Long-Term Antipsychotic Medication for Patients with a First Psychotic Episode: Further Evidence

Amsterdam, November 29, 2010: An unanswered question in the management of patients with first-episode psychosis is whether or not they should receive long-term, continuous treatment with antipsychotic medications. In some cases patients themselves are unwilling to receive indefinite treatment for several reasons including lack of insight and concern about potential side effects of medication. Their physicians may also have reservations about continued treatment because of the knowledge that 10–15% of first-episode patients will never have a recurrence.1

This topic was the focus of a symposium at the 7th International Conference on Early Psychosis.

Evidence – The evidence for prolonged therapy in the treatment of schizophrenia indeed has seemed somewhat inconsistent. Although guidelines recommend continuing treatment for 12–24 months in patients whose symptoms are now stable,2 few antipsychotic maintenance trials have continued beyond one year. A literature review of 66 studies including 4365 patients found, over a mean follow-up period of 9.7 months, a mean relapse rate of 53% in patients who discontinued treatment vs. 16% in those who had maintenance therapy.3

Although these findings suggest that some patients who stop therapy will not relapse, most of the contributing studies  were  in patients with multiple psychotic episodes and  therefore are not relevant to the management of those with a first episode, explained Professor Robin Emsley, University of Stellenbosch, Tygerberg, Cape Town, South Africa.

Relapse After Discontinuation ­–  Relapse increases the risk that patients will harm themselves or others and jeopardise their relationships, education and employment prospects. Some observers also have proposed (although empirical evidence is lacking) that each relapse is associated with a progressive deterioration in function and that treatment refractoriness may emerge.4Consequently, there is a growing opinion that first-episode patients need a sustained and possibly indefinite period of medication.5

Professor Emsley conducted a 24-month, open-label study of risperidone long-acting injection (RLAI) in 50 patients with new-onset schizophrenia or related disorders.6 Thirty-six patients (72%) completed the trial of whom 32 (64%) achieved remission, and 62% remained in remission throughout the study. An extension to this study7 examined the clinical outcome in those patients who then discontinued their antipsychotic medication.

Patients and their families were informed of the risks and benefits of treatment discontinuation and were offered but declined the option of ongoing maintenance treatment. They were also informed about the early warning signs of relapse and given a 24-hour mobile telephone number to contact the trial coordinator. Formal assessments were conducted every 2 months during the first year and at 3-monthly intervals thereafter, with more frequent contact with staff provided as needed. Relapse was defined if patients met any of the following criteria: psychiatric hospitalisation; a 25% increase in Positive and Negative Syndrome Scale (PANNS) total score; significant clinical deterioration defined as a CGI-C score of 6 (much worse); deliberate self injury; emergence of clinically significant suicidal or homicidal ideation; violent behaviour resulting in significant injury to another person or significant property damage. Patients who experienced relapse received immediate treatment with oral risperidone and RLAI.

A prespecified interim analysis showed that two years after stopping antipsychotic therapy all but one of the patients (94%) had relapsed.8  Relapse was unpredictable and rather abrupt with PANNS scores increasing rapidly over days or, at most, weeks, to very high levels – similar to those recorded during the first episode. Professor Emsley concluded that the majority of patients with early psychosis respond well to treatment with most achieving sustained remission. However, relapse rates in this group of patients are very high following treatment discontinuation. “What our patients need most seems to be uninterrupted, ongoing, antipsychotic medication.”


1) Moller H, von Ziersen, D. Course and outcome of schizophrenia. In: Hirsh SR, Weinberger, DR, editor. Schizophrenia. Oxford: Blackwell; 1995.

2) McEvoy JP et al. Treatment of schizophrenia 1999. The expert consensus guideline series. J Clin Psychiatry. 1999;60 Suppl 11:3-80.

3) Gilbert PL, Harris MJ, McAdams LA, Jeste DV. Neuroleptic withdrawal in schizophrenic patients. A review of the literature. Arch Gen Psychiatry. 1995;52:173-88.

4) Wyatt RJ, Green MF, Tuma AH. Long-term morbidity associated with delayed treatment of first admission schizophrenic patients: a re-analysis of the Camarillo State Hospital data. Psychol Med. 1997;27:261-8.

5) Zipursky RB. Psychotic recurrence after antipsychotic discontinuation. Am J Psychiatry. 2002;159:1441-2; author reply 2.

6) Emsley R, Medori R, Koen L, Oosthuizen PP, Niehaus DJ, Rabinowitz J. Long-acting injectable risperidone in the treatment of subjects with recent-onset psychosis: a preliminary study. J Clin Psychopharmacol. 2008;28:210-3.

7) Emsley R et al. A prospective study of the clinical outcome following treatment discontinuation after remission in first-episode schizophrenia.  Poster presented at the 7th biennial IEPA (International Early Psychosis Association) meeting; 2010; 29 November- 1 December: Amsterdam, The Netherlands.

8) Emsley R. Data presentation presented at the 7th biennial IEPA (International Early Psychosis Association) meeting; 2010; 29 November- 1 December: Amsterdam, The Netherlands.