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.

Cannabis Dopaminergic Effects Induce Hallucinations in a Patient with Parkinson's Disease.

Cannabis products that contain the tetrahydrocannabinol (THC) cannabinoid are emerging as promising therapeutic agents for the treatment of medical conditions such as chronic pain. THC elicits psychoactive effects through modulation of dopaminergic neurons, thereby altering levels of dopamine in the brain. This case report highlights the complexity associated with medicinal cannabis and the health risks associated with its use. A 57-year-old male with Parkinson's disease was experiencing worsening tremors and vivid hallucinations despite therapy optimization attempts. It was discovered that the patient took cannabis for chronic back pain, and a pharmacogenomics (PGx) test indicated the presence of variants for the COMT and HTR2A genes. These variants could increase dopamine levels and predispose patients to visual hallucinations. Once the cannabis was discontinued, the patient's hallucinations began to slowly dissipate. Cannabis use continues to expand as it gains more acceptance legally and medicinally, but cannabis can affect the response to drugs. This patient case suggests that cannabis use in combination with dopamine-promoting drugs, especially in a patient with genetic variants, can increase the risk for vivid hallucinations. These conditions support the importance of considering herb-drug interactions and PGx data when performing a medication safety review.

Nightmares and hallucinations with aprepitant and opium powder: a suspected drug-drug interaction.

Polypharmacy of elderly oncology patients and fragmented medication management are well-known risk factors for drug-drug interactions (DDIs). These interactions can occur among antineoplastic, ongoing chronic treatment(s) and chemotherapy-associated treatments, like antiemetics. Clinically relevant interactions based on enzyme- or transporter-inhibition phenomena of active drugs can increase the frequency of their DDIs. We describe a strongly suspected elderly cancer patient's DDI between aprepitant and opium powder in the context of an irinotecan-based regimen manifested by nightmares and visual hallucinations. We discuss this DDI's hypothetical pharmacological mechanisms and management.

Serotonergic Hallucinogen-Induced Visual Perceptual Alterations.

Serotonergic hallucinogens, such as lysergic acid diethylamide (LSD), psilocybin, and N,N-dimethyltryptamine (DMT), are famous for their capacity to temporally and profoundly alter an individual's visual experiences. These visual alterations show consistent attributes despite large inter- and intra-individual variances. Many reports document a common perception of colors as more saturated, with increased brightness and contrast in the environment ("Visual Intensifications"). Environmental objects might be altered in size ("Visual illusions") or take on a modified and special meaning for the subject ("Altered self-reference"). Subjects may perceive light flashes or geometrical figures containing recurrent patterns ("Elementary imagery and hallucinations") influenced by auditory stimuli ("Audiovisual synesthesia"), or they may envision images of people, animals, or landscapes ("Complex imagery and hallucinations") without any physical stimuli supporting their percepts. This wide assortment of visual phenomena suggests that one single neuropsychopharmacological mechanism is unlikely to explain such vast phenomenological diversity. Starting with mechanisms that act at the cellular level, the key role of 5-HT2A receptor activation and the subsequent increased cortical excitation will be considered. Next, it will be shown that area specific anatomical and dynamical features link increased excitation to the specific visual contents of hallucinations. The decrease of alpha oscillations by hallucinogens will then be introduced as a systemic mechanism for amplifying internal-driven excitation that overwhelms stimulus-induced excitations. Finally, the hallucinogen-induced parallel decrease of the N170 visual evoked potential and increased medial P1 potential will be discussed as key mechanisms for inducing a dysbalance between global integration and early visual gain that may explain several hallucinogen-induced visual experiences, including visual hallucinations, illusions, and intensifications.

Increased thalamic resting-state connectivity as a core driver of LSD-induced hallucinations.

OBJECTIVE: It has been proposed that the thalamocortical system is an important site of action of hallucinogenic drugs and an essential component of the neural correlates of consciousness. Hallucinogenic drugs such as LSD can be used to induce profoundly altered states of consciousness, and it is thus of interest to test the effects of these drugs on this system. METHOD: 100 µg LSD was administrated orally to 20 healthy participants prior to fMRI assessment. Whole brain thalamic functional connectivity was measured using ROI-to-ROI and ROI-to-voxel approaches. Correlation analyses were used to explore relationships between thalamic connectivity to regions involved in auditory and visual hallucinations and subjective ratings on auditory and visual drug effects. RESULTS: LSD caused significant alterations in all dimensions of the 5D-ASC scale and significantly increased thalamic functional connectivity to various cortical regions. Furthermore, LSD-induced functional connectivity measures between the thalamus and the right fusiform gyrus and insula correlated significantly with subjective auditory and visual drug effects. CONCLUSION: Hallucinogenic drug effects might be provoked by facilitations of cortical excitability via thalamocortical interactions. Our findings have implications for the understanding of the mechanism of action of hallucinogenic drugs and provide further insight into the role of the 5-HT2A -receptor in altered states of consciousness.

[Behavioural impairments and hallucinations after consumption of boldo leaf infusions]. / Troubles du comportement et hallucinations après consommation d'infusions de feuilles de boldo.

We report a case of behavioural impairments with hallucinations in a twelve-year-old girl, after consumption of boldo leaf infusions. The main alkaloid of boldo, named boldine, is very likely responsible for temporary neuropsychiatric disturbances present in the patient. The emergence of behavioural problems and hallucinations without any obvious cause, should lead to search for consumption of boldo leaf infusion ("tisanes"). This consumption must be avoided in children.

From divination to madness: features of acute intoxication with Salvia use.

Salvia divinorum is a psychoactive botanical plant that is increasingly used for the 'legal' highs that it can produce. It is readily available for purchase on the Internet, and most abusers are unaware of the toxicity and abuse potential associated with its use. As the use of novel compounds among abusers is not uncommon, physicians need to increase their awareness and recognition of these new substances. Herein, we report a case of an acute presentation of Salvia intoxication.

[Intractable diarrhoea and severe weight loss by roflumilast]. / Diarrea intratable y pérdida ponderal acusada secundarias a roflumilast.

BACKGROUND AND OBJECTIVE: Roflumilast is a recently marketed drug, indicated for maintenance treatment of severe chronic obstructive pulmonary disease associated with chronic bronchitis in adult patients with a history of frequent exacerbations as add on to bronchodilator treatment. MATERIAL AND METHODS: The safety data of this drug have always been subjected to controversy and concerns. The Food and Drug Administration rejected the drug after the first evaluation, asking the company to clarify the adverse reactions during the investigation process, the European Medicines Agency approved the drug including a Risk Management Plan, designed to promote a safe use of the drug. RESULTS: During the first months after the marketing process, the Spanish Pharmacovigilance System has already been acquainted of several adverse events notifications; therefore, these patients may be closely monitored, mainly because of digestive and psychiatric disorders. CONCLUSIONS: Here we report the case of a female patient who showed a serious digestive clinical profile and a severe weight loss, more than 25% of her initial weight, when a treatment with roflumilast was started. The suspicion of a side effect as the cause of the reported clinical profile and its resolution required 3 hospital admissions.

Towards evidence-based emergency medicine: best BETs from the Manchester Royal Infirmary. BET 3: what are the clinical features of Salvia divinorum toxicity?

A short-cut review was carried out to determine the clinical features associated with acute intoxication with Salvia divinorum. Sixty-six papers were found using the reported searches, of which three presented the best evidence to answer the clinical question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these best papers are tabulated. It is concluded that the most common features of intoxication are tachycardia, hallucinations and acute alteration in mental status.

Hallucinations and comorbid renal tubular acidosis caused by topiramate in a patient with psychiatric history.

Few studies have shown that topiramate may induce psychiatric symptoms and metabolic disorders, respectively. Here, we reported a 13-year-old female who presented with topiramate-induced hallucinations and comorbid renal tubular acidosis. She had a history of psychiatric illness and had been taking the medication for 3 months without prior side effects. After the discontinuation of topiramate, she was treated with supplementary potassium and sodium bicarbonate. Subsequently, her psychiatric symptoms and biochemical findings improved. Recognition of drug-induced psychotic symptoms and renal tubular acidosis is important during concomitant topiramate therapy in psychiatric clinic.

Neuroleptic malignant syndrome-like reaction precipitated by antipsychotics in a patient with gamma-butyrolactone withdrawal.

We report the case of a patient with chronic abuse of gamma-butyrolactone (GBL, 3 bottles per week for 4 months), who in the course of the management of acute agitation and hallucinations developed symptoms compatible with both neuroleptic malignant syndrome and GBL withdrawal symptoms.Some GHB withdrawal symptoms are similar to those of neuroleptic malignant syndrome, and the administration of antipsychotics might worsen the neurological condition of patients. So, it seems important to rapidly detect drugs taken by patients with mental agitation, to optimize management and minimize complications related to drugs.

Salvia divinorum: exposures reported to a statewide poison control system over 10 years.

BACKGROUND: Salvia divinorum, a hallucinogenic herb, has in recent years become popular among teenagers and young adults. Salvia is presently marketed as a "legal" alternative to other drugs of abuse, but little is known about the clinical toxicity of this substance. OBJECTIVES: The purpose of this study is to describe the clinical and demographic features of this emerging substance of recreational abuse using data obtained from the records of a poison control center. METHODS: We performed retrospective review of exposures to the herbal hallucinogen Salvia divinorum as reported to the California Poison Control System (CPCS) over the last 10 years. Demographic and clinical data were collected and compiled from the computerized records of the CPCS for the search terms "salvia" and "sage." RESULTS: There were 37 exposures to S. divinorum and 96 exposures to non-hallucinogenic Salvia species. Eighteen (49%) of the exposures were to S. divinorum alone. Intentional Salvia exposures resulted in a variety of neurologic, cardiovascular, and gastrointestinal effects. Notably, the use of concomitant substances of abuse was associated with a high rate of complications and psychomotor disturbances. CONCLUSIONS: Intentional use of S. divinorum, whether alone or in combination with alcoholic beverages and other drugs, causes neurologic, cardiovascular, and gastrointestinal effects. This poison-center-based review helps to characterize the clinical toxicity of S. divinorum, but more clinical and pharmacologic research is warranted for this rapidly emerging substance of abuse.

Can "steroid switching" improve steroid-induced musical hallucinations in a patient with terminal cancer?

The patient was a 57-year-old woman with malignant pleural mesothelioma. She had a past history of anxiety neurosis but not had any history of otological diseases. On admission to our hospice (day 1), she complained of dyspnea and wheezing associated with the progression of her underlying disease. After we started oral betamethasone (2 mg/d), dyspnea was alleviated and the frequency of wheezing was reduced. On day 3, she began to experience musical hallucinations that were manifested in opera/piano concert music and a child's voice. The episodes of musical hallucinations occurred approximately 10 times a day and disappeared spontaneously within several minutes. She had not experienced these symptoms before. We reduced the dose of betamethasone to 1 mg/d, but the musical hallucinations continued. Then on day 11, we switched betamethasone (1 mg/d) to prednisolone (10 mg/d) and we then gradually tapered off prednisolone. The frequency of musical hallucinations decreased and she ceased to experience musical hallucinations on day 29. However, on day 40, her dyspnea was aggravated again, so we started treatment with prednisolone (5 mg/d). Dyspnea was alleviated and no musical hallucinations occurred. On Day 51, dyspnea was worsened and we switched prednisolone to betamethasone (4 mg/d), which she hoped to use. The betamethasone alleviated the dyspnea but she developed musical hallucinations that were similar to the previous episodes. The musical hallucinations disappeared spontaneously 4-5 days later without changing the betamethasone. Musical hallucinations never occurred thereafter. She later died due to the exacerbation of disease.

A case of beta-carboline alkaloid intoxication following ingestion of Peganum harmala seed extract.

Beta-carboline alkaloids harmine, harmaline, and tetrahydroharmine can stimulate the central nervous system by inhibiting the metabolism of amine neurotransmitters, or by direct interaction with specific receptors; they are found in numerous plants, including Peganum harmala, Passiflora incarnata and Banisteriopsis caapi, and in the entheogen preparation Ayahuasca, which is traditionally brewed using B. caapi to enhance the activity of amine hallucinogenic drugs. The ingestion of plant preparations containing beta-carboline alkaloids may result in toxic effects, namely visual and auditory hallucinations, locomotor ataxia, nausea, vomiting, confusion and agitation. We report a case of intoxication following intentional ingestion of P. harmala seed infusion; P. harmala seeds were bought over the Internet. The harmala alkaloids were identified by gas chromatography-mass spectrometry in the seed extract and the patient's urine. This is, to our knowledge, the first case of P. harmala intoxication corroborated by toxicological findings.