The role of pharmacogenetics in the treatment of anxiety disorders and the future potential for targeted therapeutics

ABSTRACT

Introduction

Anxiety disorders (AD) are among the most common mental disorders worldwide. Pharmacotherapy, including benzodiazepines, selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, and tricyclic antidepressants is currently based on ‘trial-and-error,’ and is effective in a subset of patients or produces partial response only. Recent research proposes that treatment response and tolerability of the drugs are associated with genetic factors.

Areas covered

In the present review, we provide information on pharmacogenetics (PGx) in AD, including pharmacokinetic and pharmacodynamic genes. Moreover, we discuss the future potential of PGx for personalized treatment.

Expert opinion

In psychiatry, PGx testing is still in its infancy, especially in the treatment of AD. As of today, implementation in clinical routine is recommended only for CYP2D6 and CYP2C19, mainly in terms of safety of treatment and potentially of treatment outcome in general. However, the evidence for PGx testing addressing pharmacodynamics for specific AD is limited to date. Nevertheless, PGx may develop into a valuable and promising tool to improve therapy in AD, but there is a need for more research to fully exploit its possibilities. Future perspectives include research into single genes, polygenic risk scores, and pharmacoepigenetics to provide targeted therapy.

KEYWORDS:

• Anxiety disorders
• pharmacodynamics
• pharmacoepigenetics
• pharmacogenetics
• pharmacokinetics
• targeted treatment

Article highlights

• PGx studies addressing drug exposure of first-line long-term treatment options in AD are rare, however, evidence from pharmacokinetic studies in treating depression are applicable also in anxiety disorders.

• CYP2D6 and CYP2C19 genotyping is recommended when considering treatment with SSRIs, venlafaxine, and TCAs.

• There only is limited evidence for the use of PGx addressing pharmacodynamic genes and treatment response in clinical routine for specific AD.

• Future perspectives for PGx in anxiety disorders include research into single genes, polygenic risk scores and pharmacoepigenetics to provide targeted therapy.

By now, implementation of PGx in clinical routine is recommended mainly to enhance safety, but only less to predict efficacy of treatment in specific AD.

Declaration of interest

J Deckert is the co-recipient of a grant of the Bavarian State Government to BioVariance and an investigator in a European Grant to P1Vital. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

This paper was not funded.