Why Antidepressants Don’t Work The Same Way For Everyone

Anyone who has ever seen how differently people react to antidepressants knows this: what helps one person may have little effect on another or trigger severe side effects. Some report a noticeable stabilization, while others experience nausea, sleep problems, inner restlessness, or the feeling of being “out of sync.” This is often accompanied by a long period of trial and error: dose adjustments, switching medications, hope, waiting, and renewed disappointment. “Longevity” pharmacist Carole Holzhäuer explains why treatments often become a test of patience.

Antidepressants do not work the same way for everyone. For a long time, this variability was considered an inevitable part of psychiatric treatment. However, it is becoming increasingly clear that many of these experiences are due not only to the complexity of mental illness, but also to a very specific biological factor—the individual way in which the body processes medications.

Why the same medication doesn’t work the same way for everyone

Antidepressants do not work in a vacuum. They must be absorbed, metabolized, and broken down by the body. This is precisely where individual biology comes into play. Two people can take the same medication at the same dosage and still develop very different levels of the active ingredient in their blood. The result: While one person experiences a good therapeutic effect, in the other the active ingredient either disappears too quickly or remains active in high concentrations in the body for too long.

These differences often have to do with enzymes involved in the breakdown of medications in the liver. The enzymes CYP2D6 and CYP2C19 are particularly important here. They belong to the so-called cytochrome P450 family and play a central role in the metabolism of many antidepressants.

Metabolism plays a role

The activity of these enzymes is partly determined by genetics. This means that not everyone breaks down medications at the same rate. Some people metabolize certain active ingredients more slowly, while others do so much more quickly. This is precisely what can explain why an antidepressant causes side effects in one person even at a low dose, while another person feels little improvement despite taking the standard dose.

People who break down an active ingredient slowly may have higher levels of the active ingredient in their blood. This can increase the likelihood of unwanted effects—such as fatigue, nausea, sleep disturbances, or sexual dysfunction. Conversely, very rapid metabolism can mean that the active ingredient is not available in sufficient concentration for long enough to produce the desired effect. What appears from the outside to be an “inappropriate medication” is therefore often a metabolic issue.

Why psychiatric treatments often take so long

Time is a particularly sensitive factor in psychiatry. Antidepressants generally do not work immediately; it takes weeks before their effects can be reliably assessed. Once it becomes clear after several weeks that a medication is not helping or is poorly tolerated, the next phase of trial and error often begins. For those affected, this means not only physical strain but also emotional exhaustion.

Pharmacogenetics changes the perspective at this point. It makes it clear that these lengthy adjustment phases are not always due solely to the illness or the active ingredient. Sometimes the body’s individual metabolism simply does not match the chosen substance or dose. This is an important insight—not least because it offers relief. Not every perceived treatment failure means that “nothing helps.” Sometimes a more precise biochemical classification is simply missing.

Personalized medicine Is becoming a reality

The term “personalized medicine” often sounds like something from the future or high-tech. In reality, it describes something very concrete: tailoring treatments more closely to a person’s individual biological characteristics. In the case of antidepressants, this means considering not only the diagnosis and symptoms, but also the way the body processes the active ingredient.

Pharmacogenetic findings can help plan therapies more precisely. They do not replace a psychiatric or medical evaluation, but they can provide additional insights—for example, when a treatment causes an unusually high number of side effects or repeatedly fails to produce the desired results. This can make a significant difference, especially with sensitive issues like depression and anxiety disorders. Less suffering, fewer unnecessary changes, greater safety: This is not a theoretical promise, but a very practical benefit.

What this means for patients

For people living with mental health challenges, every phase of treatment is linked to hope. This makes it all the more difficult when medications don’t work or cause additional side effects. A look at pharmacogenetics opens up a new way of understanding this: The response to a medication is not just a matter of diagnosis, but often also a matter of biochemistry. This can help make discussions with treating physicians more nuanced. It reinforces the idea that mental health should not be treated with a one-size-fits-all approach, but with as much individual precision as possible.

Conclusion

Antidepressants do not work the same way for everyone, and there are often sound biological reasons for this. Enzymes such as CYP2D6 and CYP2C19 influence how quickly or slowly an active ingredient is metabolized, and thus also how effective it is or how severe the side effects are. Pharmacogenetics brings these differences to light and thereby changes our perspective on psychiatric treatments. Not every treatment failure is due to a problem with the drug itself. Sometimes it is a metabolic issue. And this is precisely where the opportunity lies for a more modern, precise, and humane approach to treatment.