This work may not be copied, distributed, displayed, published, reproduced, transmitted, modified, posted, sold, licensed, or used for commercial purposes. By downloading this file, you are agreeing to the publisher’s Terms & Conditions.

See free commentaries by Paris, Ingenhoven, and Silk

The Use of Psychotropic Medication in Patients With Emotionally Unstable Personality Disorder Under the Care of UK Mental Health Services

Carol Paton, BSc; Michael J. Crawford, MD; Sumera F. Bhatti, MSc; Maxine X. Patel, MD; and Thomas R. E. Barnes, DSc

Vertical divider

ABSTRACT

Background: Guideline recommendations for the pharmacologic treatment of personality disorder lack consensus, particularly for emotionally unstable personality disorder (EUPD), and there is limited information on current prescribing practice in the United Kingdom.

Objective: To characterize the nature and quality of current prescribing practice for personality disorder across the United Kingdom, as part of a quality improvement program.

Method: A cross-sectional survey of self-selected psychiatric services providing care for adults with personality disorder (ICD-10 criteria) was conducted. Data were collected during May 2012.

Results: Of 2,600 patients with a diagnosis of personality disorder, more than two-thirds (68%) had a diagnosis of EUPD. Almost all (92%) patients in the EUPD subgroup were prescribed psychotropic medication, most commonly an antidepressant or antipsychotic, principally for symptoms and behaviors that characterize EUPD, particularly affective dysregulation. Prescribing patterns were similar between those who had a diagnosed comorbid mental illness and those who had EUPD alone, but the latter group was less likely to have had their medication reviewed over the previous year, particularly with respect to tolerability (53% vs 43%).

Conclusions: The use of psychotropic medication in EUPD in the United Kingdom is largely outside the licensed indications. Whether the treatment target is identified as intrinsic symptoms of EUPD or comorbid mental illness may depend on the diagnostic threshold of individual clinicians. Compared with prescribing for EUPD where there is judged to be a comorbid mental illness, the use of off-label medication for EUPD alone is less systematically reviewed and monitored, so opportunities for learning may be lost. Treatment may be continued long term by default.

J Clin Psychiatry 2015;76(4):e512–e518

Submitted: April 29, 2014; accepted July 30, 2014 (doi:10.4088/JCP.14m09228).

Corresponding author: Carol Paton, BSc, Oxleas NHS Foundation Trust, Pinewood House, Pinewood Place, Dartford, Kent DA5 7WG, England (carol.paton@oxleas.nhs.uk).

People with personality disorder have long-standing, pervasive patterns of thinking, feeling, and relating to others that lead to social dysfunction and poor mental health. Compared with the general population, they are more likely to experience suicidal thoughts and behavior and symptoms of depression, anxiety, and psychosis; exhibit impulsive behavior; and fulfill diagnostic criteria for a range of mental disorders.1

Among people in contact with mental health services, the most common type of personality disorder is emotionally unstable personality disorder (EUPD), characterized by affective instability, impulsivity, anger, transient psychotic or dissociative symptoms, and unstable relationships. The National Institute for Health and Care Excellence (NICE) guideline1 on the treatment and management of borderline personality disorder (BPD) acknowledges that this condition does not exist as a distinct diagnostic category within ICD-10,2 although there is “an equivalent category of disorder termed ‘emotionally unstable personality disorder, borderline type’ characterized by instability in emotions, self-image and relationships.”1(p17) ICD-10 includes a brief description of BPD as a subcategory of EUPD.

No drug treatments are currently licensed for EUPD or BPD. The American Psychiatric Association (APA) guidelines for BPD endorse a symptom-targeted approach and provide pharmacologic algorithms for impulsivity, aggression, and affective instability3; these guidelines have not been revisited since 2001. The current (2008) NICE guidelines1 state that, while comorbid mental health problems should be treated, drug treatment should not be used specifically to alleviate intrinsic features of the disorder. Australian guidelines, published in 2012, recommend that medicines should not be a primary therapy but that time-limited use for specific symptoms can be considered as an adjunct to psychological therapy.4

In clinical practice, the high levels of emotional distress experienced by some people with personality disorder, together with a perceived need to offer rapidly effective treatments when patients present in crisis, mean that drug treatments are often used. Both international and relatively small local UK surveys of prescribing practice for people with personality disorder suggest that psychotropic medication is prescribed for the majority, often over long periods of time, and that polypharmacy is common.5–10

We report here on selected findings from a large, UK-wide study of prescribing practice for people with personality disorder, addressing the prevalence of prescribing of psychotropic drugs for people with EUPD, the clinical rationale for such prescriptions, and the quality of medication review.

METHOD

The Prescribing Observatory for Mental Health11 invited all National Health Service Trusts and other health care organizations (hereafter referred to as “Trusts”) in the United Kingdom providing specialist mental health services to participate in an audit-based quality improvement program focusing on the use of psychotropic medication in people with personality disorder. All services were self-selected in that they chose to participate and were asked to submit data on a randomly selected sample of patients with a confirmed ICD-10 diagnosis of personality disorder. In UK mental health services, ICD-10 diagnoses are recorded as part of routine clinical care.

clinical points

Data collected on each patient included age, gender, ethnicity, subtype of personality disorder, comorbid psychiatric diagnoses, psychotropic medication prescribed and the duration of prescription, clinical indications for such medication, availability of a patient-specific crisis plan and whether this mentioned the role of medication, the date of the most recent medication review and whether therapeutic response and tolerability were addressed, and the clinical service providing care.

All data were collected from clinical records with the exception of the clinical rationale for treatment; clinical teams were asked to identify the treatment targets for each medication prescribed, selecting from a list of potential symptoms and behaviors generated by a panel of clinical experts or providing a free-text response.

Data were collected during May 2012 using SNAP (electronic survey software; Snap Surveys Ltd) and analyzed using SPSS Version 20.0.12 Descriptive statistics were used to compare those patients with personality disorder alone with those who had a comorbid ICD-10 mental illness.

RESULTS

Demographic and Clinical Characteristics of the Sample

Forty-one Trusts submitted data for 2,600 patients from 438 clinical teams: 1,054 (40.5%) of these patients had a personality disorder as their sole psychiatric diagnosis, while 1,546 (59.5%) had personality disorder with at least 1 comorbid psychiatric illness. The demographic and clinical characteristics of these 2 subgroups are shown in Table 1.

Table 1

Click figure to enlarge

Almost two-thirds (63%) of the sample were under the care of general adult psychiatric services, and just under a quarter (24%) were under the care of specialist personality disorder services. Most (88%) were outpatients.

When the subgroups with and without a comorbid psychiatric diagnosis were compared, there was a higher prevalence of dissocial personality disorder (21% vs 15%, χ21 = 13.81, P < .001) and a lower prevalence of EUPD (64% vs 75%, χ21 = 32.14, P < .001) in the former. The subgroups were similar with respect to all other demographic characteristics and personality disorder diagnoses.

Of the 1,054 patients with personality disorder alone, 82% were prescribed at least 1 psychotropic medication, while the figure for those who had personality disorder and at least 1 comorbid psychiatric diagnosis (n = 1,546) was 94%.

Emotionally Unstable Personality Disorder

The most common personality disorder diagnosis was EUPD (n = 1,776: 68% of the total sample). Patients in the EUPD group, as compared with those with the other subtypes of personality disorder, were more likely to be female (73% vs 29%, χ21 = 484, P < .001) and less likely to have a diagnosis of schizophrenia spectrum disorder (9% vs 29%, χ21 = 158, P < .001). All other demographic and clinical characteristics were similar to those in the total sample of people with personality disorder (see Table 1).

Prescribing Practice for EUPD

Patterns of prescribing in those with EUPD alone or with comorbid depression, schizophrenia spectrum disorder, or bipolar disorder are shown in Figure 1. In the majority of patients with EUPD, medicines had been prescribed for at least 4 weeks.

Antipsychotics and mood stabilizers were prescribed more often in those with a comorbid diagnosis of schizophrenia spectrum disorder or bipolar disorder than in those whose only psychiatric diagnosis was EUPD. However, all groups of psychotropic medications were also commonly prescribed in the latter group.

Figure 1

Click figure to enlarge

Ninety-two percent of the patients with EUPD were prescribed psychotropic medication. Of the 786 patients who had EUPD as their sole psychiatric diagnosis, 101 (13%) were not prescribed psychotropic medication; 164 (21%) were prescribed psychotropic medication from 1 class; 218 (28%), from 2; 179 (23%), from 3; and 124 (16%), from 4 or more. The clinical reasons for prescribing each of the main groups of psychotropic medicines are shown in Table 2.

Table 2

Click figure to enlarge

The availability of crisis plans, the involvement of patients in the development of these plans, and the proportion of patients whose crisis plan incorporated the role of medication are shown in Table 3. When those with and without a comorbid psychiatric diagnosis were compared, the former were more likely to have had a crisis plan that mentioned medication and to have had their medication reviewed in the last year and for this review to have addressed the side effects of medication. These data are shown in Tables 3 and 4.

Table 3

Click figure to enlarge

Table 4

Click figure to enlarge

DISCUSSION

In this large sample of people with personality disorder who were in contact with mental health services, over half had a diagnosed comorbid mental illness, and more than two-thirds had a diagnosis of EUPD. That EUPD was the most common personality disorder diagnosis is consistent with other surveys.6,13,14

Almost all of the patients in the EUPD subgroup were prescribed psychotropic medication, most commonly to target symptoms and behaviors that characterize personality disorder. Those patients with EUPD alone were less likely to have had medication mentioned in their crisis plan and to have had their prescribed medication reviewed in the previous year compared with those who had a diagnosed comorbid mental illness. This suggests that the regular and thorough monitoring recommended when using medicines for unlicensed indications15 is not happening in clinical practice.

Most EUPD Patients Had Comorbid Mental Illness

The relatively high prevalence of comorbid mental illness in patients with personality disorder is consistent with the published literature.1,8,9,16

Many of the symptoms of EUPD overlap with those of mental illness but may not reach the qualitative or quantitative criteria required for a comorbid diagnosis in that they are not severe enough or do not last long enough. In routine practice, clinicians are likely to differ in their individual thresholds for a diagnosis of a comorbid condition, with, for example, some considering even severe mood lability to be consistent with a diagnosis of EUPD, while others would diagnose comorbid bipolar disorder. By comparing those patients not considered by their treating clinicians to have mental illness comorbid with their EUPD with those with a diagnosed comorbid illness, we were able to examine in detail the clinical rationale for prescribing psychotropic medication for the former group.

High Prevalence of Psychotropic Drug Prescribing for EUPD

Our finding that at least 4 of 5 patients with EUPD were prescribed psychotropic medication is consistent with other surveys of prescribing practice.5,7–9 Polypharmacy was also common with two-thirds of patients with EUPD alone prescribed psychotropic drugs from at least 2 different classes and almost a fifth from at least 4. This is consistent with Zanarini et al,6 who reported that 11% of those with EUPD were taking 5 or more psychotropic drugs, although these investigators included patients with comorbid mental illness. Those patients with EUPD alone who are under the care of mental health services are likely to be those with more severe and disabling symptoms. Nevertheless, that almost 1 in 5 of those with EUPD alone was prescribed psychotropic drugs from at least 4 classes suggests that these patients displayed a range of symptoms and behaviors that clinicians considered potentially responsive to drug treatment. Such an approach to prescribing is consistent with the symptom-based recommendations made by the APA3 and the conclusions of recent systematic reviews,17,18 but not the NICE recommendations for the NHS.1

In our subgroup of patients with EUPD alone, three-quarters were prescribed an antidepressant; three-fifths, an antipsychotic drug; one-third, a benzodiazepine; and one-fifth, a z-hypnotic or mood stabilizer. The high prevalence of antidepressant use is consistent with other surveys of prescribing practice8–10 but in contrast with the findings from clinical studies that these drugs are not effective in treating affective symptoms in patients with EUPD17 and are relatively less effective in treating depression in people with comorbid personality disorder than in those without.19,20 A higher proportion of our patients with EUPD were prescribed an antipsychotic than the 40% reported by Pascual et al8 in a naturalistic study of 226 consecutive patients with BPD admitted to an outpatient program, although these investigators noted an increasing prevalence of antipsychotic prescribing over time. In contrast, our prevalence of prescribing of mood stabilizers and benzodiazepines was considerably lower than the 60% reported by the same authors.

The prevalence of antipsychotic prescribing in those with EUPD alone was almost double the figure we found in a smaller audit of prescribing practice for personality disorder across 3 London mental health Trusts.9 In this earlier audit, variation in prescribing practice was seen across services, with those patients in contact with specialist personality disorder services less likely to be prescribed psychotropic medication than those under the care of general adult psychiatry. This suggests that clinicians in these specialist services may be more aware of the evidence base underpinning the use of psychotropic drugs in people with personality disorder and/or may have more time and access to skills to manage the symptoms and behaviors associated with EUPD.

Most Prescriptions for Personality Disorder Rather Than Comorbid Mental Illness

There was evidence that some prescribing for people with EUPD was targeted toward comorbid mental illness in that antidepressants were more frequently prescribed for those with a diagnosis of depression than for those without, while antipsychotics and mood stabilizers were more frequently prescribed for those who had a diagnosis of a schizophrenia spectrum disorder or bipolar illness than for those who did not. Further, those with a comorbid diagnosis of bipolar disorder were marginally less likely to be prescribed an antidepressant than those with EUPD alone, a finding that, perhaps, reflects awareness of the growing literature reporting on the poor efficacy of antidepressants for bipolar depression.21,22 However, the pattern of prescribing was sufficiently similar between those with EUPD with or without a comorbid mental illness to suggest that most prescribing was not clearly targeting comorbid conditions. It is therefore reasonable to conclude that clinicians extrapolate from the symptoms/behaviors associated with mental illness and, for those patients with EUPD alone, prescribe medication that targets these phenomena. Such a pragmatic approach to prescribing is consistent with the recommendations of the APA guideline for BPD3 but in direct contrast with the UK NICE guideline.1

Emotionally unstable personality disorder is a complex condition in that a range of psychiatric symptoms and aberrant behaviors are seen, with common crises that are characterized by impulsive behavior, emotional distress, suicidal thoughts or acts, and aggression. The suicide rate in EUPD is at least as high as that for schizophrenia, bipolar disorder, or depression,23 a concern that may prompt clinicians to actively intervene during periods of crisis and in the longer term. However, the evidence base underpinning the management of EUPD is limited and difficult to interpret: the majority of pharmacologic studies are underpowered to detect any treatment effect should one exist, varying inclusion criteria are used (with/without a variety of key symptoms or comorbidities), and a large number of rating scales and outcome measures are employed that render meta-analysis difficult, if not impossible. When there is such a limited literature, small randomized controlled trials, case series, and even single case studies that are published in widely read journals may disproportionately influence clinical practice. Clinicians also rely on their past experience and on the opinions of their peers. The resultant combination of an urgent clinical problem, the absence of a robust evidence base on which to base treatment decisions with reliance on lower levels of evidence, and extrapolation from what is known about the treatment of conditions with which there is overlap of symptoms may partly explain the range of drugs being prescribed in clinical practice to treat a variety of symptoms.

According to the APA guidelines, pharmacologic management of BPD can be informed by the identification of prominent symptom domains or clusters.3,24 Table 2 lists the reasons given by clinicians for prescribing individual drug classes. Allowing for some lack of alignment between target symptoms identified by UK expert clinicians and the APA domains, it appears that the affective disorder domain is the target for most prescriptions, with cognitive-perceptual symptoms being a less-frequent target.

Depressive symptoms were the most common treatment target, identified in over half of those patients with EUPD alone. The most common pharmacologic intervention for this indication was antidepressant medication. While this may be considered to reflect a symptom-targeted approach, it should be noted that the risk-benefit ratio associated with antidepressant treatment is not considered to be favorable in subsyndromal depression, with20 or without25 personality disorder. In contrast, there is some evidence17 that mood stabilizers are effective against depressed mood in the context of personality disorder, although drugs from this group were rarely prescribed for this indication.

The second most common reason for prescribing for EUPD alone was affective/emotional instability. Antipsychotics were prescribed for this indication in over a quarter of patients, while antidepressants and mood stabilizers were each prescribed for almost a fifth. Evidence supports only the use of mood stabilizers.17

The APA3 recommends symptom-specific algorithms for managing impulsivity and aggression; these behaviors have been shown in a variety of electrophysiologic, endocrine, and neuroimaging studies to have demonstrable neurobiological correlates26 and so may be considered potentially legitimate targets for drug treatments. However, while the use of a mood stabilizer to reduce impulsivity was supported by a recent review18 of the evidence, the APA recommendation to use an antipsychotic for such a purpose was not. We found that almost 1 in 5 patients was prescribed medication to manage aggression/hostility, and a further 1 in 5 was prescribed medication to reduce impulsivity. The most frequently used pharmacologic intervention in both cases was an antipsychotic. Antipsychotics were also used to treat transient psychotic-like experiences or symptoms, a strategy for which there is only modest supporting evidence.18,27 Benzodiazepines and other sedatives were used primarily to treat anxiety and disturbed sleep, indications for which they are licensed. Distress, which may of course lead to or result from anxiety and insomnia, was also a target symptom.

Crisis Plans and Medication Review

The role of medication was more likely to be described in the crisis plan for patients who had a comorbid mental illness than for those with a EUPD diagnosis alone (34% vs 27%), and the former group was also more likely to have their medication reviewed, particularly with respect to tolerability (53% vs 43%). Although the magnitudes of these differences were numerically relatively small, they suggest that comorbidity may drive more frequent review of treatment and side effects. Off-label prescribing may be less likely to conform to practice guidelines,15 that is, not be in the context of an individual treatment trial or meet monitoring requirements, and the opportunity to learn may be lost. A possible consequence is that patients remain on treatment by default, and this is one potential explanation for the high prevalence of long-term prescribing of psychotropic drugs that we found. Further, when medication is not reviewed, it is not possible to determine if the benefits of treatment outweigh the risks, and patients with EUPD may be unnecessarily exposed to both short- and long-term side effects associated with psychotropic medication. These include the metabolic side effects of antipsychotic drugs in a population known to have higher rates of cardiovascular disease and associated premature mortality than the general population.28

Limitations of the Study

Services were asked to select a random sample of people with personality disorder under their care, but we cannot know if this was done. However, the large size of the total national sample makes systematic selection bias unlikely, and, as such, the sample is likely to be representative of patients with personality disorder under the care of mental health services in the United Kingdom. We did not verify that the patients in our sample met the diagnostic criteria for EUPD or any comorbid diagnoses that they had been given by their treating clinician. Nevertheless, given that the prevalence of comorbid conditions in our sample is similar to other surveys,13,14 our sample is credibly representative of people with EUPD in the United Kingdom in this respect.

Author affiliations: Prescribing Observatory for Mental Health, Royal College of Psychiatrists Centre for Quality Improvement, (Dr Barnes and Mss Paton and Bhatti); Centre for Mental Health, Imperial College (Drs Crawford and Barnes); Institute of Psychiatry, Psychology and Neuroscience, King’s College (Dr Patel), London; and Oxleas NHS Foundation Trust, Dartford, Kent (Ms Paton), England.

Potential conflicts of interest: Ms Paton has participated in advisory boards for Roche, Janssen, and Sunovion. Dr Patel holds a Clinician Scientist Award supported by the National Institute for Health Research; has received consultancy fees, lecturing honoraria, and/or research funding from Janssen, Eli Lilly, Endo, Lundbeck, Otsuka, and Wyeth; and has worked or is currently working on clinical drug trials and studies for Eli Lilly, Amgen, and Lundbeck. Dr Barnes has received lecturing honoraria from Roche and Eli Lilly and has undertaken consultancy work for Sunovion and Otsuka/Lundbeck. Dr Crawford and Ms Bhatti have no conflicts to declare.

Funding/support: The work was conducted by the Prescribing Observatory for Mental Health (POMH-UK), a quality improvement initiative within the Royal College of Psychiatrists in the United Kingdom. The POMH-UK is wholly funded by subscriptions from mental health services in the United Kingdom.

Role of sponsor: Clinicians from the mental health services contributed to the design and content of quality improvement programs but not to data analyses or interpretation of the findings.

Disclaimer: The views expressed are those of the authors and not necessarily those of the National Institute for Health Research or the Department of Health.

Previous presentation: Presented as a poster at the summer meeting of the British Association for Psychopharmacology (Paton C, Bhatti SF, Crawford MJ, et al. Nature and prevalence of psychotropic drug prescribing for people with personality disorder. J Psychopharmacology. 2013;27[Abstract Suppl 8]:A41).

Acknowledgments: The authors acknowledge the National Health Service clinicians and administrators in the participating Trusts who collected the audit data and Krysia Zalewska, BSc, POMH-UK program manager. The POMH-UK (http://www.rcpsych.ac.uk/workinpsychiatry/qualityimprovement/nationalclinicalaudits/
prescribingpomh/prescribingobservatorypomh.aspx
) is based at the Centre for Quality Improvement at the Royal College of Psychiatrists in the United Kingdom. Ms Zalewska has no conflicts of interest to report.

REFERENCES

1. National Institute for Clinical Excellence. Borderline Personality Disorder—Treatment and Management. London, England: National Institute for Clinical Excellence; 2008.

2. The ICD-10 Classification of Mental and Behavioural Disorders: Clinical Descriptions and Diagnostic Guidelines. Geneva, Switzerland: World Health Organization; 1992.

3. American Psychiatric Association. Practice guidelines for the treatment of patients with borderline personality disorder. Am J Psychiatry. 2001;158(suppl):1–52.

4. National Health and Medical Research Council. Clinical practice guideline for the management of borderline personality disorder. National Health and Medical Research Council, Canberra, Australia. 2012. http://www.nhmrc.gov.au/_files_nhmrc/publications/attachments/
mh25_borderline_personality_guideline.pdf
. Accessed January 27, 2015.

5. Bender DS, Dolan RT, Skodol AE, et al. Treatment utilization by patients with personality disorders. Am J Psychiatry. 2001;158(2):295–302. PubMed doi:10.1176/appi.ajp.158.2.295

6. Zanarini MC, Frankenburg FR, Hennen J, et al. Mental health service utilization by borderline personality disorder patients and Axis II comparison subjects followed prospectively for 6 years. J Clin Psychiatry. 2004;65(1):28–36. PubMed doi:10.4088/JCP.v65n0105

7. Baker-Glenn W, Steels M, Evans C. Use of psychotropic medication among psychiatric outpatients with personality disorder. Psychiatric Bull. 2010;34(3):83–86. doi:10.1192/pb.bp.108.021758

8. Pascual JC, Martín-Blanco A, Soler J, et al. A naturalistic study of changes in pharmacological prescription for borderline personality disorder in clinical practice: from APA to NICE guidelines. Int Clin Psychopharmacol. 2010;25(6):349–355. PubMed doi:10.1097/YIC.0b013e32833e23ed

9. Crawford MJ, Kakad S, Rendel C, et al. Medication prescribed to people with personality disorder: the influence of patient factors and treatment setting. Acta Psychiatr Scand. 2011;124(5):396–402. PubMed doi:10.1111/j.1600-0447.2011.01728.x

10. Oldham JM, Bender DS, Skodol AE, et al. Testing an APA practice guideline: symptom-targeted medication utilization for patients with borderline personality disorder. J Psychiatr Pract. 2004;10(3):156–161. PubMed doi:10.1097/00131746-200405000-00003

11. Prescribing Observatory for Mental Health. What is POMH-UK? http://www.rcpsych.ac.uk/workinpsychiatry/qualityimprovement/nationalclinicalaudits/
prescribingpomh/prescribingobservatorypomh.aspx
. Accessed January 27, 2015.

12. IBM SPSS Statistics for Windows Version 20.0 [computer program]. Armonk, NY: IBM Corp; 2011.

13. Coid J, Yang M, Bebbington P, et al. Borderline personality disorder: health service use and social functioning among a national household population. Psychol Med. 2009;39(10):1721–1731. PubMed doi:10.1017/S0033291708004911

14. Coid J, Yang M, Tyrer P, et al. Prevalence and correlates of personality disorder in Great Britain. Br J Psychiatry. 2006;188(5):423–431. PubMed doi:10.1192/bjp.188.5.423

15. Use of licensed medicines for unlicensed applications in psychiatric practice. College Report CR142. London, UK: Royal College of Psychiatrists; January 2007. https://www.rcpsych.ac.uk/files/pdfversion/cr142.pdf. Accessed January 27, 2015.

16. Zanarini MC, Frankenburg FR, Dubo ED, et al. Axis I comorbidity of borderline personality disorder. Am J Psychiatry. 1998;155(12):1733–1739. PubMed doi:10.1176/ajp.155.12.1733

17. Ingenhoven T, Lafay P, Rinne T, et al. Effectiveness of pharmacotherapy for severe personality disorders: meta-analyses of randomized controlled trials. J Clin Psychiatry. 2010;71(1):14–25. PubMed doi:10.4088/JCP.08r04526gre

18. Lieb K, Vollm B, Rucker G, et al. Pharmacotherapy for borderline personality disorder: Cochrane systematic review of randomized trials. Br J Psychiatry. 2010;196(1):4–12. doi:10.1192/bjp.bp.108.062984 PubMed

19. Newton-Howes G, Tyrer P, Johnson T. Personality disorder and the outcome of depression: meta-analysis of published studies. Br J Psychiatry. 2006;188(1):13–20. PubMed doi:10.1192/bjp.188.1.13

20. Gorwood P, Rouillon F, Even C, et al. Treatment response in major depression: effects of personality dysfunction and prior depression. Br J Psychiatry. 2010;196(2):139–142. PubMed doi:10.1192/bjp.bp.109.067058

21. Sachs GS, Nierenberg AA, Calabrese JR, et al. Effectiveness of adjunctive antidepressant treatment for bipolar depression. N Engl J Med. 2007;356(17):1711–1722. PubMed doi:10.1056/NEJMoa064135

22. Sidor MM, MacQueen GM. An update on antidepressant use in bipolar depression. Curr Psychiatry Rep. 2012;14(6):696–704. PubMed doi:10.1007/s11920-012-0323-6

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

24. Nelson K, Schulz SC. Pharmacologic treatment of borderline personality disorder. Current Psychiatry. 2011;10(8):31–40.

25. Anderson IM, Ferrier IN, Baldwin RC, et al. Evidence-based guidelines for treating depressive disorders with antidepressants: a revision of the 2000 British Association for Psychopharmacology guidelines. J Psychopharmacol. 2008;22(4):343–396. PubMed doi:10.1177/0269881107088441

26. Ripoll LH, Triebwasser J, Siever LJ. Evidence-based pharmacotherapy for personality disorders. Int J Neuropsychopharmacol. 2011;14(9):1257–1288. PubMed doi:10.1017/S1461145711000071

27. Ingenhoven TJ, Duivenvoorden HJ. Differential effectiveness of antipsychotics in borderline personality disorder: meta-analyses of placebo-controlled, randomized clinical trials on symptomatic outcome domains. J Clin Psychopharmacol. 2011;31(4):489–496. PubMed doi:10.1097/JCP.0b013e3182217a69

28. Fok MLY, Hayes RD, Chang CK, et al. Life expectancy at birth and all-cause mortality among people with personality disorder. J Psychosom Res. 2012;73(2):104–107. PubMed doi:10.1016/j.jpsychores.2012.05.001