A pilot randomized controlled trial of ketamine in Borderline Personality Disorder

Abstract

This study is the first randomized controlled trial to test the effects of ketamine in Borderline Personality Disorder (BPD). BPD remains undertreated in the community and no medication has FDA approval for this indication. People with BPD experience chronic mood disturbances with depressed mood, suicidal ideation, and severe social difficulties. In this double-blind, randomized controlled pilot study, we tested the effects of one infusion of ketamine (0.5 mg/kg, n = 10) or the psychoactive comparator drug midazolam (0.04 mg/kg, n = 12) in adults with BPD. Infusions were well tolerated in both groups. Dissociative symptoms during infusion were more intense with ketamine than midazolam (t(12.3) = 3.61, p = 0.01), but they resolved by 40 min after infusion in both groups. Post-infusion adverse events were at the expected low levels in both groups. For our primary outcome measure of suicidal ideation and our secondary outcome measure of depression, we found numerical reduction but not significant group or group x timepoint difference (p > 0.05). For our secondary outcome measures of anxiety and BPD symptoms, we did not observe group or group x timepoint differences. There was a group x timepoint effect for socio-occupational functioning (F(1,20.12) = 5.16, p = 0.03, at Day 14, ketamine group showed more improvement than midazolam group). An exploratory analysis revealed that improvement in socio-occupational functioning was correlated with improvement in depression in the ketamine group (r(8) = 0.65, p = 0.04) but not midazolam group (r(9) = 0.41, p = 0.216). This pilot study provides the first randomized controlled evidence of the effects of antidepressant-dosed ketamine in people with BPD. Our results provide reason for optimism that antidepressant-dosed ketamine will be well-tolerated in larger studies and may provide clinical benefit for mood symptoms and related impairments in people with BPD.

Fig. 1. Consort diagram.

Participants were assessed for eligibility through phone screens and baseline procedures, resulting in 22 participants being randomized (12 received midazolam and 10 received ketamine).

Fig. 2. Intra-infusion changes in dissociation.

Intra-infusion dissociative symptoms were transient in both groups (A) and did not correlate with peak change in depressive symptoms (B). Ketamine-group participants with history of dissociative symptoms experienced more intense but not more prolonged dissociative experiences during the infusion (C CADSS total score) or positive symptoms of psychosis (D BPRS positive symptom scale). For A, C, and D, error bars represent standard error of the mean. For B, shaded regions represent 95% confidence intervals. Abbreviations: Clinician-Administered Dissociative States Scale (CADSS), minutes (min), Beck Depression Inventory (BDI), Day 3 timepoint (D3), Brief Psychiatric Rating Scale Positive Symptom subscale (BPRS Positive Sx).

Fig. 3. Change in clinical symptoms and socio-occupational functioning.

Change from baseline in suicidal ideation (BSS score), A depression (BDI score), B anxiety (BAI score), C BPD symptoms (ZAN-BPD-SRV), D, and socio-occupational functioning (SAS-SR score, E) from before (BL) to each timepoint after infusion. Error bars represent standard error of the mean. In F, we show correlation between socio-occupational functioning at Day 14 (when group difference was observed) and depression score. Shaded areas represent 95% confidence intervals. For all panels, solid black lines with solid dots indicate ketamine group results, and dashed line with open triangles indicate midazolam group results. Abbreviations: Beck Scale for Suicide Ideation (BSS), Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), Zanarini Scale for Borderline Personality Disorder Self Report Version (ZAN_BPD_SRV), Borderline Personality Disorder (BPD), Social Adjustment Scale–Self Report (SAS-SR), Baseline (BL), 1 h (1HR), Day 1 (D1), Day 3 (D3), Day 7 (D7), Day 14 (D14), Day 28 (D28).