Towards limiting QT interval prolongation and arrhythmia risk in citalopram use.

Citalopram is a serotonin-selective reuptake inhibitor (SSRI) widely used in the treatment of major depression and sometimes also anxiety-associated conditions, obsessive compulsive disorder and behavior disturbances associated with dementia [1, 2]. Citalopram is relatively well tolerated and has been considered to have comparatively low potential for drug–drug interactions and anti-adrenergic and anti-cholinergic effects, making it an attractive treatment option for elderly patients [1, 2]. The drug is chiral and the serotonin reuptake inhibitory activity of citalopram resides in the S(+)-enantiomer (available as escitalopram) with no therapeutic benefit of the R(–)-enantiomer. There is limited evidence that at equivalent doses (i.e. matched concentrations of the S-enantiomer), escitalopram is more effective clinically than is citalopram, raising the possibility of a potential inhibitory effect of the R-enantiomer [3–5]. Data from studies, in which serotonin reuptake transporter (SERT) occupancy has been examined in humans, suggest that on repeated dosing with racemic citalopram, R-citalopram levels may exceed those of the S-enantiomer, leading to reduced S-citalopram occupancy of SERT [6].