Antipsychotic medication and remission of psychotic symptoms 10 years after a first-episode psychosis
Introduction
Schizophrenia is a mental disorder displaying great heterogeneity regarding symptomatology, long-term outcome and functioning (Harrow and Jobe, 2010, Austin et al., 2013). This aspect of diversity calls for a treatment strategy that takes the various outcomes into consideration. Existing guidelines recommend 1–2 years of antipsychotic medication after a first episode psychosis, however continuous use of antipsychotic medication is preferred among multiple episode patients in order to minimize the risk of relapse. The recommendations are based upon results from randomized clinical trials showing that discontinuation increases the risk of relapse (Takeuchi et al., 2012, Hasan et al., 2013, Leucht et al., 2012).
A recent review on discontinuation has reported trials with relapse rates as high as 79% within 12 months of discontinuation. Yet, none of the trials followed the patients for > 3 years and long-term studies are lacking (Zipursky et al., 2013, Emsley et al., 2013). At present, no consensus exists on the optimal duration of antipsychotic medication after remission of psychotic symptoms, but there is a tendency towards recommending long-term treatment (Takeuchi et al., 2012, Hasan et al., 2013, Leucht et al., 2012). A recent study on patients with first-episode psychosis that applied a guided discontinuation/dose reduction strategy revealed that 20% of the patients were able to obtain stable remission without continuous use of antipsychotic medication or dose reduction. Patients who discontinued had twice the relapse rate after 18 months (Wunderink et al., 2007). However, the 7-year follow-up showed no significant difference in relapse rate between patients on antipsychotic medication and patients who completed discontinuation or dose reduction (Wunderink et al., 2013).
Since antipsychotic medication can cause adverse effects e.g. extrapyramidal symptoms and a highly increased risk of metabolic syndrome, it is important to identify which patients might be able to obtain stable remission without continuous use of this medication (Leucht et al., 1999, Mitchell et al., 2013). This subgroup is not fully taken into account in the present guidelines and further investigation on long-term perspectives is needed. Regardless of antipsychotic medication, proper management of symptoms both on short and long-term basis is of great importance, since it has a major effect on functional outcome (Cassidy et al., 2010).
The Danish OPUS trial and cohort has investigated patients with a first episode psychosis in a time course of 10 years, which has enabled a thorough investigation on long-term outcome. This study design allows for a large degree of generalizability due to the long follow-up period and the large patient population with a high level of representativity (Petersen et al., 2005). The purpose of this study is to examine the proportion of patients who did not receive antipsychotic medication at the 10-year follow-up and who at the same time had remission of psychotic symptoms. Furthermore, we aim to identify different characteristics associated with this favourable outcome.
Section snippets
Study design
This study was based on data from the Danish OPUS-cohort, consisting of 578 patients, aged between 18 and 45 years and diagnosed with psychotic illness, i.e. within the F20–F29 spectrum according to the ICD-10. Patients with a diagnosis of schizotypal disorder were excluded from the data set, given that the main focus of this study is on psychotic illness, resulting in a study population of 496 patients.
At the time of recruitment the patients had not received antipsychotic medication for > 12
Participants
At the 10-year follow-up 303 patients participated resulting in a follow-up rate on 61%. At the 10-year follow-up 33 were deceased and 18 had emigrated and when excluding these patients, the follow-up rate was 68% (Austin et al., 2013). At the time of the baseline inclusion, participants had an average age of 26.3 years, 55.4% were male and the majority of the patients were diagnosed with schizophrenia (79.2%), whereas the remaining participants were diagnosed with different psychotic disorders
Long-term remission of psychotic symptoms
This longitudinal cohort study investigated the long-term outcome in patients with a first episode of psychosis regarding the use of antipsychotic medication and psychotic symptoms. One of the main findings was that 30% of the patient population obtained remission of psychotic symptoms and were not treated with antipsychotic medication at the time of the 10-year follow-up.
Numerous cohort studies have examined the long-term outcome in patients with psychotic illness, including remission of
Conclusion
In this study we found that 10 years after being diagnosed with a first episode of psychosis, almost a third of the patients achieved remission of psychotic symptoms and at the same time did not use antipsychotic medication at the time of the follow-up. Female gender, absence of substance abuse, high GAF-F and having a job were significantly associated with a favourable long-term outcome.
The fact that such a large proportion of patients was in the Remitted-off-medication group after 10 years
Author's contributions
Merete Nordentoft, Carsten Hjorthøj, Ditte Resendal Gotfredsen and Regitze Sølling Wils initiated and planned the study. Regitze Sølling Wils and Ditte Resendal Gotfredsen drafted and revised the manuscript supervised by Merete Nordentoft and Carsten Hjorthøj. Regitze Sølling Wils and Ditte Resendal Gotfredsen conducted statistical analyses, supervised by Carsten Hjorthøj. Stephen Austin and Gry Secher interviewed and tested the patients at year 10. Ole Mors organized the 10-year follow-up in
Conflict of interest
All authors declare that they have no conflicts of interest.
Funding
The Danish Council for Independent Research (Medical Sciences; 9601612 and 9900734); Trygfonden; The Mental Health Services of the Capital Region of Denmark; the Danish Ministry of Health (96-0770-71); the Danish Ministry of Social Affairs; and the Psychiatry and Social Service Department in Central Denmark Region.
Ethics committee approval
The local ethics committee approved the trial (KF 01-387-97).
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These authors contributed equally to this work.