Clinical trial NCT03248180: Guided Dose Reduction of Antipsychotic in Patients With Psychosis in Remitted States
Official title: Impact of Guided Antipsychotic Dose Reduction in Patients With Psychosis Under Remitted States: a Randomized Control Trial and Prospective Follow-up Study
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Psychosis
Remission
Keywords: antipsychotic
guided dose reduction
maintenance treatment
remitted psychosis
relapse
Lead sponsor: National Taiwan University Hospital
Sponsor class: OTHER
First posted: 2017-08-14
Enrollment: 160
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Outpatients received follow-up at or referred to the study 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.

Eligibility criteria: 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

Primary outcomes:
measure: Relapse of psychosis defined by worsening of scores in Positive and Negative Syndrome Scale (PANSS)
timeFrame: up to 2 years
Secondary outcomes:
measure: Personal Social Performance (PSP) scores
timeFrame: up to 2 years
measure: quality of life (Euro-5D VAS)
timeFrame: up to 2 years
measure: severity of extrapyramidal symptoms
timeFrame: up to 2 years
measure: medication satisfaction questionnaire (MSQ)
timeFrame: up to 2 years
measure: neurocognitive functioning
timeFrame: up to 2 years
Other outcomes:
Locations:
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
Study officials:
affiliation: National Taiwan University Hospital
name: Chen-Chung Liu, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: