Should antipsychotic medications be stopped as early as possible after the first episode?

Should antipsychotic drugs be discontinued as early as possible after the first episode - Yes or No? This was the subject of a debate at WCBP virtual 2021 co-chaired by Siegfried Kasper (Medical University of Vienna, Austria) and Peter Falkai (Medical University of Munich, Germany). The decision remains open to debate.

Professor Merete Nordentoft (Copenhagen University Hospital, Denmark), as proponent for discontinuation, began the session with a focus on the high proportion of patients that can maintain stability without treatment.

In a study of 10-year trajectories in 496 patients with first-episode psychosis, similar proportions of patients on and off antipsychotic medication were in remission at time of follow up. At 1-, 2-, 5-, and 10-years, remission rates were 23%, 26%, 24%, and 30% versus 37% 29%, 29%, and 30% for off and on medication, respectively.1


Treatment continuation is commonly in the hand of the patient

Professor Nordentoft highlighted the fact that clinicians do not have that much control over treatment discontinuation as it is patients who make the decision to discontinue.

It’s the patients themselves who decide to stop medication, not the clinicians

There is a large group of patients who want to stop medication and we need to know in which patients this can be advised. A naturalistic study in which patients in remission after first-episode psychosis who want to discontinue their medication will be followed monthly on the Scale for Assessment of Positive Symptoms (SAPS) as well as smartphone registration of warning signs is underway.


Treatment discontinuation can have grave consequences

The case against early discontinuation was put forward by Professor Robin Emsley (Faculty of Medicine and Health Sciences, Stellenbosch University, South Africa) who presented five compelling, straightforward reasons against treatment discontinuation:

  1. Virtually all patients will relapse. Literature shows the relapse rate after discontinuation after a first psychotic episode in short-term studies is around 80% at 12 months2-4
  2. Potentially grave consequences, including distress to patients and caregivers, derailment of recovery, increased risk of suicide and homicide, and disruption to education and employment5
  3. Relapses are a critical factor in the emergence of treatment-refractory psychosis6
  4. No discontinuation strategy has been effective3,4
  5. There are no realistic alternatives to antipsychotic medications

Antipsychotic maintenance treatment should be continued indefinitely, with the lowest effective dose

Further research in this area should be of the highest priority; meanwhile, based on available evidence and experience, for patients who have benefitted from treatment, the advice is to continue antipsychotic maintenance treatment indefinitely, with the lowest effective dose, said Professor Emsley.7


Clinicians need to be part of the discontinuation process

Overall, the decision is not clear-cut commented Professor Merete and should be taken on a case-by-case basis, depending on patient risk.

Before we stop treatment, we need to know in which patients we can stop, when to stop, and how to stop said Professor Emsley. As responsible physicians, we should recommend continuation of treatment, but if the patient is set on discontinuing, it is better if the clinicians are part of the discontinuation process.

Our correspondent’s highlights from the symposium are meant as a fair representation of the scientific content presented. The views and opinions expressed on this page do not necessarily reflect those of Lundbeck.

  1. Gotfredsen DR, et al. Stability and development of psychotic symptoms and the use of antipsychotic medication - long-term follow-up. Psychol Med. 2017;47:2118-2129.
  2. Chen EY, et al. Maintenance treatment with quetiapine versus discontinuation after one year of treatment in patients with remitted first episode psychosis: randomised controlled trial. BMJ. 2010;341.
  3. Gitlin M, et al. Clinical outcome following neuroleptic discontinuation in patients with remitted recent-onset schizophrenia. Am J Psychiatry. 2001;158:1835-42.
  4. Emsley R, et al. Symptom recurrence following intermittent treatment in first-episode schizophrenia successfully treated for 2 years: a 3-year open-label clinical study. J Clin Psychiatry. 2012;73:e541-7. 
  5. Emsley R, et al. The evidence for illness progression after relapse in schizophrenia. Schizophr Res. 2013;148:117-21. 
  6. Wiersma D, et al. Natural Course of Schizophrenic Disorders: A 15-Year Follow-up of a Dutch Incidence Cohort. Schizophrenia Bulletin 1998;24:75–85.
  7. Emsley R. Guest editorial: Special issue on maintenance treatment in schizophrenia. Schizophr Res. 2020;225:1-3.
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