The myth of a linear effect

We tend to think in straight lines. More painkiller means less pain. More sleeping pill, more sleep. So you would think: more antidepressant, less depression. But the effect of psychiatric medication does not follow a simple logic. It is not a volume knob. The effects are non-linear, and they differ strongly from person to person. This is also called idiosyncratic.

That means: what works for one person may work the wrong way round for another. And what brings relief in a low dose can, in a higher dose, lead to worse complaints or side effects, without any increase in the therapeutic effect.

Antidepressants: not a matter of ‘more is better’

Take SSRIs such as sertraline or escitalopram. These medicines raise the level of serotonin in the brain, or at least that is the idea. But the exact link between serotonin and depression is still not well understood. What we do know is that the side effects often increase a good deal at higher doses: nausea, sexual problems, sleeplessness, anxiety, inner restlessness, and in some people even suicidal thoughts.

Some people feel better on a low dose. Others feel flat, numbed or more anxious. And for some the medicine simply does nothing at all, however high the dose.

Antipsychotics: more pills, more side effects?

Or look at antipsychotics such as olanzapine or aripiprazole. These medicines are often prescribed for psychosis susceptibility, but also for anxiety or mood complaints. They influence dopamine, an important chemical messenger in the brain. Here too: we understand the mechanism only in part. And the side effects can be considerable: weight gain, movement disorders (such as akathisia or muscle stiffness), tiredness, a raised risk of diabetes, or sexual side effects.

Sometimes a low dose works better than a high one. And sometimes it has nothing to do with the dose, but everything with how someone is doing in their body and their life. And sometimes it simply does not work at all. Medication does not fill in for human complexity.

Mood stabilisers: seeking balance, not a control knob

With mood stabilisers such as lithium, valproate or lamotrigine we see no straight link between dose and effect either. Lithium can work well in preventing mania, for example, but the therapeutic margin is narrow: a little too much and people can get tremors, thirst, memory problems or even signs of poisoning. Lamotrigine is often used for bipolar depression, but the dose has to be built up extremely slowly because of the risk of serious skin reactions. And with valproate, weight gain, hair loss and liver problems can occur.

Here too: the side effects often increase in line with the dose, the effect seldom does. Or not at all.

What do we really know about brain and mind?

The most honest answer? Not as much as we would like. We know there are links between brain activity, neurotransmitters and mood or behaviour. But the bridge between brain chemistry and inner experience remains largely a mystery. We do not know, for example, why some people become suicidal on antidepressants while others get better on them. Or why antipsychotics bring calm to one person and restlessness or anxiety to another.

The lesson: listening, tuning, respecting

Psychiatric medication can help. For some people it is an important support. But the thought that more of something also works better is misleading, and it can be downright harmful. It takes fine-tuning, patience, self-knowledge and mutual trust to discover what helps and what does not.

Above all it asks for recognition of something that is often forgotten in medical logic: that a human being is not a machine. That mind and body do not always fit into one clear scheme. And that ‘effect’ is always something personal.

So if you start medication, or already use it, know this: you are the expert on your own experience. And your experience counts.

Read more: Shared decision-making when tapering off.

Do you need help now?

PsychosisNet offers information. We do not offer a chat, a helpline or crisis support. If you or someone else is in immediate danger, call the emergency number in your country. If you are thinking about suicide, or you need to talk to someone now, see Need help now? for helplines by country.

Prof. dr. Jim van Os, Chair Division Neuroscience, Utrecht University Medical Centre. Jim works at the interface of ‘hard’ brain science, health services research, art and subjective experiences of people with ‘lived experience’ in mental healthcare. 

Jim has been appearing on the Thomson-Reuter Web of Science list of ‘most influential scientific minds of our time’ since 2014. In 2014 he published his book ‘Beyond DSM-5‘, and in 2016 the book ‘Good Mental Health Care’. In 2026 he published 'Wat psychisch lijden is'.

Want to read more?

Blogs by Jim van Os can be read here

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