Intravenous and intranasal ketamine for borderline personality disorder to treat comorbid depression, BPD symptoms and suicidality: a systematic review

While psychotherapy is the standard form of treatment for borderline personality disorder (BPD), there are no pharmacological medications approved to treat this condition. Many individuals with BPD also experience depression and suicidal ideation, highlighting the need for effective interventions. One potential treatment option is ketamine, some formulations of which have already been approved for treating treatment-resistant depression and severe suicidal ideation. We conducted a systematic review examining the safety and potential benefits of intravenous and intranasal racemic ketamine in adults formally diagnosed with BPD or with elevated borderline features. The primary outcomes were depression, BPD symptoms, and suicidality, while the secondary outcome was the adverse effects of ketamine treatment. We searched MEDLINE, Embase, and CENTRAL for relevant studies published up to February 2026. Five studies met the inclusion criteria, consisting of two randomized controlled trials (RCTs) and three cohort studies. Four studies evaluated intravenous ketamine, while one evaluated intranasal racemic ketamine. Across four studies, 81 participants identified as having BPD received ketamine; one additional study included 31 ketamine-treated participants with elevated borderline features without a confirmed BPD diagnosis. The studies differed substantially in design, method of BPD ascertainment, ketamine protocol, comparator, and outcome measurement. Across the studies, ketamine appeared to be generally well tolerated over short follow-up in supervised settings, although transient side effects, including dissociation, were reported. Several studies reported reductions in depressive symptoms or suicidal ideation following treatment; however, most were not designed or adequately powered to evaluate efficacy specifically in BPD. Comparative findings were inconsistent and did not establish equivalent treatment response between participants with and without borderline pathology. Evidence regarding improvement in BPD symptoms was sparse. The current evidence is insufficient to determine whether ketamine has a clinically meaningful role in treating depression, BPD symptoms, and suicidality in patients with BPD, but further study appears warranted. The available findings are limited by small samples, heterogeneous populations and treatment protocols, exploratory or retrospective analyses, and short follow-up periods. Ketamine treatment specifically targeting BPD should therefore be considered investigational. Adequately powered, BPD-specific randomized trials with standardized outcomes and longer follow-up are required before conclusions regarding efficacy, safety, or clinical implementation can be made.