Modifying the role of serotonergic 5‐HTTLPR and TPH2 variants on disulfiram treatment of cocaine addiction: a preliminary study |
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| Authors: | D A Nielsen M J Harding S C Hamon W Huang T R Kosten |
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| Institution: | 1. Menninger Department of Psychiatry and Behavioral Sciences;2. Michael E. DeBakey V.A. Medical Center (MEDVAMC), Baylor College of Medicine, , Houston, TX, 77030 USA;3. Laboratory of Statistical Genetics, The Rockefeller University, , New York, NY, 10065 USA |
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| Abstract: | Disulfiram is a cocaine pharmacotherapy that may act through increasing serotonin, benefiting patients with genetically low serotonin transporter levels (5‐HTTLPR, S′ allele carriers) and low serotonin synthesis (TPH2, A allele carriers). We stabilized 71 cocaine and opioid co‐dependent patients on methadone for 2 weeks and randomized them into disulfiram and placebo groups for 10 weeks. We genotyped the SLC6A4 5‐HTTLPR (rs4795541, rs25531) and TPH2 1125A>T (rs4290270) variants and evaluated their role in moderating disulfiram treatment for cocaine dependence. Cocaine‐positive urines dropped from 78% to 54% for the disulfiram group and from 77% to 76% for the placebo group among the 5‐HTTLPR S′ allele carriers (F = 16.2; df = 1,301; P < 0.0001). TPH2 A allele carriers responded better to disulfiram than placebo (F = 16.0; df = 1,223; P < 0.0001). Patients with both an S′ allele and a TPH2 A allele reduced cocaine urines from 71% to 53% on disulfiram and had no change on placebo (F = 21.6; df = 1,185; P < 0.00001). |
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| Keywords: | Cocaine disulfiram gene polymorphism serotonin treatment |
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