An Open-Label, Single-Arm Clinical Trial Evaluating the Safety and Efficacy of Amisulpride in Treating Patients With Schizophrenia and Schizoaffective Disorder Who Have Treatment-Resistant Positive Symptoms (AmisulprideTRS)

Inclusion Criteria: 1. Signed and dated written informed consent. 2. Age 18-65 years 3. Male or female*. 4. *For participants assigned female sex at birth: A participant is eligible to participate if not pregnant, and one of the following conditions applies: (1) Is not able to become pregnant; (2) is a person able to be pregnant (PABP) and using a contraceptive method that is highly effective, with a failure rate of <1%. 5. Diagnosis of schizophrenia or schizoaffective disorder according to DSM-V criteria 6. Treatment-resistant positive symptoms defined by subjects receiving an antipsychotic but continuing to score 4 or greater one of the following Positive and Negative Syndrome Scale (PANSS) items: P1 (delusions), P3 (hallucinations), P6 (suspiciousness or persecution), or G9 (unusual thought content). 7. Subjects receiving clozapine will also be included if there is a concern that the side effect burden from clozapine has led the clinician and the patient to consider changing to another medication. 8. English-speaking. 9. Subjects only partially responsive to other antipsychotics will also be included. 10. Non-suicidal self-injurious behavior may be included if approved by the study clinician. 11. Able to provide informed consent. Exclusion Criteria: Diagnosis of any other psychiatric disorder. History of intolerance or allergy to amisulpride. Known history of severe cardiac arrhythmia or prolonged QT interval. Concomitant use of medications that may interact with amisulpride or prolong QT interval (see section 4.3, "Concomitant Therapy"). Lactating patients, patients with prolactin-dependent tumors, and patients with breast cancer will be excluded. Patients with laboratory- and/or imaging-confirmed pheochromocytoma will be excluded. Columbia-Suicide Severity Rating Scale: Suicidal ideation score of 4 or greater within the last month of the assessment at a frequency of once a week or more. Suicidal ideation score of 5 within the last 6 months of the assessment. Any suicidal behavior, including suicide attempts or preparatory acts, within the last 6 months of the assessment. Current moderate or severe alcohol and substance use disorders, which could pose a safety concern or interfere with the therapeutic process. Existing relevant physical health problems: such as cardiovascular disease, previous problems with prolactin, impaired liver/renal function or epilepsy. Any medical condition that the PI determines could jeopardize the safety of the study subject or compromise the integrity of the data. Planning to start a new drug, diet, or behavioral intervention during the study. A previous trial of amisulpride. Unable to perform or cooperate with study requirements.