Hedges and Woon and R-citalopram have afﬁnity for the histamine 1 receptor, whereas escitalopram does not. It is likely that binding to the serotonin transporter initi- ates a series of effects in the brain beyond serotonin reuptake inhibition. Although little such data exist for escitalopram, functional neuroimaging data from citalopram are intriguing. In a study using single photon emission computed tomography, Carey et al (2004) found that citalopram treatment was associated with signiﬁcant deactivation in the cingulate cortex, right thalamus, and left hippocampus in several anxiety disorders including OCD. Citalopram treatment may affect other metabolic factors in addition to cerebral blood ﬂow. For example, citalopram use in OCD was asso- ciated with prefrontal and frontal white matter increases in N-acetylaspartate (Jang et al 2006), showing that citalopram can substantially alter brain function in various brain regions. While comparable data for escitalopram are not available, escitalopram may well cause cerebral blood-flow and metabolic effects similar to those reported with citalopram because of the racemic nature of citalopram. Pharmacokinetics of escitalopram In general, the pharmacokinetics of escitalopram appear favorable. For instance, the relationship between escitalopram dose and plasma concentrations is linear, which allows for plasma levels to be predicted from dose (Burke 2002). The absorption of escitalopram is not affected by food, and it reaches peak serum levels in three to four hours (Baldwin and Nair 2005). The half-life of escitalopram varies from approximately 27 to 32 hours (Burke 2002), enabling once daily dosing and eliminating the need for multiple daily doses. In people over age 65 though, the half-life can increase to 40 hours (Baldwin and Nair 2005), necessitat- ing dosage adjustments in the elderly (Dhillon et al 2006). Steady state plasma concentrations in healthy volunteers occur in 7 to 10 days (Dhillon et al 2006). Like all other SSRIs, escitalopram undergoes extensive metabolism by cytochrome P450 enzymes, which convert escitalopram to S-desmethyl-citalopram and then to S-didesmethyl-citalopram (von Moltke et al 2001), neither of which metabolites appear to signiﬁcantly affect serotonin reuptake (Dhillon, Scott and Plosker 2006). An in vitro study found that the cytochrome P450 enzymes 2C19, 2D6, and 3A4 accounted for 37%, 28%, and 35% respectively of the metabolism of escitalopram (von Moltke et al 2001). Drugs that inhibit these enzymes can increase escitalopram concentrations (Dhillon et al 2006). Compared with some other SSRIs, escitalopram may have weak or minimal interactions with the cytochrome P450 458 system (von Moltke et al 2001; Burke 2002), reducing the potential for cytochrome P450 drug–drug interactions (von Moltke et al 2001). In vivo work, in contrast, shows that escitalopram can inhibit cytochrome P450 2D6 (Dhillon, Scott and Plosker 2006), an effect that requires further study to more fully understand escitalopram’s potential for drug-drug interactions. Escitalopram efﬁcacy studies To date, escitalopram has shown efﬁcacy in adult major depression (Burke 2002; Burke et al 2002), a condition in which it may have a faster antidepressant response than citalopram (Lepola et al 2003). A number of rela- tively short-term trials have found that escitalopram has efﬁcacy for social anxiety disorder, panic disorder, and generalized anxiety disorder (Burke 2002). For example, in a double-blind, placebo-controlled trial over 12 and 24 weeks, Lader et al (2004) found escitalopram to be superior to placebo for the management of social anxiety disorder. Similarly, Kasper et al (2005) found escitalopram in a double-blind, placebo-controlled, randomized trial to be superior to placebo in social anxiety disorder, despite a high placebo response in this study. Investigating generalized social anxiety disorder in a double-blind, placebo-controlled, randomized trial, Montgomery et al (2005) found escitalo- pram to be effective and well tolerated over a 24 week study. Another double-blind, placebo-controlled study also found escitalopram to be effective in generalized anxiety disorder, with discontinuation rates from escitalopram not signiﬁcantly different from those from placebo (Davidson et al 2004). In their review of the use of escitalopram for the treatment of generalized anxiety disorder, Baldwin and Nair (2005) note that escitalopram has shown efﬁcacy in generalized anxiety for up to 6 months. Despite findings that escitalopram appears to have efﬁcacy in several anxiety disorders, little work so far has examined directly the efﬁcacy of escitalopram in OCD. Several case reports suggest that escitalopram may be effective for conditions having either obsessive features or argued by some researchers to be related to OCD (Hollander, Friedberg, Wasserman et al 2005). For instance, in a case report of a 15-year-old male with transvestic fetishism thought by the authors to have a compulsive quality, the addi- tion of escitalopram resulted in diminished recurrent thoughts (Praharaj 2004). Another case report found escitalopram use in a 10-year-old boy to be associated with a reduction of trichotillomania (Bhatia and Sapra 2004), a condition that shares some similarities with OCD and may be part of an Neuropsychiatric Disease and Treatment 2007:3(4)