Pharmacogenetics and Analgesic Effects of Antidepressants in Chronic Pain Management

Frédérique Rodieux; Valérie Piguet; Patricia Berney; Jules Desmeules; Marie Besson


Personalized Medicine. 2015;12(2):163-175. 

In This Article

Future Perspective

The effect of antidepressants or analgesics exhibits highly variable interindividual efficacy or tolerability. Because half of the patients treated for chronic pain are not relieved and a substantial proportion exhibit side effects that lead to treatment discontinuation, the exploration of the reason of this variability should be more systematically conducted in clinical practice. Antidepressants interact with several molecular targets, and as such, their ability to relieve pain may not be attributable to a single molecular mechanism. The identification of genetic biomarkers that can predict the antidepressant treatment response and genetically guide the prescription of drugs could definitively improve clinical practice.

Many antidepressants have dose- and concentration-response curves developed for their application to treat depression. Therapeutic drug monitoring is the first step for monitoring a treatment. In patient requiring long-term treatment, genotypic or phenotypic tests have added value, particularly in exploring the origin of a low concentration and to rule out the adherence issue.

During the past years, the ability to test for polymorphisms, particularly in cytochromes, has become more accessible, inexpensive and usable in clinical practice, and these are guidelines that link the results to therapeutic recommendations. Tests are also easily available for P-gp and COMT, although these are more rarely performed. All of the tests should be routinely discussed with a clinical pharmacologist in cases of exaggerated response as well as in cases of nonresponse. If a genetic variant is identified, the predicted clinical consequences should be assessed, and clinical adjustments, such as modifying the dose, modifying the dosing schedule or changing the medication, should be considered. Even if the current dosage adjustment guidelines for antidepressants, which were developed from data collected in depressed patients, in other words, who receive higher drug doses than those prescribed for pain treatment, are thus not directly applicable to patients with chronic pain, they can help guide the treatment adaptation. The pharmacogenetics of antidepressants in the context of pain management remains a field with a high amount of missing information. There are other candidate genes, particularly the genes encoding MAO, the sodium channels and the noradrenaline transporter, whose genetic variability may also be translated to individual variations in the treatment response. However, for these other genes, further studies are needed before the pharmacogenetics can be integrated into an individualized prescription.

These approaches are the first steps toward individualized prescription medicine, particularly in an area where many objective tests are not available to help guiding the treatment. Pharmacogenetic testing may allow fewer medication-related side effects, an improved selection of medication and a reduction in the burden and cost of chronic pain.