Adult separation anxiety in treatment nonresponders with anxiety disorders: delineation of the syndrome and exploration of attachment-based psychotherapy and biomarkers.

Clinically significant separation anxiety [SA] has been identified as being common among patients who do not respond to psychiatric interventions, regardless of intervention type (pharmacological or psychotherapeutic), across anxiety and mood disorders. An attachment formation and maintenance domain has been proposed as contributing to anxiety disorders. We therefore directly determined prevalence of SA in a population of adult treatment non-responders suffering from primary anxiety. In these separation anxious nonresponders, we pilot-tested an SA-focused, attachment-based psychotherapy for anxiety, Panic-Focused Psychodynamic Psychotherapy-eXtended Range [PFPP-XR], and assessed whether hypothesized biomarkers of attachment were engaged. We studied separation anxiety [SA] in 46 adults (ages 23-70 [mean 43.9 (14.9)]) with clinically significant anxiety symptoms (Hamilton Anxiety Rating Scale [HARS]≥15), and reporting a history of past non-response to psychotherapy and/or medication treatments. Thirty-seven (80%) had clinically significant symptoms of separation anxiety (Structured Clinical Interview for Separation Anxiety Symptoms [SCI-SAS] score≥8). Five of these subjects completed an open clinical trial of Panic Focused Psychodynamic Psychotherapy eXtended Range [PFPP-XR], a 21-24 session, 12-week manualized attachment-focused anxiolytic psychodynamic psychotherapy for anxiety. Patients improved on "adult threshold" SCI-SAS (current separation anxiety) (p=.016), HARS (p=0.002), and global severity, assessed by the Clinical Global Impression Scale (p=.0006), at treatment termination. Salivary oxytocin levels decreased 67% after treatment (p=.12). There was no significant change in high or low frequency HRV after treatment, but change in high frequency HRV inversely correlated with treatment change in oxytocin (p<.02), and change in low frequency HRV was positively associated with change in oxytocin (p<.02). SA is surprisingly prevalent among non-responders to standard anti-anxiety treatments, and it may represent a novel transdiagnostic target for treatment intervention in this population. Anxiety and global function improved in a small trial of a brief, manualized, attachment-focused psychodynamic psychotherapy, potentially supporting the clinical relevance of attachment dysfunction in this sample. The large decrease in oxytocin levels with treatment, although not statistically significant in this very small sample, suggests the need for further study of oxytocin as a putative biomarker or mediator of SA response. These pilot data generate testable hypotheses supporting an attachment domain underlying treatment-resistant anxiety, and new treatment strategies.