Number Needed to Treat (NNT) and Number Needed to Harm (NNH) from Two Phase 3 Studies of Sublingual Dexmedetomidine for Treating Acute Agitation in Patients with Schizophrenia and Bipolar Disorder

BACKGROUND: Sublingual dexmedetomidine is a selective alpha2-adrenergic receptor agonist recently approved for the treatment of agitation in adults with schizophrenia or bipolar disorder. In phase 3 studies sublingual dexmedetomidine significantly reduced acute agitation at 2h, as measured by the Positive and Negative Syndrome Scale-Excited Component (PEC). OBJECTIVE: Calculation of NNT and NNH for sublingual dexmedetomidine METHODS: Post hoc analysis of data from two phase 3 studies in adults with schizophrenia or bipolar disorder experiencing acute agitation. Patients were randomized to a single dose of180 mcg, 120 mcg, or placebo. Primary endpoint was change from baseline in PEC total score. Therapeutic response was defined as a  40% reduction in PEC total at 2h. NNT was calculated as1/absolute risk reduction for PEC response rate versus placebo. NNH was determined from the incidence of adverse events versus placebo. RESULTS: NNT (95% CI) was 3 (2, 3) for 180 mcg and 3 (3, 4) for 120 ug in patients with schizophrenia and 3 (2, 3) for 180 mcg and 4 (3, 6) for 120 ug in patients with bipolar disorder. NNH was greater than 10 for all AEs except somnolence, where NNH was 7 (5, 10) for all doses pooled from both studies. Likelihood to be helped or harmed values were greater than 1 for efficacy versus applicable tolerability outcomes in all cases. CONCLUSIONS: This post hoc analysis demonstrated favorable NNT and NNH values for sublingual dexmedetomidine in the treatment of acute agitation in adults with schizophrenia or bipolar disorder.