Efficacy and tolerability of asenapine compared with olanzapine in borderline personality disorder: an open label randomized controlled trial

Background Asenapine is a new second generation antipsychotic, that is understudied in borderline personality disorder (BPD). Only one study investigating the use of the drug in this indication (an open-label pilot study) has been conducted to date. Objective The present open label randomised controlled trial aimed to evaluate the efficacy and tolerability of asenapine in comparison with olanzapine, the most broadly studied antispychotic in BPD. Methods 51 outpatients aged between 18 and 50 years, with a diagnosis of BPD based on DSM-5 criteria were assigned for 12 weeks to: (1) asenapine (5-10 mg/day) or (2) olanzapine (5-10 mg/day). Participants were assessed at baseline and after 12 weeks with: Clinical Global Impression Scale, Severity item (CGI-S), Hamilton Depression Rating Scale (HAM-D), Hamilton Anxiety Rating Scale (HAM-A), Social Occupational Functioning Assessment Scale (SOFAS), Borderline Personality Disorder Severity Index (BPDSI), Barratt Impulsiveness Scale, version 11 (BIS-11), Modified Overt Aggression Scale (MOAS), Self Harm Inventory (SHI), and Dosage Record and Treatment Emergent Symptom Scale (DOTES). Analysis of variance repeated measures was performed. Intention to treat analysis with last observation carried forward was conducted. Results Drop-outs were 11 (21.57%): six patients taking asenapine and five patients receiving olanzapine. Two patients who received asenapine stopped the drug, one due to oral hypoesthesia and the other due to moderate anxiety. Two patients receiving olanzapine discontinued the treatment for a significant weight gain ( ≥ 3 Kg). The remaining seven drop-outs resulted from the lack of compliance with the trial prescription. Forty out of the 51 patients (78%) completed the trial: 19 patients received asenapine, while 21 patients received olanzapine.We found a significant within- subjects effect (trial duration) for all rating scales, except from the HAM-D, the MOAS, and two items of the BPDSI: namely, “identity disturbance” and “parasuicidal behaviors”. A significant effect between subjects was found for the two items of the BPDSI: “affective instability” and “dissociation/paranoid ideation”. Asenapine was found superior to olanzapine in reducing the affective instability score (P = 0.001), whereas olanzapine was found superior to asenapine in reducing dissociation/paranoid ideation (P = 0.012). However, the study was found to be underpowered to detect a difference between the drugs on the dissociation/paranoid ideation item of the BPDSI. Two patients receiving asenapine experienced akathisia and another two restlessness/anxiety, while three patients receiving olanzapine reported somnolence and two fatigue. Conclusions Asenapine and olanzapine were demonstrated to have a similar efficacy. While asenapine was found to be more efficacious than olanzapine in treating affective instability, olanzapine was superior to asenapine in treating paranoid ideation and dissociation. However, the study was underpowered to detect a difference between groups on the dissociation/paranoid ideation item. Both medications were well tolerated, with asenapine being related to a higher frequency of oral hypoaestesia and akathisia, and olanzapine being prone to induce weight gain. The open label study design, lack of a placebo group, and small sample size constituted major limitations of this trial. Our findings require to be replicated in further studies. The trial was registered in the Australian New Zealand Clinical Trials Registry (code: ACTRN12614000551695).