Paliperidone in the treatment of borderline personality disorder: a pilot study of efficacy and tolerability

Antipsychotics are widely used in clinical practice for treating borderline personality disorder (BPD) related symptoms. Although this use has not been approved by the FDA, APA guidelines recommend the use of atypical antipsychotics, primarily for their effects on cognitive perceptual disturbances, such as transient psychotic or dissociative symptoms, but also for their efficacy in reducing affective symptoms (mood instability, anxiety, anger). Atypical antipsychotics promise to be superior to traditional neuroleptics, probably due to their dual mechanism of action, involving both serotonergic and dopaminergic dysfunctions that have been related to borderline phenomena. Newer antipsychotics are also associated with fewer extrapyramidal side effects and with a lower risk of tardive dyskinesia than traditional neuroleptics. Two preliminary studies supported a good efficacy of risperidone on a large spectrum of BPD psychopathology, particularly on affective instability, aggressiveness and hostility, and psychotic-like symptoms. Paliperidone is the active metabolite of risperidone (9-hydroxyrisperidone) and has a similar profile of action (a greater affinity for 5-HT2A blockade relative to D2 blockade and a low affinity for muscarinic receptors resulting in absence of anticholinergic side effects). Paliperidone ER is the first atypical antipsychotic with an extended release, which is achieved by the osmotic-controlled release oral delivery system. This mechanism offers several advantages: a stable plasmatic level allows to avoid initial dosage adjustment and reduces antidopaminergic effects. The aim of the present study is to investigate efficacy and safety of paliperidone in patients with BPD. Eight consecutive outpatients with a DSM-IV-TR diagnosis of BPD were treated for 12 weeks with paliperidone ER 3-6 mg/die. Patients fulfilled a series of exclusion criteria. Criteria for exclusion were lifetime diagnosis of dementia or other cognitive disorders, schizophrenia or other psychotic disorders, and/or bipolar disorders; a co-occurring major depressive episode and/or substance abuse disorder in the last six months. Current use of psychotropic medications, and/or psychotherapy in the three months before recruitment were also excluded. Female patients in childbearing use were excluded if they were not using adequate birth control methods. Assessments were done at baseline, week 4 and week 12, using the Clinical Global Impression-Severity (CGI-S), the Brief Psychiatric Rating Scale (BPRS), the Hamilton Scales for Depression and Anxiety (HDR-S, HAR-S), the Social Occupational Functioning Assessment Scales (SOFAS), and the BPD Severity Index (BPDSI). Adverse events were evaluated with the Dosage Record and Treatment Emergent Symptom Scale. Statistical analysis was performed with the ANOVA for repeated measures. Significant level was p  0.05. Two patients dropped-out: one for non-compliance, one for gastrointestinal adverse effects. Others mild adverse effects were EPS, insomnia and agitation. Significant changes were found for: CGI-S (p = 0.003), BPRS (p = 0.002), BPDSI total scores (p = 0.001) and items “outbursts of anger” (p = 0.0005), “impulsivity” (p = 0.021) and “dissociative symptoms and paranoid ideation” (p = 0.001). Initial results indicate that paliperidone is efficacious in reducing global symptoms and a few core symptoms of BPD and is well tolerated. Further controlled studies on larger samples are required to verify these findings.