Clinical trial NCT01926340: Early Medication Discontinuation and Long-term Clinical Outcome in FEP
Official title: The Impact of Early Medication Discontinuation on Long-term Clinical Outcome in First Episode Psychosis
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Schizophrenia
Lead sponsor: The University of Hong Kong
Sponsor class: OTHER
Collaborators: name: Research Grants Council, Hong Kong
name: AstraZeneca
name: Food and Health Bureau, Hong Kong
name: University of British Columbia
First posted: 2013-08-20
Enrollment: 178
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Trained research assistants will approach patients at their upcoming out-patient consultations to introduce the follow-up study and to obtain written informed consent. Those who are not active cases in the Hong Kong Hospital Authority (HA) system will be invited by letter and telephone to participate in the study.

Brief summary: The study aims to examine the relationship between early maintenance therapy decisions in first episode psychosis, and the subsequent long-term clinical outcome at 9-10 years by comparing a group of patients who were randomized to discontinue (placebo) or continue medication (quetiapine) in the early stage of their psychotic disorders.

Detailed description: Design: This is a follow up or extension to the double-blind randomized placebo-controlled 12-month study (Chen et al., BMJ 2010;341:C4024-4). At any point during the 12-month study, patients who had relapsed or discontinued would stop the study medication (quetiapine or placebo) and that would be the end point of the randomized phase of the study. After completion of the randomized phase, patients will receive clinical guideline-based, open-label treatment. Trained research assistants will approach patients at their upcoming out-patient consultations to introduce the follow-up study and to obtain their written informed consent.

Data analysis plan \& handling of missing outcome data: Statistical analyses will be carried out according to the intention-to-treat principle. The primary outcome measure of the long-term clinical outcomes (suicide, clozapine treatment, persistent positive symptoms) between the groups randomized to early treatment discontinuation (placebo) or maintenance treatment (quetiapine) will be compared using risk ratios \[RR\] and 95% confidence intervals \[CI\].

For all patients, long-term outcome assessments will include longitudinal chart review over the follow-up period indicating suicide or clozapine treatment. Positive symptom will be assessed at the 10-year face-to-face interview, or in the situations where this data is not available, will be based on the last positive symptom assessment from the randomized study. We will assess the possible effect of this approach by conducting sensitivity analyses, namely re-classifying patients with missing end-point interviews as either all good outcome, or all poor outcome. A mediation analysis will also carried out to examine whether the effects of the intervention on long-term outcome are linked to relapse during the randomized phase.

The secondary outcome measures of social and occupational functioning will be analysed using RR or independent t-tests. Standardized mortality ratios (SMRs) based on age-sex population mortality rate and age-sex suicide rate will also be calculated.

Eligibility criteria: Inclusion Criteria:

* A diagnosis of schizophrenia or non-affective psychosis (schizophreniform disorder, schizoaffective disorder, brief psychotic disorder, or psychosis not otherwise specified) (DSM-IV)
* Aged 18 to 65 years
* Had been treated with antipsychotic drugs for at least 12 months
* No history of relapse or exacerbation or had to be asymptomatic (free of positive symptoms of psychosis) at study entry.

Exclusion Criteria:

* A diagnosis of drug-induced psychosis
* Current treatment with clozapine, with mood stabilizing medications (lithium, valproate or carbamazepine) or with depot medication
* Had high risk of suicide or violence
* Had poor adherence to treatment (missing\>50% of drug, \>50% missed clinic visits, or a history of medication discontinuation)

Primary outcomes:
measure: Poor clinical outcome
timeFrame: In one month previous to the final assessment
Secondary outcomes:
measure: Social and occupational functioning
timeFrame: In one month previous to the final assessment
Other outcomes:
measure: Relapse
timeFrame: During the randomized phase of the study
measure: Quality of life
timeFrame: In one month previous to the final assessment
Locations:
city: Hong Kong
country: Hong Kong
facility: Research Site
Study officials:
affiliation: The University of Hong Kong
name: Eric YH Chen, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hui CLM, Honer WG, Lee EHM, Chang WC, Chan SKW, Chen ESM, Pang EPF, Lui SSY, Chung DWS, Yeung WS, Ng RMK, Lo WTL, Jones PB, Sham P, Chen EYH. Long-term effects of discontinuation from antipsychotic maintenance following first-episode schizophrenia and related disorders: a 10 year follow-up of a randomised, double-blind trial. Lancet Psychiatry. 2018 May;5(5):432-442. doi: 10.1016/S2215-0366(18)30090-7. Epub 2018 Mar 15.