Polymorphism of the 5-HT transporter and response to antidepressants: Randomised controlled trial

Glyn Lewis, Jean Mulligan, Nicola Wiles, Philip Cowen, Nick Craddock, Masashi Ikeda, Detelina Grozeva, Victoria Mason, David Nutt, Deborah Sharp, Debbie Tallon, Laura Thomas, Michael C. O'Donovan, Tim J. Peters

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

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 72.04 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.

Original languageEnglish
Pages (from-to)464-471
Number of pages8
JournalBritish Journal of Psychiatry
Volume198
Issue number6
DOIs
Publication statusPublished - 01-06-2011

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Antidepressive Agents
Serotonin Uptake Inhibitors
Serotonin
Randomized Controlled Trials
Citalopram
Norepinephrine
Depression
Serotonin Plasma Membrane Transport Proteins
Random Allocation
Norepinephrine Plasma Membrane Transport Proteins
Equipment and Supplies
Telephone
General Practitioners
Registries
Genotype
Pharmacology
Therapeutics
reboxetine

All Science Journal Classification (ASJC) codes

  • Psychiatry and Mental health

Cite this

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. / Polymorphism of the 5-HT transporter and response to antidepressants : Randomised controlled trial. In: British Journal of Psychiatry. 2011 ; Vol. 198, No. 6. pp. 464-471.
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abstract = "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 72.04 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.",
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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, MC & Peters, TJ 2011, 'Polymorphism of the 5-HT transporter and response to antidepressants: Randomised controlled trial', British Journal of Psychiatry, vol. 198, no. 6, pp. 464-471. https://doi.org/10.1192/bjp.bp.110.082727

Polymorphism of the 5-HT transporter and response to antidepressants : Randomised controlled trial. / 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.

In: British Journal of Psychiatry, Vol. 198, No. 6, 01.06.2011, p. 464-471.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Polymorphism of the 5-HT transporter and response to antidepressants

T2 - Randomised controlled trial

AU - Lewis, Glyn

AU - Mulligan, Jean

AU - Wiles, Nicola

AU - Cowen, Philip

AU - Craddock, Nick

AU - Ikeda, Masashi

AU - Grozeva, Detelina

AU - Mason, Victoria

AU - Nutt, David

AU - Sharp, Deborah

AU - Tallon, Debbie

AU - Thomas, Laura

AU - O'Donovan, Michael C.

AU - Peters, Tim J.

PY - 2011/6/1

Y1 - 2011/6/1

N2 - 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 72.04 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.

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