A Comparative Effectiveness Study of Lorazepam or IVIg Versus no Treatment for Down Syndrome Regression Disorder

Down syndrome regression disorder (DSRD) is manifested by acute or subacute onset of bradykinesia, catatonia, mutism, and neuropsychiatric symptoms. Both benzodiazepines and immunotherapy have been effective in treating DSRD, although no study has compared these treatments directly. This observational study compares the response of lorazepam and intravenous immunoglobulin (IVIg) to no therapy over 6 months. This prospective, non-randomized, observational natural history study assessed therapeutic responses in 212 patients meeting international criteria for DSRD. Outcomes were measured at baseline, 12, and 24 weeks using the Bush–Francis Catatonia Rating Scale (BFCRS), 25-foot walk (25FW), Clinical Global Impression-Severity (CGI-S), and Neuropsychiatric Inventory Total (NPIT) and Severity (NPIST) scores. Linear mixed-effect models were used to examine changes in outcomes. Patients received lorazepam (n = 85, 40%), IVIg (n = 68, 32%) or no therapy (n = 59, 28%). By 12 weeks, both active therapies outperformed no therapy on all outcomes (all p < 0.001), with IVIg showing additional advantages over lorazepam on BFCRS mean difference (95% CI): − 2.24 (− 3.72, − 0.75), NPIT − 9.22 (− 11.22, − 7.23), and NPIST − 3.16 (− 4.07, − 2.26). By 24 weeks, IVIg was superior to lorazepam on all outcomes 25FW: − 1.80 (− 2.58, − 1.02); BFCRS: − 7.09 (− 8.58, − 5.60); CGI-S: − 0.63 (− 1.01, − 0.25); NPIT: − 12.23 (− 14.22, − 10.23); NPIST: − 3.80 (− 4.71, − 2.89). Treatment response varied by lumbar puncture abnormality (BFCRS), any neurodiagnostic study abnormality (CGI-S, NPIT), and serum cytokines and MRI abnormality (NPIT), with IVIg demonstrating greater benefits among patients with such abnormalities. At the endpoint of 24 weeks, both IVIg and lorazepam were superior to no treatment for DSRD but IVIg was superior to lorazepam for all five outcomes. Between 12 and 24 weeks of treatment, IVIg showed greater improvement in all outcomes than did lorazepam, suggesting that at least a 24-week treatment course is necessary for maximum IVIg benefit.