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Influence of ACE gene on differential response to sertraline versus fluoxetine in patients with major depression: a randomized controlled trial

  • Pharmacogenetics
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Background

Extensive distribution of the different components of renin angiotensin system (RAS) in the brain, along with their roles in promoting anxiety, depression and brain inflammation, opposes RAS as a potential therapeutic target in major depression. Actions of angiotensin II, the main product of RAS, are reduced by antidepressants and this signifies the complex interplay of different mechanisms involved in response to therapy. Here, we hypothesized that genetic polymorphisms of RAS may affect the outcome of therapy in depressed patients.

Methods

The frequencies of variants of genes encoding for angiotensin-converting enzyme (ACE) insertion/deletion (I/D), rs4291 and rs4343 polymorphisms were determined in extracted DNAs of 200 newly diagnosed depressed patients. Patients were randomly divided into two groups, one treated with fluoxetine and the other treated with sertraline for 12 weeks. Responsive patients were determined by psychiatrist using Hamilton questionnaire and were compared with regard to their genetic variants.

Results

Carriers of the D allele and patients with DD genotype responded significantly better to sertraline than to fluoxetine (P = 0.0006, odds ratio (OR) = 3.0, 95 % confidence interval (CI) = 1.80–5.08; P = 0.006, OR = 3.7, 95 % CI = 1.66–8.29, respectively). Mutant genotypes (GG and TT) of rs4343 and rs4291 polymorphisms were also more frequent in patients responding to sertraline, though not achieving the significance level (P = 0.162 and P = 0.256, respectively).

Conclusion

These findings suggest that special genetic variants of RAS may influence or be an indicator for better response to sertraline.

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Author information

Authors and Affiliations

  1. Noncommunicable Diseases Research Center, Fasa University of Medical Sciences, Fasa, Iran

    Ehsan Bahramali & Negar Firouzabadi

  2. Department of Pharmacology & Toxicology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran

    Negar Firouzabadi & Mohammad Reza Hooshangi Shayesteh

  3. School of Pharmacy, Shiraz University of Medical Sciences, International Branch, Shiraz, Iran

    Ilnaz Yavarian & Roja Asadpour

  4. Cancer Immunology Group, Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

    Nasrallah Erfani

  5. Department of Psychiatry, School of Medicine, Hafez Hospital, Shiraz University of Medical Sciences, Shiraz, Iran

    Ali Alavi Shoushtari

Authors
  1. Ehsan Bahramali
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  2. Negar Firouzabadi
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  3. Ilnaz Yavarian
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Corresponding author

Correspondence to Negar Firouzabadi.

Ethics declarations

This work was conducted in line with The Code of Ethics of the World Medical Association (Declaration of Helsinki) and Uniform Requirements for manuscripts submitted to biomedical journals. The local committee for ethics of medical experiments on human subjects of Shiraz University of Medical Sciences approved the study. Prior to interview, the written consent was attained from the participants. All patients were Caucasian and from the same geographical region.

Conflict of interest

The authors declare that they have no conflict of interest.

Role of the funding source

This work was financially supported by a grant from Shiraz University of Medical Sciences, International Branch, Shiraz, Iran (Grant No. PVB/18/91).

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Bahramali, E., Firouzabadi, N., Yavarian, I. et al. Influence of ACE gene on differential response to sertraline versus fluoxetine in patients with major depression: a randomized controlled trial. Eur J Clin Pharmacol 72, 1059–1064 (2016). https://doi.org/10.1007/s00228-016-2079-0

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  • DOI: https://doi.org/10.1007/s00228-016-2079-0

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