Polymorphism of the 5-HT transporter and response to antidepressants: randomised controlled trial.
BACKGROUND: Antidepressants exhibit a variety of pharmacological actions including inhibition of the serotonin and noradrenaline transporters. We wished to investigate whether genetic variation could be used to target or personalise treatment, in a comparison of selective serotonin reuptake inhibito...
| Autores principales: | , , , , , , , , , , , , , |
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| Formato: | Journal article |
| Lenguaje: | English |
| Publicado: |
2011
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| _version_ | 1826264386265677824 |
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| author | Lewis, G Mulligan, J Wiles, N Cowen, P Craddock, N Ikeda, M Grozeva, D Mason, V Nutt, D Sharp, D Tallon, D Thomas, L O'Donovan, M Peters, T |
| author_facet | Lewis, G Mulligan, J Wiles, N Cowen, P Craddock, N Ikeda, M Grozeva, D Mason, V Nutt, D Sharp, D Tallon, D Thomas, L O'Donovan, M Peters, T |
| author_sort | Lewis, G |
| collection | OXFORD |
| description | BACKGROUND: Antidepressants exhibit a variety of pharmacological actions including inhibition of the serotonin and noradrenaline transporters. We wished to investigate whether genetic variation could be used to target or personalise treatment, in a comparison of selective serotonin reuptake inhibitors (SSRIs) with noradrenaline reuptake inhibitors (NARIs). AIMS: To test the hypothesis that patients homozygous for the long (insertion) polymorphism of the serotonin transporter (5-HTTLPR) have an increased response to SSRI antidepressants but not to NARI antidepressants. METHOD: In an individually randomised, parallel-group controlled trial, people meeting criteria for a depressive episode who were referred by their general practitioner were randomised to receive either citalopram (an SSRI) or reboxetine (an NARI). Randomisation was by means of a remote automated system accessed by telephone. The main outcome was depressive symptoms, measured by Beck Depression Inventory (BDI) total score 6 weeks after randomisation. The trial was registered with the International Standard Randomised Controlled Trials Number registry (ISRCTN31345163). RESULTS: Altogether 298 participants were randomised to receive citalopram and 303 were randomised to reboxetine. At 6 weeks follow-up, complete data were available for 258 participants taking citalopram and 262 taking reboxetine. We found no evidence to support an influence of 5-HTTLPR on outcome following antidepressant treatment. The interaction term for BDI score 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 similar irrespective of 5-HTTLPR genotype. CONCLUSIONS: It is unlikely that the 5-HTTLPR polymorphism alone will be clinically useful in predicting response to antidepressants in people with depression. |
| first_indexed | 2024-03-06T20:06:58Z |
| format | Journal article |
| id | oxford-uuid:2933d2e3-69a5-4135-be8f-c1f0c0e57617 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T20:06:58Z |
| publishDate | 2011 |
| record_format | dspace |
| spelling | oxford-uuid:2933d2e3-69a5-4135-be8f-c1f0c0e576172022-03-26T12:17:48ZPolymorphism of the 5-HT transporter and response to antidepressants: randomised controlled trial.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:2933d2e3-69a5-4135-be8f-c1f0c0e57617EnglishSymplectic Elements at Oxford2011Lewis, GMulligan, JWiles, NCowen, PCraddock, NIkeda, MGrozeva, DMason, VNutt, DSharp, DTallon, DThomas, LO'Donovan, MPeters, TBACKGROUND: Antidepressants exhibit a variety of pharmacological actions including inhibition of the serotonin and noradrenaline transporters. We wished to investigate whether genetic variation could be used to target or personalise treatment, in a comparison of selective serotonin reuptake inhibitors (SSRIs) with noradrenaline reuptake inhibitors (NARIs). AIMS: To test the hypothesis that patients homozygous for the long (insertion) polymorphism of the serotonin transporter (5-HTTLPR) have an increased response to SSRI antidepressants but not to NARI antidepressants. METHOD: In an individually randomised, parallel-group controlled trial, people meeting criteria for a depressive episode who were referred by their general practitioner were randomised to receive either citalopram (an SSRI) or reboxetine (an NARI). Randomisation was by means of a remote automated system accessed by telephone. The main outcome was depressive symptoms, measured by Beck Depression Inventory (BDI) total score 6 weeks after randomisation. The trial was registered with the International Standard Randomised Controlled Trials Number registry (ISRCTN31345163). RESULTS: Altogether 298 participants were randomised to receive citalopram and 303 were randomised to reboxetine. At 6 weeks follow-up, complete data were available for 258 participants taking citalopram and 262 taking reboxetine. We found no evidence to support an influence of 5-HTTLPR on outcome following antidepressant treatment. The interaction term for BDI score 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 similar irrespective of 5-HTTLPR genotype. CONCLUSIONS: It is unlikely that the 5-HTTLPR polymorphism alone will be clinically useful in predicting response to antidepressants in people with depression. |
| spellingShingle | Lewis, G Mulligan, J Wiles, N Cowen, P Craddock, N Ikeda, M Grozeva, D Mason, V Nutt, D Sharp, D Tallon, D Thomas, L O'Donovan, M Peters, T Polymorphism of the 5-HT transporter and response to antidepressants: randomised controlled trial. |
| title | Polymorphism of the 5-HT transporter and response to antidepressants: randomised controlled trial. |
| title_full | Polymorphism of the 5-HT transporter and response to antidepressants: randomised controlled trial. |
| title_fullStr | Polymorphism of the 5-HT transporter and response to antidepressants: randomised controlled trial. |
| title_full_unstemmed | Polymorphism of the 5-HT transporter and response to antidepressants: randomised controlled trial. |
| title_short | Polymorphism of the 5-HT transporter and response to antidepressants: randomised controlled trial. |
| title_sort | polymorphism of the 5 ht transporter and response to antidepressants randomised controlled trial |
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