Psychosis
Conditions
Keywords
antipsychotic, N-Acetylcysteine, pilot trial, psychosis, relapse, remission, schizophrenia, tapering
Brief summary
The investigators are going to observe if add-on of n-acetylcysteine (NAC) 1200 or 2400 mg/d during tapering of antipsychotics in patients with remitted psychosis can help to reduce the pre-requisite of stabilization to 3 months (compared to the 6 months prerequisite of a previous Guided Antipsychotic Reduction to Minimum Effective Dose (GARMED) trial,) smoothly, without increased risk of relapse or frequency of adverse events compared to the 2-year results of the GARMED trial
Detailed description
Trial procedure * Pretreatment: more instructions were delivered regarding the extent and the tempo of dose reduction, warning signal of relapse, timing to call for help if in need to resume rescue dose, and a shared decision-making process during tapering. Pre-treatment of NAC 1200 mg/d will be given for 1-2 weeks and then titrated up to 2400 mg/d to test tolerability. Patients will stay at either dose throughout the remaining of the course as preferable. * Dose tapering schedule: In the beginning, no more than one-quarter of the baseline antipsychotic dose will be reduced at a time. Patients need to be monitored every 4 weeks (or 1 month) by phone or in person. If they can maintain stabilized for 12 weeks (or 3 months) in a reduced dose, they can take next tapering of no more than one quarter of their current dose again, yielding 9/16 (3/4x3/4) of baseline dose. The subsequent dose reduction will be a reiteration of the previous step, cutting off one-quarter of the current dose following the formula (3/4) powered by n, rather than cutting off another 1/4 of the initial dose. The processes will be reiterated for 4 steps for one year. * Conditions during tapering: Noteworthily, when the patient is eligible to consider next dose reduction, he or she is empowered to take shared decision-making as they might opt to stay at their current dose for a more extended time for any reason. Patients can reach the study team during the course whenever they felt unsure if any relapse sign might be re-emerging. As needed use of benzodiazepines or hypnotics will be allowed to help control suspected signs of relapse. Patients will be supervised to stay at current dose for a longer term or even re-escalate to previous higher dose if any sign of suspected relapse re-emerges, and then will be closely monitored if their symptoms can be stabilized within 2 weeks. * Defining relapse: If a patient's recurrent psychotic symptoms cannot be controlled (any PANSS score \> 3 in P1, P2, P3, G5, or G9) within 2 weeks under an antipsychotic dose equal to their baseline dose, the patient will be designated as having a relapse. * Practicability of dosing: The actual dose taken would not always be precisely the number calculated by the formula (3/4)n, as it was impractical to cut off a quarter or even smaller piece of a tablet for daily dosing. Several versions of intermittent or irregular dosing schedules have been generated to meet the needs. * Extent of dose reduction: The percentage of doses reduced at a designated time point will be calculated by the following formula: \[1- (current dose)/(baseline dose)\]x100%.
Interventions
DRUGN-Acetylcysteine
regular dose or high dose add-on
Sponsors
National Taiwan University Hospital
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
1. Both male and female outpatients or patients at psychiatric daycare service 2. Age 18-60 years old at the time of screening 3. A diagnosis of schizophrenia, schizophreniform disorder, psychosis NOS, based on the DSM-5 criteria 4. 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 5. 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 6. Currently receiving antipsychotic treatment at a fixed dose for at least 3 months, including long-acting injectable antipsychotic 7. No revised use of benzodiazepines, antidepressants, anticholinergics, or other concomitant medications during the 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 the acute psychiatric unit during the 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 the past 6 months 9. Currently in pregnancy or breastfeeding 10. A history of allergy to N-Acetylcysteine 11. Patient with phenylketonuria ( because the Actein Effervescent Tablet 600 mg/tab contains aspartame)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Relapse rate (%) | 1 year | If a patient's recurrent psychotic symptoms cannot be controlled (any PANSS score \> 3 in P1, P2, P3, G5, or G9) within 2 weeks under an antipsychotic dose equal to their baseline dose, the patient will be designated as having a relapse |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Personal and Social Functioning | 1 year | Personal and Social Performance scale (PSP) (0-100, worst to best) |
| Extent of dose reduction (%) | 1 year | The percentage of doses reduced at a designated time point will be calculated by the formula: \[1- (current dose)/(baseline dose)\]x100% |
| Clinical severity: symptoms | 1 year | Positive and Negative Syndrome Scale (PANSS) (1 to 7, 1: normal; 7: profound severity) |
| Self-report of subjective wellbeing | 1 year | EuroQoL-5D visual analogue scale (EQ-5D-VAS) (0-100, worst to best) |
| Self-report of Quality of Life | 1 year | Mandarin Chinese version of the WHOQOL-BREF (1\ 5, 1: very dissatisfied; 5: very satisfied) |
| Clinical severity: global | 1 year | Clinical Global Impression of Severity (CGI-S) (1 to 7, 1: no illness; 7: most severe) |
Other
| Measure | Time frame | Description |
|---|---|---|
| Self-report of Medication Satisfaction | 1 year | 7-point Likert scale for medication satisfaction (1: most dissatisfied; 7: most satisfied) |
| Adverse events | 1 year | checklist of Udvalg for Kliniske Undersogelser (UKU) Side-effects Rating Scale |
| Self-report of Medication Adherence | 1 year | 5-point Likert scale for medication adherence (1: \< 20%; 2: 20\ 40%; 3: 40\ 60%; 4: 60\ 80%; 5: \> 80%) |
| Qualitative measurements by semi-structured interview | 1 year | At each time point of shared decision-making regarding whether to taper down dose or not, we will conduct a semi-structure interview to explore patient's key considerations, such as psychosocial issues, soundness of supportive system, and self-assessed risk of relapse, which prompt the patient to feel comfortable about continuing tapering, or to halt at current dose for a longer term. |
Contacts
Primary ContactChen-Chung Liu, MD, PhD
Outcome results
None listed