Table 2.
Eligibility criteria for participant recruitment.
| Inclusion criteria | Exclusion criteria |
|---|---|
| 1) Age between 16-55 | 1) Levels of leukocytes <3500/mm3 and neutrophils <2000/mm3 |
| 2) Main diagnosis of intelectual deficit (DSM-V) and confirmed using the brief Kaufman intelligence test (Annex V), IQ: 35-70 | 2) Hypersensitivity to clozapine or its excipients |
| 3) Diagnosis of psychotic disorder (DSM-V) confirmed by clinical interview | 3) History of Myeloproliferative Syndrome |
| 4) Resistance to antypsychotic treatment (at least two different, except clozapine) at the maximum dose for a duration of treatment ≥ 6 weeks | 4) Epilepsy not controlled with medication in the previous 2 years |
| 5) Behavioral alterations, self-harm and/or severe stereotypes during the 6 months prior to inclusion | 5) Paralytic ileus 3 months before inclusion |
| 6) Consent by written to participate in the trial of patients and/or their legal representatives | 6) Patients diagnosed at study entry or selection visit itself of autism spectrum disorders |
| 7) Capacity and availability to carry out the assesments of the trial protocol or facilitated | 7) Pregnant women at the time of study entry or wishing to start pregnancy within 12 months after entering the same |
| 8) In case of potential risk of pregnancy, negative pregnancy test and/or contraception | 8) Women who are breast-feeding at the time of entry into the study who do not accept its withdrawal |
| 9) Demonstrated medical pathology (heart disease, intestinal transit disorders…) that contraindicate the use of clozapine | |
| 10) Any serious medical pathology not controlled at the time of entry into the hospital | |
| 11) Treatment at the beginning of the study that cannot be withdrawn with any prohibited drug during the study | |
| 12) Patients in whom a high risk of suicide is detected at the screening visit, according to the criteria established by Columbia University according to the evaluation of said risk using the C-SSRS scale (Annex V) | |
| 13) Patients who are participating in another clinical trial with active treatment (1) meeting DSM-IV criteria for drug dependence; (2) meeting DSM-IV criteria for mental retardation; (3) having a history of neurological disease or head injury | |
| Based on efficacy criteria | Based on safety criteria |
| 1) Patients with a drug compliance level below 80% | 1) Any adverse event that, at the clinician’s discretion, requires study withdrawal. |
| 2) Patients who, at any time during the study period, show a high risk of suicide based on criteria established by Columbia University, as assessed by the C-SSRS scale. | 2) When, for any reason, the treatment is no longer safe for the patient. |
| 3) Female patients who test positive for pregnancy during their participation in the study | 3) Any other reason that could endanger the patient’s life or have serious consequences for them. |
| 4) Patients who experience a convulsive seizure during their participation in the study | Based non-compliance or violation of the norms outlined in the protocol criteria |
| 5) Patients randomized to the clozapine branch who have white blood cell counts <3500/mm3 and neutrophil counts <2000/mm3 at any time during their participation in the study | 1) If the patient fails to comply with the trial’s norms, they may be withdrawn at the discretion of the responsible investigator or due to loss of follow-up. |
| 6) Patients randomized to the clozapine branch who need to start treatment with drugs known to cause agranulocytosis or bone marrow depression | Follow-up of prematurely withdrawn patients |
| 7) Patients randomized to the clozapine branch who require hospitalization due to intestinal obstruction or develop paralytic ileus | 1) If a patient is prematurely withdrawn from the trial, the investigator will provide the main reason for the suspension; the standard treatment protocols for their condition will be followed at the discretion of the responsible clinician. |
| 8) Patients randomized to the clozapine branch who, after the transition period to monotherapy with CZP, require treatment with more than one antipsychotic drug, ECT, or rTMS based on clinical criteria | |
| 9) Patients randomized to the clozapine branch who need to start treatment with medications that significantly interfere with clozapine metabolism through the cytochrome P450 pathway: macrolides, antifungals, proton pump inhibitors, and trihexyphenidyl |