Schizophrenia affects about 1 in 100 people worldwide, causing hallucinations, delusions, and difficulties with thinking and motivation. Current treatment centers on antipsychotic medications that block dopamine receptors, helping many people manage psychotic symptoms but often leaving negative symptoms like social withdrawal and cognitive problems largely untreated.
What's actually going on in research
Trials are testing drugs that work beyond dopamine — including muscarinic receptor agonists that act on acetylcholine pathways, trace amine-associated receptor agonists, and glutamate-targeting compounds. Researchers are also studying early intervention in people at high risk, long-acting injectable formulations to improve medication adherence, and add-on treatments for cognitive symptoms and negative symptoms that current drugs miss.
Muscarinic receptor agonists
Drugs like xanomeline-trospium (KarXT) work on acetylcholine pathways rather than dopamine, potentially treating psychosis without the movement side effects and weight gain common with current antipsychotics. FDA approval came in 2024 for adults with schizophrenia.
TAAR1 agonists
Trace amine-associated receptor 1 agonists modulate dopamine in a different way than standard antipsychotics. Early trials suggest they may reduce psychotic symptoms with fewer metabolic side effects.
Early intervention
Studies are identifying people at high risk before full psychosis develops and testing whether early treatment can prevent or delay schizophrenia. This research aims to catch the illness at a stage when intervention might have the most impact.
What to know before you search
Eligibility typically depends on diagnosis confirmation, current symptom severity, prior antipsychotic response, and whether the trial targets first-episode psychosis or chronic schizophrenia.
What types of trials are currently open
- Antipsychotic trials — Testing new medications or novel mechanisms to reduce hallucinations and delusions, often comparing them to existing drugs like risperidone or olanzapine.
- Negative symptom trials — Testing drugs specifically for withdrawal, lack of motivation, and reduced emotional expression — symptoms poorly treated by current antipsychotics.
- Cognitive trials — Testing treatments aimed at improving memory, attention, and problem-solving, which often remain impaired even when psychotic symptoms are controlled.
- Long-acting injectable trials — Studies of monthly or quarterly injections that maintain steady medication levels, designed to help people who struggle with daily pills.
- Early psychosis trials — Testing interventions in people experiencing their first episode of psychosis or at high risk, when treatment may have the greatest chance of altering long-term outcomes.
Recently added Schizophrenia trials
Health Assessment in People With Severe Mental Illness
People living with severe mental illness (SMI) experience substantial physical health inequalities, including an increased prevalence of cardiovascular disease, obesity, metabolic disorders, reduced physical fitness, and premature mortality. Physical inactivity, prolonged sedentary behavior, sleep disturbances, and the metabolic effects of psychiatric medications may contribute to these health problems. The PHASMI study aims to provide a comprehensive assessment of physical health, cardiorespiratory fitness, cardiometabolic risk, physical functioning, lifestyle characteristics, emotional well-being, and health-related quality of life in adults with severe mental illness. The primary objective is to investigate associations between sociodemographic, clinical, and lifestyle characteristics and cardiorespiratory fitness, assessed through peak oxygen uptake (VO2peak). PHASMI is an observational, descriptive, cross-sectional study conducted in Álava, Spain. The anticipated sample comprises 275 adults aged 18 to 65 years with a diagnosis of severe mental illness according to DSM-5 criteria established by psychiatry specialists. Participants will be recruited through the Mental Health Network of Álava, including individuals receiving community-based psychiatric care and hospitalized patients. Participants will undergo a comprehensive health assessment involving cardiopulmonary exercise testing on a treadmill using a modified Bruce protocol, the Modified Shuttle Walk Test, anthropometric measurements, body composition analysis, blood pressure measurements, electrocardiography, laboratory analyses, handgrip strength testing, and standardized assessments of physical functioning. Physical activity, sedentary behavior, and sleep will be assessed using standardized questionnaires and a wrist-worn ActiGraph GT3X+ accelerometer over eight consecutive days. Emotional well-being and health-related quality of life will be evaluated using validated questionnaires. The main in-person assessments will be conducted over two consecutive days at the University of the Basque Country and the Psychiatric Hospital of Álava. Written informed consent will be obtained before participation. No experimental treatment or therapeutic intervention will be assigned. By examining associations between physical fitness, cardiometabolic health, lifestyle characteristics, and psychological well-being, PHASMI seeks to identify potentially modifiable factors associated with poorer physical health and inform future prevention and health promotion strategies for people living with severe mental illness.
Sequential Treatment Approaches for Treatment-Resistant Schizophrenia
The goal of this study is to optimize treatment strategies for Chinese patients with treatment-resistant schizophrenia (TRS). It will compare two types of treatment: 1. Drug therapy with clozapine alone or in combination with other medications. 2. Neuromodulation therapy, modified electroconvulsive therapy (MECT) or magnetic seizure therapy (MST). The study aims to determine which approach provides better symptom improvement, fewer cognitive side effects, and greater overall safety. The results may provide important clinical evidence to guide future treatment decisions for patients with TRS.
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