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New Biological Treatments for Borderline Personality Disorder

Can medicines treat the BPD syndrome, or can they only treat single symptoms?

Key points

  • Medicines affecting glutamate, rather than the usual neurotransmitters, are being studied to treat Borderline Personality Disorder (BPD).
  • The "love hormone," oxytocin, may improve BPD relationships.
  • Assessing BPD as a specific diagnosis, or as a collection of related symptoms, is an open question.

Twenty years ago, the American Psychiatric Association published Practice Guidelines for the Treatment of Borderline Personality Disorder (BPD). This consensus document affirmed the position that psychotherapy is the primary treatment consideration for BPD. Over the ensuing 20 years, this view has not changed. Focus for treatment during these years has been on developing new therapy approaches specifically designed to address this disorder. Several specialized treatment methods—Dialectical Behavioral Therapy, Mentalization Based Therapy, Transference Focused Therapy, Good Psychiatric Management (a specific program with a title that should actually be appropriate for all psychiatric treatment!), and others—have demonstrated value in improving symptoms of BPD.

Medications have played a peripheral role in treatment. BPD patients usually present with accompanying diagnoses. Concurrent Major Depressive Disorder or Generalized Anxiety Disorder may be appropriately treated with medicines. Studies have demonstrated that some specific symptoms of BPD may respond to medications. Mood instability has responded to certain antidepressants and antipsychotic medicines. Uncontrolled impulsivity has also responded to those drugs and to certain anticonvulsant medicines. Opiate blockers have shown some efficacy for treating self-mutilating behavior. No drug, however, has been approved for the specific treatment of BPD. That hasn’t discouraged pharmaceutical companies from trial investigations seeking indications for treating the BPD diagnosis. Most of these have involved antipsychotic medications. However, no studies have achieved a threshold for FDA approval.

The classes of drugs studied for treating BPD have focused mostly on specific neurotransmitters that enable pathways between various parts of the brain. Research on these chemical messengers have focused primarily on serotonin, norepinephrine, and dopamine, which are thought to affect mood changes, impulsivity, and cognition. Recent attention has turned to a different neurotransmitter, glutamate.

Preliminary studies on substances that impact glutamate include N-acetylcysteine (for the treatment of respiratory diseases and Tylenol overdose), dextromethorphan (cough suppressant), riluzole (Rilutek® for the treatment of amyotrophic lateral sclerosis). These showed some promise in treating self-harming behavior or mood. A more recent, small study investigated memantine (Namenda® for the treatment of Alzheimer’s Disease).1 This study compared memantine to placebo using the ZAN-BPD scoring system, which measured change in the general severity of the BPD diagnosis, rather than on a single symptom. After two weeks, the treated patients exhibited significant reductions in total symptoms measured by the ZAN-BPD.

Another recent avenue of research has investigated oxytocin. This hormone facilitates uterine contractions during childbirth and milk production for nursing. Oxytocin, sometimes referred to as the “love hormone,” is thought to increase maternal bonding to the newborn and general social interactions including empathy and warm feelings for others. Past studies have suggested that women with BPD have lower levels of oxytocin.

In one recent study,2 a group of BPD women was compared to a control cohort. Utilizing self-report scales, BPD patients reported lower levels of empathy measures than healthy women. Compared to BPD women who received placebo, BPD patients who received intranasal oxytocin expressed significant improvement in some empathy measures and motivation for social interaction that equaled levels of healthy controls.

A confounding issue in considering biological treatment of BPD is whether BPD can be considered a single syndrome or merely a collection of symptoms that frequently occur together. Pneumococcal pneumonia, in contrast, is a bacterial disease with identifiable etiology that dictates treatment of the pneumococcus germ with a specific antibiotic. We have yet to identify a borderlineococcus pathogen. Perhaps biological therapy will continue for the foreseeable future to focus on treating individual symptoms. In any event, continued research will search for more treatment options for this challenging illness.


1. Kulkarni J, Thomas N, Hudaib AR, et al. Effect of the glutamate NMDA receptor antagonist memantine as adjunctive treatment in borderline personality disorder: an exploratory, randomised, double-blind, placebo-controlled trial. CNS Drugs. 2018;32(2):179-187. doi: 10.1007/s40263-018-0506-8

2. Domes G, Ower N, von Dawans B, et al. Effects of intranasal oxytocin administration on empathy and approach motivation in women with borderline personality disorder: a randomized controlled trial. Transl Psychiatry. 2019;9(1):328. doi: 10.1038/s41398-019-0658-4

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