibition. Clearly SPD falls within the schizophrenia spectrum, but precisely the nature of what predicts full-blown schizophrenia as opposed to the milder symptoms of SPD is not yet clear.

Oxytocin administration attenuates stress reactivity in borderline personality disorder: A pilot study

Article

May 2011

Oxytocin has known stress-reducing and attachment-enhancing effects. We thus hypothesized that oxytocin would attenuate emotional and hormonal responses to stress in borderline personality disorder (BPD). Fourteen BPD and 13 healthy control (HC) adults received 40 IU intranasal oxytocin or placebo in double-blind randomized order followed by the Trier Social Stress Test. Subjective dysphoria (Profile of Mood Changes) and plasma cortisol levels were measured. Childhood trauma history, attachment style, and self-esteem were also rated. A significant "Group × Drug × Time" interaction effect for dysphoria (p=.04) reflected a proportionately greater attenuation of stress-induced dysphoria in the BPD group after oxytocin administration. Additionally, a marginally significant "Group × Drug" interaction effect for cortisol (p=.10) reflected a tendency toward greater attenuation of the stress-induced cortisol surge in the BPD group after oxytocin administration. In the combined sample, the oxytocin-placebo difference in the emotional stress reactivity was significantly predicted by childhood trauma alone (p=.037) and combined with self-esteem (p=.030), whereas the oxytocin-placebo difference in cortisol stress reactivity was predicted only by insecure attachment (p=.013). Results suggest that oxytocin may have a beneficial impact on emotional regulation in BPD, which merits further investigation and could have important treatment implications.

Oxytocin Promotes Human Ethnocentrism

Article

Jan 2011
P NATL ACAD SCI USA

Human ethnocentrism--the tendency to view one's group as centrally important and superior to other groups--creates intergroup bias that fuels prejudice, xenophobia, and intergroup violence. Grounded in the idea that ethnocentrism also facilitates within-group trust, cooperation, and coordination, we conjecture that ethnocentrism may be modulated by brain oxytocin, a peptide shown to promote cooperation among in-group members. In double-blind, placebo-controlled designs, males self-administered oxytocin or placebo and privately performed computer-guided tasks to gauge different manifestations of ethnocentric in-group favoritism as well as out-group derogation. Experiments 1 and 2 used the Implicit Association Test to assess in-group favoritism and out-group derogation. Experiment 3 used the infrahumanization task to assess the extent to which humans ascribe secondary, uniquely human emotions to their in-group and to an out-group. Experiments 4 and 5 confronted participants with the option to save the life of a larger collective by sacrificing one individual, nominated as in-group or as out-group. Results show that oxytocin creates intergroup bias because oxytocin motivates in-group favoritism and, to a lesser extent, out-group derogation. These findings call into question the view of oxytocin as an indiscriminate "love drug" or "cuddle chemical" and suggest that oxytocin has a role in the emergence of intergroup conflict and violence.

The effect of Olanzapine and Sertraline on personality disorder in patients with methadone maintenance therapy

Article

Dec 2010
PSYCHIAT DANUB

Various drugs have been suggested for treatment of Borderline Personality Disorder (BPD)-a disabling disease affecting two percent of the general population. If a drug could alleviate a wide range of symptoms, it would be more suitable. In these disorders drug addiction is very common. This fact makes the symptoms complicated and the treatment more difficult. This study is designed to evaluate the effect of Olanzapine and Sertraline in patients suffering from personality disorders who are on methadone maintenance therapy. This study is a clinical trial. 120 males and females were chosen for methadone maintenance therapy through interview by a psychiatrist based on DSM-IV-TR diagnostic criteria for BPD. Afterwards they were randomly divided into two groups. These groups separately received Olanzapine (5-10 mg daily) and Sertraline (50-100 mg daily) therapy. The SCL-90 questionnaire was filled by all participants before treatment and at the 4th, 8th and 12th weeks of treatment. According to this clinical trial, Olanzapine and Sertraline are effective in ameliorating symptoms of depression, anxiety and aggression, reducing sensitivity in interpersonal relationships and alleviating obsessive symptoms, pessimistic behaviors and somatization disorders in patients with personality disorders on methadone maintenance therapy. As result of this study it appears that Olanzapine and Sertraline are definitely effective in alleviating symptoms of patients with personality disorder, prescribing theses drugs are recommended for these patients.

Integrating theory-driven and empirically-derived models of personality development and psychopathology: A proposal for DSM V

Article

Feb 2011

Although there is growing consensus that the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM) should replace the categorical view of mental disorders with a dimensional approach rooted in personality theory, no consensus has emerged about the dimensions that should be the basis of the new classification system. Moreover, recent attempts to bridge the gap between psychiatric nosology and personality theories have primarily relied on empirically-derived dimensional personality models. While this focus on empirically-derived personality theories may result in a psychometrically valid classification system, it may create a classification system that lacks theoretical and empirical comprehensiveness and has limited clinical utility. In this paper, we first argue that research findings increasingly suggest that an integration of theory-driven and empirically-derived models of personality development is not only possible, but also has the potential to provide a more comprehensive and clinically-relevant approach to classification and diagnosis than either approach alone. Next, we propose a comprehensive model of personality development and psychopathology based on an integration of contemporary theory-driven and empirically-derived models of personality. Finally, we outline the implications of this approach for the future development of DSM, and especially its potential for developing research that addresses the interactions between psychosocial and neurobiological processes implicated in personality development and psychopathology.

The Neuropeptide Oxytocin Regulates Parochial Altruism in Intergroup Conflict Among Humans

Article

Jun 2010
SCIENCE

Humans regulate intergroup conflict through parochial altruism; they self-sacrifice to contribute to in-group welfare and to aggress against competing out-groups. Parochial altruism has distinct survival functions, and the brain may have evolved to sustain and promote in-group cohesion and effectiveness and to ward off threatening out-groups. Here, we have linked oxytocin, a neuropeptide produced in the hypothalamus, to the regulation of intergroup conflict. In three experiments using double-blind placebo-controlled designs, male participants self-administered oxytocin or placebo and made decisions with financial consequences to themselves, their in-group, and a competing out-group. Results showed that oxytocin drives a “tend and defend” response in that it promoted in-group trust and cooperation, and defensive, but not offensive, aggression toward competing out-groups.

The 10-year Course of Psychosocial Functioning among Patients with Borderline Personality Disorder and Axis II Comparison Subjects

Article

Feb 2010
ACTA PSYCHIAT SCAND

The purpose of this study was to determine the 10-year course of the psychosocial functioning of patients with borderline personality disorder (BPD). The social and vocational functioning of 290 inpatients meeting both the Revised Diagnostic Interview for Borderlines (DIB-R) and DSM-III-R criteria for BPD and 72 axis II comparison subjects were carefully assessed during their index admission. Psychosocial functioning was reassessed using similar methods at five contiguous 2-year time periods. Borderline patients without good psychosocial functioning at baseline reported difficulty attaining it for the first time. Those who had such functioning at baseline reported difficulty retaining and then regaining it. In addition, over 90% of their poor psychosocial functioning was due to poor vocational but not social performance. Good psychosocial functioning that involves both social and vocational competence is difficult for borderline patients to achieve and maintain over time. In addition, their vocational functioning is substantially more compromised than their social functioning.

Olanzapine Versus Haloperidol in the Management of Borderline Personality Disorder

Article

Feb 2010
J CLIN PSYCHOPHARM

The newer atypical antipsychotics seem to be as effective as previous antipsychotics for impulsivity and aggressiveness of patients with borderline personality disorder (BPD). Objective of this assessment was to compare the effectiveness of olanzapine versus haloperidol in BPD. Twenty-eight female inpatients, meeting the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision, criteria for BPD, were randomly entered in one of the 2 matching contemporaneous groups for an 8-week parallel double-blind study. This included the random assignment to olanzapine or haloperidol in a 1:1 ratio. Primary outcome measurements were as follows: Brief Psychiatric Rating Scale, Clinical Global Impression-Severity Scale, Buss-Durkee Hostility Inventory. Baselines were created at the beginning of the trial through patient assessments and final assessments at the end of the experiment. Analysis of effect size, calculation of confidence intervals and power analysis were also prepared. All of the patients from within both groups completed the study. Intragroup analysis at the eighth week interval revealed significant positive response by both olanzapine and haloperidol in comparison with the baseline (P < 0.05); however, the between-group analysis showed no significant difference, among the patients, at the end of the experiment. The analysis of specific Brief Psychiatric Rating Scale subscales in both groups revealed considerable and comparable improvements in anxiety, tension, depressive mood, and hostility. The effect size analyzes illustrated remarkable improvements with both groups. There seems to be no significant difference between olanzapine and haloperidol regarding the management of mental and behavioral symptoms of patients with BPD.

The Interpersonal Dimension of Borderline Personality Disorder: Toward a Neuropeptide Model

Article

Dec 2009
AM J PSYCHIAT

Borderline personality disorder is characterized by affective instability, impulsivity, identity diffusion, and interpersonal dysfunction. Perceived rejection and loss often serve as triggers to impulsive, suicidal, and self-injurious behavior, affective reactivity, and angry outbursts, suggesting that the attachment and affiliative system may be implicated in the disorder. Neuropeptides, including the opioids, oxytocin, and vasopressin, serve a crucial role in the regulation of affiliative behaviors and thus may be altered in borderline personality disorder. While clinical data are limited, the authors propose alternative neuropeptide models of borderline personality disorder and review relevant preclinical research supporting the role of altered neuropeptide function in this disorder in the hope of stimulating more basic research and the development of new treatment approaches.

A developmental, mentalization-based approach to the understanding and treatment of borderline personality disorder

Article

Nov 2009
DEV PSYCHOPATHOL

The precise nature and etiopathogenesis of borderline personality disorder (BPD) continues to elude researchers and clinicians. Yet, increasing evidence from various strands of research converges to suggest that affect dysregulation, impulsivity, and unstable relationships constitute the core features of BPD. Over the last two decades, the mentalization-based approach to BPD has attempted to provide a theoretically consistent way of conceptualizing the interrelationship between these core features of BPD, with the aim of providing clinicians with a conceptually sound and empirically supported approach to BPD and its treatment. This paper presents an extended version of this approach to BPD based on recently accumulated data. In particular, we suggest that the core features of BPD reflect impairments in different facets of mentalization, each related to impairments in relatively distinct neural circuits underlying these facets. Hence, we provide a comprehensive account of BPD by showing how its core features are related to each other in theoretically meaningful ways. More specifically, we argue that BPD is primarily associated with a low threshold for the activation of the attachment system and deactivation of controlled mentalization, linked to impairments in the ability to differentiate mental states of self and other, which lead to hypersensitivity and increased susceptibility to contagion by other people's mental states, and poor integration of cognitive and affective aspects of mentalization. The combination of these impairments may explain BPD patients' propensity for vicious interpersonal cycles, and their high levels of affect dysregulation and impulsivity. Finally, the implications of this expanded mentalization-based approach to BPD for mentalization-based treatment and treatment of BPD more generally are discussed.

Personality Trait Dimensions and the Pharmacological Treatment of Borderline Personality Disorder

Article

Nov 2009
J CLIN PSYCHOPHARM

The number of well-designed placebo-controlled studies on pharmacological treatment of borderline personality disorder has been small. We present a breakdown of results of placebo-controlled pharmacological studies, sorting target symptoms into the trait dimensions of affective instability, anxiety inhibition, cognitive-perceptual disturbances, and impulsivity-aggression. Twenty randomized placebo-controlled pharmacological trials studying typical and atypical antipsychotics, selective serotonin reuptake and monoamine oxidase inhibitors, tricyclic antidepressants, mood stabilizers, and benzodiazepines were included. A relative measure of the weight of an outcome was determined by (1) dividing the number of positive comparisons for a drug class by the total number of comparisons of all drugs of all classes for each dimension and (2) dividing the number of positive comparisons for a drug class by the total number of comparisons for that particular drug class for that trait dimension. Antipsychotics (neuroleptics and atypicals) had the most evidence for each of the traits with both methods. Our results are compared with the results of 2 meta-analyses, 1 guideline set, and 1 other systematic review. We found little concordance across these studies. We propose a consortium to discuss guidelines for future studies, including agreement as to what should be measured to determine the outcome and adoption of standardized instruments to measure that outcome.

A preliminary study of lamotrigine in the treatment of affective instability in borderline personality disorder

Article

Jul 2009

The objective of this study was to evaluate the effectiveness of lamotrigine in reducing affective instability in borderline personality disorder (BPD). We conducted a 12-week, double-blind, placebo-controlled study of 28 patients who met Revised Diagnostic Interview for Borderlines and Diagnostic and Statistical Manual of Mental Disorders, fourth edition criteria for BPD. Patients could not meet Diagnostic and Statistical Manual of Mental Disorders, fourth edition criteria for bipolar disorder. Patients could be taking one antidepressant during the study. Patients were randomly assigned to treatment with flexible-dose lamotrigine or placebo in a 1 : 1 manner. The primary outcome measures were: (i) the Affective Lability Scale total score; and (ii) the Affective Instability Item of the Zanarini Rating Scale for Borderline Personality Disorder (ZAN-BPD). The study randomized 15 patients to receive lamotrigine and 13 patients to receive placebo. Patients in the lamotrigine group had significantly greater reductions in the total Affective Lability Scale scores (P<0.05) and significantly greater reductions in scores on the affective instability item of the ZAN-BPD (P<0.05). A secondary finding was that patients in the lamotrigine group had significantly greater reductions in scores on the ZAN-BPD impulsivity item (P = 0.001). Results from the study suggest that lamotrigine is an effective treatment for affective instability and for the general impulsivity characteristic of BPD.

Meta-Analyses of Mood Stabilizers, Antidepressants and Antipsychotics in the Treatment of Borderline Personality Disorder: Effectiveness for Depression and Anger Symptoms

Article

May 2009

The objective of our study was to complete separate meta-analyses of randomized controlled trials of mood stabilizers, antidepressants and antipsychotics to determine whether these medications are efficacious for depression and anger symptoms in borderline personality disorder (BPD). Studies were obtained from OVID Medline, Cochrane Central Register of Controlled Trials, and PsychInfo. References of all original papers and reviews were searched for additional studies. Index terms included: BPD, randomized controlled trials, drug therapy, medication, and treatment. Studies were included if they were randomized doubleblind placebo-controlled trials, published in a peer reviewed journal, had a majority of patients with BPD or included patients with BPD where anger was a target of treatment. Preference was given to studies using outcome measures that were well known, validated, objective, and based on intent-to-treat data. Where available, measures of anger that incorporated verbal and other indirect forms of aggression were utilized. The StatsDirect meta-analysis program was used to calculate an effect size and 95% confidence interval for each study. Mood stabilizers, with the exception of divalproic acid, were found to have a large pooled effect size (-1.75, 95% CI = -2.77 to -0.74) for anger. Divalproic acid and carbamazepine had a moderate effect on depression. Antidepressants had a moderate effect on anger reduction, but a small effect on depression. Antipsychotics had a moderate effect on anger; however aripiprazole had a much larger effect-size than other antipsychotics. Antipsychotics did not have an effect for depression. Sources of variation between studies included length of treatment (5-24 weeks), drop out rates (5% to 65%), proportion of patients in psychotherapy (0- 100%) and with comorbid mood disorders (0-100%). Unfortunately most

The Course of Eating Disorders in Patients with Borderline Personality Disorder: A 10-Year Follow-up Study

Article

Nov 2009
INT J EAT DISORDER

The purpose of this study was to describe the longitudinal course of eating disorders in patients with borderline personality disorder. The SCID I was administered to 290 borderline inpatients and 72 participants with other axis II disorders during their index admission and at five contiguous 2-year follow-up periods. The prevalence of anorexia, bulimia, and eating disorder not otherwise specified (EDNOS) declined significantly over time for those in both study groups but the prevalence of EDNOS remained significantly higher among borderline patients. While over 90% of borderline patients meeting criteria for anorexia, bulimia, or EDNOS at baseline experienced a stable remission by the time of the 10-year follow-up, diagnostic migration was common, particularly for those with anorexia or bulimia. In addition, both recurrences (52%) and new onsets (43%) of EDNOS were more common among borderline patients than recurrences and new onsets of anorexia (28% and 4%) and bulimia (29% and 11%). The results of this study suggest that the prognosis for both anorexia and bulimia in borderline patients is complicated, with remissions being stable but migrations to other eating disorders being common. The results also suggest that EDNOS may be the most prevalent and enduring of the eating disorders in these patients.

Efficacy and tolerability of duloxetine in the treatment of patients with borderline personality disorder: A pilot study

Article

Sep 2008

Guidelines of the American Psychiatric Association for borderline personality disorder (BPD) indicate selective serotonin reuptake inhibitors and the serotonin and noradrenaline reuptake inhibitor (SNRI) venlafaxine for treating affective dysregulation and impulsive behavioural dyscontrol symptoms. The SNRI duloxetine has been studied in patients with major depression, generalized anxiety disorder and fibromyalgia, showing particular efficacy on somatic complaints. This study investigates duloxetine in the treatment of patients with BPD. Eighteen outpatients with a DSM-IV-TR diagnosis of BPD were treated with open-label duloxetine, 60 mg/day, for 12 weeks. Patients were assessed at baseline, week 4 and 12 with the CGI Severity item, the BPRS, the HAM-D, the HAM-A, the SOFAS, the BPD Severity Index (BPDSI) and the HSCL-90-Somatization Subscale (HSCL-90 SOM). Adverse effects were evaluated using the Dosage Record Treatment Emergent Symptom Scale. Statistics were performed with the analysis of variance. Significant P values were <or=0.05. Fourteen patients completed the study. Four patients (22.2%) discontinued treatment in the first 4 weeks because of non-compliance. A significant change was found for: BPRS, HAM-D, SOFAS, BPDSI total score and items 'impulsivity', 'outbursts of anger' and 'affective instability' and HSCL-90 SOM. Adverse effects were mild headache and nausea. Initial results suggest that duloxetine is an effective and well-tolerated treatment for BPD, with positive effects on somatic symptoms.

A psychobiologic perspective on the personality disorders

Article

Jan 1992

A preliminary but growing body of evidence supports the existence of genetic and biological substrates of personality, suggesting the utility of a psychobiological perspective on the personality disorders. The investigation of biological correlates of personality disorders can provide an empirical base to explore the relationship between biological predispositions and psychological function. The authors propose a psychobiological model based on dimensions of cognitive/perceptual organization, impulsivity/aggression, affective instability, and anxiety/inhibition. These dimensions span the DSM-III-R axis I and axis II disorders. The authors review phenomenological, genetic, and biological evidence in relation to each of these dimensions. Although such an approach remains heuristic, this model provides a promising vantage point from which to generate investigation of the development and treatment of the personality disorders.

Phenelzine, imipramine, and placebo in borderline patients meeting criteria for atypical depression

Article

Feb 1989
Psychopharmacol Bull

In planning psychopharmacologic treatment of patients with borderline personality disorder (BPD), three partially validated subtypes should be considered. The validity of the schizotypal subtype is supported by their favorable response to neuroleptics as well as by familial and genetic studies. The validity of emotionally unstable character disorder (EUCD) is supported by the presence of neurological soft signs, their negative response to antidepressants, and their positive response to chlorpromazine and lithium. The data presented in this paper suggest that some patients who meet borderline criteria and have atypical depression (patients meeting DSM-III-R criteria for major depression or dysthymia who have reactive mood and any atypical symptoms) clearly benefit from treatment with antidepressant medication. Although some patients with atypical depression who meet borderline criteria will improve with tricyclic therapy, a significantly greater proportion will improve with the monoamine oxidase inhibitor (MAOI), phenelzine.

Serotonergic Studies in Patients with Affective and Personality Disorders: Correlates with Suicidal and Impulsive Aggressive Behavior

Article

Aug 1989
ARCH GEN PSYCHIAT

Dysfunction of the central serotonergic system has been variously associated with depression and with suicidal and/or impulsive aggressive behavior. To evaluate central serotonergic function in relation to these variables, prolactin responses to a single-dose challenge with fenfluramine hydrochloride (60 mg orally), a serotonin releasing/uptake-inhibiting agent, were examined in 45 male patients with clearly defined major affective (n = 25) and/or personality disorder (n = 20) and in 18 normal male control patients. Prolactin responses to fenfluramine among all patients were reduced compared with responses of controls. Reduced prolactin responses to fenfluramine were correlated with history of suicide attempt in all patients but with clinician and self-reported ratings of impulsive aggression in patients with personality disorder only; there was no correlation with depression. These results suggest that reduced central serotonergic function is present in a subgroup of patients with major affective and/or personality disorder and is associated with history of suicide attempt in patients with either disorder, but with impulsive aggression in patients with personality disorder only.

Cowdry RW, Gardner DL. Pharmacotherapy of borderline personality disorder. Arch Gen Psychiatry 45: 111-119

Article

Mar 1988
ARCH GEN PSYCHIAT

Sixteen female outpatients with borderline personality disorder and prominent behavioral dyscontrol, but without a current episode of major depression, were studied in a double-blind, crossover trial of placebo and the following four active medications: alprazolam (average dose, 4.7 mg/d); carbamazepine (average dose, 820 mg/d); trifluoperazine hydrochloride (average dose, 7.8 mg/d); and tranylcypromine sulfate (average dose, 40 mg/d). Each trial was designed to last six weeks. Tranylcypromine and carbamazepine trials had the highest completion rates. Physicians rated patients as significantly improved relative to placebo while receiving tranylcypromine and carbamazepine. Patients rated themselves as significantly improved relative to placebo only while receiving tranylcypromine. Patients who tolerated a full trial of trifluoperazine showed improvement, those receiving carbamazepine demonstrated a marked decrease in the severity of behavioral dyscontrol, and those receiving alprazolam had an increase in the severity of the episodes of serious dyscontrol. As an adjunct to psychotherapy, pharmacotherapy can produce modest but clinically important improvement in the mood and behavior of patients with borderline personality disorder. As a research tool, patterns of pharmacological response may provide clues to biological mechanisms underlying dysphoria and behavioral dyscontrol.

Amitriptyline and haloperidol in unstable and schizotypal borderline disorder

Article

Feb 1986
Psychopharmacol Bull

Although these are preliminary results of a study in progress, several important observations arise from our data. Significant medication effects are found consistently in self-rated measures - not interview based ratings. The sensitivity and relevance of our interview based measures to specific borderline symptoms warrant further study. There is a need for measures of change more relevant to this disorder. We are unable to determine if interviewer bias plays a role in minimizing reported effects, since expectation of clinical change is understandably modest given the degree of chronic impairment. Similarly, the interview setting may affect patients' willingness to report change. The disappointing response to AMI in patients with strong depressive symptoms suggests that more attention be given to the atypical pattern of depressive presentations in borderline patients as a possible indication for future research with monoamine oxidase inhibitor antidepressants. Despite these limitations, our preliminary results support the use of low-dose neuroleptics in borderline disorder and demonstrate significant efficacy against a broad range of symptoms including hostility, paranoia, anxiety, and depression. Despite the prevalence of affective symptoms in this population, AMI is no better than HAL against depression and little better than PLC against a wide range of associated borderline symptoms. Medication effects are modest in magnitude, generally attributable to decreased severity and occur early in the treatment course. Both unstable and schizotypal borderline patients demonstrate some improvement. We are unable to separate borderline subtypes by medication response or support the clinical prejudice predicting selective efficacy for HAL in schizotypal patients and AMI in unstable borderlines. Rather, we have shown that HAL is broadly effective while AMI adds little to the treatment of borderline disorder.

Paradoxical Effects of Amitriptyline on Borderline Patients

Article

Jan 1987

A paradoxical increase in suicide threats, paranoid ideation, and demanding and assaultive behavior occurred among 15 borderline inpatients receiving amitriptyline in a double-blind study. This pattern differed significantly from that of 14 nonresponding patients receiving placebo.

Behavioural dyscontrol in borderline patients treated with Amitriptyline

Article

Feb 1987
Psychopharmacol Bull

Lithium Carbonate in Emotionally Unstable Character Disorder

Article

Nov 1972
ARCH GEN PSYCHIAT

Continuation pharmacotherapy of borderline personality disorder with haloperidol and phenelzine

Article

Jan 1994

The aim of this study was to assess the effectiveness of low-dose neuroleptic medication and monoamine oxidase inhibitor (MAOI) antidepressant medication in continuation pharmacotherapy of patients with borderline personality disorder. The authors conducted a double-blind, placebo-controlled study comparing continuation therapy with a neuroleptic (up to 6 mg/day of haloperidol), an MAOI antidepressant (up to 90 mg/day of phenelzine), and placebo in 14 men and 40 women with borderline personality disorder. Continuation medication trials lasted 16 weeks, following 5 weeks of acute therapy. Continuing haloperidol demonstrated efficacy only for the treatment of irritability. Higher levels of depression, hypersomnia, and leaden paralysis were noted in the patients who received haloperidol than in those who received phenelzine and those who received placebo. The dropout rate during the first 8 weeks of the continuation study was significantly higher for the patients receiving haloperidol (64%) than for those receiving placebo (28%). Continued phenelzine demonstrated only modest efficacy for the treatment of depression and irritability. An activating effect of phenelzine was shown on measures of excitement and reactivity. No evidence of efficacy was found for continuation therapy with haloperidol in the treatment of borderline personality disorder other than in the treatment of irritability. Little evidence of efficacy was found for continuation therapy with phenelzine for borderline personality disorder other than modest improvements in irritability and depressive symptoms. There is currently no clear pharmacological treatment of choice for the continuation therapy of borderline personality disorder.

Efficacy of Phenelzine and Haloperidol in Borderline Personality Disorder

Article

Jun 1993
ARCH GEN PSYCHIAT

To compare the efficacy of a neuroleptic (haloperidol) to a monoamine oxidase inhibitor antidepressant (phenelzine sulfate) against the affective, cognitive, and impulsive-aggressive symptoms of criteria-defined borderline inpatients in an effort to dissect apart affective and schizotypal symptom patterns or subtypes using medication response. Randomized, double-blind, placebo-controlled trial. Inpatient unit of a tertiary care university psychiatric hospital serving a large public catchment area. One hundred eight consecutively admitted borderline inpatients defined by Gunderson's Diagnostic Interview for Borderline Patients and DSM-III-R criteria, randomly assigned to 38 phenelzine, 36 haloperidol, and 34 placebo trials. Following 1 week free of medication, haloperidol (average dose, 4 mg/d), phenelzine sulfate (average dose, 60 mg/d), or placebo were given for 5 weeks with weekly symptom ratings and plasma drug level determinations. Efficacy was measured on depression (Hamilton Rating Scale, Beck Depression Inventory), global severity (Global Assessment Scale, Symptom Checklist-90 items [SCL-90]), anxiety, anger-hostility (SCL-90, Inpatient Multidimensional Psychiatric Scale [IMPS], Buss-Durkee Hostility Inventory), psychoticism (Schizotypal Symptom Inventory, SCL-90, IMPS), impulsivity (Ward Scale, Barratt Impulsiveness Scale, Self-Report Test of Impulse Control), and borderline psychotherapy (Borderline Syndrome Index). Three-way comparisons between groups indicated superior efficacy for phenelzine, followed by placebo and haloperidol on measures of depression, borderline psychopathologic symptoms, and anxiety. Pairwise comparisons between medication and placebo revealed significant efficacy for phenelzine against anger and hostility but no efficacy against atypical depression or hysteroid dysphoria. We were unable to replicate prior reports of efficacy for the neuroleptic. Pharmacologic dissection of borderline personality disorder patients into affective and schizotypal subtypes could not be demonstrated.

Relationship of Prolactin Response to d-Fenfluramine and Ipsapirone Challenge Correlate with Indices of Agression in Males with Personality Disorder

Article

Oct 1995
INT CLIN PSYCHOPHARM

Hormonal responses to challenge with the 5-HT2A/2C probe d-fenfluramine and hormonal and thermal responses to challenge with the 5-HT1A probe ipsapirone were correlated with self-report and historical assessments of aggression in a pilot sample of eight male personality-disordered individuals. Prolactin responses to d-fenfluramine and cortisol responses to ipsapirone challenge were inversely correlated with self-reported assaultiveness. Thermal responses to ipsapirone were inversely correlated with a historical assessment of aggression. Since none of these physiological indices of 5-HT system function were intercorrelated, it is possible that simultaneous assessment of these 5-HT indices may yield a more comprehensive assessment of the relationship between central 5-HT system function and aggressive behavior in humans.

Distinguishing borderline personality disorder from bipolar disorder: Differential diagnosis and implications

Article

Oct 1996

Iis often difficult to establish whether certain patients should he given the diagnosis of bipolar disorder, borderline personality disorder, or both. This case high- lights how knowledgeable psychi- atnists can have contrasting diag- nostic views about patients with volatile moods and impulsivity and how such disagreement can create problems in providing effective treatment. The patient described in this case report conceptualized her psychiatric problem as due to hipo- lan disorder, which she was told meant a biochemical illness charac- tenized by mood swings not under her control. She was told that this genetically determined disease could he stabilized by using the proper combination of medica- tions. This conceptualization of her illness sharply contrasted with the diagnosis developed during consul- tation-horderline personality dis- order. At that point the patient was told that she suffered from a psy- chiatnic disorder caused by devel- opmental difficulties that are best treated by psychosocial treatments, with psychopharmacology as an adjunctive treatment. With this di- agnosis she was expected to in- creasingly take responsibility for managing her mood swings and im-

d,l-fenfluramine Response in Impulsive Personality Disorder Assessed with [18F]fluorodeoxyglucose Positron Emission Tomography

Article

Jun 1999

Reduced serotonergic activity has been associated with impulsive aggression in personality disordered patients in metabolite and pharmacologic challenge studies. This study used positron emission tomography to explore whether reduced serotonergic function occurs in critical brain regions such as orbital frontal and cingulate cortex that, may play a role in modulating aggression. Six impulsive-aggressive patients and five healthy volunteers were evaluated for changes in regional glucose metabolism after administration of the serotonergic releasing agent d,l-fenfluramine (60 mg, p.o.) or placebo. Volunteers demonstrated increases in orbital frontal and adjacent ventral medial frontal cortex, cingulate, and inferior parietal cortex, whereas impulsive-aggressive patients showed no significant increases in glucose metabolism after fenfluramine in any region. Compared with volunteers, patients showed significantly blunted metabolic responses in orbital frontal, adjacent ventral medial and cingulate cortex, but not in inferior parietal lobe. These results are consistent with reduced serotonergic modulation of orbital frontal, ventral medial frontal, and cingulate cortex in patients with impulsive-aggressive personality disorders.

Evenden JL. Impulsivity: a discussion of clinical and experimental findings. J Psychopharmacol 13: 180-192

Article

Feb 1999
J PSYCHOPHARMACOL

J L Evenden

Impulsivity can often be an important clinical problem in psychiatry and neurology. In psychiatry, the manifestation of impulsive behaviour in syndromes such as personality disorders, attention deficit hyperactivity disorder and in substance abuse may be different, and this has led to conflicting definitions. There has also been a tendency to concentrate on the nature of the behavioural manifestation (problems with the law, aggression, drug use, behavioural problems in school) rather than shared psychological processes, and to ignore the fact that impulsivity can also have positive aspects. In a normal population, the personality trait of impulsivity has been analysed using personality inventory questionnaires. Analysis of these data lead to the suggestion that impulsivity as commonly defined and understood may be made up of several independent factors, which may have separate biological bases. These self-rating questionnaires have been complemented by objective tests that are now often computerized, and which have been used in man (e.g. with criminal offenders, children, or patients who have undergone brain surgery). Some of these tests, such as the differential reinforcement of low rates procedure or the delay of reinforcement procedure, have also been used to study impulsivity in animals. Analysis of the behavioural principles of these tests suggests that they too may reflect different aspects of impulsivity. Many different biological systems have been proposed to contribute to the neurobiological basis of impulsivity. The serotonergic neurotransmitter system has recently received the most attention, with evidence of its involvement coming from animal studies as well as from studies in psychiatric patients. The frontal lobes have been proposed to play an important role in regulating impulsivity, although it unclear how specific this is. None of this biological knowledge has yet led to reliable pharmacotherapy for excessive impulsivity and, as yet, there is little understanding of the mechanisms by which those drugs, which have been found empirically to have some efficacy (e.g. the psychomotor stimulants in attention deficit hyperactivity disorder), exert their therapeutic effect. By bringing together knowledge from different areas of research it is hoped that a cross fertilization will be achieved, which will lead to a sharpening of concepts, an improvement in methodology and the stimulation of biological studies.

The effects of exogenous analgesia in a patient with borderline personality disorder (BPD) and severe self-injurious behaviour

Article

Feb 2000

In order to analyse the effects of potent exogenous analgesia with opioids in borderline personality disorder (BPD), we present a case report in which the application of morphine abolished the perception of pain during self-injury and intensified self-injurious activities. On the basis of our observations, we concluded that the use of potent analgesics might aggravate psychopathology in BPD.

Borderline personality, opioids, and naltrexone

Article

Nov 2000

J R Saper

Treatment histories of borderline inpatients

Article

Mar 2001
COMPR PSYCHIAT

In this study, we describe the types and amounts of psychiatric treatment received by a well-defined sample of borderline personality disorder (BPD) inpatients, and compare these parameters with those of a group of carefully diagnosed personality-disordered controls. Finally, we assess the risk factors associated with a history of intensive, high-cost treatment, which we defined as having had two or more prior psychiatric hospitalizations. The treatment histories of 290 borderline inpatients and 72 axis II controls were assessed using a reliable semistructured interview. All nine forms of treatment studied except electroconvulsive therapy (ECT) were common among borderline patients (36% to 96%). In addition, a significantly higher percentage of borderline patients than axis II controls reported a history of individual and group therapy, day and residential treatment, psychiatric hospitalization, participating in self-help groups, and taking standing medications. They were also significantly younger when they first entered individual therapy and began to take standing medications. In addition, borderline patients spent more time than axis II controls in individual therapy and psychiatric hospitals, and were on standing medications for a significantly longer period of time. They also reported a significantly higher number of psychiatric hospitalizations, lifetime number of standing medications, and number of psychotropic medications taken at the same time. In addition, we found a highly significant multivariate predictive model for multiple prior hospitalizations. The six significant predictors were age 26 or older, a history of quasi psychotic thought, lifetime number of self-mutilative efforts and suicide attempts, a childhood history of reported sexual abuse, and an adult history of being physically and/or sexually assaulted. Taken together, these results confirm clinical impressions concerning the high rates of mental health services used by borderline patients. They also suggest that particularly high rates of costly inpatient treatment are associated with a complex admixture of older age, BPD symptoms in the cognitive and impulse realms, and traumatic life experiences occurring in both childhood and adulthood.

Clinical psychopharmacology of borderline personality disorder: An update on the available evidence in light of the Diagnostic and Statistical Manual of Mental Disorders - 5

Abstract

No full-text available

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