Other interventions that showed efficacy are thiamine (tested also as a prophylactic drug), dexmedetomidine, and hemodialysis. Other pharmaceuticals have been tested in a preclinical setting showing some activity: trifluoperazine, morin, caffeic acid phenethyl ester (CAPE), and alpha lipoic acid (ALA). The aim of this review is to gather the current knowledge about the mechanisms underlying the IIE and the current therapeutic approach and the future perspectives.

P3, N=140, Recruiting, Mahidol University

P=N/A, N=125, Recruiting, University of Liverpool | Trial primary completion date: Jul 2025 --> Dec 2025 | Trial completion date: Aug 2025 --> Jun 2026

P1, N=36, Recruiting, Teva Branded Pharmaceutical Products R&D, Inc. | Trial completion date: Jan 2025 --> Jun 2025 | Trial primary completion date: Jan 2025 --> Jun 2025

P1, N=91, Completed, Teva Branded Pharmaceutical Products R&D, Inc. | Active, not recruiting --> Completed

P2, N=120, Recruiting, Boryung Pharmaceutical Co., Ltd

P3, N=675, Completed, Teva Branded Pharmaceutical Products R&D, Inc. | Active, not recruiting --> Completed

P2, N=36, Recruiting, Austin Hospital | Not yet recruiting --> Recruiting

P1, N=30, Recruiting, Intra-Cellular Therapies, Inc. | N=12 --> 30 | Trial completion date: Mar 2025 --> Sep 2025 | Trial primary completion date: Mar 2025 --> Sep 2025

P1, N=8, Not yet recruiting, Intra-Cellular Therapies, Inc.

P=N/A, N=40, Completed, Seattle Institute for Biomedical and Clinical Research | Active, not recruiting --> Completed | Trial completion date: Dec 2025 --> Dec 2024

P4, N=104, Recruiting, The Guthrie Clinic | Trial completion date: Nov 2024 --> Nov 2029 | Trial primary completion date: Nov 2024 --> Nov 2028

P2, N=180, Recruiting, Central Institute of Mental Health, Mannheim | Trial completion date: Dec 2025 --> Jun 2026 | Trial primary completion date: Dec 2024 --> Jun 2026

P2, N=150, Terminated, Central Institute of Mental Health, Mannheim | Trial completion date: Jun 2025 --> Sep 2024 | Active, not recruiting --> Terminated | Trial primary completion date: Dec 2024 --> Sep 2024; Following the expiry of the original research grant, no follow-up financing could be provided to complete the study.

We report elevated resistin and IL-4 levels and decreased adiponectin levels in first-episode, treatment resistant schizophrenia patients after clozapine treatment. These findings may be at least partly due to the anti-inflammatory action of clozapine, although sub-clinical metabolic disturbances may also have played a role as far as resistin and adiponectin are concerned. In a subgroup of these patients we report reduced TGF-β2 and adiponectin levels after two unsuccessful trials with risperidone and olanzapine comparing them with the ones of the same subgroup in the drug-naïve phase.

P4, N=30, Not yet recruiting, New York State Psychiatric Institute

The elevated expression level of GPX4 in oral cancer biopsies was also found to correlate with a poor prognosis. Together, these results provide evidence that TFP selectively induces GPX4-mediated, autophagy-dependent ferroptosis, thereby exerting anti-cancer effects against oral cancer and preventable death.

P=N/A, N=40, Active, not recruiting, Seattle Institute for Biomedical and Clinical Research | N=20 --> 40

P2, N=705, Recruiting, Intra-Cellular Therapies, Inc. | Trial completion date: Jan 2027 --> Jun 2027 | Trial primary completion date: Dec 2026 --> Jun 2027

P2, N=570, Recruiting, Intra-Cellular Therapies, Inc.

P=N/A, N=6, Completed, McMaster University | Unknown status --> Completed | N=20 --> 6

P=N/A, N=200, Recruiting, Centre Hospitalier St Anne | Not yet recruiting --> Recruiting

The calmodulin-inhibitors trifluoperazine and ophiobolin A mediated delayed activation of ADAM10, which apparently did not depend on intracellular Ca2+ in the case of trifluoperazine...Finally, ADAM10 activation was observed after the entry of Ca2+ through certain channels, such as canonical members of transient receptor potential (TRP) channels. Therefore, the opening of particular channels for Ca2+ entry points and subsequent Ca2+ flux as well as the temporal aspects of the consequent increase in Ca2+ levels, must be considered for future therapeutic options involving the increasing or decreasing ADAM10 activity.

P1, N=95, Active, not recruiting, Teva Branded Pharmaceutical Products R&D, Inc. | Recruiting --> Active, not recruiting

ARI de-sensitizes Fao cells to stress signaling, while OLA has the opposite effect. These findings contribute to our understanding of the metabolic risks associated with prolonged AAP use and may inform future therapeutic strategies.

P2, N=320, Recruiting, Intra-Cellular Therapies, Inc.

Our results indicate that serum IL-2, IL-8, IL-10, and TNF-α levels may be involved in the pathophysiological mechanisms of schizophrenia and correlate with the effects of olanzapine.

P3, N=654, Not yet recruiting, Qilu Pharmaceutical Co., Ltd.

The synergistic combination of PER and TMZ has potential as a novel combination treatment strategy for GBM.

P3, N=164, Completed, Cairo University | Recruiting --> Completed

Our findings from this computational study presents cyanidin (-8.822 kcal/mol) as better binder to the allosteric site of MALT1 based on the molecular docking and pharmacokinetic profiling than thioridazine...Hence, cyanidin is a potential allosteric inhibitor of MALT1. However, an urgent need for in vitro and in vivo validations is required to ascertain the efficacy of cyanidin in the fight against cancer and other MALT1-related diseases.

P=N/A, N=200, Not yet recruiting, Centre Hospitalier St Anne

P4, N=60, Completed, All India Institute of Medical Sciences, Bhubaneswar | Recruiting --> Completed

P2, N=170, Enrolling by invitation, Englewood Hospital and Medical Center | Trial completion date: Dec 2023 --> Dec 2026 | Trial primary completion date: Dec 2022 --> Dec 2026

We investigated fluspirilene, perphenazine, and sulpiride, three classic anti-schizophrenic drugs, as possible anti-GBM agents. In fluspirilene-treated cells, FOXM1 protein was decreased, indicating that KIF20A was downregulated in the presence of the drug due to decreased FOXM1 protein. These results demonstrate that fluspirilene is an effective anti-GBM agent that works by suppressing the FOXM1-KIF20A oncogenic axis.

P2, N=36, Not yet recruiting, Austin Hospital

In vivo, TFP inhibited subcutaneous OS cell proliferation and induced OS cell apoptosis without noticeable side effects. In conclusion, our findings imply that TFP is a potential treatment for OS.

P=N/A, N=200, Completed, Central South University | Recruiting --> Completed

P2, N=156, Not yet recruiting, Second Affiliated Hospital of Nanchang University

These findings suggest that fluphenazine has the potential to be used as an anti-breast cancer drug by inducing cuproptosis. Therefore, this research provides an insight for the development of novel cuproptosis-dependent anti-cancer agents.

P1, N=50, Not yet recruiting, Lawson Health Research Institute

The research emphasizes the significance of SUSD3 as a potential marker for BC, providing insights into the underlying molecular mechanisms implicated in tumorigenesis. SUSD3 holds promise in helping the classification of breast cancer pathological groups, predicting prognosis, and facilitating targeted therapy.