Retracing our steps to understand ketamine in depression: A focused review of hypothesized mechanisms of action

Introduction: MDD represents a significant burden worldwide, and while a number of approved treatments exist, there are high rates of treatment resistance and refractoriness. Ketamine, an N-methyl-d-aspartate receptor (NMDAR) antagonist, is a novel, rapid-acting antidepressant, however the mechanisms underlying the efficacy of ketamine are not well understood and many other mechanisms outside of NMDAR antagonism have been postulated based on preclinical data. This focused review aims to present a summary of the proposed mechanisms of action by which ketamine functions in depressive disorders supported by preclinical data and clinical studies in humans. Methods: A literature search was completed using the PubMed and Google Scholar databases. Results were limited to clinical trials and case studies in humans that were published in English. The findings were used to compile this article. Results: The antidepressant effects associated with ketamine are mediated via a complex interplay of mechanisms; key steps include NMDAR blockade on ?-aminobutyric acid interneurons, glutamate surge, and subsequent activation and upregulation of ?-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor. Discussion: Coadministration of ketamine for MDD with other psychotropic agents, for example benzodiazepines, may attenuate antidepressant effects. Limited evidence exists for these effects and should be evaluated on a case-by-case basis

An update on recently approved long-acting injectable second-generation antipsychotics: Knowns and unknowns regarding their use

There are now 9 available FDA-approved second-generation long-acting injectable antipsychotics including aripiprazole (3), olanzapine (1), paliperidone (3), and risperidone (2). These high-cost medications are commonly used with the goal of improving adherence and patient outcomes. With almost 2 decades of use, key aspects have been well studied, including population pharmacokinetics, CYP interactions and various clinical and economic outcomes. However, there are still unknowns with these medications. Issues including adherence, transition from oral antipsychotics, renal dosing, pharmacogenomics, and managing missed doses will be addressed in the context of 4 patient cases

Vertigoheel induced psychosis: A patient case report

Objective: To describe a case of a patient who developed psychosis after ingestion of Vertigoheel for treatment of dizziness. Case Summary: A 28-year-old male with no psychiatric history presented with 5 days of worsening depression and psychosis. He denied current use of prescription medications, alcohol, or illicit substances. Approximately 2 weeks prior, while visiting family in Germany, he developed dizziness. A provider in Germany prescribed Vertigoheel, 1 tablet to be taken every hour until symptom improvement. This did not improve his dizziness but did cause him to feel as if he were “in a dream.” He stopped taking the medication after 2 days but continued to feel amotivated with decreased appetite and insomnia. Several days later, he developed ego-dystonic auditory hallucinations. He returned to the United States; was admitted to an inpatient psychiatric unit for 4 days; and given olanzapine 5 mg at bedtime, lorazepam 1 mg every evening, and melatonin 6 mg every evening. He experienced gradual improvement in symptoms and was discharged with olanzapine 5 mg daily and outpatient follow-up. Discussion: Vertigoheel is a homeopathic preparation containing ambra grisea, Cocculus indicus, Conium maculatum, and petroleum. Psychosis was not reported in any of the randomized controlled trials evaluating the use of Vertigoheel for treatment of vertigo. A literature search revealed no published reports of psychosis as a result of administration of any components of Vertigoheel. Conclusion: A possible causal relationship was observed between the homeopathic supplement Vertigoheel and an acute episode of psychosis in a young male patient with no comorbidities

Loxapine in patient with clozapine-resistant psychosis

Clozapine is recognized as the drug of choice for treatment-refractory schizophrenia, but use may be limited because of strict monitoring requirements and adverse effects including severe neutropenia, seizures, and myocarditis. Loxapine is a first-generation antipsychotic with similarities to clozapine in both structure and receptor binding. This case describes a 57-year-old male with a history of severe paranoid schizophrenia despite treatment with clozapine and other psychotropic agents, who experienced clinical improvement after a cross titration from clozapine to loxapine. Loxapine may be a reasonable alternative in patients with treatment-refractory schizophrenia who do not tolerate or respond to clozapine

Identifying olanzapine induced liver injury in the setting of acute hepatitis C: A case report

Olanzapine is linked to asymptomatic, transient elevations of liver aminotransferases but is historically thought to rarely cause significant hepatotoxicity. Underlying liver disease is a risk factor for drug-induced liver injury and may complicate the differential diagnosis of acute transaminitis in patients taking medications associated with hepatotoxicity. Ms L presented with 2 months of new psychotic symptoms resulting in hospitalizations. Although psychosis previously improved with haloperidol, she reported symptoms concerning for akathisia. Restlessness improved and psychotic symptoms resolved after initiation of olanzapine. Concurrently, her alanine aminotransferase (ALT) was elevated, prompting further workup and new diagnosis of acute hepatitis C. Over the course of hospitalization, her ALT increased exponentially. Initially attributed solely to acute hepatitis C infection, ALT rapidly decreased after holding olanzapine, implying it was contributing to her liver injury. Subsequently, given her prior response, haloperidol was retrialed with close monitoring for adverse effects. Her subjective restlessness was treated with additional agents, and she was then transitioned to monthly haloperidol decanoate injections to further assist her adherence. Prior to discharge, she had resolution of psychosis and transaminitis. Olanzapine may contribute to hepatotoxicity with concurrent viral hepatitis, and clarity can be obtained by a trial of stopping the suspected medication. Furthermore, olanzapine, when combined with underlying liver disease, may have an additive effect on liver injury, resulting in accelerated elevations in liver aminotransferases