Escitalopram pharmacogenetics. Issue 11 (November 2015)

• Record Type: Journal Article
• Authors: Bishop, Jeffrey R.; Najjar, Fedra; Rubin, Leah H.; Guter, Stephen J.; Owley, Thomas; Mosconi, Matthew W.; Jacob, Suma; Cook, Edwin H.
• Is Part Of: Pharmaocogenetics and genomics. Volume 25:Issue 11(2015:Nov.)
• Publication Date: 2015-11
• Subjects: Pharmacogenetics -- Periodicals; Pharmacogenomics -- Periodicals; Genetic toxicology -- Periodicals; Biomedical genetics -- Periodicals; 615.7
• DOI: 10.1097/FPC.0000000000000173
• Languages: English
• ISSNs: 1744-6872

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <sec> <title>Background and aim</title> <p>Selective serotonin reuptake inhibitors such as escitalopram are commonly used to treat patients with autism spectrum disorder (ASD), but there are individual differences in treatment response and tolerability. <italic>CYP2C19</italic> encodes the primary enzyme responsible for escitalopram metabolism and we investigated whether polymorphisms in <italic>CYP2C19</italic> were related to symptoms and dosing in a pharmacogenetic study of ASD.</p> </sec> <sec> <title>Participants and methods</title> <p>Participants completed the Aberrant Behavior Checklist – Community Version (ABC-CV) weekly for 6 weeks. Escitalopram was initiated at a dose of 2.5 mg per day, with weekly increases to 20 mg unless intolerable side-effects occurred. Three <italic>CYP2C19</italic> metabolizer groups, including ultrarapid, extensive, and reduced metabolizers, were examined in relation to symptom improvement and tolerated dose.</p> </sec> <sec> <title>Results</title> <p>ABC-CV scores improved over the course of treatment (<italic>P</italic><0.0001). No differences were identified in the rate of improvement across metabolizer groups for the ABC-CV irritability subscale, which was the primary outcome for clinical symptoms. There was a trend for a metabolizer group by time interaction with respect to dose (<italic>P</italic>=0.10). This interaction was driven by the linear rate of change from week 1 to study endpoint between the reduced metabolizers and ultrarapid metabolizer groups (<italic>P</italic>=0.05). Post-hoc analyses identified significant differences in the rate of dose escalation between ultrarapid metabolizers and extensive metabolizers and for ultrarapid metabolizers compared with reduced metabolizers (<italic>P</italic>'s<0.04), whereby ultrarapid metabolizers showed a slower rate of change in dose over time.</p> </sec> <sec> <title>Conclusion</title> <p> <italic>CYP2C19</italic> ultrarapid metabolizers were associated with reduced tolerance to a fixed titration schedule of open-label escitalopram in this ASD study sample. Possible explanations may involve the altered kinetics of faster metabolizers or previously unknown activities of escitalopram metabolites.</p> </sec> </abstract>