Recovery and functional remission rates at 7 years following first-episode psychosis in patients treated using a dose-reduction/discontinuation strategy during the early stages of remission were more than double those in patients who received maintenance therapy in a randomized controlled trial.
The recovery rate was 40.4% in 52 patients who were randomly assigned to the dose reduction/discontinuation (DR) strategy after experiencing 6 months of remission, compared with 17.6% in 51 patients randomized to receive maintenance therapy for 18 months after 6 months of remission (odds ratio, 3.49). The functional remission rates were 46.2% and 19.6% in the two groups, respectively (OR, 4.62), Dr. Lex Wunderink of Friesland Mental Health Services, Leeuwarden, the Netherlands, and his colleagues reported. The results were published online July 3 in JAMA Psychiatry.
Symptomatic remission, at 69.2% and 66.7% in the groups, respectively, did not differ significantly (JAMA Psychiatry 2013 July 3 [doi: 10.1001/jamapsychiatry.2013.19]).
The findings, which are among the first to demonstrate major advantages of a dose reduction versus maintenance therapy strategy in patients with remission of first-episode psychosis, are also the first to look at long-term outcomes. Earlier studies demonstrated higher relapse rates and no advantages with DR, but those studies had follow-up of no more than 2 years, the investigators noted.
To evaluate the long-term outcome of an early-course DR strategy compared with maintenance therapy, they conducted this 7-year follow-up assessment of 103 out of 128 patients with first-episode psychosis who participated in one of the earlier trials with enrollment, at the start of their first remission, between October 2001 and December 2002.
Of note, time to first relapse during the experimental phase of the trial was about twice as high in the DR group initially, but "the curves then approached each other and came on par at approximately 3 years of follow-up. From then on, the findings were not significantly different," the investigators reported.
"The major issue is, of course, whether these striking results may be attributed to the treatment strategies in the original trial. There were no significant differences in any of the conceivable confounding variables between the two groups. Therefore, it seems likely that the original treatment strategy, be it dose reduction or maintenance therapy, has a profound effect on long-term outcome," they wrote, noting that the differences are largely the result of effects in the domains of functional remission and recovery.
The gains in functional capacity in the DR arm could be associated with the fact that successful discontinuation in the early course of first-episode psychosis was sustained for many years in almost all patients, who, on average, used a lower dose of antipsychotic drugs than did those in the maintenance therapy group.
The psychological impact of having been treated using a dose reduction strategy also might have played a role in the effects on functional capacity, but this was not measured, they said.
"The results of this study lead to the following conclusions: schizophrenia treatment strategy trials should include recovery or functional remission rates as their primary outcome and should also include long-term follow-up for more than 2 years, even up to 7 years or longer," the investigators said. The results "merit replication by other research groups," and underscore a need for also studying other alternative treatment strategies, such as extended-interval dosing strategies, they added.
This study was funded by unconditional grants from Janssen-Cilag Netherlands and Friesland Mental Health Services. The authors reported having no disclosures.