a pilot trial of tapering antipsychotics for patients in remitted psychosis co-administering with n-acetylcysteine

Conditions: Psychosis

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

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)

Keywords: antipsychotic n-acetylcysteine pilot trial psychosis relapse remission schizophrenia tapering