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The SLC6A4 gene and response to antidepressants: Why the evidence still isn’t enough

Growing scientific evidence shows a link between the SLC6A4 gene and response to antidepressants. The SLC6A4 gene is involved in regulating serotonin – the brain chemical that influences everything from sleep to appetite to mood.

Some genetic testing companies test SLC6A4 gene variations, promising to predict your response to antidepressants (specifically a class of antidepressant called SSRIs – or selective serotonin reuptake inhibitors).

So why doesn’t a Pillcheck test include SLC6A4 gene variations? The SLC6A4 gene is very complex, with many variations that could potentially influence response to antidepressants. Most scientific studies focus on a well-known variation, called 5-HTTLPR. Unfortunately, this ‘popular’ variation doesn’t always give us the whole picture, and other variations in this gene can also impact test results.

Simply put, there is not enough scientific evidence available to make reliable drug recommendations based on current research. A lack of clinical guidelines for SLC6A4 also means that recommendations made by different psychiatry genetic tests do not always agree.

Since a Pillcheck test provides drug recommendations that can alter your treatment plan and affect your health, we consider the strength of scientific evidence and clinical guidelines very carefully. Pillcheck also uses the PharmGKB database, hosted by Stanford University, to determine the level of scientific evidence for drug recommendations. PharmGKB collects world-wide scientific data and rates the level of evidence from level 1a (highest) to level 4 (lowest or ‘preliminary’). As of today, 5-HTTLPR has a level of evidence at 2, meaning there is correlation with response to antidepressants (SSRIs) but useful guidance on drug dose or therapeutic alternatives is not provided. For this reason, Pillcheck does not yet include the 5-HTTLPR variant of the SLC6A4 gene until more “actionable” guidelines become available.

In today’s market, genetic testing companies vary wildly. Commercial tests claim to predict everything from diet and exercise advice, to your response to marijuana, and even life expectancy. But as the adage goes: buyer beware. Some of these tests, unfortunately, are based on shaky evidence.

We take your health seriously and constantly review the science supporting our test. Your Pillcheck report is not only based on high-level scientific evidence, but also reviewed by a clinical pharmacist specializing in Pharmacogenomics.

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