Seizures and Neuropsychiatric Toxicity in Patients with Non-Metastatic CRPC Treated with New Antiandrogens: Systematic Review and Meta-Analysis

Introduction: Recently, enzalutamide, apalutamide, and darolutamide have shown benefits in metastasis-free survival in non-metastatic castration-resistant prostate cancer (nmCRPC) patients compared to placebo. Previous evidence about the safety profile of these new androgens is limited. This meta-analysis studies seizure and neuropsychiatric effects of new anti-androgens compared to placebo in nmCRPC patients. Methods: PubMed and Cochrane databases were systematically reviewed until 1 March 2020 by 2 independent researchers using a pre-specified search strategy. Placebo-compared randomized controlled trials (RCTs) of nmCRPC patients treated with new anti-androgens providing data on neuropsychiatric events and seizures were included. Variables were seizure, headache, mental impairment, and dizziness. Pooled risk ratios (RR) were calculated using the Mantel-Hansel random effects model and Review Manager v5.3 software. Results: After systematic review, 3 eligible RCTs were selected that included 4,104 patients; 2,687 comprised the treatment group and 1,417 the control group. No significant increase in RR for seizures was registered with the new anti-androgens compared to placebo (RR 1.96; 95% confidence interval [CI] 0.40–9.61). However, 2 trials excluded patients with risk factors or a history of seizures. There was also no significant increase RR for grade ≥3 seizures (RR 2.50; 95% CI 0.12–52.02). RR for suffering dizziness (any grade) was 1.57 (95% CI 1.07–2.32) with the new anti-androgens, but no significant differences were found in the other study regarding neuropsychiatric events or grade ≥3 events. Conclusions: New anti-androgens (i.e., enzalutamide, apalutamide, and darolutamide) are acceptably safe in terms of seizures and neuropsychiatric toxicity compared to placebo in patients with nmCRPC.

A case of quinacrine-induced psychosis: case report

: Quinacrine is an older antimalarial drug that remains in use for a variety of illnesses including treatment resistant giardiasis. We report a patient with no prior psychiatric history who developed mild, prodromal psychiatric symptoms when treated with quinacrine for treatment resistant giardiasis. Symptoms resolved when the drug was stopped, recurred with greater severity (requiring involuntary psychiatric hospitalization) when restarted and promptly resolved again when finally stopped. Although quinacrine remains in use today, providers may be unaware of its potential for serious neuropsychiatric toxicity.

Chimeric antigen receptor T-cell neuropsychiatric toxicity in acute lymphoblastic leukemia

ABSTRACTChimeric antigen receptor T cells are used in the treatment of B-cell leukemias. Common chimeric antigen receptor T-cell toxicities can range from mild flu-like symptoms, such as fever and myalgia, to a more striking neuropsychiatric toxicity that can present as discrete neurological symptoms and delirium. We report here two cases of chimeric antigen receptor T-cell neuropsychiatric toxicity, one who presented as a mild delirium and aphasia that resolved without intervention, and one who presented with delirium, seizures, and respiratory insufficiency requiring intensive treatment. The current literature on the treatment and proposed mechanisms of this clinically challenging chimeric antigen receptor T-cell complication is also presented.

The Heart of the Matter

This chapter considers the evidence linking carbon disulfide and heart disease. It first examines how the viscose rayon industry fared in the aftermath of World War II, paying attention to changes in the landscape for rayon and cellophane, including the growing presence of synthetic polymers. It then discusses carbon disulfide poisoning cases, including cases of central nervous system disease consistent with vascular insult. It also looks at Enrico Vigliani's 1955 publication that included experimental laboratory studies evaluating potential mechanisms by which carbon disulfide might induce atherosclerosis, zeroing in on lipid metabolism; John Tiller and Richard Schilling's study of possible heart disease deaths among the workers of the three Courtaulds factories in North Wales; and Dr. Thomas Mancuso's investigation of the neuropsychiatric toxicity of carbon disulfide—his analysis concentrated on death by suicide.

Psychiatric consequences of cancer treatments: therapeutic monoclonal antibodies

The adverse psychiatric consequences of a range of monoclonal antibodies used to treat cancer are reviewed. Bevacizumab disrupts endothelial function at the blood–brain barrier and can provoke posterior reversible encephalopathy syndrome. The immune checkpoint inhibitors cause autoimmune hypophysitis and thyroiditis with associated psychopathology. Rituximab causes profound immunosuppression of B lymphocytes, and hence can reactivate childhood JC virus infection to cause progressive multifocal leucoencephalopathy. The marked neuropsychiatric toxicity of blinatumomab is described.