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Day # 137: Medications for Borderline Personality Disorder

Today we will continue our current theme of cluster B personality disorders as we discuss pharmacological options for borderline personality disorder.

  • See day #135 (BPD part 1) for a full discussion on the diagnostic criteria, epidemiology, pathogenesis, and clinical pearls for BPD.

  • See day #136 (BPD part 2) for a full discussion on psychotherapy for borderline personality disorder.


  • The first-line treatment for borderline personality disorder (BPD) is psychotherapy. There are a number of specific therapies that have been shown to reduce the core symptoms of BPD as well as comorbid symptoms.

  • Adjunctive use of pharmacotherapy for comorbidities, targeted symptoms, and periods of acute decompensation may also be useful.


General Principles 3, 4

  • There are no FDA-approved medications for the treatment of borderline personality disorder, however medications are commonly used. A recent survey found that >90% of patients with BPD had been prescribed psychotropic medication, most commonly antidepressants or antipsychotics.

  • The evidence base for pharmacological treatment of BPD is limited but demonstrates a modest effect. Existing studies are limited due to relatively small sample sizes, high rates of placebo response, and brief trial durations. In spite of this, pharmacotherapy has been shown to be more useful in BPD than in any other personality disorder.

  • There is very limited data for any single medication improving overall BPD severity and this has led to symptom-based approaches, often resulting in unnecessary polypharmacy despite little benefit.

  • Pharmacological treatment should be considered as an adjunct to high quality therapy in order to target distressing symptoms, and provide support during periods of acute decompensation. Commonly targeted symptoms include mood instability, transient stress-related psychotic symptoms, impulsivity, and suicidal and self-harming behavior.

  • Pharmacological treatment should also be considered to treat comorbidities since mood disorders, anxiety disorders, PTSD, ADHD, eating disorders, and substance use disorders are all more common in BPD than in the general clinical population.

  • Other important principles include: provide early psychoeducation regarding the adjunctive role of medications in the treatment plan; regular re-evaluation of the risks vs benefits of treatment; taper unhelpful medications; minimize polypharmacy; and minimize medications with high lethality / narrow therapeutic index.

Antidepressants 5, 6

  • SSRIs, SNRIs, and other antidepressants are indicated for the treatment of comorbid conditions such as depressive disorders, anxiety disorders, and post-traumatic stress disorder.

  • Antidepressants currently lack strong recommendations in treating any of the core symptoms of BPD. Several open studies have found that antidepressants reduce depressed mood, impulsivity, aggression, and possibly affective lability in patients with BPD, but these findings have not been replicated in randomized controlled trials. Recent systematic reviews have highlighted a limited role for antidepressants in BPD. They may be considered on a case by case basis.

Antipsychotics 5, 6

  • Several open studies have found benefit for a wide range of symptoms in BPD when treated with first (FGA) or second generation antipsychotics (SGA). Randomized controlled trials have also shown modest improvement in a number of symptoms.

  • Symptoms that may respond include affective lability, impulsivity, anger, paranoia, brief psychotic episodes, and interpersonal sensitivity.

  • SGA's are often chosen over FGA's due to lower risks of extrapyramidal symptoms and tardive dyskinesia.

  • There is no clear agent that is superior to others, but olanzapine and aripiprazole may be the most studied among SGA's. Clozapine has been used in severe cases and has shown a reduction in aggression, self-harming behaviors, and reduced hospitalizations.

  • Remember that antipsychotic medications are associated with a wide range of adverse effects and self-discontinuation of medications are common.

Mood Stabilizers 5, 6

  • Up to 50% of patients with borderline PD may also be diagnosed with a bipolar spectrum disorder, particularly rapid-cycling variants, due to overlap of mood lability and impulsivity. Such diagnoses are controversial and associated interpersonal sensitivity and identity disturbances distinguish affective dysregulation in borderline PD.

  • As a class, mood stabilizers / anticonvulsant medications, offer moderate-to-large effects on certain symptom clusters in BPD. There is some evidence for reduction of impulsivity, anger/aggression, affect dysregulation, and overall functioning in people with BPD. Some data suggests a potentially greater effect size when compared with antipsychotic treatment.

  • Carbamazepine: Potential improvement in impulsivity, but inconsistent results in more recent clinical trials with no strong improvement over placebo. Possibly associated with worsening depressive symptoms. Lamotrigine, valproate, and topiramate offer greater therapeutic benefits in treating affective instability and impulsivity in BPD. In one study Oxcarbazepine demonstrated improvements to impulsivity, affective instability, and anger outbursts but data is overall limited.

  • Lamotrigine: Shown to improve impulsivity, anger, and affective instability in some studies. In contrast, a large 12-month randomized controlled trial of lamotrigine for BPD published in 2018 (LABILE) found no evidence that lamotrigine led to overall improvements. Lamotrigine is more suitable for reliable patients due to lengthy titration and given risks of life-threatening rash and toxicity with inconsistent use.

  • Valproate: Appears to be effective in BPD patients with prominent impulsive aggression and interpersonal sensitivity rather than affective instability. Keep in mind that a disproportionate number of patients diagnosed with BPD are young females of childbearing age and valproate has a black box warning for causing neural tube defects such as spina bifida.

  • Topiramate: Trials suggest improvement in a number of symptom clusters in BPD, particularly in anger, interpersonal functioning, anxiety, and self-reported quality of life. May also be used if comorbid binge eating disorder. Adverse cognitive symptoms (reductions in verbal fluency, processing speed, attention, and memory) may interfere with psychotherapy for some patients with BPD.

  • Lithium: Older studies have shown some benefit for BPD particularly for impulsive aggression, intentional self-harm, suicidality, and affective stability. There is limited overall data for use in BPD. Limited by risks associated with noncompliance, toxicity, and frequent monitoring requirements.

Miscellaneous 6

  • Management of crisis: Drug treatments may be considered during periods of acute decompensation. The duration of treatment with sedative agents should be agreed upon with patients but should be no longer than one week. The use of benzodiazepines are strongly discouraged in treating BPD due to risks of disinhibition, worsening impulsivity, and suicidality. Patients with BPD may also be at increased risk for benzodiazepine dependence. Other options include a sedative antihistamine such as hydroxyzine or promethazine, sedative antipsychotics, or alpha agonists such as clonidine.

  • Naltrexone: Limited evidence demonstrates reduction of self-harm and dissociative symptoms. May also improve impulsivity and interpersonal functioning. Overall there is mixed evidence with some studies failing to demonstrate significant improvement.

  • Propranolol or Clonidine: Sometimes used to target symptoms of hypervigilance, aggression, anxiety, or insomnia. Has proved effective in treating comorbid post-traumatic stress disorder (PTSD) and BPD, but this seemed more specific to PTSD symptoms.

  • Oxytocin: Oxytocin is associated with empathic processing and affiliative bonding and this has led to considerations for treating interpersonal dysfunction in BPD. There is no demonstrated benefit so far in clinical trials and further research is required before advising clinical use in BPD.

  • Omega-3 fatty acids: One trial showed some improvement to aggression and affective symptoms.


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