Guided Dose Reduction of Antipsychotic in Patients With Psychosis in Remitted States (GDR)

Impact of Guided Antipsychotic Dose Reduction in Patients With Psychosis Under Remitted States: a Randomized Control Trial and Prospective Follow-up Study

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.

Study Overview

• Status: Unknown
• Conditions: Psychosis; Remission

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 Type: Observational
• Enrollment (Anticipated): 160

Contacts and Locations

Study Locations

• Taiwan
  • Taipei, Taiwan, 100
    • Recruiting
    • National Taiwan University Hospital
    • Contact: Chen-Chung Liu, MD, PhD; Phone Number: 66130 886-2-23123456; Email: chchliu@ntu.edu.tw

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Outpatients received follow-up at or referred to the study hospital

Description

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 Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Guided dose reduction (GDR); Patients in the GDR group will be advised to reduce < 25% of their current dose of antipsychotic agents estimated on a weekly base and follow-up every 4 weeks for at least 12 weeks.
Maintenance treatment group (MTG); Patients in the MTG will be advised to stay on their current dose of antipsychotics throughout the observational period, follow-up every 12 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relapse of psychosis defined by worsening of scores in Positive and Negative Syndrome Scale (PANSS)	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.	up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Personal Social Performance (PSP) scores	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	up to 2 years
quality of life (Euro-5D VAS)	Patients report their quality of life using a 20-cm visual analogue at baseline and annually.	up to 2 years
severity of extrapyramidal symptoms	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.	up to 2 years
medication satisfaction questionnaire (MSQ)	Patients will be asked to fill a self-rated 7-point Likert scale for medication satisfaction at baseline and annually.	up to 2 years
neurocognitive functioning	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.	up to 2 years

Collaborators and Investigators

• Sponsor: National Taiwan University Hospital
• Investigators: Principal Investigator: Chen-Chung Liu, MD, PhD, National Taiwan University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 24, 2017
• Primary Completion (Anticipated): December 31, 2020
• Study Completion (Anticipated): December 31, 2020

Study Registration Dates

• First Submitted: August 6, 2017
• First Submitted That Met QC Criteria: August 9, 2017
• First Posted (Actual): August 14, 2017

Study Record Updates

• Last Update Posted (Actual): August 14, 2017
• Last Update Submitted That Met QC Criteria: August 9, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Keywords: relapse; antipsychotic; maintenance treatment; guided dose reduction; remitted psychosis
• Additional Relevant MeSH Terms: Schizophrenia Spectrum and Other Psychotic Disorders; Psychotic Disorders; Mental Disorders
• Other Study ID Numbers: 201703002MIND

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No