Nowadays, a third of people with depression are treatment-resistant. Even in the best-case scenario, common antidepressants might take six weeks or more to kick in. Relatively few studies have examined the association between genetic variations and outcomes in patients treated with alternative antidepressants. Genetic tests for depression hit the market 10 years ago, but have surged in popularity in the last five years. The era of pharmacogenomic testing has just begun and psychiatrists predict that, given more research, they may one-day guide decision-making in the clinic.
На даний момент третина людей, що страждають на депресію, мають резистентність до лікування. Навіть у найкращому випадку, звичайним антидепресантам може знадобитися шість тижнів або більше для того, щоб почати діяти. Відносно мало досліджень вивчало зв'язок між генетичними варіаціями та результатами у пацієнтів, які отримували альтернативні антидепресанти. Генетичні тести на депресію потрапили на ринок 10 років тому, але за останні п'ять років популярність зросла. Ера фармакогеномічного тестування лише розпочалася, і психіатри прогнозують, що, за наявності більшої кількості досліджень, подібне тестування одного дня зможе керувати прийняттям рішень у пианні лікування пацієнтів з цим діагнозом.
The World Health Organization estimates that depression will be the second-most common cause of disease and premature death worldwide by 2020 [
Recent guidelines on pharmacological treatments of MDD indicate the use of selective serotonin reuptake inhibitors (SSRIs) or serotonin noradrenaline reuptake inhibitors (SNRIs) as first-line treatment, along with other antidepressants (ADs), including agomelatine, bupropion, mirtazapine, and vortioxetine. Tricyclic antidepressants (TCAs), trazodone, levomilnacipran, and vilazodone are recommended as second-line agents, whereas third-line recommendations include monoamine oxidase inhibitors (MAOIs) and the SNRI, reboxetine [
A possible reason for the high rate of unsatisfactory responses to ADs is that MDD is a very heterogeneous disorder concerning symptom presentation and, possibly, its underlying mechanisms [
The sequencing of the human genome early in this millennium was lauded for the breadth of the scientific achievement and was expected to revolutionize medicine. Genomics would provide the links between our genes and biological events, whether normal or pathological. Armed with this blueprint, disease biomarker development would proceed rapidly and greatly improve clinical practice. Medical treatment would be individualized with targeted medicines based on the genetic and molecular profile of the patient [
The NIH defines a biomarker as “a characteristic that is objectively measured and evaluated as an indicator of normal biologic processes, pathogenic processes or pharmacologic responses to a therapeutic intervention [
Pharmacogenetic testing is a useful and increasingly widespread tool to assist in antidepressant prescription. More than ten antidepressants (including tricyclics, selective serotonin reuptake inhibitors and venlafaxine) have already genetic biomarkers of response/side effects in clinical guidelines and drug labels. These are represented by functional genetic variants in genes coding for cytochrome enzymes (CYP2D6 and CYP2C19) [
Candidate genes involved in antidepressant metabolism (pharmacokinetics) have sufficiently robust scientific evidence for clinical applications, as documented in clinical guidelines such as those curated by the Clinical Pharmacogenetics Implementation Consortium (CPIC) and Dutch Pharmacogenetic Working Group (DPWG) [10, 11]. These genes are those coding for cytochrome P450 (CYP450) enzymes responsible for antidepressant metabolism, namely CYP2D6 and CYP2C19. Functional genetic variants within these genes are common in the population and they result in significant variation in the enzymatic activity, which can be classified in four main groups (poor metabolizers [PMs], intermediate metabolizers [IMs], extensive metabolizers [EMs] and ultrarapid metabolizers [UMs]). These metabolizing groups were associated with pharmacokinetic parameters (e.g., drug and metabolites plasma concentration) for several antidepressants, demonstrating an impact on drug metabolism [
Polymorphisms in other CYP450 genes (e.g., CYP1A2, CYP3A4/A5, CYP2B6) have probably not clinically relevant consequences on drug metabolism because their level of activity is much more dependent from environmental factors (e.g., smoking, diet, concomitant drugs) than genetic factors [
Pharmacogenetics is still not implemented in routine clinical practice in most countries, with some exceptions (for example, Switzerland). The main barrier consists of the need to invest resources to create standard procedures for test prescription and genotyping, but also for the standard interpretation of the genotyping results in prescriptive recommendations. This would mean educational programs for clinicians and other health care professionals, costs for sample transport and genotyping, integration of Clinical Decision Support (CDS) tools in clinical settings, in other words: time and money.
A few published studies are looking at the cost-effectiveness of pharmacogenetic testing in guiding antidepressant prescription compared to standard care [
Pharmacogenetics already represents an available tool in assisting antidepressant prescription. Despite not a definitive consensus on when and to whom testing should be recommended, the available evidence supports that testing can be useful in patients who did not respond or tolerate at least one previous pharmacological treatment [
The author declare that no competing interests exist.