A systematic review: Pharmacological treatment of borderline personality disorder

Abstract

Borderline personality disorder (BPD) is characterised by marked instability of mood, recurrent impulsive acts, a poorly consolidated sense of self, and chronic interpersonal dysfunction. Evidence-based psychotherapies, mainly dialectical behaviour therapy (DBT) and mentalization based treatment (MBT) form the backbone of treatment, yet pharmacological agents are frequently co-prescribed to target affective dysregulation, impulsivity, and aggression. No single agent holds regulatory approval for BPD, and the evidence base underpinning current prescribing is limited and inconsistent. This review consolidates findings from 14 controlled trials conducted between 2011 and 2026, encompassing four pharmacological categories: second-generation antipsychotics, opioid receptor antagonists, mood-stabilising compounds, and a miscellaneous group comprising ketamine, psilocybin, omega-3 fatty acids, inhaled loxapine, oxytocin, and citalopram. Methodological rigor was assessed using the Cochrane Risk of Bias framework. Trial quality was predominantly low to moderate. Brexpiprazole and low-dose quetiapine yielded the most encouraging efficacy signals for core BPD pathology, whereas lamotrigine conferred no detectable benefit in the best-powered trial identified. Opioid antagonists showed preliminary signal for attenuating dissociative symptoms, and investigational agents such as ketamine and psilocybin warrant evaluation in larger, more rigorous studies. Well-powered, prospectively registered trials with harmonised outcome measures are urgently needed.