Guided Dose Reduction of Antipsychotic in Patients With Psychosis in Remitted States

• Conditions: Remission; Psychosis

• Registration Number: NCT03248180
• Lead Sponsor: National Taiwan University Hospital

Brief Summary

A 2-year prospective observational study comparing a group of patients in remitted states of psychosis undergoing guided antipsychotic dose reduction to a similar group of patients under maintenance antipsychotic treatment with the main outcome of interest that if the rates of relapse of psychosis between these two groups will be different.

Detailed Description

Early intervention at the beginning of schizophrenia and related psychotic disorders can get better treatment response. Once symptoms subsided, the majority of patients wish to discontinue medications, yet currently the mainstream opinions still recommend maintenance antipsychotic therapy because non-adherence to medication is the most significant risk factor to predict a relapse. However, recent longitudinal studies assessing patients in community for a longer term found that their functioning is not necessarily poorer despite not regularly treated with antipsychotics. Also there are studies suggesting a lower percentage of dopamine occupancy by antipsychotic is acceptable in stable patients with psychosis. To elucidate such discrepancies, a hypothetical compromised approach "guided dose reduction, but not aiming at discontinuation"is proposed. In this study, we will recruit outpatients with schizophrenia related psychotic disorders under remitted states, randomize into guided dose reduction group (GDR, n = 80) and maintenance treatment group (MTG), including those who willing to have dose reduction but assigned to maintenance group (MTG1, n = 40) and those who willing to continue medication serving as naturalistic observation group (MTG2, n = 40), and follow up for at least 2 years. The main outcomes of interests are differences in relapse rates, personal social performance, quality of life, drug-related adverse reactions, medication satisfaction, and neurocognitive function between groups.We will also have patients to keep logs of medication status, blood tests for therapeutic drug monitoring, biochemistry, and potential biomarkers, as well as take into account demographic variables such as age, gender, education, employment status, and supportive system, and clinical variables such as age of onset, duration of illness, history of psychiatric admission, the highest and the lowest doses of antipsychotics during previous treatment, the number of different antipsychotics having being tried before, if a history of impending relapse during tapering down dose of antipsychotics, and concomitant psychotropic agents, to test whether these variables are related to outcomes during follow-up. Hopefully we can identify a satisfactory and balanced solution between improving patient's psychosocial and neurocognitive outcomes and prevention of relapse by redefining the role of antipsychotics.

Study Timeline

• Study Start: 2017-07-24
• Status Verified: 2017-08
• Study First Submitted: 2017-08-06
• Study First Submitted QC: 2017-08-09
• Last Update Submitted: 2017-08-09
• Study First Posted: 2017-08-14
• Last Update Posted: 2017-08-14
• Primary Completion: 2020-12-31
• Study Completion: 2020-12-31

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 160

Inclusion Criteria

1. A diagnosis of schizophrenia, schizophreniform disorder, psychosis NOS, based on the DSM-5 criteria
2. With a Positive and Negative Syndrome Scale (PANSS), score < 3 in all 3 positive symptoms (P1: delusion, P2: conceptual disorganization, P3: hallucination) and 2 general symptoms (G9: unusual thought, G5: mannerism and posturing) for at least 3 months
3. With a PANSS score < 4 in all 3 negative symptoms (N1: blunted affect, N4: social withdrawal, N6: lack of spontaneity/flow in conversation) for at least 3 months
4. Currently receiving antipsychotic treatment at a fixed dose for at least 3 months, including long-acting injectable antipsychotic
5. A second antipsychotic agent only used for a low-dose, as needed adjuvant purpose
6. No revised use of benzodiazepines, antidepressants, anticholinergics, or other concomitant medications during past 3 months -

Exclusion Criteria

1. A score of 5 or more on any of the 30 PANSS rating items at screening
2. Admission to acute psychiatric unit during past 6 months
3. A change in dose of current antipsychotic medication in recent 3 months
4. Concomitant use of mood stabilizers, such as lithium, valproic acid or other anti-epileptic drugs
5. Mental retardation known as IQ below 70 prior to the diagnosis of schizophrenia
6. A history of pervasive mental disorder or bipolar disorder
7. A medical condition with significant cognitive sequelae
8. A history of substance dependence during past 6 months
9. Currently in pregnancy or breastfeeding

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Relapse of psychosis defined by worsening of scores in Positive and Negative Syndrome Scale (PANSS)	up to 2 years	Patients will be measured with a Positive and Negative Syndrome Scale (PANSS) every 4 weeks for 3 times (during 12 weeks) if conducting dose reduction or every 12 weeks if staying on the same dose to observe if any worsening of symptoms. Patient has a PANSS score \> 4 in any item of those 3 positive symptoms (P1: delusion, P2: conceptual disorganization, P3: hallucination) and 2 general symptoms (G9: unusual thought, G5:mannerism and posturing) during observational period for more than 1 week will be recognized as having a relapse of psychosis.

Secondary Outcome Measures

Name	Time	Method
severity of extrapyramidal symptoms	up to 2 years	Patient's severity of extrapyramidal symptoms will be rated by their psychiatrists using Simpson-Angus Scale, the Abnormal Involuntary Movement Scale, and the Barnes Akathisia Rating Scale at each visit.
Personal Social Performance (PSP) scores	up to 2 years	Patients will be rated by their attending psychiatrists with PSP scale to evaluate their functioning in 4 aspects of life, including socially useful activities, personal and social relationships, self-care, and disturbing and aggressive behaviors as to give a summary score at baseline and annually
quality of life (Euro-5D VAS)	up to 2 years	Patients report their quality of life using a 20-cm visual analogue at baseline and annually.
medication satisfaction questionnaire (MSQ)	up to 2 years	Patients will be asked to fill a self-rated 7-point Likert scale for medication satisfaction at baseline and annually.
neurocognitive functioning	up to 2 years	Patients will be assessed with the module for schizophrenia of the Cambridge Neuropsychological Test Automatic Battery (Cantab) at baseline and at the exit of the study.

Trial Locations

Locations (1)

National Taiwan University Hospital; 🇨🇳 Taipei, Taiwan