Continue with antipsychotics or taper off?

After a first psychotic episode (first-episode psychosis, FEP) people are almost always prescribed antipsychotics. Current guidelines advise continuing the medication for at least 1 to 2 years after recovery, because that reduces the risk of relapse. At the same time, many people want to reduce or stop as soon as possible after recovery, mainly because of side effects such as weight gain, fatigue, sexual problems, loss of motivation and cognitive slowing. The question whether early tapering may in fact be favourable in the long term for personal, social and societal functioning (think of work, study and relationships) has been central to research for years.

What do we know from the tapering trials so far?

The Dutch study by Wunderink and colleagues (2007, with a 7-year follow-up published in JAMA Psychiatry in 2013) was the first large study to suggest that guided dose reduction or discontinuation (DRD) led to better functional recovery in the long term (40.4% versus 17.6% with continuation), despite a higher relapse rate in the first 18 months. For a long time this result was the main argument for early tapering.

The study by Chen and colleagues (BMJ 2010), with the 10-year follow-up by Hui et al. (Lancet Psychiatry 2018), showed the opposite, however: in the discontinuation group 39% had a poor outcome, against 21% in the maintenance group. The Danish TAILOR study (Stürup et al.) in FEP patients from OPUS teams showed clearly higher relapse rates with tapering (around 53% versus 19% with maintenance treatment), without a demonstrable benefit for functioning within the relatively short follow-up. These studies cast doubt on how far the Wunderink findings can be generalised, and showed how sensitive the outcomes are to the length of follow-up and the pace of tapering.

The recently published HAMLETT study

The HAMLETT study (Handling Antipsychotic Medication Long-Term Evaluation of Targeted Treatment), carried out by UMC Groningen, UMC Utrecht and 26 Dutch psychosis centres, is with 347 participants the largest randomised study on this question. The results appeared on 1 October 2025 as a brief report in JAMA Psychiatry (Sommer et al.). Participants were followed for 4 years after randomisation to early dose reduction or discontinuation (DRD; n=168) or maintenance treatment (n=179).

The main outcomes:

On the primary patient-reported measure of functioning (WHODAS 2.0) there was no difference between the two groups over the whole study period. In the first year the tapering group had an increased risk of relapse (odds ratio 2.84) and a lower quality of life. From 3 years onwards, however, the tapering group showed better researcher-rated global functioning (GAF), with at 4 years also a trend towards lower symptom severity (PANSS). Strikingly, from 12 months onwards the average doses in the two groups were roughly equal. So the long-term benefit cannot be attributed directly to the lower medication. The authors interpret this as a “learning experience”: a guided attempt at tapering seems to give patients more insight into their vulnerability and more ownership of their treatment, which benefits long-term functioning. Safety was comparable between the groups, although it must be mentioned that 3 people in the tapering group died by suicide against 1 in the maintenance group.

In women, tapering seemed to turn out relatively more favourably, possibly because they are more often overdosed in standard treatment. A related HAMLETT/OPHELIA analysis (Gangadin et al., World Psychiatry 2025) showed that the speed of tapering in itself did not predict relapse, but the affinity of the antipsychotic for the D2 receptor did: caution is called for above all with strongly D2-antagonising drugs.

And in people with more than one psychosis?

It is important to stress that the HAMLETT findings cannot simply be carried over to people who have already been through several psychotic episodes. Other considerations apply there, and the risk of relapse is higher in this group. The results of the two largest recent randomised trials in multi-episode patients agree on this point.

The British RADAR study (Moncrieff et al., Lancet Psychiatry 2023), with 253 participants with long-term psychotic disorders, found no difference in social functioning between guided tapering and maintenance treatment after 2 years, while the risk of a severe relapse (including hospital admission) roughly doubled in the tapering group. The Taiwanese GARMED study (Liu et al., Psychological Medicine 2023), a dose reduction to the “minimum effective dose” without complete discontinuation in stable patients, likewise found no difference in social functioning or relapse rate between the groups, which suggests that careful dose reduction is safer than stopping completely. For multi-episode patients, maintenance treatment, possibly with careful dose optimisation towards the lowest effective dose, therefore seems the most responsible strategy.

There is nuance here too: some of the people with several episodes who taper off do succeed, and without relapse. For those who are strongly motivated to reduce, an individually agreed, very gradual and guided process remains possible, but with realistic expectations and a clear safety net if symptoms return.

The PsychosisNet tapering advice

In collaboration with the HAMLETT researchers, PsychoseNet has developed tapering advice for antipsychotics. The guide is practical in set-up and helps both patients and clinicians to make balanced choices. It contains information on when tapering is or is not wise, how to shape a tapering schedule in small, hyperbolic steps (instead of linear ones, which often go too fast), how to recognise early signs of an approaching relapse, and how loved ones can be involved. For the actual fine-grained tapering, tapering strips are available, with which a slightly lower dose can be taken each day. That makes safe tapering at a low dose level practically feasible, precisely on the stretch where most tapering problems occur.

Important: the guide is expressly not an encouragement to start reducing on your own. It is meant as an aid within a joint process with your clinician and loved ones. Stopping suddenly or tapering too fast is almost always a bad idea and raises the risk of relapse considerably.

How to weigh these results, and the limitations of tapering research

Randomised tapering trials are methodologically hard to carry out. In HAMLETT, 40% of the “maintenance group” in the end tapered anyway, against the protocol, which matches what we see in daily practice. Conversely, a considerable part of the tapering group keeps using medication. The pace of tapering in many older studies was also presumably too fast; gradual hyperbolic tapering in small steps, as applied in HAMLETT, is increasingly seen as the most responsible method. Furthermore, trial outcomes are mainly averages: they do not say what the best choice is for one person.

Because that is perhaps the most important message: tapering is fundamentally a personal weighing-up. For some people, reducing side effects, getting back energy and motivation, or regaining charge of their own life weighs heavily. For others, preventing a new relapse, with all its consequences for relationships, work and self-confidence, is decisive. Sex, the type of antipsychotic, the severity and course of the episode(s), social support and personal wishes all play a part.

Practical recommendation

Never start tapering on your own. Always discuss the possibility with your clinician and your loved ones, and do it step by step and with guidance. Use the tapering advice and, where needed, tapering strips for the fine dose reduction. The HAMLETT results confirm that guided tapering can be valuable in the long term for some people after a first psychosis, provided that extra vigilance is built in during the first year because of the increased risk of relapse. In people with several episodes more restraint is called for, and careful dose optimisation usually seems wiser than complete discontinuation.

Do not taper off on your own; always do this in consultation with your clinician and, where possible, loved ones and/or an expert by experience.

The HAMLETT study was carried out by UMC Utrecht and UMCG.

Do you need help now?

• Immediate danger to yourself or someone else: call the emergency number in your country.
• If you are thinking about suicide, or are worried about someone: contact a suicide prevention line in your country.
• Acute mental distress: call your GP or the out-of-hours medical service.

See Need help now? for emergency numbers and helplines per 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'.

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Blogs by Jim van Os can be read here

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