 |
|
Effects of the Serotonin Transporter Gene Promoter Polymorphism on Mirtazapine and Paroxetine Efficacy and Adverse Events in Geriatric Major Depression
Greer M. Murphy, Jr, MD, PhD;
Steven B. Hollander, MD;
Heidi E. Rodrigues, BA;
Charlotte Kremer, MD;
Alan F. Schatzberg, MD
Arch Gen Psychiatry. 2004;61:1163-1169.
Background The "long/short"polymorphism (5HTTLPR) in the promoter of the serotonin transporter gene (SLC6A4) has been proposed as a pharmacogenetic marker for antidepressant efficacy. Some but not all studies have found that the short form of 5HTTLPR (S allele) results in decreased efficacy of selective serotonin reuptake inhibitors.
Objective To determine if the 5HTTLPR polymorphism influences the efficacy and tolerability of mirtazapine and paroxetine hydrochloride, 2 frequently prescribed antidepressants with differing pharmacologic profiles, in geriatric depression.
Design Double-blind, randomized 8-week study.
Setting Eighteen academic and private outpatient clinics.
Patients We evaluated 246 cognitively intact patients 65 years or older with major depression.
Interventions Antidepressant therapy with 15 to 45 mg/d of mirtazapine (n = 124) or 20 to 40 mg/d of paroxetine (n = 122).
Main Outcome Measures The Hamilton Depression Rating Scale–17 and Geriatric Depression Scale, severity of adverse events and dosing compliance indexes, and discontinuations due to adverse events. Outcome measures were stratified according to 5HTTLPR genotypes.
Results Geriatric Depression Scale scores indicated that S allele carriers treated with paroxetine showed a small impairment in antidepressant response. Among mirtazapine-treated patients, there was little indication that the 5HTTLPR genotype affected antidepressant efficacy. However, the 5HTTLPR polymorphism had a dramatic effect on adverse events. Among paroxetine-treated subjects, S allele carriers experienced more severe adverse events during the course of the study, achieved significantly lower final daily doses, and had more discontinuations at days 14, 21, 28, 42, and 49. Surprisingly, among mirtazapine-treated subjects, S allele carriers had fewer discontinuations due to adverse events, experienced less severe adverse events, and achieved higher final daily doses.
Conclusions These results support the hypothesis that the S allele of 5HTTLPR at the SLC6A4 locus is associated with a poor outcome after treatment with selective serotonin reuptake inhibitors. However, the major effect was on the tolerability of these drugs rather than efficacy. Results from mirtazapine-treated patients indicate that the effect of this polymorphism on outcome may depend on the mechanism of antidepressant action.
Author Affiliations: Neuroscience Research Laboratories, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, Calif (Drs Murphy and Schatzberg); and Medical Affairs, Organon Pharmaceuticals USA, Inc, Roseland, NJ (Drs Hollander and Kremer and Ms Rodrigues).
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati  Twitter
What's this?
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES
|
Moderation of antidepressant response by the serotonin transporter gene
Huezo-Diaz et al.
Br. J. Psychiatry 2009;195:30-38.
ABSTRACT
| FULL TEXT
Treatment-Resistant Depression and Mortality After Acute Coronary Syndrome
Carney and Freedland
Am. J. Psychiatry 2009;166:410-417.
ABSTRACT
| FULL TEXT
A meta-analysis of clinical trials comparing mirtazapine with selective serotonin reuptake inhibitors for the treatment of major depressive disorder
Papakostas et al.
J Psychopharmacol 2008;22:843-848.
ABSTRACT
Evidence-based guidelines for treating depressive disorders with antidepressants: A revision of the 2000 British Association for Psychopharmacology guidelines
Anderson et al.
J Psychopharmacol 2008;22:343-396.
ABSTRACT
Effectiveness of paroxetine in the treatment of acute major depression in adults: a systematic re-examination of published and unpublished data from randomized trials
Barbui et al.
CMAJ 2008;178:296-305.
ABSTRACT
| FULL TEXT
Depression and Coronary Heart Disease: More Pieces of the Puzzle
Carney and Freedland
Am. J. Psychiatry 2007;164:1307-1309.
FULL TEXT
Association of a Serotonin Transporter Polymorphism (5-HTTLPR) With Depression, Perceived Stress, and Norepinephrine in Patients With Coronary Disease: The Heart and Soul Study
Otte et al.
Am. J. Psychiatry 2007;164:1379-1384.
ABSTRACT
| FULL TEXT
Association Between a Functional Serotonin Transporter Promoter Polymorphism and Citalopram Treatment in Adult Outpatients With Major Depression
Hu et al.
Arch Gen Psychiatry 2007;64:783-792.
ABSTRACT
| FULL TEXT
Pharmacogenomics in Psychiatry
Leckband et al.
Journal of Pharmacy Practice 2007;20:252-264.
ABSTRACT
TRDB--The Tandem Repeats Database
Gelfand et al.
Nucleic Acids Res 2007;35:D80-D87.
ABSTRACT
| FULL TEXT
Pharmacogenomics of Antidepressant Medications
Ehret
Journal of Pharmacy Practice 2006;19:342-352.
ABSTRACT
Monoamine Transporter Gene Polymorphisms and Antidepressant Response in Koreans With Late-Life Depression
Kim et al.
JAMA 2006;296:1609-1618.
ABSTRACT
| FULL TEXT
Contribution of allelic variations in transporters to the phenotype of drug response
Kirchheiner et al.
J Psychopharmacol 2006;20:27-32.
ABSTRACT
Application of microarray technology in psychotropic drug trials
Murphy
J Psychopharmacol 2006;20:72-78.
ABSTRACT
Recent Studies of the Biology and Treatment of Depression
Schatzberg
Focus 2005;3:14-24.
ABSTRACT
| FULL TEXT
|
