Psychiatric Adverse Reactions Research Articles

Spectrum of psychiatric adverse reactions to cyclin-dependent kinases 4/6 inhibitors: A pharmacovigilance analysis of the FDA adverse event reporting system.

The emergence of cyclin-dependent kinases 4/6 inhibitors (CDK4/6i) represented a major breakthrough in the treatment of breast cancer over the past decade. In both clinical trials and real-world settings, it was observed that patients using CDK4/6i might experience psychiatric adverse events (PAEs). Herein, we conducted a pharmacovigilance study to comprehensively assess the correlation between CDK4/6i and PAEs. We obtained individual case safety reports submitted to the FDA Adverse Events Reporting System (FAERS) during the period from January 2015 to December 2023. In disproportionality analysis, the reporting odds ratio (ROR) and information component (IC) values were calculated for each adverse event-drug combination. Univariate logistic regression analysis was utilized to explore factors associated with PAEs following CDK4/6i treatment. A total of 95,591 reports related to CDK4/6i were identified, with 6.72% reporting PAEs, and this proportion exhibited an annual upward trend. Based on the ROR and IC values, 17 categories of PAEs were defined as CDK4/6i-related PAEs. Among these PAEs, insomnia, stress, eating disorder, depressed mood, and sleep disorder were very common, each accounting for over 10% of CDK4/6i reports. Ribociclib showed the highest risk signal of CDK4/6i-related PAEs (ROR = 1.89[1.75-2.04], IC025 = 0.79), followed by palbociclib (ROR = 1.47[1.41-1.53], IC025 = 0.49), while abemaciclib did not exhibit a significant signal (ROR = 0.52[0.44-0.62], IC025 = -1.13). Female sex, younger age and weight exceeding 80 kg were significant risk factors for the incidence of CDK4/6i-related PAEs. Using data from a real-world, large-scale spontaneous reporting system for adverse drug reactions, our study delineated the spectrum of PAEs to CDK4/6i. This potentially offered valuable insights for healthcare professionals to manage the risk of PAEs in patients receiving CDK4/6i treatment, particularly those with psychiatric disorders.

A Natural Language Processing Framework for Detecting Adverse Drug Reactions in Clinical Structured Drug Reviews

Background: Adverse drug reactions (ADRs) pose significant concerns in healthcare, yet their underreporting remains a challenge. Extracting spontaneous and non-automatic reports from free-text narratives contributes to this low rate of reporting. An automatic ADR detection system can mitigate these issues by identifying, summarizing, and reporting ADRs in a document. This study presents an adverse drug reaction detector (ADRD), a natural language processing (NLP) framework applied to the psychiatric treatment adverse reactions (PsyTAR) dataset. Aiming to automate ADR analysis, the framework explores the relationship between ADRs and patient satisfaction. Methods: A comprehensive eight-phase approach was employed in the ADRD framework, utilizing Python programming language libraries and NLP tools. The dataset underwent meticulous preprocessing, and the subsequent phases involved data summarization, pattern identification, data cleaning, sentiment calculation, assessment of drug effectiveness and usefulness, analysis of medical conditions, and identification of the most effective and ineffective drugs for each condition. Results: Analyzing 891 comments related to four unique drugs (i.e., Zoloft, Lexapro, Cymbalta, and Effexor XR) from patients with 285 distinct conditions, the framework offered insights into the dataset structure, statistical indicators, distribution of ratings and ADR counts, the impact of ratings on ADR counts, and length of comments’ influence on ratings. Conclusion: The challenges of extracting ADR reports from free-text narratives have led to their underreporting. ADRD offers an automated and insightful approach for enhancing ADR analysis and reporting processes, making strides toward bridging the gap in ADR reporting.

Depressive and Other Adverse CNS Effects of Fluoroquinolones.

Fluoroquinolones (FQs) are widely used drugs around the world. This is a result of their broad spectrum of antibacterial activity, high bioavailability, and known efficacy. Since they appeared on the market, their prescribing frequency has gradually increased. In 2011, FQs became the third most prescribed class of antibiotics in the US. Widespread use of these drugs resulted in an increasing number of reported side effects. In 2016, the FDA warned about significant side effects, including mental disorders in the form of anxiety, psychotic symptoms, insomnia, and depression. Psychiatric adverse reactions to FQs occur with a frequency of 1 to 4.4% and the mechanism of their formation is not entirely clear. It is believed that the antagonistic effect of FQs on the GABA receptor or interaction with the main receptor for the glutamatergic system-NMDA-is responsible for this. The paper is a structured review of 68 selected publications and the latest summary of CNS adverse effects that occur during FQ use. Prescribers should be aware of the risk factors for FQ toxicity, including elderly patients with underlying medical conditions or receiving concomitant medication; however, these adverse events may also occur in other groups of patients.

Psychiatric adverse reactions to non-selective RET multi-kinase inhibitors: a large-scale pharmacovigilance analysis.

Objective: The development of non-selective multi-kinase inhibitors (MKIs) has improved the. survival outcomes of patients with cancers. Psychiatric disorders represent an MKIs related AE of particular concern, as they are often ignored and may harm the patient's personal and social functioning. Therefore, we use the public database to describe and evaluate psychiatric adverse events related to various non-selective RET MKIs. Provide evidence for optimizing drug administration in the clinic. Methods: We analyzed spontaneous reports submitted to the Food and Drug Administration Adverse Events Reporting System FDA Adverse Event Reporting System in an observational and retrospective manner. Selecting psychiatric AEs to non-selective RET multikinase inhibitors (sorafenib, lenvatinib, vandetanib, cabozantinib, and sunitinib). We used Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and multi-item gamma Poisson shrinker (MGPS) algorithms to analyze suspected adverse reactions of psychiatric related induced by non-selective RET MKIs between January 2004 and September 2022. Results: As of September 2022, 1,108 non-selective RET MKIs ICSRs were related to psychiatric AEs. 706 were ADR ICSRs, and 402 were non-ADR ICSRs. There were more ADR cases in males (69.5%), and 71.8% of the cases were submitted from North America. The age group most frequently affected by psychiatric ADRs was individuals aged 50-64years for sorafenib, whereas 65-74years for sunitinib, cabozantinib, and lenvatinib. In all psychiatric ADRs ICSRs, excluding missing data (n = 329), the most common adverse outcome was hospitalization (260/377, 69.0%), and the most serious was death (100/377, 26.5%). What calls for special attention is that the percentage of death rate for sunitinib was highest (24/54, 44.4%) in sunitinib-related psychiatric ADRs ICSRs, (excluding missing data, n = 44), followed by lenvatinib (4/14, 28.6%). Based on ROR, PRR, BCPNN, and MGPS methods, sorafenib, sunitinib, cabozantinib, and lenvatinib are significantly associated with all ADRs, the strongest association was the association between cabozantinib and feeding disorder. Conclusion: Despite the limitations, our study found that, except for vandetanib, other four drugs have been reported to have significant psychiatric side effects. Clinicians need to recognize and monitor these potentially fatal adverse events. If it is suitable for treatment with vandetanib, doctors should choose vandetanib for treatment.

Self‐reported neuropsychiatric adverse reactions in people receiving bictegravir combined with emtricitabine/tenofovir alafenamide

AbstractThe integrase‐inhibitor bictegravir combination antiretroviral therapy (ART) Biktarvy became available in Australia in October 2018. Neuropsychiatric adverse drug reactions (ADRs) are associated with bictegravir and may affect persistence and adherence to treatment. The aim of this study was to describe the type and frequency of reported neuropsychiatric reactions in people dispensed Biktarvy. Ethics approval was obtained from Alfred Hospital Ethics Committee (Project No. 541/20). Data were collected from records of people dispensed Biktarvy between October 2018 and May 2020 and who subsequently had a new neuropsychiatric reaction reported to the organisation's ADR Review Committee. Data were sourced from ADR reports, medical and dispensing records, and included demographics, medical history, and concurrent medicines with known psychiatric adverse reactions. Data were analysed descriptively. Biktarvy was dispensed to 1265 patients. Twenty‐two (1.7%, 95% confidence interval [CI] 1.0–2.5%) people reported 50 neuropsychiatric ADRs, including abnormal dreams (n = 13), sleep disorders (n = 5), and headaches (n = 5). The median time from initiation to reaction was 13 (interquartile range [IQR] 4–94) days. Eighteen patients discontinued Biktarvy (1.4%, 95% CI 0.85–2.24). There was no statistically significant difference in discontinuation of Biktarvy between people who did or did not have a pre‐existing psychiatric diagnosis (p = 0.58). Concurrent medicines with known psychiatric adverse reactions were used by 10 people. A low rate of reported neuropsychiatric ADRs lead to discontinuation of Biktarvy, similar to rates in Biktarvy trials. This study adds to the post‐marketing surveillance data of Biktarvy tolerance amongst people living with human immunodeficiency virus (HIV).

Spectrum of Serious Neurological and Psychiatric Adverse Events in Indian COVID-19 Vaccine Recipients: A Systematic Review of Case Reports and Case Series.

Indian data regarding serious neurological and psychiatric adverse events, following coronavirus disease 2019 (COVID-19) vaccination, are lacking. We, therefore, systematically evaluated cases of post-vaccinal serious neurological and psychiatric adverse reactions published from India. A systematic review of cases published from India, which were archived in PubMed, Scopus, and Google Scholar databases, was performed; pre-print databases along with ahead-of-print contents were searched in addition. Retrieved articles, as on June 27, 2022, were evaluated following PRISMA guidelines. EndNote 20 web tool was used to make a PRISMA flow chart. Individual patients' data were compiled in a tabular form. The protocol of the systematic review was registered with PROSPERO (CRD42022324183). A total of 64 records describing 136 instances of serious neurological and psychiatric adverse events were identified. More than 50% (36/64) reports were from the following four states, namely, Kerala, Uttar Pradesh, New Delhi, and West Bengal. The mean age of persons developing these complications was 44.89 ± 15.77 years. In the majority, adverse events occurred within 2 weeks of administration of the first dose of COVISHIELD vaccine. Immune-mediated central nervous system (CNS) disorders were identified in 54 instances. Guillain-Barre syndrome and other immune-mediated peripheral neuropathies were reported in 21 cases. Post-vaccinal herpes zoster was recorded in 31 vaccine recipients. Psychiatric adverse events were recorded in six patients. In Indian recipients of COVID-19 vaccine, a variety of serious neurological complications were reported. The overall risk appears minuscule. Immune-mediated central and peripheral neuronal demyelinations were the most frequently reported post-vaccinal adverse events. A large number of cases of herpes zoster have also been reported. Immune-mediated disorders responded well to immunotherapy.

Post-Marketing Surveillance of Statins-A Descriptive Analysis of Psychiatric Adverse Reactions in EudraVigilance.

Statins are included in the category of high-frequency prescription drugs, and their use is on an upward trend worldwide. In 2012, the FDA issued a warning about possible cognitive adverse drug reactions (ADRs) related to statins, some of which are listed in the Summary of Product Characteristics, but there are still concerns about their potential risk of psychiatric events. The aim of this research was to investigate spontaneous reports containing psychiatric ADRs associated with statins by analyzing the EudraVigilance (EV) database. From January 2004 to July 2021, a total of 8965 ADRs were reported for the Systems Organ Class (SOC) "psychiatric disorders", of which 88.64% were registered for atorvastatin (3659), simvastatin (2326) and rosuvastatin (1962). Out of a total of 7947 individual case safety reports (ICSRs) of the 3 statins mentioned above, in 36.3% (2885) of them, statins were considered the only suspected drug, and in 42% (3338), no other co-administered drugs were mentioned. Moreover, insomnia has been reported in 19.3% (1536) of cases, being the most frequent adverse reaction. A disproportionality analysis of psychiatric ADRs was performed. The Reporting Odds Ratio (ROR) and 95% confidence interval (95% CI) were calculated for simvastatin, atorvastatin and rosuvastatin compared with antiplatelets and antihypertensive drugs. The reporting probability for most ADRs of these statins compared to antiplatelets was higher. The reporting probability for insomnia, nightmares and depression produced by statins compared to antihypertensive drugs was also higher. The results of this analysis augment the existing data about a possible correlation between the administration of statins and the occurrence of psychiatric side effects.

Disproportionality analysis of adverse neurological and psychiatric reactions with the ChAdOx1 (Oxford-AstraZeneca) and BNT162b2 (Pfizer-BioNTech) COVID-19 vaccines in the United Kingdom

ABSTRACT Background Information on neurological and psychiatric adverse events following immunization (AEFIs) with COVID-19 vaccines is limited. Research design & methods We examined and compared neurological and psychiatric AEFIS reports related to BNT162b2 (Pfizer-BioNTech) and ChAdOx1 (Oxford-AstraZeneca) COVID-19 vaccines and recorded in the United Kingdom Medicines and Healthcare products Regulatory Agency between 9 December 2020 and 30 June 2021. Results As of 30 June 2021, 46.1 million doses of ChAdOx1 and 30.3 million doses of BNT162b2 had been administered. The most frequently reported AEFI was headache with 1,686 and 575 cases per million doses of ChAdOx1 and BNT162b2, respectively. AEFIs more frequently reported after CHAdOx1 compared with BNT162b2 vaccination were Guillain-Barré syndrome (OR, 95% CI = 2.53, 1.82–3.51), freezing (6.66, 3.12–14.22), cluster headache (1.53, 1.28–1.84), migraine (1.23,1.17–1.30), postural dizziness (1.24,1.13–1.37), tremor (2.86, 2.68–3.05), headache (1.40, 1.38–1.43), paresthesia (1.11, 1.06–1.16), delirium (1.85, 1.45–2.36), hallucination (2.20, 1.82–2.66), poor quality sleep (1.53, 1.26–1.85), and nervousness (1.54, 1.26–1.89) Reactions less frequently reported with ChAdOx1 than with BNT162b2 were Bell’s palsy (0.47, 0.41–0.55), anosmia (0.58, 0.47–0.71), facial paralysis (0.35, 0.29–0.41), dysgeusia (0.68, 0.62–0.73), presyncope (0.48, 0.42–0.55), syncope (0.63, 0.58–0.67), and anxiety (0.75 (0.67–0.85). Conclusion Neurological and psychiatric AEFIs were relatively infrequent, but each vaccine was associated with a distinctive toxic profile.

New-onset hallucinations with amiodarone: a case report

BackgroundAmiodarone is a commonly used antiarrhythmic for the treatment of atrial fibrillation with a unique pharmacokinetic profile. While general side effects can be frequently associated with amiodarone, psychiatric adverse reactions to this medication are uncommon. The relationship between amiodarone and hallucinations independent of delirium has been rarely reported in the literature.Case presentationWe report the case of a 63-year-old female with a history of estrogen and progesterone receptor positive invasive ductal carcinoma with osseous metastases to the ribs and skull, major depressive disorder, and unspecified anxiety. She was diagnosed with invasive ductal carcinoma 12 years prior and underwent a lumpectomy with axillary lymph node dissection and radiation, currently maintained on anastrozole and trastuzumab for the past 11 years. Her symptoms of major depressive disorder and anxiety have remained in remission on a regimen of bupropion extended release, duloxetine, and trazodone without recent dose changes. This patient presented to the emergency department with dyspnea and was admitted to the general medical floor with new-onset atrial fibrillation. She was subsequently started on amiodarone for rhythm control. Shortly after its initiation, the patient developed new onset auditory and visual hallucinations with an unremarkable extensive medical evaluation. Auditory hallucinations consisted of music and unintelligible conversations, while visual hallucinations were of a family member crying on the floor and a man carrying a gun. The differential diagnoses included depression with psychotic features, delirium, and amiodarone-induced hallucinations. Given the lack of current depressive symptoms, absence of altered cognition, and the temporal relationship between the initiation of amiodarone and the onset of hallucinations, amiodarone was suspected to be probable etiology of her hallucinations. For this reason, amiodarone was replaced with dronedarone. Visual and auditory hallucinations ceased within less than 3 days after the discontinuation of amiodarone.ConclusionsPsychiatric adverse events from amiodarone are uncommon, and associated isolated hallucinations have only been rarely reported in the literature. While the risk of visual and auditory hallucinations appears to be low with amiodarone initiation, clinicians should be aware of this potential side effect.

Levetirazetam: antiepileptic-induced psychosis

IntroductionLevetirazetam is an antiepileptic drug with psychiatric adverse reactions. It includes psychosis, paranoia or hallucinations. The frequency is less than 1%.ObjectivesTo describe a case of Psychosis produced by LevetirazetamMethodsRetrospective review of clinical records and complementary test, including psychiatry, electrophysiology and neurology. Diagnosis schales such as Salamanca Questionnaire were used as suport.ResultsA 42-year-old woman diagnosed with tuberous sclerosis and undergoing treatment with levetirazetam acudes to the emergency department for behavioral disorders. She has presented an episode of aggression against a relative threatening him with a kitchen knife. The family reports that since the change in antiepilepticus 1 month ago, the patient has presented strange behaviors. Te Patient is conscious, uncooperative. Barely Approachable. Suspicious of her surroundings, with psychomotor restlessness, self-reference ideas and sparse speech. Auditory hallucinations seem to be present, as well as depressed and irritable mood. Psychic and somatic anxiety is found.Levetirazetam is discontinued, being replaced by valproic acid. Risperidone is started at a 3 mg dose. Treatment is well tolerated, and clinical stability is achived. Cluster A personality traits are found. Complementary test Blood and Urine simples, Imaging tests (CT and MRI), electroencephalogram and Electrocardiogram show no alterationsConclusionsLevetirazetam can cause psychiatric adverse effects. it is important to make a proper diagnosis before a first psychotic outbreak in later life. Drugs that can produce psychiatric side effects should be identified and patients should be inform.DisclosureNo significant relationships.

Psychiatric adverse events reported after COVID-19 vaccination in the European Union (EU), the United States (US) and the United Kingdom (UK)

IntroductionSeveral psychiatric adverse events can occur after vaccination. Passive surveillance reporting systems can support the identification of rare adverse events and contribute to hypothesis generation for potential causal associations.ObjectivesTo describe the psychiatric adverse reactions associated with various COVID-19 vaccines reported in the WHO database (VigiBase®)MethodsWe for individual case reports (ICSRs) for “Psychiatric disorders” linked to COVID-19 vaccines authorized in the EU, the US and the UK. Reporting rates were calculated using the number of administered doses as a denominator. Disproportional reporting was investigated through frequentist and Bayesian approaches by the calculation the information component (IC) for adverse psychiatric adverse not included in the vaccine label.Results63322 ICSRs including 76,163 psychiatric adverse events were identified, 21878 (34.6 %) were serious events. Mean age in the reports was 48.8 years old (SD: 17.8) and involved 44441 (70.2%) female and 17975 (28.4%) women; sex was not specified in 906 (1.4%) reports. Rate of reported psychiatric adverse events per million administered doses were 52.0, 110.3, 164.8 and 170.8 for Tozinameran/Cominarty (Pfizer-BioNTech), Elasomeran (Moderna), Vaxzevria (AstraZeneca) and Ad26.COV2-S (Janssen) vaccines respectively. UK recorded the highest rates. The most frequently reported events were insomnia (21.6%), confusional state (13.6%) and anxiety (13.5%). Disproportionality was found for: habit cough (IC:3.6), clinomania (IC: 2.2), exploding head syndrome (IC: 2.2) and autoscopy (IC: 2.1).ConclusionsRates of reported psychiatric adverse events are very low. Doctors and patients should be aware of these potential adverse reactions. Continuing monitoring of emerging potential safety signals is advised.DisclosureNo significant relationships.

Serious Adverse Drug Reactions in Children and Adolescents Treated On- and Off-Label with Antidepressants and Antipsychotics in Clinical Practice.

Introduction Despite the growing evidence base for psychotropic drug treatment in pediatric patients, knowledge about the benefit-risk ratio in clinical practice remains limited. The ‘Therapeutic Drug Monitoring (TDM)-VIGIL’ study aimed to evaluate serious adverse drug reactions (ADRs) in children and adolescents treated with antidepressants and/or antipsychotics in approved (‘on-label’), and off-label use in clinical practice. Methods Psychiatric pediatric patients aged 6-18 years treated with antidepressants and/or antipsychotics either on-label or off-label were prospectively followed between October 2014 and December 2018 within a multicenter trial. Follow-up included standardized assessments of response, serious ADRs and therapeutic drug monitoring. Results 710 youth (age=14.6±2.2 years, female=66.6%) were observed for 5.5 months on average; 76.3% received antidepressants, 47.5% antipsychotics, and 25.2% both. Altogether, 55.2% of the treatment episodes with antidepressants and 80.7% with antipsychotics were off-label. Serious ADRs occurred in 8.3% (95%CI=6.4–10.6%) of patients, mainly being psychiatric adverse reactions (77.4%), predominantly suicidal ideation and behavior. The risk of serious ADRs was not significantly different between patients using psychotropics off-label and on-label (antidepressants: 8.1% vs. 11.3%, p=0.16; antipsychotics: 8.7% vs 7.5%, p=0.67). Serious ADRs occurred in 16.6% of patients who were suicidal at enrollment versus 5.6% of patients who were not suicidal (relative risk 3.0, 95%CI=1.9-4.9). Conclusion Off-label use of antidepressants and antipsychotics in youth was not a risk factor for the occurrence of serious ADRs in a closely monitored clinical setting. Results from large naturalistic trials like ours can contribute to bridging the gap between knowledge from randomized controlled trials and real-world clinical settings.

Behavioral And Psychiatric Adverse Events Induced By Brivaracetam: A Case Report

Background: Brivaracetam (BRV) is an anti-convulsant belonging to third-generation antiepileptic and approved by FDA as an add-on therapy as well as monotherapy for management of partial onset seizures in both adults and pediatrics as young as 1 month of age. Brivaracetam induces psychiatric adverse reactions, including non-psychotic and psychotic symptoms. Case Report: A 26-year-old male patient having a past medical history of dyslexia was diagnosed with Seizure disorder during February 2021. Initially, the patient was prescribed Levetiracetam 500 mg BD to control his seizure. The drug was well tolerated and there were no episodes of seizure for a period of 6 months. In August 2021, the patient had a recurrence of convulsions. As a consequence, Brivaracetam 50mg BD and Sodium Valproate 500mg BD were prescribed. The patient gradually started exhibiting unusual behavioral and psychiatric adverse events. The reaction was primarily ascribable to brivaracetam based on the temporal association between non-contributable disease and co-medication. The WHO causality assessment scale graded the ADR to be ‘probable’ and Naranjo’s algorithm with a score of 6. The physician recommended discontinuation of Brivaracetam and advised to continue Sodium Valproate 500mg BD, while Clobazam 5mg BD was added to patient treatment regimen. The patient’s symptoms progressively alleviated, and his behavior returned to normal within one week of discontinuing the Brivaracetam. Conclusion: When initiating treatment with Brivaracetam, close clinical assessment and monitoring is required and recommended to identify any behavioral and psychiatric adverse effects to achieve optimum treatment outcome.

Psychiatric Adverse Reactions to Anaplastic Lymphoma Kinase Inhibitors in Non-Small-Cell Lung Cancer: Analysis of Spontaneous Reports Submitted to the FDA Adverse Event Reporting System.

BackgroundThe development of anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) has improved the survival outcomes of patients with advanced ALK-rearranged non-small-cell lung cancer (NSCLC). The adverse events (AEs) related to ALK inhibitors are fairly well known; notably, about 20% of patients receiving lorlatinib experienced cognitive effects and behavioral alterations in pivotal trials. Therefore, psychiatric disorders could represent AEs of special interest for all ALK TKIs, deserving careful assessment in the post-marketing setting.ObjectiveWe conducted a real-world pharmacovigilance study on psychiatric AEs with marketed ALK inhibitors in subjects with advanced NSCLC.Patients and methodsWe performed an observational, retrospective analysis of spontaneous reports submitted to the Food and Drug Administration Adverse Events Reporting System (FAERS, as of December 2020), selecting psychiatric AEs to ALK TKIs approved in NSCLC (crizotinib, ceritinib, alectinib, brigatinib, lorlatinib). These AEs were independently scrutinized by three oncologists applying predefined exclusion criteria, described in terms of clinical/demographic features and assessed for drug-related causality according to an adaptation of the WHO–UMC system, a standardized probabilistic algorithm.ResultsAmong 584 reported psychiatric AEs, 95 cases were selected as potentially treatment related, with higher reporting frequency for lorlatinib (26, 2.8%), followed by brigatinib (10, 1.2%), alectinib (18, 0.7%), ceritinib (12, 0.6%), and crizotinib (29, 0.3%). Reported psychiatric symptoms were mood disorders (39), psychotic disorders (24), and anxiety, agitation, and irritability (25). In the majority (74%) of cases, psychiatric AEs were serious and required hospitalization in about 32% of patients; 15.8% of retained cases were considered as highly probable and 69.5% as probable. Drug discontinuation was recorded in 31.6% of the reported cases, with the highest proportion for lorlatinib (65.4%).ConclusionNotwithstanding limitations, our study found a higher proportion of psychiatric AEs with lorlatinib, but also raised the hypothesis of psychiatric reactions as a class effect of ALK TKIs. Supplementary InformationThe online version contains supplementary material available at 10.1007/s11523-021-00865-8.

Neuropsychological adverse drug reactions of Remdesivir: analysis using VigiBase, the WHO global database of individual case safety reports.

Although remdesivir (GS-5734) has recently demonstrated clinical benefits against the pandemic outbreak of coronavirus disease 2019 (COVID-19), neuropsychological adverse reactions (ADRs) remain to be examined in real-world settings. Therefore, we aimed to identify and characterize the neuropsychological ADRs associated with remdesivir use. We obtained data for this international pharmacovigilance cohort study from individual case safety reports (ICSRs) in a World Health Organization database (VigiBase) from the first report on remdesivir on February 17, 2020, until August 30, 2020 (n=1,403,532). ADRs reported to be relevant to remdesivir were compared with the full database by using a Bayesian neural network method to calculate the information component (IC). A total of 2,107 reported cases of neuropsychological ADRs suspected to be associated with remdesivir were identified from among all ICSRs in the database during the observation period. Although 108 neuropsychological ADRs (64 neurologic events and 44 psychologic events) were reported in association with the medication, no statistically significant pharmacovigilance signal could be detected; the IC025 value was negative for all of the neuropsychological dysfunctions (anxiety [n=13, 0.62%], seizures [n=12, 0.57%], lethargy [n=6, 0.28%], agitation [n=5, 0.25%], cerebral infarction [n=3, 0.14%], ischemic stroke [n=3, 0.14%], and hemiparesis [n=3, 0.14%]). Our study demonstrates that remdesivir, a novel drug applied to the treatment of COVID-19, does not have a significant association with adverse neurologic or psychiatric reactions in the real-world setting.

Perampanel-Induced Psychosis in a Young Woman: A Case Report

A case of perampanel-induced psychosis in a young woman is reported, a side effect that has only rarely been reported in the literature. We describe a case of a young woman with epilepsy and no psychiatric history with perampanel-associated altered behavior and psychotic symptoms, requiring hospitalization in an acute psychiatry ward. We also provide a literature review on the possible neurobiological pathways implicated. Perampanel is believed to block a small proportion of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor current, retarding epileptiform discharges while sparing most normal synaptic transmission. Most common adverse events are related to central nervous system (including dizziness, drowsiness, blurred vision and imbalance) and psychiatric symptoms have been reported. The biological vulnerability to psychiatric and behavioral adverse reactions of antiepileptic drugs is multifactorial and different mechanisms and clinical predisposing factors may interact. For this reason, patients starting these antiseizure drugs need long-term and comprehensive clinical monitoring.

Levetirazetam psychosis

IntroductionLevetirazetam is an antiepileptic drug with psychiatric adverse reactions. It includes psychosis, paranoia or hallucinations. The frequency is less than 1%.ObjectivesTo describe and study a case of Psychosis produced by LevetirazetamMethodsRetrospective review of clinical records and complementary test, including psychiatry, electrophysiology and neurology. Diagnosis schales such as Salamanca Questionnaire were used as suport.ResultsA 42-year-old woman diagnosed with tuberous sclerosis and undergoing treatment with levetirazetam acudes to the emergency department for behavioral disorders. She has presented an episode of aggression against a relative threatening him with a kitchen knife. The family reports that since the change in antiepilepticus 1 month ago, the patient has presented strange behaviors. Te Patient is conscious, uncooperative. Barely Approachable. Suspicious of her surroundings, with psychomotor restlessness, self-reference ideas and sparse speech. Auditory hallucinations seem to be present, as well as depressed and irritable mood. Psychic and somatic anxiety is found. Levetirazetam is discontinued, being replaced by valproic acid. Risperidone is started at a 3 mg dose. Treatment is well tolerated, and clinical stability is achived. Cluster A personality traits are found. Complementary test Blood and Urine simples, Imaging tests (CT and MRI), electroencephalogram and Electrocardiogram show no alterationsConclusionsLevetirazetam can cause psychiatric adverse effects. it is important to make a proper diagnosis before a first psychotic outbreak in later life. Drugs that can produce psychiatric side effects should be identified and patients should be inform.DisclosureNo significant relationships.

“Covid madness”

IntroductionWe present the case of a man who, after receiving treatment for Covid-19 pneumonia, suffers a manic episode induced by medication.ObjectivesThis case is chosen to present as an example of a psychiatric illness derived from Covid-19, in this case secondary to its treatment.MethodsWe present a manic episode induced by covid medication.ResultsComplementary examinations are carried out in which organic pathology is ruled out, being diagnosed of a manifest episode in probable relation to the treatments used and hospital admission is decided due to the impossibility of home management. Neuroleptic and anxiolytic treatment was started at low doses with a good response, and he was discharged with complete recovery and critiqued of the episode.ConclusionsIt is estimated that between 20-40% of patients with COVID infection have presented neuropsychiatric symptoms. Mania secondary to treatment was reported in 13 (0 · 7%) of 1744 patients with coranavirus included in a study (1). The Spanish Pharmacivigilance System of Medicines for Human Use (SEFV-H) closely monitors the suspected adverse reactions reported with drugs considered potential therapeutic strategies for SARS-CoV-2 infection. 327 cases of adverse reactions have been reported, of which 18 cases include 28 thermal cases of suspected psychiatric adverse reactions. The interest of this case lies in the fact that it illustrates a psychiatric disorder derived from Covid-19, in this case secondary to the treatment used, which causes a manifest episode with a typical evolution in this type of case with rapid improvement at low doses of antipsychotics.

Musical Hallucination Caused by Ceftazidime in a Woman with a Hearing Impairment.

Musical hallucinations remain a poorly understood clinical phenomenon, possibly because these types of hallucination have multiple causes and are rarely the focus of published reports. Here, the case of a 51-year-old female patient with a hearing impairment who developed musical hallucinations during treatment with ceftazidime, a third-generation cephalosporin, is presented. She responded to the discontinuation of ceftazidime and the initiation of low-dose olanzapine treatment. Musical hallucinations associated with ceftazidime are very rare, and the mechanisms underlying its occurrence remain unknown. Further studies will be necessary to determine the pathophysiology of adverse psychiatric reactions associated with ceftazidime.

Effects of Empowerment Program on the Burden of Care in Mothers of Children with Phenylketonuria.

Phenylketonuria (PKU) is a genetic disease of children that need a lifelong diet for its treatment. Because of the high burden of care, parents and particularly mothers are prone to mental disorders or psychiatric adverse reactions. We aimed to investigate the effect of empowerment of mothers on the burden of caring for children with PKU. This was a semi-experimental (before-after with control group) study. Overall, 50 mothers of children with PKU that were referred to Endocrine Clinic in Qods Hospital of Qazvin City, northwestern Iran in 2016, were selected and randomly divided into intervention and control groups. Data collection was made by using demographic characteristics of mothers and children and also the Zarit burden interview questionnaires. Empowerment program was delivered during nine sessions of holistic and family oriented empowerment model in the intervention group. The control group received routine services. Data were analyzed using descriptive and inferential statistics through SPSS software. In intervention group, the mean score of overall care burden and its dimensions in the mothers of children with PKU in post-test was significantly lower than the pre-test (41.20 ± 5.04 vs. 58.24 ± 3.96; P<0.001); but pre-test and post-test scores in the control group had no significant difference (58.4 ± 5.22 vs. 58.96 ± 4; P=0.327). In other words empowerment program was able to reduce the burden of caring in mothers. Empowerment program can reduce the burden of care in mothers of children with PKU. Thus empowerment training is necessary for this group of mothers in the form of workshops and educational pamphlets.