Lidocaine Ineffectiveness Suggests New Psychopharmacology Drug Target

Objectives: The mechanism of many neuropsychiatric disorders remains unknown, but the ineffectiveness of the sodium channel blocker lidocaine has been suggested to be a biomarker for Attention Deficit Hyperactivity Disorder (ADHD) and a severe form of Premenstrual Syndrome (PMS) that is considered psychiatric. We conducted single-arm double-blind clinical trials to test whether lidocaine ineffectiveness can be used as a biomarker to identify people with these conditions and provide a clue as to the molecular mechanism and potential psychopharmacological intervention. Experimental Design: We developed a noninvasive taste test for lidocaine ineffectiveness, validated by comparing lidocaine injections to pain testing in 12 subjects, and assessed it in individuals with ADHD and PMS. Principal Observations: Lidocaine ineffectiveness had a strong association in women with ADHD + PMS in a sample of 53 subjects and controls (p < 0.001). Conclusions: These results suggest the possibility of the biological understanding of the combination of ADHD and PMS that is characteristic of the psychiatric disorder Premenstrual Dysphoric Disorder (PMDD). These results and comparison to family pedigrees of a neuromuscular channelopathy with overlapping symptoms suggest the possibility that the clinical phenotype in PMDD is produced by sensory overstimulation, and amenable to molecular understanding and treatment.