The Current State of BPD Pharmacotherapy
For decades, the cornerstone of treatment for Borderline Personality Disorder has been psychotherapy, with Dialectical Behavior Therapy (DBT) considered the gold standard. While medications are widely used to manage specific symptoms or co-occurring conditions, none have received official FDA approval for BPD itself. This landscape is, however, slowly evolving with new clinical research and repurposed drugs offering hope for improved symptom management.
The Promising Phase III Candidate: Vafidemstat
One of the most significant recent developments is the progress of vafidemstat, an experimental drug developed by Oryzon Genomics. In March 2025, Oryzon announced its plans to proceed with a Phase III clinical trial (PORTICO-2) for the treatment of agitation and aggression in BPD. This follows positive results from the earlier Phase IIb PORTICO trial.
Vafidemstat's mechanism of action involves inhibiting Lysine Specific Demethylase 1 (LSD1), an enzyme that regulates gene expression. By modulating specific neural pathways, the drug is intended to reduce symptoms related to aggression and agitation, which are central to the BPD experience. If successful, vafidemstat could be the first medication ever approved specifically for a core symptom cluster of BPD, marking a major milestone in pharmacological treatment for the disorder.
Repurposing Existing Medications for BPD Symptoms
In addition to new drug candidates, researchers are exploring novel uses for existing medications. Ketamine, a well-known anesthetic and antidepressant, has shown potential in alleviating BPD symptoms.
- Ketamine: A study from September 2025 reported in Psychiatry Research showed that ketamine infusions may help reduce the severity of BPD symptoms, particularly in patients with co-occurring treatment-resistant depression. By acting as an NMDA receptor antagonist, ketamine modulates glutamate neurotransmission, which may improve mood regulation and reduce suicidality.
- Memantine: Another repurposed drug, memantine, an Alzheimer's medication, is currently being trialed for BPD. Like ketamine, memantine targets the glutamate system to address the cognitive disturbances underlying BPD symptoms. Preliminary findings from an Australian trial have shown a reduction in emotional reactivity and self-harming behaviors.
Continued Role of Off-Label Medications
Pending the development of specific BPD drugs, clinicians continue to prescribe off-label medications to target specific symptoms. The goal is to provide symptomatic relief and manage comorbidities like depression, anxiety, and impulsive behavior. It is important to note that a doctor must weigh the potential benefits against the risks and side effects of these medications.
Commonly used off-label medications include:
- Mood Stabilizers/Anticonvulsants: These are used to manage emotional instability, impulsivity, and anger.
- Examples include lamotrigine (Lamictal), valproate (Depakote), and topiramate (Topamax).
- Antipsychotics: Atypical antipsychotics are often used to reduce impulsivity, hostility, aggression, and transient psychotic-like symptoms.
- Examples include aripiprazole (Abilify), olanzapine (Zyprexa), and quetiapine (Seroquel).
- Antidepressants: Primarily used to treat co-occurring depression and anxiety, their effectiveness on core BPD symptoms is limited.
- Examples include SSRIs like fluoxetine (Prozac) and sertraline (Zoloft).
- Anxiolytics (Anti-Anxiety): Short-term use of benzodiazepines like lorazepam (Ativan) is sometimes considered for crisis management but is generally avoided due to the high potential for dependence and risk of disinhibition.
The Importance of a Multimodal Treatment Approach
Ultimately, medication is most effective when integrated into a comprehensive treatment plan that prioritizes psychotherapy. This multimodal approach provides the best chance for sustained improvement in emotional regulation, interpersonal skills, and overall quality of life.
Comparison of Investigational and Off-Label BPD Medications
| Feature | Vafidemstat (Investigational) | Ketamine (Repurposed) | Standard Off-Label Medications (e.g., SSRIs, Antipsychotics, Mood Stabilizers) |
|---|---|---|---|
| Approval Status | In Phase III Clinical Trials for BPD | Not approved for BPD; FDA-approved for other conditions (e.g., depression) | Not approved for BPD; FDA-approved for other conditions (e.g., depression, bipolar disorder, psychosis) |
| Mechanism | LSD1 inhibitor, regulates gene expression | NMDA receptor antagonist, modulates glutamate neurotransmission | Varies widely; alters neurotransmitter systems like serotonin, dopamine, etc. |
| Primary Target Symptoms | Aggression and agitation | Depression, mood dysregulation, suicidality | Co-occurring depression, anxiety, mood instability, impulsivity, transient psychosis |
| Primary Treatment Role | Potential first-in-class targeted treatment for specific BPD symptoms | Investigational rapid-acting treatment for mood/suicidality, typically in severe cases | Symptom management for comorbidities; adjunctive to psychotherapy |
| Administration | Oral | Intravenous infusion or nasal spray | Oral |
Conclusion
While the quest for what is the new drug for borderline personality disorder continues, the field is showing encouraging signs of progress. The most significant development is Oryzon's vafidemstat, a Phase III drug specifically targeting aggression and agitation. Alongside this, repurposed drugs like ketamine and memantine are undergoing research for their potential benefits. Until a specific medication is approved, the standard of care remains a holistic approach combining specialized psychotherapy, such as DBT, with the cautious, individualized use of off-label medications to manage symptoms and comorbidities effectively. This combined strategy offers patients the best path forward, leveraging both therapeutic skills and pharmacological support to build a more stable and fulfilling life.
How to Stay Informed
For the latest information on clinical trials and updates regarding new drug developments for BPD, you can consult reliable sources such as the National Institutes of Health (NIH) Clinical Trials database at clinicaltrials.gov. This resource provides information on ongoing research studies, including eligibility and locations.
