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:<\/p>\n
\u201cThis is the drug for you.\u201d<\/p>\n
More than twenty years have passed.<\/p>\n
So where are we now?<\/p>\n
Genetics has turned out to be useful. But not quite in the way many of us imagined back then.<\/p>\n
Today, a genetic test still cannot reliably answer the question that matters most to patients:<\/p>\n
\u201cWhich antidepressant will work best for me?\u201d<\/p>\n
It is much better at answering a different question:<\/p>\n
\u201cHow will my body process certain medications?\u201d<\/p>\n
These are fundamentally different questions.<\/p>\n
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.<\/p>\n
If metabolism is very rapid – the concentration may be lower.<\/p>\n
This is why a red category on a commercial genetic test usually does not mean:<\/p>\n
\u201cThis drug will not work.\u201d<\/p>\n
It more often means:<\/p>\n
\u201cThere is a genetic factor related to this medication that the clinician should take into account.\u201d<\/p>\n
That may mean a different dose, more cautious prescribing, or considering an alternative.<\/p>\n
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.<\/p>\n
But if genetics cannot yet identify the ideal drug for us, does that mean we are still treating patients by trial and error?<\/p>\n
To some extent – yes.<\/p>\n
We still cannot guarantee in advance that a particular medication will help a particular person.<\/p>\n
But that does not mean the choice is random.<\/p>\n
A good clinician does not simply cycle through antidepressants blindly.<\/p>\n
Every prescription is a clinical hypothesis.<\/p>\n
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.<\/p>\n
On that basis, we try to select the treatment with the profile most likely to fit that individual.<\/p>\n
So this is not \u201cguessing.\u201d<\/p>\n
It is a probability-based decision informed by knowledge, followed by evaluation of what actually happens in that particular person.<\/p>\n
And this is where things become especially interesting.<\/p>\n
It is not enough simply to ask:<\/p>\n
\u201cDoes this person have depression?\u201d<\/p>\n
We need to understand what is actually causing the greatest difficulty.<\/p>\n
For one person, severe anxiety and constant inner tension may dominate.<\/p>\n
For another – insomnia.<\/p>\n
For another – excessive sleepiness, low energy, and lack of initiative.<\/p>\n
For another – chronic pain.<\/p>\n
For another – panic attacks.<\/p>\n
For another – difficulty concentrating.<\/p>\n
For some patients, avoiding sexual side effects or weight gain may be especially important.<\/p>\n
All of this can change both the choice of medication and the overall treatment strategy.<\/p>\n
And, of course, diagnostic accuracy is crucial.<\/p>\n
Is this truly unipolar depression?<\/p>\n
Has there ever been hypomania?<\/p>\n
Could there be ADHD, PTSD, an anxiety disorder, a sleep disorder, or a substance-related condition?<\/p>\n
Could a medical illness be contributing to the symptoms?<\/p>\n
What other medications is the person taking?<\/p>\n
What have they already tried, and how did they respond?<\/p>\n
Very often, this information turns out to be more useful than any laboratory test.<\/p>\n
There is another important point.<\/p>\n
The best medication today and the best medication six months from now may not necessarily be the same medication.<\/p>\n
Imagine someone whose main problems were severe anxiety and depression.<\/p>\n
We start treatment.<\/p>\n
The anxiety improves substantially. The depression lifts. The person is working again, socialising, and living their life.<\/p>\n
But several months later they say:<\/p>\n
\u201cI feel much better. But now I have no motivation. I find it hard to concentrate. I don\u2019t want to start anything. I feel emotionally flat.\u201d<\/p>\n
What do we do then?<\/p>\n
The first question is to understand what is actually happening.<\/p>\n
Are these residual symptoms of depression?<\/p>\n
A medication side effect?<\/p>\n
Emotional blunting?<\/p>\n
Sleep deprivation?<\/p>\n
ADHD that became more noticeable once the anxiety improved?<\/p>\n
Or something else entirely?<\/p>\n
This is where we should not automatically think:<\/p>\n
\u201cThe medication helped, so we should leave everything exactly as it is.\u201d<\/p>\n
Sometimes keeping the treatment unchanged is indeed the right decision.<\/p>\n
Sometimes it makes sense to lower or adjust the dose.<\/p>\n
Sometimes to add another treatment.<\/p>\n
Sometimes to switch gradually to a medication with a different pharmacological profile.<\/p>\n
This is why treatment is often better understood in stages.<\/p>\n
At the beginning of an illness, the main goal may be to reduce severe anxiety, insomnia, suicidal thinking, or profound depression.<\/p>\n
But once the person improves, the goals change.<\/p>\n
Now we may care more about energy, motivation, concentration, emotional range, sexual functioning, return to work, relationships, and normal day-to-day activity.<\/p>\n
Treatment must be able to change as well.<\/p>\n
So is a well-chosen antidepressant a matter of luck or knowledge?<\/p>\n
I would put it this way:<\/p>\n
It is knowledge that increases the probability of making a good choice, but still cannot guarantee the outcome in advance.<\/p>\n
Sometimes we genuinely get lucky and the first medication works extremely well.<\/p>\n
Sometimes several steps are needed.<\/p>\n
But the quality of those steps depends enormously on how well we understand the person in front of us.<\/p>\n
Yes, genetics has become another useful tool.<\/p>\n
But personalised psychiatry has turned out to be much broader than a single DNA test.<\/p>\n
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.<\/p>\n
And one more important point.<\/p>\n
Even a perfectly chosen antidepressant is not supposed to solve every problem in a person\u2019s life.<\/p>\n
It may reduce pathological anxiety.<\/p>\n
It may help someone emerge from severe depression.<\/p>\n
It may restore sleep, energy, and the ability to think and work.<\/p>\n
It may make pleasure, relationships, plans, and action possible again.<\/p>\n
But medication cannot automatically repair destructive relationships, chronic stress, loneliness, psychological trauma, or a lack of meaning and structure in life.<\/p>\n
Those problems may require psychotherapy, work on sleep and lifestyle, treatment of comorbid conditions, changes in the person\u2019s environment, and other approaches.<\/p>\n
So today I am much less interested in the question:<\/p>\n
\u201cHow do we find the perfect antidepressant?\u201d<\/p>\n
And much more interested in another question:<\/p>\n
\u201cHow can we use everything we know about a particular person to make the most informed decisions possible at every stage of treatment?\u201d<\/p>\n
That is what personalised psychiatry really means.<\/p>\n","protected":false},"excerpt":{"rendered":"
In the early 2000s, as a young researcher in psychopharmacology, […]<\/p>\n","protected":false},"author":2,"featured_media":4688,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[21],"tags":[],"class_list":["post-4689","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-good-to-know"],"yoast_head":"\n