The
therapeutics of
obsessive-compulsive disorder (OCD) involves the serotonergic system in the brain; the
selective serotonin reuptake inhibitors (
SSRIs) are the only class of drugs to be consistently effective for this disorder. Preclinical studies in the orbito-frontal cortex - a brain area known to be involved in mediation of OCD symptoms - show that sustained administration of SSRI for 2 months leads to enhanced
5-HT release. Initially, raised
5-HT levels, resulting from
serotonin (5-HT) reuptake inhibition, over-activates the cell body 5-HT1A
autoreceptor, which has an inhibitory effect on the neuronal firing rate. However, after long-term administration of
SSRIs, these 5-HT1A
autoreceptors become desensitized to the raised extracellular
5-HT levels, and increase
5-HT transmission. The recovery of neuronal firing rate is faster with
escitalopram (the active S-enantiomer of
citalopram) than with
citalopram, which may be due to different mechanisms of action. The
5-HT system has reciprocal interactions with the
noradrenaline (NA) system. Although not a major mediator in the treatment of OCD symptomatology, patients with
anxiety disorders such as
panic disorder have increased NA reactivity and/or tone. Long-term SSRI administration reduces the firing rate of NA neurones, unlike
5-HT neurones. Evidence indicates that accrued
5-HT levels have an inhibitory modulatory effect on NA transmission, thus indicating the clinical relevance of SSRI treatment for
anxiety disorders. The different effectiveness of the
SSRIs escitalopram and
citalopram in enhancing synaptic
5-HT levels may be due to the inhibitory action of the R-enantiomer in racemic
citalopram on S-enantiomer binding to the
5-HT transporter. This allows
escitalopram to produce higher extracellular
5-HT levels than can be achieved by the equivalent S-enantiomer dose of
citalopram.
Escitalopram is therefore a viable front-line treatment option for people with
anxiety disorders, and possibly for those who have failed to respond to conventional SSRI
therapies.