A Pilot Trial of Tapering Antipsychotics for Patients in Remitted Psychosis Co-administering With N-Acetylcysteine

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

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%.

Eligibility Criteria:
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)