The Perilous Journey of First-Episode Psychosis

July 13, 2016

What is the risk of symptom recurrence after antipsychotic discontinuation in first-episode psychosis?


According to the Texas Medication Algorithm Project for schizophrenia, “A trial period off antipsychotics may be reasonable for some patients early in the course of illness. This, an individualized decision, depends on a number of factors that do not lend themselves to an algorithmic approach. . . .Thus, the schizophrenia algorithm contains no guidelines for antipsychotic medication discontinuation.”1 Similarly, the American Psychiatric Association Practice Guideline for the Treatment of Patients with Schizophrenia, 2nd edition, concluded:

“Unfortunately there is no reliable indicator to differentiate the minority who will not from the majority who will relapse with drug discontinuation. Indefinite maintenance antipsychotic medication is recommended for patients who have had multiple prior episodes or two episodes within five years.”2

Thus, the optimal duration of antipsychotic treatment in first-episode psychosis (FEP) is not explicitly clear. One study found that in patients with remitted FEP, antipsychotic dose reduction or discontinuation during the early phases of illness may be associated with better long-term functional outcome.3

[[{"type":"media","view_mode":"media_crop","fid":"49475","attributes":{"alt":"","class":"media-image media-image-right","id":"media_crop_7117907629933","media_crop_h":"0","media_crop_image_style":"-1","media_crop_instance":"6103","media_crop_rotate":"0","media_crop_scale_h":"0","media_crop_scale_w":"0","media_crop_w":"0","media_crop_x":"0","media_crop_y":"0","style":"float: right; width: 272px; height: 247px;","title":"©Blackjack/Shutterstock","typeof":"foaf:Image"}}]]Mayoral-van Son and colleagues4 investigated long-term illness relapse and functional outcomes at 18 and 36 months after antipsychotic treatment discontinuation in patients with a functional recovery from first-episode nonaffective psychosis using an open-label, non-randomized design. Participants in the study came from an ongoing longitudinal intervention program of first-episode psychosis (PAFIP) at the University Hospital Marques de Valdecilla, Santander, Cantabria, Spain.

Inclusion criteria were (1) antipsychotic treatment for ≥ 18 months, (2) satisfies clinical remission criteria for ≥ 12 months, (3) satisfies functional recovery criteria for ≥ 6 months, and (4) stabilized at the lowest effective antipsychotic dose for ≥ 3 months. Sixty-eight subjects met these criteria and agreed to participate, of whom 46 were willing to discontinue and 22 opted to continue the prescribed antipsychotic medication.

All participants had clinical and functional assessments during the 3-year follow-up period. In the treatment discontinuation group, patients were seen monthly for 6 months, then every 2 months for the next 12 months, and then at the discretion of the treatment psychiatrist. Patients in the maintenance group were regularly seen at the discretion of the treating psychiatrist.

In the discontinuation group, duration of untreated psychosis, baseline positive symptoms, living with family, and family history were not significant predictors of relapse.


Patients in the maintenance group had higher baseline clinical global impression scores, a higher mean chlorpromazine equivalent antipsychotic dose at study entry, and a shorter duration of antipsychotic treatment than those in the discontinuation group.

In the discontinuation group, 31 patients (67%) relapsed during the 3-year study period, with a mean time to relapse of 209 days; 40% of relapses occurred within the first 6 months after discontinuation. In the discontinuation group, duration of untreated psychosis, baseline positive symptoms, living with family, and family history were not significant predictors of relapse.

In the maintenance group, 7 patients (31%) relapsed at least once during the 3-year study period, with a mean time to relapse of 608 days. None of these patients had a relapse at 12 months.

These between-group differences were statistically significant. Of note, the majority (30 of 38) of patients who relapsed had no subsequent relapses/exacerbations during the remaining observation period after resuming antipsychotic treatment. Furthermore, there were no differences in the severity of symptoms and functional status at 3 years between subject groups. The authors noted the non-randomized, open-label design, and modest sample size were important factors to consider in the interpretation of study findings.

The bottom line
The authors found an extremely high rate of symptom recurrence following self-elected discontinuation of antipsychotic medication in functionally recovered patients with FEP.


Dr. Miller is Associate Professor in the Department of Psychiatry and Health Behavior at Augusta University in Augusta, GA, and Schizophrenia Section Editor for Psychiatric Times. He reports no conflicts of interest concerning the subject matter of this article.


1.  Moore TA, Buchanan RW, Buckley PF, et al. The Texas Medication Algorithm Project antipsychotic algorithm for schizophrenia: 2006 update. J Clin Psychiatry. 2007;68:1751-1762.
2. Lehman AF, Lieberman JA, Dixon LB, et al. Practice guideline for the treatment of patients with schizophrenia, second edition. Am J Psychiatry. 2004;161(suppl 2):1-56.
3. Wunderink L, Nienhuis FJ, Sytema S, et al. Guided discontinuation versus maintenance treatment in remitted first-episode psychosis: relapse rates and functional outcome. J Clin Psychiatry. 2007;68:654-661.
4. Mayoral-van Son J, Ortiz-Garcia de la Foz V, Martinez-Garcia O, et al. Clinical outcome after antipsychotic treatment discontinuation in functionally recovered first-episode nonaffective psychosis individuals: a 3-year naturalistic follow-up study. J Clin Psychiatry. 2016;77:492-500.