Efficacy of omega-3 fatty acids in the treatment of borderline personality disorder: a study of association with valproic acid

Purpose of the study: Omega-3 fatty acids have received increasing interest for their stabilizing effects on plasmatic membranes and cell signalling. In recent years, a growing number of clinical trials on omega-3 fatty acids, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have got promising results supporting their use in several psychiatric disorders, in particular mood disorders and other syndromes characterized by impulsivity, hostility, and aggression. As disturbances in regulation of mood and impulse behaviors are core features of borderline personality disorder, omega-3 fatty acids may represent a potential tool for the treatment of this clinical population. Data concerning the use of these agents in BPD patients are still sparse. Only two trials [1] and [2] have tested the effects of (EPA) and (DHA) in patients with BPD. In order to further investigate the role of omega-3 fatty acids in the therapy of BPD, the present study is aimed to assess the efficacy and tolerability of EPA and DHA in association with the mood stabilizer valproic acid. Methods: 43 outpatients who received a DSM-IV-TR diagnosis of BPD were recruited. Patients were randomly assigned to one of two treatment arms for 12 weeks: (1) valproic acid (at a dose corresponding to a plasma level of 50-100 µg/ml); (2) EPA (1.2 g/day) and DHA (0.8 g/day) in combination with the same dose of valproic acid. Patients were evaluated at baseline and after 12 weeks with: CGI – Severity Item, HAM-D, HAM-A, SOFAS, BPDSI for BPD related symptoms, BIS-11 for impulsivity, MOAS for aggressiveness, SHI for self-injuries, and DOTES for adverse effects. Statistical analysis was performed on each rating scale with the univariate General Linear Model with two factors: duration and type of treatment. Results: statistical analysis was conducted on the 34 completers. Changes of CGI-S, SOFAS, and HAM-A scores did not differ between treatments. The time factor and the interaction between time and treatment factors had both a significant effect on the HAM-D score and on the item affective instability of the BPDSI. The time and the treatment factors had both a significant effect on the SHI score. Significant effects on the BIS-11 score, the BPDSI total score, and the items ‘impulsivity’ and ‘outbursts of anger’ were found for the time factor, the treatment factor and the interaction between time and treatment factors. Conclusions: valproate monotherapy and combination of valproate and omega-3 fatty acids can both be proposed as useful therapeutic options for the treatment of BPD: they have a similar efficacy on global symptoms, anxiety, and socio-relational functioning. However, combined therapy with fatty acids and valproate is more effective than valproate alone in reducing severity of several BPD symptoms, such as impulsivity, outbursts of anger, and self-mutilating conducts. The difference between treatments on depressive symptoms and mood instability is not significant at 12 weeks, but increases with the length of therapy. Adverse effects were mild to moderate dyspepsia, nausea, and weight gain. References: [1] Zanarini MC, Frankenburg FR. Omega-3 Fatty acid treatment of women with borderline personality disorder: a double-blind, placebo-controlled pilot study. Am J Psychiatry 2003;160:167-9. [2] Hallahan B, Hibbeln JR, Davis JM, et al. Omega-3 fatty acid supplementation in patients with recurrent self-harm. Single-centre double-blind randomised controlled trial. Br J Psychiatry 2007;190:118-22.