The Risk of Neuropsychiatric Adverse Events With Use of Leukotriene Receptor Antagonists in Patients With Asthma: Analysis of Korea's National Health Insurance Sharing Service Database.

BACKGROUND: Montelukast, a selective leukotriene receptor antagonist, is a commonly prescribed allergy medication but its potential association with neuropsychiatric adverse events is concerning. OBJECTIVE: To analyze Korea's National Health Insurance System claims records to identify the risk of neuropsychiatric adverse events in patients with asthma treated with montelukast. METHODS: This retrospective population-based study analyzed the National Health Insurance claims records of the entire Korean population between 2008 and 2015. We compared the risk of neuropsychiatric adverse events among patients with asthma using inhaled corticosteroids and/or long-acting ß2-agonists with montelukast or pranlukast and those not using leukotriene receptor antagonists (control group). RESULTS: There was no increased risk of the composite outcome of all measured neuropsychiatric adverse events in patients with asthma who were prescribed montelukast or pranlukast compared with those who were not. However, montelukast use was associated with an increased risk of hallucinations (inverse probability treatment weighting hazard ratio, 1.45; 95% CI, 1.07-1.96) and attention problems (inverse probability treatment weighting hazard ratio, 1.24; 95% CI, 1.01-1.52). Significant negative hazards for disorientation, anxiety, stress reactions, and somatic symptoms were observed in the montelukast group. When grouped by sex, the risk of hallucinations and attention problems was higher in men prescribed montelukast compared with the controls. CONCLUSIONS: We did not observe an increase in all neuropsychiatric adverse events in the leukotriene receptor antagonist-treated group; however, an increased risk of hallucinations and attention problems was observed in those taking montelukast, regardless of the medication administration period.

Varenicline induced auditory hallucinations in a young female with bipolar disorder: a case report.

BACKGROUND: Creating appropriate and sustainable treatment plans for patients with concurrent disorders presents a challenge to psychiatrists and addiction medicine specialists alike. Although varenicline has been found to be the most effective medication for smoking cessation and abstinence when compared to results from placebo medications, nicotine patches and bupropion, caution is needed when starting patients on this medication. With the high prevalence of concurrent mental health and substance use disorders in vulnerably-housed populations in Canada, it becomes increasingly important to advocate for increased guidance and research into treating concurrent disorders. CASE PRESENTATION: In this case, a young female patient provisionally diagnosed with bipolar I disorder was hospitalized for a manic episode in the context of substance use and medication noncompliance. She also endorsed a long history of tobacco, alcohol, cocaine, cannabis and ketamine use. Perceptual abnormalities, including auditory hallucinations, were not recorded at admission. In addition to being stabilized for bipolar diagnosis, the patient was started on nicotine replacement therapy on Day 7 of admission followed by initiation of varenicline for smoking cessation on Day 14 of admission. Soon after the varenicline treatment was started, the patient developed auditory hallucinations, paranoia and referential beliefs. However, her insight was intact, and she had minimal thought form disorganization. In this case, these symptoms were thought to be secondary to varenicline after the consideration of potential alternative contributors. CONCLUSION: The occurrence of side effects as a result of varenicline use in patients with diagnosed mental health conditions is rare and underlying psychiatric illness is not labeled as an absolute contraindication in the prescription of varenicline. However, it is important to advocate for increased guidance and research on the treatment of substance use disorders in patients with bipolar I disorder. Patients may also benefit from increased collaboration between psychiatric and addiction services as that may allow for earlier recognition and intervention of symptoms to minimize distress.

Confusion and Hallucination in a Geriatric Patient. Pitfalls of a Rare Differential: Case Report of an Anti-LGI1-Encephalitis.

Background: Confusion and hallucinations in geriatric patients are frequent symptoms and typically associated with delirium, late-life psychosis or dementia syndromes. A far rarer but well-established differential in patients with rapid cognitive deterioration, acute psychosis, abnormal movements and seizures is autoimmune encephalitis. Exemplified by our case we highlight clinical and economic problems arising in management of geriatric patients with cognitive decline and psychotic symptoms. Case Presentation: A 77-year-old female caucasian patient with an unremarkable medical history was hospitalized after a fall in association with diarrhea and hyponatremia. Upon adequate therapy, disorientation and troubled short-term memory persisted. Within a week the patient developed visual hallucinations. Basic blood and urine samples and imaging (cranial computed tomography and magnetic resonance imaging) were unremarkable. With progressive cognitive decline, amnestic impairment, word finding difficulty and general apathy, psychiatric and neurologic expertise was introduced. Advanced diagnostics did not resolve a final diagnosis; an electroencephalogram showed unspecific generalized slowing. Extended clinical observation revealed visual hallucinations and faciobrachial dystonic seizures. A treatment with anticonvulsants was initiated. Cerebrospinal fluid ultimately tested positive for voltage-gated potassium channel LGl1 (leucine-rich-inactivated-1) antibodies confirming diagnosis of autoimmune anti-LGI1 encephalitis. Immediate immunotherapy (high-dose glucocorticoids and administration of intravenous immunoglobulin G) led to a rapid improvement of the patient's condition. After immunotherapy was tapered, the patient had one relapse and completely recovered with reintroduction of glucocorticoids and initiation of therapy with rituximab. Conclusion: Rapidly progressive dementia in geriatric patients demands a structured and multidisciplinary diagnostic approach. Accurate management and financially supportable care is a major issue in rare diseases such as anti-LGI1-encephalitis. Education and awareness about autoimmune encephalitis of all physicians treating a geriatric population is important in order to involve expertise and establish treatment within reasonable time.

Propensity score-matching analysis comparing safety outcomes of appetite-stimulating medications in oncology patients.

PURPOSE: Anorexia and weight loss are common complications in the elderly, advanced cancer population. Appetite stimulants are commonly used therapies for oncology patients with weight loss, yet their safety comparison remains unknown. METHODS: This was a two-center, retrospective, study conducted in New York City at Mount Sinai Beth Israel and New York University Langone from January 2016 to July 2019 in adult patients with histologic evidence of malignancy who were taking either megestrol acetate or mirtazapine as an appetite-stimulating medication. Endpoints included safety concerns of mortality, QTc prolongation, venous thromboembolism, fall, somnolence, xerostomia, and hallucinations. Effectiveness of weight gain or maintenance of weight was not assessed. A propensity score-matching analysis was performed using a logistic regression analysis to assess the two comparable groups. RESULTS: The study included 350 patients (69.56 ± 13.31 years) with the most common malignancies being gastrointestinal, breast, and hematologic with metastasis present in over half the patients. Adverse events were commonly seen in the oncology population. After a propensity score-matched analysis, all safety outcomes associated with mirtazapine compared to megestrol acetate were similar; all-cause mortality (7%, n = 7 vs. 12%, n = 12, p = 0.23), QTc prolongation (31%, n = 31 vs. 31%, n = 31, p = 1.00), thromboembolism (11%, n = 11 vs. 11%, n = 11, p = 1.00), somnolence (29%, n = 30 vs. 22%, n = 23, p = 0.34), xerostomia (27%, n = 28 vs. 18%, n = 19, p = 0.24), and hallucinations (17%, n = 18 vs. 8%, n = 8, p = 0.06), respectfully. CONCLUSION: There were no safety differences seen when evaluating both agents.

[Isolated metamorphopsia and visual pseudohallucinations in a patient with anti-NMDA receptor encephalitis]. / Isolierte Metamorphopsien und visuelle Pseudohalluzinationen bei einem Patienten mit Anti-NMDA-Rezeptor-Enzephalitis.

This article reports the case of a 40-year-old male patient with isolated metamorphopsia and visual pseudohallucinations lasting for 2 weeks. As the ophthalmological findings were not pathological, a further neurological examination was performed. After diagnosis of anti-N-methyl-D-aspartate (NMDA) receptor encephalitis, which can be manifested in various psychiatric, neurological and ophthalmological ways, the oligosymptomatic patient received high-dose corticosteroid treatment with intravenous immunoglobulins, which stopped the symptoms.

Subacute Neuropsychiatric Syndrome in Girls With SHANK3 Mutations Responds to Immunomodulation.

Phenotypic and biological characterization of rare monogenic disorders represents 1 of the most important avenues toward understanding the mechanisms of human disease. Among patients with SH3 and multiple ankyrin repeat domains 3 (SHANK3) mutations, a subset will manifest neurologic regression, psychosis, and mood disorders. However, which patients will be affected, when, and why are important unresolved questions. Authors of recent studies suggest neuronal SHANK3 expression is modulated by both inflammatory and hormonal stimuli. In this case series, we describe 4 independent clinical observations of an immunotherapy responsive phenotype of peripubertal-onset neuropsychiatric regression in 4 girls with pathogenic SHANK3 mutations. Each child exhibited a history of stable, mild-to-moderate lifelong developmental disability until 12 to 14 years of age, at which time each manifested a similar, subacute-onset neurobehavioral syndrome. Symptoms included mutism, hallucinations, insomnia, inconsolable crying, obsessive-compulsive behaviors, loss of self-care, and urinary retention and/or incontinence. Symptoms were relatively refractory to antipsychotic medication but improved after immunomodulatory treatment. All 4 patients exhibited chronic relapsing courses during a period of treatment and follow-up ranging from 3 to 6 years. Two of the 4 girls recovered their premorbid level of functioning. We briefly review the scientific literature to offer a conceptual and molecular framework for understanding these clinical observations. Future clinical and translational investigations in this realm may offer insights into mechanisms and therapies bridging immune function and human behavior.

Excited catatonia in a patient with fatal pulmonary embolism and a successful treatment strategy.

BACKGROUND: Patients with psychiatric disorders in critical condition are difficult to treat. In this study, we report on a patient with underlying schizoaffective disorder who developed catatonia, cardiac arrest, and pulmonary embolism, as well as a successful treatment strategy. CASE PRESENTATION: The inpatient is a 41-year-old morbidly obese male with schizoaffective disorder whose clozapine dosage was titrated from 100 mg to 175 mg due to auditory hallucination and agitation. The patient abruptly developed acute cardiopulmonary symptoms associated with an elevated troponin-I level. He was transferred to a cardiac intensive care unit, where he remained for 3 days. He was also found to have excited catatonic symptoms, and the lorazepam-diazepam protocol was initiated to quickly relieve the catatonia. Once the coronary angiogram was read as normal, the patient was transferred back to the psychiatric ward. However, the patient then suffered from in-hospital cardiac arrest. He was resuscitated and again transferred to the medical intensive care unit. Computed tomography confirmed the diagnosis of a pulmonary embolism. The patient was treated with Rivaroxaban 30 mg/d for the first 21 days, followed by 20 mg daily for 3 months. To control his severe and refractory psychotic symptoms, the patient was re-prescribed clozapine. During the 15-month follow-up period, the patient demonstrated a fair response and tolerability to clozapine 150 mg without symptoms relapse and no thromboembolic event. CONCLUSION: This report can serve to remind psychiatrists and physicians to be aware of fatal conditions in patients with psychiatric diseases and physical illnesses.

Rare presentation of intrathecal morphine withdrawal psychosis.

We report a case of a 57-year-old male patient with intrathecal morphine pump failure who presented with psychosis as part of a clinical presentation of opioid withdrawal. The patient was being treated for chronic back pain with an intrathecal morphine pump for several years. The patient spontaneously started to experience psychotic symptoms which included disorganized thinking, delusional thoughts, paranoia, auditory and visual hallucinations. Upon interrogation of intrathecal pump, it was found not to be functioning, thereby not delivering intrathecal morphine. After opioid rotation with administration of oral oxycodone, the patient's psychosis improved dramatically within a few days, clinically confirming psychosis due to morphine withdrawal. Therefore, it is important for physicians to consider opioid withdrawal in patients experiencing isolated psychosis.

Anti-NMDA (a-NMDAR) receptor encephalitis related to acute consumption of metamphetamine: Relevance of differential diagnosis. / Encefalitis antirreceptores (a-NMDAR) en un paciente con ingesta aguda de metanfetanima: importancia del diagnóstico diferencial.

A 19-year-old male came to the Emergency Room of our hospital due to an episode of dystonic movements and disorientation 4 days after consuming methamphetamine, which evolved to a catatonic frank syndrome and eventually to status epilepticus. Definitive diagnosis was anti-NMDA receptor encephalitis, an acute inflammation of the limbic area of autoimmune origin in which early diagnosis and treatment are key elements for the final outcome. In this case, initial normal tests and previous methamphetamine poisoning delayed diagnosis, because inhaled-methamphetamine poisoning causes similar clinical symptoms to anti-NMDA receptor encephalitis. Methamphetamine poisoning may have caused an immune response in the patient, bringing on the progress of the pathology.

Clinical nonmotor aspect of A2A antagonist in PD treatment.

The chapter discusses with clinical case study if adenosine A2A receptor antagonist, as a novel therapeutic class for symptomatic improvement of Parkinson's disease (PD), can also be expected to have an improvement of nonmotor symptoms related with PD.

N-acetylcysteine modulates hallucinogenic 5-HT(2A) receptor agonist-mediated responses: behavioral, molecular, and electrophysiological studies.

N-acetylcysteine (NAC) has been reported to reverse the psychotomimetic effects in the rodent phencyclidine model of psychosis and shown beneficial effects in treating patients with schizophrenia. The effect of NAC has been associated with facilitating the activity of cystine-glutamate antiporters on glial cells concomitant with the release of non-vesicular glutamate, which mainly stimulates the presynaptic metabotropic glutamate receptor subtype 2 receptors (mGluR2). Recent evidence demonstrated that functional interactions between serotonin 5-HT2A receptor (5-HT(2A)R) and mGluR2 are responsible to unique cellular responses when targeted by hallucinogenic drugs. The present study determined the effects of NAC on hallucinogenic 5-HT(2A)R agonist (±)1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI)-elicited behavioral and molecular responses in mice and DOI-evoked field potentials in the mouse cortical slices. NAC significantly attenuated DOI-induced head twitch response and expression of c-Fos and Egr-2 in the infralimbic and motor cortex and suppressed the increase in the frequency of excitatory field potentials elicited by DOI in the medial prefrontal cortex. In addition, the cystine-glutamate antiporter inhibitor (S)-4-carboxyphenylglycine (CPG) and the mGluR2 antagonist LY341495 reversed the suppressing effects of NAC on DOI-induced head twitch and molecular responses and increased frequency of excitatory field potentials, supporting that NAC attenuates the 5-HT(2A)R-mediated hallucinogenic effects via increased activity of cystine-glutamate antiporter followed by activation of mGluR2 receptors. These findings implicate NAC as a potential therapeutic agent for hallucinations and psychosis associated with hallucinogen use and schizophrenia.

Trimethoprim-sulfamethoxazole-related hallucinations.

Although adverse drug reactions are a well-recognized cause of mental status changes in the elderly, antimicrobials are not often implicated. Trimethoprim-sulfamethoxazole-induced hallucinations in immune-competent patient with switching to nitrofurantoin and risperidone, without associated polypharmacy, have not been reported in the literature. In this case report, we present an 86-year-old Caucasian immune-competent female with major depressive disorder and insomnia who developed hallucinations when treated with two trimethoprim-sulfamethoxazole tablets (80 mg/400 mg) in every 12 hours (4 tablets daily) because of lower urinary infection. After trimethoprim-sulfamethoxazole discontinuation and switching to nitrofurantoin and risperidone, symptoms significantly improved.

Neuropsychiatric manifestations and treatment of disseminated neurocysticercosis: a compilation of three cases.

BACKGROUND: Neurocysticercosis (NCC) is the most serious form of cysticercal infection and is a major public health problem in the developing world. NCC presents with a range of psychiatric symptoms besides neurological symptoms. There have been few reports from the Asian continent describing the neuropsychiatric manifestations. Our aim was to report manifestations and treatment issues in three cases with disseminated NCC. METHODS AND RESULTS: Informed consent was obtained from all the three patients for the purpose of reporting. All three had multiple cysticerci in the brain and presented with several neuropsychiatric manifestations. All the patients had epilepsy and in addition they had varying psychiatric symptoms of delusions, hallucinations and catatonia, and cognitive symptoms. Also, interestingly in one patient, worsening of psychiatric and neurological symptoms correlated with anti-helminthic treatment. The psychotic symptoms responded to anti-psychotic treatment in one case. Anti-epileptics and steroid courses when given improved the clinical status. CONCLUSION: NCC presents with a myriad of manifestations. Epilepsy, psychotic and cognitive symptoms respond to symptomatic treatment. Use of anti-parasitic agents might worsen the symptoms as has been reported in a few cases earlier.

Escitalopram for antipsychotic nonresponsive visual hallucinosis: eight patients suffering from Charles Bonnet syndrome.

BACKGROUND: The Charles Bonnet syndrome (CBS) is characterized by distinct visual hallucinations and ocularpathology causing visual impairment in patients with insight and the absence of psychiatric comorbidity. The number of reported cases of CBS is expanding as the population ages and the prevalence of vision disorders increases. Antipsychotic medications are often prescribed. However, their efficacy in CBS has been based on sketchy evidence. The use of serotonin selective reuptake inhibitor (SSRI) for CBS was anecdotally reported. We herein describe effectiveness of escitalopram in a series of patients suffering from CBS who were unresponsive to antipsychotic treatment. METHODS: Eight consecutive patients suffering from CBS who did not respond to standard antipsychotic treatment were switched to escitalopram. CBS severity prior to escitalopram treatment was quantified using the Clinical Global Impression (CGI) scale and again after eight weeks of treatment. All had undergone brain CT and cognitive assessment. Brain CT imaging was normal except for an incidental finding of a small frontal meningioma in one patient. All had Mini-Mental Status Examination scores of ≥ 27/30. RESULTS: There were four men and four women, with a mean age of 81.7 ± 7.3 years. Previous antipsychotic treatment was mostly with risperidone, 1.0 to 3.0 mg/daily. Mean CGI-severity upon switching to escitalopram treatment was 5.7. This was significantly reduced to 1.8 (p < 0.001) after eight weeks of escitalopram treatment (mean dose: 11.8 mg/daily). There were no side effects, nor any adverse events were reported. CONCLUSIONS: This is the first case-series to show that SSRI is an effective and well-tolerated treatment for visual hallucinations associated with vision impairment such as in CBS.

Thyrotoxic psychosis in an elderly woman and haloperidol use: a case report.

Thyrotoxic patients may occasionally present with affective disorders. Here, we discuss a case of a 61-year-old woman with misidentification and persecutory delusions, olfactory hallucinations, and apathy associated with thyrotoxicosis. After definitive antithyroid and antipsychotic agent haloperidol treatments, the patient was released within 4 weeks. Thyrotoxic psychosis with apathy is a rare entity that can be misdiagnosed as affective psychosis. Haloperidol may be an alternative treatment in resolving psychotic features beside the treatment of hyperthyroid state.

Treatment of delirium with risperidone in cancer patients.

AIM: Antipsychotic medications have frequently been regarded as the treatment of choice for delirium. This study examined the clinical efficacy of risperidone for the treatment of delirium in cancer patients, combined with a repeated assessment of underlying medical severity levels. METHODS: The study included consecutive referrals of 29 delirious cancer patients (mean age, 68.9 ± 12.5 years; male, 69%) to the psychiatric consultation service. Risperidone was given orally once per day (mean dosage, 1.4 ± 1.3 mg/day). Study participants were assessed using quantitative standardized scales of cognitive function, delirium, and physical impairment at baseline and at the end of the study (seventh day). RESULTS: Risperidone with routine clinical management was effective for the treatment of delirium: 48% of the patients responded and 38% achieved remission. The reduction of delirium severity occurred in 79% of the patients. Changes in delirium severity were unrelated to age, gender, general cognitive dysfunction, or to severity of attendant medical conditions. In addition to changes in agitation and perceptional disturbances, risperidone was also effective for other specific delirium symptoms. CONCLUSIONS: Risperidone with routine clinical management is effective in the treatment of delirium in advanced cancer patients, independent of changes in the underlying medical condition.