Data from countries such as Finland show that people with psychosis who use antipsychotics regularly live longer than people who do not use them. Even so, more and more questions are being asked about the long-term use of antipsychotics. Here we describe where things stand, so that you can use it to your advantage.
Antipsychotics and health
Antipsychotics raise the risk of obesity, heart rhythm problems and disturbances of fat metabolism, in some cases to the point that insulin resistance and diabetes develop. The newer, so-called second-generation antipsychotics do this more than first-generation antipsychotics. In this way antipsychotics contribute to the shorter life expectancy of people who are treated for psychosis. Read more about the metabolic syndrome.
The implication is that long-term use of antipsychotics has to be kept to a minimum in any case or, where possible, stopped. There has to be an active policy around the risk of weight gain and diabetes.
Long-term research shows that at least 20 to 30% of people with psychosis who use antipsychotics can stop the medication. For each person a balance has to be found between the protective and the toxic effects of the medication.
Antipsychotics and the brain
Neuroimaging research (MRI) of the brain in participants with psychosis shows changes. Some of those changes may have to do with psychosis susceptibility itself, or with the environmental risk factors that contribute to it, such as trauma. It is also clear that many of the changes have to do with a range of non-specific factors such as antipsychotics, smoking, obesity and the use of drugs.
Animal research has confirmed that antipsychotics contribute to brain changes. It is not known how far these effects come with specific risks, or how far lasting changes can occur.
Antipsychotics and negative symptoms
Antipsychotics work by making people a little indifferent. The importance of the psychosis decreases and symptoms can fade. The problem is that the indifference antipsychotics bring about does not concern the psychosis alone; it extends to everything the person experiences. Emotions are dampened, so that the person becomes flatter and takes less initiative.
How far this goes differs from person to person, but it can be very limiting. This flattening through antipsychotics is called ‘secondary negative symptoms‘. That is confusing, because it is not possible to tell primary negative symptoms (through the psychosis) from secondary ones (through the antipsychotics).
In practice the rule of thumb has to be: negative symptoms (flattening, loss of initiative) are a consequence of the antipsychotics until the opposite is proven.
In other words: they have to be treated, and not wrongly attributed to the psychosis when the medication is the cause.
Do antipsychotics make psychosis worse? The dopamine supersensitivity syndrome
If someone uses antipsychotics for a long time, the body will try to compensate for the effects of the medication. Because antipsychotics work by blocking the dopamine D2 receptor, the body will try to undo this blockade in one way or another. As early as the late 1970s the researcher Chouinard described that this can lead to ‘supersensitivity’ of the dopamine D2 receptor, so that psychosis susceptibility can increase, not decrease.
Symptoms of the dopamine supersensitivity syndrome are:
- Abnormal movements, also called tardive dyskinesia
- Increasing psychosis susceptibility
- Needing more and more medication to suppress psychosis
- Becoming psychotic more and more often after stressful events
The existence of DSS has not been demonstrated beyond doubt, but in practice it is increasingly taken into account. There is research suggesting that people who reduce their medication, or even stop it, have a higher chance of a new psychosis in the first years (perhaps through the ‘supersensitive’ D2 receptor), but function better in the longer term (once the ‘supersensitive’ D2 receptor has settled) than people who continue on the usual, higher dose. Read what the research shows on continuing antipsychotics or tapering off.
Many psychiatrists are still not familiar with DSS
It is important to recognise DSS at an early stage, to prevent people ending up on a very high dose of antipsychotics with a strongly increased psychosis susceptibility.
The antipsychotic clozapine can offer a way out, because it binds less tightly to the D2 receptor, so that the receptor can settle and psychosis susceptibility can decrease, as can the abnormal movements. Animal research also shows that the so-called ‘partial dopamine agonists‘ may carry less risk of DSS.
Conclusion
Thinking about antipsychotics is changing fast. If you use antipsychotics, take the risk of DSS into account. Doctors who prescribe antipsychotics have to do the same.
From the very start of antipsychotic use, there has to be an active search for strategies to reduce the dose to a minimum, with an eye for physical health and effects on the brain. Partial dopamine agonists or clozapine can be an alternative. Read our tips for tapering off your medication.
Learning to deal with psychotic phenomena, for example with acceptance and commitment therapy (ACT), is used far too little in practice. Helping people find their way back to education and work, at an adapted level where needed, may well be the best medicine: taking part in the social world helps people recover.
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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