BRAIN INSIGHTS - Borderline Personality Disorder: The Neuropsychopharmacological Nuance

28th Feb 2022

Brain Insights LogoBrain Insights is the dedicated student section published in the British Neuroscience Association (BNA) Bulletin. It represents the voice of the BNA student: written by students for students. In this student article, postgraduate Sammy Green, 2nd Year Pharmacology MSci Student, University of Bristol, explores borderline personality disorder.

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Early neurodevelopmental and environmental influences are integral in shaping brain activity and behaviour. Whilst sufficient protective factors may be in place to mitigate exposure to risk factors such as childhood trauma for many individuals, this may not always be the case. In Borderline Personality Disorder (BPD) (which has an estimated prevalence of 1.6% in the general population (1)) it has been observed that exposure to severe early life trauma can precipitate the onset of the condition, and is accompanied by functional and structural brain changes (2). Individuals with BPD may have increased genetic risk to reduced grey matter volume (including that of the amygdalae) alongside metabolic activity in the prefrontal cortex (3). From the perspective of the early editions of the Diagnostic and Statistical Manual of Mental Disorders (DSM), BPD was considered a complex psychiatric disorders which whilst dissociable from affection disorders and schizophrenia, was difficult to distinguish from other personality disorders (1). For individuals with BPD, experiences of long-term emotional distress are common. BPD was originally denoted as the “border” between psychotic and neurotic, and contemporary classifications feature 9 primary traits, including an intense fear of abandonment, impulsive and self-destructive behaviour, chronic suicidal ideation, and intense, unstable relationships tormented by extreme switches between idealisation and devaluation.

BPD diagnosis

For some, receiving a BPD diagnosis can be a relief; an explanation to years of suffering and unexplained symptoms which may be dismissed as treatment-resistant, co-morbid anxiety and depression. For others, a BPD diagnosis can be harrowing, with ~10% of those with BPD taking their life (4). Treatments for BPD can involve group (therapeutic communities, care programmes) or individual therapies (mentalisation-based therapy, schema-focused therapy) or potentially a mixture of the two (5). The National Institute for Health and Care Excellence (NICE) guidelines highlight Dialectical Behavioural Therapy (DBT) as the primary treatment for BPD (6), having originally been designed for the disorder specifically (7).  However, for many DBT is inaccessible due to waiting lists and lack of funding in secondary care services, and when other therapies fail, treatment coordinators often resort to medication (8).

BPD and medication

Unlike depression, bipolar disorder, and schizophrenia, BPD has not been attributed to a specific biological mechanism, and as such cannot be treated with just one class of psychiatric medication. The first line medication often considered is antidepressants, primarily selective serotonin re-uptake inhibitors (SSRIs) (9), however many BPD patients do not tolerate SSRIs for unknown reasons. More promising antidepressants include serotonin-norepinephrine reuptake inhibitors (SNRIs) and sometimes tricyclic antidepressants (TCAs) (8), but both of these often have intolerable adverse effects (e.g. high blood pressure, nausea, dizziness). Another issue with medicating BPD with antidepressants is that mood instability is a core part of BPD, meaning there is a higher risk of antidepressant-induced mania than in patients with only depression (10). Because of this, patients may be prescribed a mood stabiliser, such an antipsychotic (e.g. quetiapine) or anticonvulsants (e.g. lamotrigine)8. Quetiapine specifically has been shown to reduce impulsivity, cognitive disturbances and relationship instability in BPD patients, but can produce a host of side effects including tiredness, dry mouth and weight gain. Equally, the mood stabiliser lithium has shown some promise in treating BPD, especially with reducing aggression and suicidal behaviour (11), although lithium is a high maintenance drug, with regular blood tests required and significant risk to the thyroid and kidneys.

In summary, BPD can be managed on a case-by-case basis using treatments which are appropriate (tolerable, accessible) for the individual. Pharmacotherapy and psychotherapy offer two such routes of treatment which can be explored to titrate dosages/therapeutic flexibility in order to optimise the quality of life for individuals with BPD.


1. Chapman J, Jamil RT, Fleisher C. Borderline Personality Disorder. In: StatPearls (Internet). (Updated 2021). Available from: (Accessed 13th December 2021).
2. Kulacaoglu F, Kose S. Borderline Personality Disorder (BPD): In the Midst of Vulnerability, Chaos, and Awe. Brain Sci. 2018;8(11):201. Available from: 10.3390/brainsci8110201  
3. Soloff P, Nutche J, Goradia D, Diwadkar V. Structural brain abnormalities in borderline personality disorder: A voxel-based morphometry study. Psychiatry Res. 2008;164(3):223-236. Available from: 10.1016/j.pscychresns.2008.02.003
4. Biskin, R. The Lifetime Course of Borderline Personality Disorder. Can J Psychiatry. 2015;60(7):303-308. Available from: 10.1177/070674371506000702
5. Choi-Kain L, Finch E, Masland S, Jenkins J, Unruh B. What Works in the Treatment of Borderline Personality Disorder. Curr Behav Neurosci Rep. 2017;4(1):21-30. Available from: 10.1007/s40473-017-0103-z
6. National Institute for Health and Care Excellence. Borderline Personality Disorder: recognition and management. Available from: (Accessed 13th December 2021).
7. Chapman A. Dialectical Behaviour Therapy. Psychiatry (Edgmont). 2006;3(9):62-68. Available from: (Accessed 13th December 2021).
8. Ripoli L. Psychopharmacologic treatment of borderline personality disorder. Dialogues Clin Neurosci. 2013;15(2):213-224. Available from: 10.31887/DCNS.2013.15.2/lripoll
9. Yadav D. Prescribing in borderline personality disorder – the clinical guidelines. Progress in Neurology and Psychiatry. 2020;24(2):25-30. Available from:
10. Yasgur B. Antidepressant-Associated Hypomania: Navigating Clinical Challenges. Available from:
11. Belli H, Ural C, Akbudak M. Borderline Personality Disorder: Bipolarity, Mood Stabilizers and Atypical Antipsychotics in Treatment. J Clin Med Res. 2012;4(5):301-308. Available from: 10.4021/jocmr1042w

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