Early Medication Discontinuation and Long-term Clinical Outcome in FEP

Study Overview
=================
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.

Official Title
-----------------
The Impact of Early Medication Discontinuation on Long-term Clinical Outcome in First Episode Psychosis

Conditions
-----------------
Schizophrenia

Participation Criteria
=================
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)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Early maintenance treatment group<br>Drug (quetiapine, 400mg/d) during the 12-month randomized phase of the study | |
| Early discontinuation group<br>Drug (placebo) during the 12-month randomized phase of the study | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Poor clinical outcome | Define categorically as any of: persistent positive symptoms of psychosis, requirement for clozapine or death from suicide. Good clinical outcome: meeting none of the criteria for Poor clinical outcome (as above) | In one month previous to the final assessment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Social and occupational functioning | Define using employment status, social and occupational functioning score, and role functioning score | In one month previous to the final assessment |