Pharmacogenetic testing improves depression treatment in youth and reduces suicide risk
If you are the parent of a child or adolescent (teen) who has been diagnosed with clinical depression, you may be worried about your child and the implications of treatment. Children and adolescents with moderate to severe depression generally require psychotherapy and one or more medications. Yet, prescribing antidepressants in youth is associated with the risk of suicide. Therefore, anyone considering the use of an antidepressant in a child or adolescent must balance the risk of increased suicidality with the clinical need. In addition, pharmacogenetic (PGx) testing can help identify which medications better suit each individual’s drug metabolism. Such genetics-guided prescribing also reduces the risk of side effects, including suicidality.
New study links genetics to suicide risk in children treated with antidepressants
A recent large-scale retrospective Danish study assessed the response to antidepressants for >17,000 people suffering from depression and anxiety treated with antidepressants. This is the most extensive study confirming pharmacogenetics’ vital role in depression treatment and suicide prevention in youth. Below is a summary of the most critical findings:
- Children and adolescents with poor or ultrarapid CYP2C19 metabolism treated with escitalopram or citalopram were at high risk of suicide attempt/self-harm and were much more likely to switch to another treatment.
- Similarly, youths treated with sertraline who had poor CYP2C19 metabolism also were more likely to require a switch to another medication due to slow drug clearance and a higher frequency of side effects.
- Young adults with significantly reduced/absent CYP2D6 function treated with fluoxetine had an increased risk of emergency department contacts.
- The study estimated that administering PGx testing to children and young adults before or at treatment start with (es)citalopram can prevent a suicide attempt/suicide.
- Although a lower impact was observed in adults (>25 years of age), PGx testing also explained the poor treatment tolerability of fluoxetine and (es)citalopram in people with poor or too rapid drug metabolism.
Accurate genetic testing technology is essential for guiding antidepressant use
While this study contributes to the strong evidence of the critical role of PGx testing in mental health care, it could have been even stronger if additional markers and genes had been analyzed.
For example, sertraline (Zoloft) metabolism is determined by both CYP2B6 and CYP2C19 enzymes, while the study assessed only the latter. Although sertraline may seem a better choice for children, rapid metabolism by CYP2C19 or CYP2B6 has been shown to reduce sertraline blood concentrations, limiting its effectiveness. Alternately, poor metabolism in either enzyme can increase drug concentration in the blood and side effects.
Fluoxetine (Prozac), paroxetine and some other SSRIs are also affected by genetic variations in CYP2D6, especially by Copy Number Variations (CNV) in this gene. Gene duplication leads to faster drug clearance, while deletion greatly reduces fluoxetine metabolism. However, the genetic testing technology used by the Danish biobank did not analyze the CYP2D6 CNV.
Pillcheck is a state-of-the-art test that incorporates copy number variations and provides much more accurate genetic results for CYP2D6, CYP2C19, CYP2B6 and other enzymes. Pillcheck reports over 60 antidepressants and antipsychotic medications. The Pillcheck service also includes a medication review by a clinical pharmacist that will consider the patient’s age, metabolic profile, and prior medication experience. A parent can order the test for a child; young adults can provide their own consent and access their results.
Alternative treatment options
Bupropion (Wellbutrin) is also a commonly prescribed antidepressant that was not covered by the Danish study. Bupropion might be helpful for young adults who experience weight gain with other SSRIs. Bupropion is a prodrug that is activated by the CYP2B6 enzyme. It is worth considering for people that have altered function of both CYP2D6 and CYP2C19.
There are also other antidepressants metabolized by other enzymes. With Pillcheck results, you or your child’s doctor can better understand which medications pose a lower risk of side effects and could better manage depression and anxiety symptoms. Psychotherapy is another tool that can accelerate recovery, especially after achieving remission with an antidepressant.
- The Danish study provides critical evidence to support pharmacogenetic testing for youth at the time of depression/anxiety diagnosis.
- Parents and doctors should consider PGx testing before starting drug therapy in children with anxiety and depression – genetic test results can reduce the risk of suicide and minimize side effects.
- Clinical studies have shown that patients with PGx-guided treatment recovered faster than those who received standard treatment without PGx insights.
- The Pillcheck sample collection kit is easy to use at home for children and adolescents. The results can guide drug and dose selection to match their DNA, thus helping them feel better sooner.
- See how Pillcheck helps you and your healthcare provider choose the right mental health medications (video)
- Pillcheck for mental health
- Reimbursement for pharmacogenetic testing
- How accurate is pharmacogenetic testing?
Thiele LS et al., Clinical Impact of Functional CYP2C19 and CYP2D6 Gene Variants on Treatment with Antidepressants in Young People with Depression: A Danish Cohort Study Pharmaceuticals 2022, 15, 870. https://doi.org/10.3390/ph15070870.
Bråten LS et al., Impact of the novel CYP2C:TG haplotype and CYP2B6 variants on sertraline exposure in a large patient population Clin Transl Sci. 2022 Jun 6. doi: 10.1111/cts.13347.
Papastergiou J et al., Pharmacogenomics guided versus standard antidepressant treatment in a community pharmacy setting: A randomized controlled trial Clin Transl Sci. 2021 Jul;14(4):1359-1368. doi: 10.1111/cts.12986.