Low-Dose Clozapine Versus Aripiprazole in Borderline Personality Disorder

Background: Borderline personality disorder (BLPD) is a complex and debilitating psychiatric condition with high prevalence and clinical and psychosocial burden. Psychotherapy is the recommended first-line treatment but, in real-world clinical practice, most individuals with BLPD are prescribed psychotropic medications, including atypical antipsychotics. The literature suggests that second-generation antipsychotics may exert moderate effects on specific symptoms, but data remain limited and head-to-head comparisons are lacking. This prospective, naturalistic, follow-up study aimed to address this gap by comparing the efficacy and tolerability of low-dose clozapine versus aripiprazole in individuals with BLPD. Methods: Twenty-three patients were treated with either low-dose clozapine (n = 9) or aripiprazole (n = 14) based on clinical indication. Participants were assessed at hospital admission (T0), discharge (T1), and 3-month follow-up (T2) on emotional dysregulation, dissociative experiences, depressive symptoms, impulsivity, and quality of life. Treatment tolerability was evaluated at T1. Results: Significant improvements in dissociation, depression, impulsivity, and quality of life were observed at both T1 and T2, independently of treatment group. Compared to aripiprazole, clozapine was associated with greater reductions in dissociative experiences at hospital discharge and in depressive symptoms at follow-up. Both treatments were safe and well tolerated. Conclusions: Our results suggest that low-dose clozapine is safe and may offer superior benefits for dissociative and depressive symptoms in patients with severe BLPD. Although further research is needed, these findings highlight the role of clozapine as a valuable pharmacological option in BLPD, particularly for patients with high clinical severity and inadequate response to other antipsychotics.