PSILOCYBIN-ASSISTED PSYCHOTHERAPY FOR CLUSTER B PERSONALITY DISORDERS AND COMORBID TREATMENT-RESISTANT DEPRESSION

Introduction

Cluster B personality disorders (PDs) are highly comorbid with both major depressive disorder (MDD) and bipolar disorder (BD). An estimated 20% of individuals with MDD and 30% of people with BD (I and II) meet criteria for a concurrent cluster B PD diagnosis. This large subset of individuals with comorbid cluster B PDs and mood disorders (MDD or BD) have a substantially elevated likelihood of suicidal behaviour, which is mediated by the greater length of time spent in a depressive episode compared to those without a PD diagnosis. This suggests that treating depression symptoms in those with concurrent cluster B PD can be critical for reducing lifetime suicide risk. Despite the high rates of comorbidity with depression and association with suicide attempts, individuals with Cluster B PDs and co-occurring depression experience attenuated antidepressant response - in particular, the presence of a comorbid cluster B PD diagnosis is associated with more than double the likelihood of non-response to depression treatments compared to depression alone, inclusive of pharmacological, psychological, and neurostimulation interventions. While psilocybin-assisted psychotherapy (PAP) has shown promise for rapidly reducing depressive symptoms in treatment-resistant depression, no clinical trials to date have reported on PAP in comorbid depression and personality disorders. In fact, individuals with PDs have historically been excluded from most PAP trials.

Method

This study is the first clinical trial to describe a subgroup of ten participants with a comorbid PD and depression (MDD or BD) who underwent PAP within a larger open-label trial and followed for six months. Participants were eligible for up to three doses of psilocybin-assisted psychotherapy during this six-month period. Depression and suicidal ideation (SI) were measured using the Montgomery–Åsberg Depression Rating Scale (MADRS) and MADRS SI item. Quality of life was measured using the WHO-5. Dissociation during and after dosing was measured using the Clinician Administered Dissociative States Scale.

Results

Three participants received one dose, five received two doses, and two participants received three doses of psilocybin accompanied by the psychotherapy protocol (preparatory sessions, monitored dosing sessions, and integration sessions). Mean MADRS scores decreased from 30.4 (SD = 6.1) pre-treatment to 22.5 (SD = 11.7) at day one, 24.9 (SD = 10.9) at week 2, and 22.3 (SD = 11.5) at month 6. SI declined from 3.2 (SD = 1.7) to 1.6 (SD = 2.1) at day one, 2.3 (SD = 2.0) at week 2, and 1.2 (SD = 2.04) at month 6. WHO-5 scores improved from 11.2 (SD = 10.12) pre-treatment to 18.5 (SD = 13.61) at day one, 26.67 (SD = 28.47) at week 2, and 21.71 (SD = 18.45) at month 6. Average dissociation scores decreased post-dosing (peak: M = 13.89, SD = 3.98; post-dosing M = 5.95, SD = 4.85). No serious adverse events were recorded.

Significance

This is the first clinical trial evidence that PAP may reduce depression and SI in comorbid cluster B PDs. However, there was substantial heterogeneity within the sample and outcomes. Further study is merited regarding the inclusion of adults with comorbid personality disorders in clinical trials of psilocybin-assisted psychotherapy.