In a study approved by the Brighton and Sussex Medical School Research Governance and Ethics Committee, 58 healthy male Caucasian volunteers 18 to 32 years old were genotyped for the ADRA2B deletion polymorphism. We recorded baseline cardiovascular parameters (pulse rate and systolic and diastolic blood pressure) and the severity of adverse effects (dry mouth, anxiety, sweating, palpitations, nausea, dizziness, irritability, and tiredness) using a visual analogue scale before administering either 4 mg of reboxetine (N=30) or placebo (N=28), using a double-blind procedure. Two hours later, in keeping with the tmax for reboxetine, we repeated cardiovascular and adverse effect measures (posttreatment). In addition to a main effect of reboxetine on pulse rate (F=7.6, df=1, 53, p=0.005) and total adverse effect score (F=11.4, df=1, 53, p=0.001), we observed a significant interaction between ADRA2B genotype and the severity of posttreatment adverse effects (F=5.0, df=1, 53, p=0.03), while correcting for baseline measurements. In participants lacking a copy of the ADRA2B deletion variant (N=24; 12 each in the reboxetine and placebo groups), reboxetine was associated with a significant increase in adverse effect scores from baseline (t=3.7, df=22, p=0.001) that was absent in participants with at least one copy of the deletion allele (N=34; 18 in the reboxetine group and 16 in the placebo group) (see Figure 1). In the reboxetine group, the number needed to treat (by genotyping) to prevent an increase of ≥50 in the adverse effect score was 2.6.