Study Comparing Antipsychotic Dose Reduction vs. Maintenance Treatment in Patients With Schizophrenia Spectrum Disorder: a Personalized Medicine Approach

Prior treatment

• Patient treated with long-acting injection of antipsychotics (due to feasibility constraints and to the fact that these treatments remain essentially proposed to non-compliant patients with high risk of acute cessation and loss to follow-up);
• Patient treated with clozapine (in mono or polytherapy - highly resistant patients, specificities of the relapses under clozapine
• Patient considered by his psychiatrists to be at serious risk of harm to self or others (e.g. previous aggressive or suicidal behaviors); notably, a patient answering "yes" to C-SSRS suicidal ideation Type 4 or 5, having any suicidal behavior assessment within 6 months at Screening, or having been hospitalized or treated for suicidal behavior in the past 5 years before Screening. The investigator will rely on the results of the C-SSRS questionnaire completed at the time of inclusion (after consent has been signed) or previously completed as part of the patient's follow-up according to current practice.
• Patient involved in another Investigational Medicinal Product trial or having participated in another investigational drug trial, in which they received the investigational drug, within 60 days
• Patients with any of the following signs of substance abuse:
  • Current diagnosis or history of substance use disorder and/or substance intoxication as defined in the DSM-5-TR. If the history of substance use disorder is more than 12 months before baseline, the participant may be allowed to enroll in the trial after consultation with the sponsor (Participant must also have negative urine drug screen at the screening.)
  • A positive urine screen for drugs of abuse at screening.
  • A history of alcohol consumption exceeding 2 standard drinks per day on average (1 glass is approximately equivalent to the following: beer \[354 mL/12 oz\], wine or sake \[118 mL/4 oz\], or distilled spirits \[29.5 mL/1 oz\] per day).
  • A positive Breathalyzer test for alcohol at screening. The investigator will screen urine for drug abuse and perform an alcohol test at the inclusion visit (after consent has been signed), and may also rely on previous results obtained in the course of patient follow-up according to standard practice.

Other illness

• \- Patient hospitalized in a psychiatric ward;
• Neurological or severe medical condition other than psychosis;
• Patients with major depressive disorder (CDSS \> 5) or manic episode (DSM-5-TR)

Other

• Patient with a recent psychotic episode (during the last 6 months);
• Pregnancy (verified by urinary test at enrollment for women of childbearing potential);
• Current breastfeeding;
• Patient in an exclusion period defined by another research protocol;
• Patient under guardianship (i.e. French 'tutelle');
• Patient with care under constraint
• Patients deprived of freedom because of a judicial measure.
• Inability to give the patient the written consent form (emergency situation)
• The participant is a trial site employee, a site employee's immediate family member (for example, spouse, parent, child, sibling), or is in a dependent relationship with a site employee who is involved in conduct of this trial or may consent under duress.

• \- Patient 18-60 years of age;
• Patient affiliated to health insurance (beneficiary or beneficiary's family);
• Patient informed of the results of the preliminary medical examination;
• Patient able to understand the aims and risks of the research (assisted by his/her curator, if applicable (if subject under curatorship\*))
• Informed consent signed by patient
• Patient with a diagnosis of schizophrenia spectrum disorder (SSD): schizophrenia, schizophreniform, schizoaffective disorder or brief psychotic episode according to DSM-5;
• Patient with:
  • Either a cycloid psychosis (CP) phenotype according to By-CP (score \>=80%)
  • Or another (non-CP) psychotic phenotype; (By-CP score \< 80%)
• Outpatient followed by an ambulatory psychiatrist;
• Patient with an identified caregiver, defined as a person able to support the patient for the duration of the study, spending at least 8 hours per week with the patient or having easy access to the patient per phone.
• Patient clinically stabilized, for at least 6 months, as defined by
  • low intensity of positive symptoms, i.e. PANSS P1, P2 and P3 items \< 4.
• Patient treated with oral antipsychotics (in mono or polytherapy, with second- or first-generation antipsychotics);
• Patients with a PSP score \>70 at baseline will also be included
• The participant agrees to follow the contraceptive requirements detailed in the protocol \*Subjects under limited guardianship (i.e. French "curatelle") can participate to the study.