Long-chain omega-3 fatty acids, because of their role of stabilization of neuronal membranes, have been used in the treatment of various psychiatric disorders, including schizophrenia and unipolar and bipolar depression. The available data suggest that clinical conditions marked by high levels of impulsivity, hostility and aggression may get some benefit from these therapeutic agents. Two recent RCTs reported the efficacy of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) versus placebo in improving the psychopathology of patients with borderline personality disorder (BPD) and self-harm conducts. The aim of the present study is to assess the efficacy and tolerability of omega-3 fatty acids in combination with valproic acid in a group of BPD patients.
Materials and methods
We recruited 43 consecutive outpatients with a diagnosis of BPD (DSM-IV-TR). Patients with lifetime comorbidity with dementia, delirium and other cognitive disorders, schizophrenia and other psychotic disorders or bipolar disorder were excluded. Co-occurring Axis I or II disorders and recent substance abuse were also excluded. Patients were randomly assigned to one of two treatments for 12 weeks: (1) valproic acid (800- 1300 mg/day) (plasma range: 50-100 μg/ml), (2) EPA (1.2 g/ day) and DHA (0.6 g/day) in combination with valproic acid. Duration of study was 12 weeks. We assessed patients at baseline (T0), 4 weeks (T1) and 12 weeks (T2) with the following scales: the Clinical Global Impression Scale, Severity item (CGIS), Hamilton Rating Scales For Depression and Anxiety (HAMD, HAM-A); Social Occupational Functioning Assessment Scale (SOFAS), BPD Severity Index (BPDSI) for the severity of BPD related symptoms, Barratt Impulsiveness Scale version 11 (BIS- 11); Modified Overt Aggression Scale (MOAS), and Self Harm Inventory (SHI) for self-injurious behaviours. Adverse effects were evaluated after 4 and 12 weeks of treatment with the Dosage Record and Treatment Emergent Symptom Scale (DOTES). Statistical analysis was performed using the univariate General Linear Model with 2 factors: duration and type of treatment.
Statistical analysis was conducted on the 34 completers (M:F = 8:26, age ± DS: 25.2 ± 6.4 years). Nine drop-outs (20.9%) occurred in the first 4 weeks of therapy. Changes in the CGI-S, SOFAS, and HAM-A scores did not differ between treatments. The time factor and interaction between time and treatment factors both had a significant effect on the HAM-D score (respectively, p = 0.0005; p = 0.024) and on the item affective instability of the BPDSI (p = 0.0005; p = 0.0005). The time (p = 0.002) and treatment factor (p = 0.005) both had a significant effect on the SHI score. Significant effects on the BIS-11 score, BPDSI total score and the items ‘impulsivity’ and ‘outbursts of anger’ were found for the time factor (respectively, p = 0.0005; p = 0.0005; p = 0.0005; p = 0.0005), treatment factor (respectively, p = 0.003; p = 0.023; p = 0.012; p = 0.0005) and interaction between time and treatment factors (respectively, p = 0.010; p = 0.009; p = 0.0005; p = 0.003). The side effects reported in two patients receiving combined therapy with fatty acids were moderate in severity (dyspepsia).
Valproate monotherapy and the 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 monotherapy in reducing the severity of several BPD symptoms, such as self-rated and clinician rated impulsivity, outbursts of anger and self-mutilating conducts. The difference between treatments on depressive symptoms and mood instability was not significant at the 12 week evaluation, but increases with continued therapy.