Abstract / Summary
Background. Benzodiazepine withdrawal can be prolonged and disabling, with symptoms extending beyond anxiety and insomnia. We characterized symptom burden and functional impairment in a specialty taper cohort and evaluated an exploratory rule for organizing complex, multisystem presentations. Methods. We analyzed cross-sectional intake data from 39 consecutive patients: 37 seeking to begin a supervised taper and two who had completed tapering but remained symptomatic. All 39 returned a 233-item symptom questionnaire, and 38 completed the PROMIS-29 Profile v2.0. Questionnaire items were assigned in advance to five domains: CRH/Adrenergic, Excitatory/Neuroinflammatory, Autonomic, Basal Ganglia-Cerebellar, and MCAS-overlap. Severe symptoms ([≥]7/10) were counted across the first four domains. Patients with three or fewer severe symptoms were classified as Low-symptom; otherwise, the domain with the highest count determined the dominant-axis label, with ties classified as Mixed. MCAS-overlap was coded separately. The categorization was repeated at severity thresholds from [≥]5/10 to [≥]8/10. Results. Patients endorsed a median of 74 symptoms (IQR, 48-24), with a median of 24 rated severe (IQR, 7-42). Thirty-five of 39 patients (89.7%) had severe symptoms in at least two core domains. PROMIS-29 mean T-scores were elevated for Anxiety, Depression, Sleep Disturbance, and Fatigue and were lower for Physical Function and Ability to Participate in Social Roles and Activities; Pain Interference was close to the population mean. At the primary [≥]7/10 severity threshold, 14 patients were classified as CRH/Adrenergic, 14 as Excitatory/Neuroinflammatory, four as Autonomic, and seven as Low-symptom; none were classified as Basal Ganglia-Cerebellar or Mixed. Twenty-two patients (56.4%) met the operational criterion for MCAS-overlap. Agreement with the primary labels was 87.2% at [≥]6/10 and 69.2% at both [≥]5/10 and [≥]8/10 severity thresholds. Conclusions. This cohort had severe, multisystem symptom burden and substantial functional impairment. The five-domain framework provided a structured way to organize these presentations, but the dominant-axis labels were threshold-dependent and should be interpreted as exploratory summaries rather than discrete patient subtypes. Larger longitudinal studies using validated instruments and data-driven methods are needed to determine whether stable symptom subgroups exist.