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Clinical considerations for evidence-based treatment of borderline personality disorder (BPD) are outlined in the context of the best available evidence, discussed with reference to BPD traits currently identified in the upcoming Diagnostic and Statistical Manual of Mental Disorders – 5 (DSM-5) revision. The DSM-5 will highlight refractory affective, interpersonal, and identity symptoms in BPD as potential treatment targets. In addition to providing a framework for clinical decision-making, future research strategies will also focus on neurotransmitter systems of greater relevance to understanding overall personality functioning.Although only a few randomized controlled trials of psychopharmacological treatments for BPD have been published recently, several meta-analyses and systematic reviews converge on the consensus effectiveness of lamotrigine, topiramate, valproate, aripiprazole, olanzapine, and omega-3 fatty acid supplementation. Stronger evidence exists for treating disinhibition and antagonism than negative affectivity, particularly interpersonal facets of such traits. In addition, basic research suggests a future role for modifying glutamatergic, opioid, and oxytocinergic neurotransmitter systems to treat BPD.Clinicians should utilize omega-3, anticonvulsants, and atypical antipsychotic agents in treating specific DSM-5 BPD traits, notably disinhibition, antagonism, and some aspects of negative affectivity. Future research will focus on normalizing opioid and oxytocin dysregulation, as an adjunct to evidence-based psychotherapy, in an effort to improve interpersonal functioning.