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Question
Question: What are the long-term effects of an antipsychotic dose-reduction/discontinuation (DR) strategy compared with maintenance treatment for people in remission from a first episode of psychosis?
Patients: One hundred and twenty-eight people with first-episode psychosis (FEP) who showed response of symptoms or sustained symptom remission during 6 months of antipsychotic treatment.
Setting: Seven mental healthcare organisations and the University Medical Center Groningen in the Netherlands.
Intervention: Antipsychotic dose DR, compared with maintenance therapy (MT) for 18 months. The DR strategy consisted of gradual symptom-guided tapering of dosage and discontinuation if feasible. MT was carried out according to the American Psychiatric Association guidelines, preferably using low-dose atypical antipsychotics.
Outcomes: Recovery at 7-year follow-up, defined as symptomatic and functional remission for at least 6 months. Symptom remission was assessed using the Positive and Negative Syndrome Scale (PANSS) and defined as a score below three on all relevant PANSS items during the previous 6 months. A person could not be categorised as being in symptomatic remission if they had a relapse (PANSS-item score above 3 for at least 1 week) during the previous 6 months. Functional remission was assessed with the Groningen Social Disability Schedule and defined as scores of one or lower on all seven domains, which corresponds to no or minimal disability, during the previous 6 months.
Patient follow-up: 80.5%.
Methods
Design: Randomised controlled trial.
Allocation: Not reported.
Blinding: Unblinded.
Follow-up period: Seven years.
Main results
At 7 years, 40.4% of the DR group had recovered compared with 17.6% of the MT group (). Logistic regression showed that DR increased the odds of recovery compared with MT (OR 3.49). Symptomatic remission was similar in both groups (69.2% with DR vs 66.7% with MT) but functional remission was significantly higher with dose DR (46.2% vs 19.6% with MT). Symptomatic remission without functional remission was achieved by 38.8% of all patients (28.8% with DR vs 49% with MT), and functional remission without symptomatic remission by 3.9% of all patients (5.8% with DR vs 2% with MT). Just over a quarter of patients (28.2%) achieved neither symptomatic nor functional remission.
Conclusions
An antipsychotic dose DR strategy increases the rate of long-term recovery and functional remission compared with MT in people who have achieved remission from FEP.
Notes: Over half the eligible patients with FEP were unwilling to participate in the trial. Non-participants showed lower levels of functioning, were less adherent to therapy, and were more difficult to engage. Results from this study may not be applicable to all patients with remission after FEP.
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Commentary
Although the efficacy of antipsychotics in the treatment of FEP is well documented, the optimal duration of treatment in FEP is not explicitly clear. Medication discontinuation is highly prevalent in FEP, and associated with increased relapse risk.1 However, few studies have examined alternative dosing strategies to traditional antipsychotic maintenance, and these have generally been short term (<2 years).2
Wunderink et al3 are the first to report long-term advantages of reduced antipsychotic burden in schizophrenia. Important strengths of this study are the long duration of follow-up (7 years) and the high-patient retention rate. If replicated, these findings could have significant clinical implications. They suggest that for some patients, short-term increases in relapse risk associated with dose DR are mitigated by long-term increases in recovery rates, driven by greater functional remission. Improvements in daily functioning are likely to be more meaningful to patients than symptomatic remission alone. Furthermore, lower cumulative antipsychotic burden may reduce risks of potential adverse effects of antipsychotics, such as movement disorders and the metabolic syndrome.
It would be important to understand which specific social functioning domains were responsible for the lower functional remission rate in the MT group, as these data were not presented. Does MT negatively impact, or antipsychotic dose reduction positively impact functioning? Or both? Factors including selection bias, a non-blinded study design and non-standardised antipsychotic medications may limit the generalisability of findings. Nevertheless, this study highlights the need to appreciate functional outcomes, not just symptomatic remission, with antipsychotic treatment.
Footnotes
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Sources of funding: Janssen-Cilag Netherlands and Friesland Mental Health Services, Leeuwarden, the Netherlands.
Footnotes
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Competing interests None.