Abstract

Abstract

Abstract

Treatment-resistant schizophrenia (TRS) is a challenging condition to manage and can result in the need for dual antipsychotic prescribing especially after oral clozapine failure. Poor medication adherence is prevalent among patients with TRS, and long-acting injectable antipsychotics are frequently used to overcome this barrier. Whereas there is limited data on the risks and benefits of dual long-acting injectable antipsychotic treatment, this is a treatment modality that is being used for patients with TRS who have poor adherence. We contribute a case of successful dual long-acting injectable therapy with intramuscular paliperidone palmitate and haloperidol decanoate in a patient with TRS and an extensive history of hospitalizations who failed treatment with oral clozapine.

Abstract

Synthetic cannabinoids (SCs), such as K2 or spice, are potent, intoxicating, laboratory-produced compounds designed to mimic Δ9-tetrahydrocannabinol (Δ9-THC). Some SCs are full agonists that bind to cannabinoid receptors in the endocannabinoid system with significantly higher affinity than Δ9-THC, often causing more intense and unpredictable effects, including cardiovascular, respiratory, and neuropsychiatric complications. Due to their modifiable chemical structures, new SC variants are commonly created and can evade detection on standard toxicology screens, complicating diagnosis and treatment. A 43-year-old male with schizoaffective disorder and polysubstance dependence presented with mental status changes and respiratory depression following suspected SC use with K2. Symptoms improved with intranasal naloxone despite negative toxicology screens for opioids and known SCs. The patient later admitted to ongoing K2 use. A unit search revealed leafy substances though confirmatory testing was negative. This case raises important considerations about the limitations of routine toxicology screening and the risk of SC adulteration with opioids or other undetected substances. The patient’s repeated clinical improvement following naloxone suggests either opioid contamination or functional interactions between cannabinoid and opioid receptors. Preclinical evidence supports the existence of CB1-opioid receptor cross talk, offering a possible explanation for naloxone’s effectiveness in SC-related toxicity. Clinicians should consider naloxone in cases of suspected SC overdose even without confirmed opioid exposure. Naloxone’s safety profile and rapid onset make it an additional tool in managing undifferentiated overdose presentations. Further research is needed to delineate the mechanism behind naloxone’s potential effectiveness in SC-related toxicity.

Abstract

Lewy body dementia (LBD) is a progressive neurological disorder characterized by dementia, parkinsonism, and psychotic symptoms. Treating psychosis in LBD is particularly challenging, especially given the high risk of extrapyramidal effects of antipsychotics commonly associated with this population. If treatment with an antipsychotic is warranted, low-potency antipsychotics are preferred; however, they may not be suitable for all patients because of adverse effect profiles, safety concerns, or logistical barriers. This case study illustrates how a patient diagnosed with LBD and unable to tolerate or access commonly used antipsychotics was effectively treated with low-dose loxapine.

Abstract

Xanomeline/trospium is a newly approved agent for the management of schizophrenia. Unlike traditional antipsychotics, which are D₂ receptor antagonists, xanomeline is an M₁/M₄ muscarinic acetylcholine receptor agonist coformulated with trospium, a peripheral muscarinic antagonist. The addition of the trospium constituent aims to reduce or prevent the peripheral effects of muscarinic acetylcholine receptor agonism by xanomeline, which would include classic cholinergic adverse effects such as increased salivation, defecation, and urination. The package insert reports that some of the most frequently observed adverse reactions (incidence ≥5%) throughout clinical trials were those congruent with the expected anticholinergic effects of trospium, such as urinary retention and constipation, as well as other reactions that likely coincide with xanomeline use, such as nausea, vomiting, and diarrhea.¹ However, there is no documented incidence of polyuria secondary to xanomeline/trospium use in the current literature. We present a case of a 53-year-old White male who was treated with xanomeline/trospium for the management of schizophrenia who experienced polyuria after a dose titration to maximum dosing of xanomeline/trospium 125 mg/30 mg by mouth twice daily. Owing to the emergence of polyuria 3 days after the dose titration, the xanomeline/trospium was discontinued after discussion with the provider, and the polyuria resolved within 1 day.