In the early 2000s, as a young researcher in psychopharmacology, I had high hopes that we would discover factors that could help us predict in advance which antidepressant would work best for a particular person. At the time, this seemed like a very realistic goal. There was a genuine boom in genetic research. We were looking for genes associated with antidepressant response, side effects, and differences in the serotonin system. It felt as if we were just a few steps away from replacing lengthy medication selection with a test that could simply tell us:

“This is the drug for you.”

More than twenty years have passed.

So where are we now?

Genetics has turned out to be useful. But not quite in the way many of us imagined back then.

Today, a genetic test still cannot reliably answer the question that matters most to patients:

“Which antidepressant will work best for me?”

It is much better at answering a different question:

“How will my body process certain medications?”

These are fundamentally different questions.

For a number of antidepressants, variation in enzymes such as CYP2D6 and CYP2C19 can be clinically relevant. If a person metabolizes a medication slowly, the drug concentration may become higher than expected – increasing the likelihood of side effects.

If metabolism is very rapid – the concentration may be lower.

This is why a red category on a commercial genetic test usually does not mean:

“This drug will not work.”

It more often means:

“There is a genetic factor related to this medication that the clinician should take into account.”

That may mean a different dose, more cautious prescribing, or considering an alternative.

In other words, pharmacogenetic testing is better at predicting what the body may do with a medication than what the medication will do to the depression.

But if genetics cannot yet identify the ideal drug for us, does that mean we are still treating patients by trial and error?

To some extent – yes.

We still cannot guarantee in advance that a particular medication will help a particular person.

But that does not mean the choice is random.

A good clinician does not simply cycle through antidepressants blindly.

Every prescription is a clinical hypothesis.

We assess the diagnosis, the predominant symptoms, comorbid conditions, previous responses to medication, side effects, other medications, sleep, anxiety, energy, appetite, concentration, and many other factors.

On that basis, we try to select the treatment with the profile most likely to fit that individual.

So this is not “guessing.”

It is a probability-based decision informed by knowledge, followed by evaluation of what actually happens in that particular person.

And this is where things become especially interesting.

It is not enough simply to ask:

“Does this person have depression?”

We need to understand what is actually causing the greatest difficulty.

For one person, severe anxiety and constant inner tension may dominate.

For another – insomnia.

For another – excessive sleepiness, low energy, and lack of initiative.

For another – chronic pain.

For another – panic attacks.

For another – difficulty concentrating.

For some patients, avoiding sexual side effects or weight gain may be especially important.

All of this can change both the choice of medication and the overall treatment strategy.

And, of course, diagnostic accuracy is crucial.

Is this truly unipolar depression?

Has there ever been hypomania?

Could there be ADHD, PTSD, an anxiety disorder, a sleep disorder, or a substance-related condition?

Could a medical illness be contributing to the symptoms?

What other medications is the person taking?

What have they already tried, and how did they respond?

Very often, this information turns out to be more useful than any laboratory test.

There is another important point.

The best medication today and the best medication six months from now may not necessarily be the same medication.

Imagine someone whose main problems were severe anxiety and depression.

We start treatment.

The anxiety improves substantially. The depression lifts. The person is working again, socialising, and living their life.

But several months later they say:

“I feel much better. But now I have no motivation. I find it hard to concentrate. I don’t want to start anything. I feel emotionally flat.”

What do we do then?

The first question is to understand what is actually happening.

Are these residual symptoms of depression?

A medication side effect?

Emotional blunting?

Sleep deprivation?

ADHD that became more noticeable once the anxiety improved?

Or something else entirely?

This is where we should not automatically think:

“The medication helped, so we should leave everything exactly as it is.”

Sometimes keeping the treatment unchanged is indeed the right decision.

Sometimes it makes sense to lower or adjust the dose.

Sometimes to add another treatment.

Sometimes to switch gradually to a medication with a different pharmacological profile.

This is why treatment is often better understood in stages.

At the beginning of an illness, the main goal may be to reduce severe anxiety, insomnia, suicidal thinking, or profound depression.

But once the person improves, the goals change.

Now we may care more about energy, motivation, concentration, emotional range, sexual functioning, return to work, relationships, and normal day-to-day activity.

Treatment must be able to change as well.

So is a well-chosen antidepressant a matter of luck or knowledge?

I would put it this way:

It is knowledge that increases the probability of making a good choice, but still cannot guarantee the outcome in advance.

Sometimes we genuinely get lucky and the first medication works extremely well.

Sometimes several steps are needed.

But the quality of those steps depends enormously on how well we understand the person in front of us.

Yes, genetics has become another useful tool.

But personalised psychiatry has turned out to be much broader than a single DNA test.

It is accurate diagnosis + clinical presentation + comorbid symptoms + previous treatment experience + other medical conditions and medications + side effects + patient preferences + sometimes pharmacogenetics + continuous reassessment of the outcome.

And one more important point.

Even a perfectly chosen antidepressant is not supposed to solve every problem in a person’s life.

It may reduce pathological anxiety.

It may help someone emerge from severe depression.

It may restore sleep, energy, and the ability to think and work.

It may make pleasure, relationships, plans, and action possible again.

But medication cannot automatically repair destructive relationships, chronic stress, loneliness, psychological trauma, or a lack of meaning and structure in life.

Those problems may require psychotherapy, work on sleep and lifestyle, treatment of comorbid conditions, changes in the person’s environment, and other approaches.

So today I am much less interested in the question:

“How do we find the perfect antidepressant?”

And much more interested in another question:

“How can we use everything we know about a particular person to make the most informed decisions possible at every stage of treatment?”

That is what personalised psychiatry really means.