Borderline personality disorder: 6 studies of biological interventions

Study design

• In a double-blind, sham-controlled trial, adults who met DSM-IV-TR criteria for BPD were randomized to 3 weeks (15 sessions) of right anodal/left cathodal DLPFC tCDS (n = 15) or sham tDCS (n = 15). This study included patients with comorbid psychiatric disorders, including substance use disorders. Discontinuation or alteration of existing medications was not allowed.
• The presence, severity, and change over time of BPD core symptoms was assessed at baseline and after 3 weeks using several clinical scales, self-questionnaires, and neuropsychological tests, including the Barratt Impulsiveness Scale-11 (BIS-11), Buss-Perry Aggression Questionnaire (BP-AQ), Difficulties in Emotion Regulation Scale (DERS), Hamilton Depression Rating Scale (HAM-D), Beck Depression Inventory (BDI), Hamilton Anxiety Rating Scale (HAM-A), Irritability-Depression Anxiety Scale (IDA), Visual Analog Scales (VAS), and Iowa Gambling Task.

Outcomes

• Participants in the active tDCS group experienced significant reductions in impulsivity, aggression, and craving as measured by the BIS-11, BP-AQ, and VAS.
• Compared to the sham group, the active tDCS group had greater reductions in HAM-D and BDI scores.
• HAM-A and IDA scores were improved in both groups, although the active tDCS group showed greater reductions in IDA scores compared with the sham group.
• As measured by DERS, active tDCS did not improve affective dysregulation more than sham tDCS.

Conclusions/limitations

• Bilateral tDCS targeting the right DLPFC with anodal stimulation is a safe, well-tolerated technique that may modulate core dimensions of BPD, including impulsivity, aggression, and craving.
• Excitatory anodal stimulation of the right DLFPC coupled with inhibitory cathodal stimulation on the left DLPFC may be an effective montage for targeting impulsivity in patients with BPD.
• Study limitations include a small sample size, use of targeted questionnaires only, inclusion of patients with BPD who also had certain comorbid psychiatric disorders, lack of analysis of the contributions of medications, lack of functional neuroimaging, and lack of a follow-up phase.

2. Molavi P, Aziziaram S, Basharpoor S, et al. Repeated transcranial direct current stimulation of dorsolateral-prefrontal cortex improves executive functions, cognitive reappraisal emotion regulation, and control over emotional processing in borderline personality disorder: a randomized, sham-controlled, parallel-group study. J Affect Disord. 2020;274:93-102. doi: 10.1016/j.jad.2020.05.007

Emotional dysregulation is considered a core feature of BPD psychopathology and is closely associated with executive dysfunction and cognitive control. Manifestations of executive dysfunction include aggressiveness, impulsive decision-making, disinhibition, and self-destructive behaviors. Neuroimaging of patients with BPD has shown enhanced activity in the insula, posterior cingulate cortex, and amygdala, with reduced activity in the medial PFC, subgenual anterior cingulate cortex, and DLPFC. Molavi et al⁴ postulated that increasing DLPFC activation with left anodal tDCS would result in improved executive functioning and emotion dysregulation in patients with BPD.

Study design

• In this single-blind, sham-controlled, parallel-group study, adults who met DSM-5 criteria for BPD were randomized to receive 10 consecutive daily sessions of left anodal/right cathodal DLPFC tDCS (n = 16) or sham tDCS (n = 16).
• The effect of tDCS on executive dysfunction, emotion dysregulation, and emotional processing was measured using the Executive Skills Questionnaire for Adults (ESQ), Emotion Regulation Questionnaire (ERQ), and Emotional Processing Scale (EPS). Measurements occurred at baseline and after 10 sessions of active or sham tDCS.

Outcomes

• Participants who received active tDCS experienced significant improvements in ESQ overall score and most of the executive function domains measured by the ESQ.
• Those in the active tDCS group also experienced significant improvement in emotion regulation as measured by the cognitive reappraisal subscale (but not the expressive suppression subscale) of the ERQ after the intervention.
• Overall emotional processing as measured by the EPS was significantly improved in the active tDCS group following the intervention.

Conclusions/limitations

• Repeated bilateral left anodal/right cathodal tDCS stimulation of the DLPFC significantly improved executive functioning and aspects of emotion regulation and emotional processing in patients with BPD. This improvement was presumed to be the result of increased activity of left DLPFC.
• Study limitations include a single-blind design, lack of follow-up to assess durability and stability of response over time, reliance on self-report measures, lack of functional neuroimaging, and limited focality of tDCS.

3. Crawford MJ, Sanatinia R, Barrett B, et al; LABILE study team. The clinical effectiveness and cost-effectiveness of lamotrigine in borderline personality disorder: a randomized placebo-controlled trial. Am J Psychiatry. 2018;175(8):756-764. doi: 10.1176/appi.ajp.2018.17091006

One of the hallmark symptoms of BPD is mood dysregulation. Current treatment guidelines recommend the use of mood stabilizers for BPD despite limited quality evidence of effectiveness and a lack of FDA-approved medications with this indication. In this RCT, Crawford et al⁵ examined whether lamotrigine is a clinically effective and cost-effective treatment for people with BPD.

Continue to: Study design...