Polymorphism of the 5-HT transporter and response toantidepressants: randomised controlled trial

• Published in: British journal of psychiatry 2011-06, Vol.198 (6), p.464-471
• Main Authors: Lewis, Glyn, Mulligan, Jean, Wiles, Nicola, Cowen, Philip, Craddock, Nick, Ikeda Masashi, Grozeva Detelina, Mason, Victoria, Nutt, David, Sharp, Deborah, Tallon, Debbie, Thomas, Laura, O'Donovan, Michael C, Peters, Tim J
• Format: Article
• Language: English
• Subjects: Antidepressants; Binding sites; Bipolar disorder; Citalopram; Clinical trials; Gene polymorphism; Genetic diversity; Genotype & phenotype; Genotypes; Insertion; Mental depression; Norepinephrine; Polymorphism; Primary care; Psychiatry; Reboxetine; Serotonin; Serotonin reuptake inhibitors; Serotonin transporter; Serotonin uptake inhibitors
• ISSN: 0007-1250; 1472-1465
• DOI: 10.1192/bjp.bp.110.082727

BackgroundAntidepressants exhibit a variety of pharmacological actions includinginhibition of the serotonin and noradrenaline transporters. We wished toinvestigate whether genetic variation could be used to target orpersonalise treatment, in a comparison of selective serotonin reuptakeinhibitors (SSRIs) with noradrenaline reuptake inhibitors (NARIs).AimsTo test the hypothesis that patients homozygous for the long (insertion)polymorphism of the serotonin transporter (5-HTTLPR) have an increasedresponse to SSRI antidepressants but not to NARI antidepressants.MethodIn an individually randomised, parallel-group controlled trial, peoplemeeting criteria for a depressive episode who were referred by theirgeneral practitioner were randomised to receive either citalopram (anSSRI) or reboxetine (an NARI). Randomisation was by means of a remoteautomated system accessed by telephone. The main outcome was depressivesymptoms, measured by Beck Depression Inventory (BDI) total score 6 weeksafter randomisation. The trial was registered with the InternationalStandard Randomised Controlled Trials Number registry(ISRCTN31345163).ResultsAltogether 298 participants were randomised to receive citalopram and 303were randomised to reboxetine. At 6 weeks follow-up, complete data wereavailable for 258 participants taking citalopram and 262 takingreboxetine. We found no evidence to support an influence of 5-HTTLPR onoutcome following antidepressant treatment. The interaction term for BDIscore at 6 weeks was 0.50 (95% CI −2.04 to 3.03, P =0.70), which indicated that responses to the SSRI and NARI were similarirrespective of 5-HTTLPR genotype.ConclusionsIt is unlikely that the 5-HTTLPR polymorphism alone will be clinicallyuseful in predicting response to antidepressants in people withdepression.