Currently there is no consensus regarding how long anti-psychotics medication should be continued following a first/single psychotic episode. Clinically patients often request discontinuation after a period of remission. This is one of the first double-blind randomized-controlled studies designed to address the issue.

Patients with DSM-IV schizophrenia and related psychoses (excluding substance induced psychosis) who remitted well following a first/single-episode, and had remained well on maintenance medication for one year, were randomized to receive either maintenance therapy with quetiapine (400 mg/day), or placebo for 12 months. Relapse was defined by the presence of (i) an increase in at least one of the following PANSS psychotic symptom items to a threshold score (delusion, hallucinatory behaviour, conceptual disorganization, unusual thought content, suspiciousness); (ii) CGI Severity of Illness 3 or above; and (iii) CGI Improvement 5 or above.

178 patients were randomized. 144 patients completed the study (80.9%). The relapse rate was 33.7% (30/89) for the maintenance group and 66.3% (59/89) for the placebo group (log-rank test, chi-square=13.328, p<0.001). Relapse was not related to age or gender. Other significant predictors of relapse include medication status, pre-morbid schizotypal traits, verbal memory and soft neurological signs.

There is a substantial risk of relapse if medication is discontinued in remitted first-episode psychosis patients following one year of maintenance therapy. On the contrary 33.7% of patients discontinued medication and remained well.