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PloS One 2024This study began as a single-blind randomized controlled trial (RCT) to investigate the efficacy and safety of electroconvulsive therapy (ECT) for severe... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
This study began as a single-blind randomized controlled trial (RCT) to investigate the efficacy and safety of electroconvulsive therapy (ECT) for severe treatment-refractory agitation in advanced dementia. The aims are to assess agitation reduction using the Cohen-Mansfield Agitation Inventory (CMAI), evaluate tolerability and safety outcomes, and explore the long-term stability of agitation reduction and global functioning. Due to challenges encountered during implementation, including recruitment obstacles and operational difficulties, the study design was modified to an open-label format and other protocol amendments were implemented.
METHODS
Initially, the RCT randomized participants 1:1 to either ECT plus usual care or simulated ECT plus usual care (S-ECT) groups. As patients were enrolled, data were collected from both ECT and simulated ECT (S-ECT) patients. The study now continues in an open-label study design where all patients receive actual ECT, reducing the targeted sample size from 200 to 50 participants.
RESULTS
Study is ongoing and open to enrollment.
CONCLUSION
The transition of the ECT-AD study design from an RCT to open-label design exemplifies adaptive research methodologies in response to real-world challenges. Data from both the RCT and open-label phases of the study will provide a unique perspective on the role of ECT in managing severe treatment-refractory agitation in dementia, potentially influencing future clinical practices and research approaches.
Topics: Humans; Electroconvulsive Therapy; Psychomotor Agitation; Dementia; Single-Blind Method; Female; Male; Treatment Outcome; Aged; Aberrant Motor Behavior in Dementia
PubMed: 38941338
DOI: 10.1371/journal.pone.0303894 -
Journal of Clinical Medicine Jun 2024Autism spectrum disorder (ASD) is a persistent neurodevelopmental disorder frequently co-occurring with attention-deficit/hyperactivity disorder (ADHD) and... (Review)
Review
Treatment of Aggressive Behavior and Agitation in an 11-Year-Old Boy with Co-Occurring Autism and ADHD: A Case Report and Literature Review on the Use of Intravenous Valproate in Emergency Psychiatry.
Autism spectrum disorder (ASD) is a persistent neurodevelopmental disorder frequently co-occurring with attention-deficit/hyperactivity disorder (ADHD) and behavior-related disorders. While behavioral therapy is the first-line option to manage the core symptoms of ASD, pharmacological therapy is sometimes needed to treat acute problems, such as agitation and aggressive behaviors. Recent guidelines recommend the use of neuroleptics to reduce psychomotor agitation in patients with ASD. However, as children with ASD are often drug-resistant, alternative treatments are often justified. Reports from the literature have indicated that intravenous valproate (IV-VPA) can be effective in reducing agitation in psychiatric patients, with a lower frequency of adverse events compared to conventional treatments. However, as the related findings are occasionally inconsistent, IV-VPA is not yet an approved option in the context of clinical psychiatry. We aim to improve knowledge of the IV-VPA treatment option for emergency psychiatric treatment in pediatric patients. We report the case of an 11-year-old boy suffering from a complex neurodevelopmental condition who experienced a psychotic episode with severe aggressive and disruptive behaviors and was successfully treated with IV-VPA. Furthermore, we provide an updated literature review on this topic. In our case, first-line therapies proved to be ineffective. To the contrary, IV-VPA led to safe and prompt clinical success, which is in line with other reports. Based on our literature review, IV-VPA can be highly effective and reduces the risk of adverse events that frequently occur with the use of high-dose standard medications in emergency psychiatry.
PubMed: 38930101
DOI: 10.3390/jcm13123573 -
BMC Geriatrics Jun 202440-60% of persons living with dementia (PLWD) experience agitation and/or aggression symptoms. There is a need to understand the best method to detect agitation and/or...
OBJECTIVE
40-60% of persons living with dementia (PLWD) experience agitation and/or aggression symptoms. There is a need to understand the best method to detect agitation and/or aggression in PLWD. We aimed to identify agitation and/or aggression tools that are validated against a reference standard within the context of PLWD.
METHODS
Our study was registered on PROSPERO (CRD42020156708). We searched MEDLINE, Embase, and PsycINFO up to April 22, 2024. There were no language or date restrictions. Studies were included if they used any tools or questionnaires for detecting either agitation or aggression compared to a reference standard among PLWD, or any studies that compared two or more agitation and/or aggression tools in the population. All screening and data extraction were done in duplicates. Study quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool. Data extraction was completed in duplicates by two independent authors. We extracted demographic information, prevalence of agitation and/or aggression, and diagnostic accuracy measures. We also reported studies comparing the correlation between two or more agitation and/or aggression tools.
RESULTS
6961 articles were screened across databases. Six articles reporting diagnostic accuracy measures compared to a reference standard and 30 articles reporting correlation measurements between tools were included. The agitation domain of the Spanish NPI demonstrated the highest sensitivity (100%) against the agitation subsection of the Spanish CAMDEX. Single-study evidence was found for the diagnostic accuracy of commonly used agitation scales (BEHAVE-AD, NPI and CMAI).
CONCLUSIONS
The agitation domain of the Spanish NPI, the NBRS, and the PAS demonstrated high sensitivities, and may be reasonable for clinical implementation. However, a limitation to this finding is that despite an extensive search, few studies with diagnostic accuracy measurements were identified. Ultimately, more research is needed to understand the diagnostic accuracy of agitation and/or aggression detection tools among PLWD.
Topics: Humans; Aggression; Psychomotor Agitation; Dementia
PubMed: 38926638
DOI: 10.1186/s12877-024-05143-6 -
The Journal of International Medical... Jun 2024The aim of this short narrative review was to evaluate the existing literature regarding the clinical use of ketamine among individuals with dementia, especially those... (Review)
Review
The aim of this short narrative review was to evaluate the existing literature regarding the clinical use of ketamine among individuals with dementia, especially those with behavioral disturbances. PubMed, Cochrane, and Ovid (Embase, APA PsycINFO, and MEDLINE) databases were searched for abstracts using the search terms "ketamine" AND "dementia." Only articles describing the use of ketamine in individuals with dementia were included. Articles that did not include individuals with dementia, did not use ketamine, were published in a non-English language, primarily described animal studies, or were reviews were excluded. Three case reports met the inclusion criteria. One described the use of subcutaneous ketamine for depression, one described the use of intramuscular ketamine for acute agitation, and one described the use of S-ketamine as anesthesia during electroconvulsive therapy for depression and catatonia. No significant adverse effects were reported in any of the cases. Although the use of ketamine in the treatment of depression and agitation associated with dementia has potential, the current evidence remains limited. High-quality prospective studies are needed to confirm the observations of these case reports before ketamine can be used to treat behavioral disturbances in individuals with dementia.
Topics: Ketamine; Humans; Dementia; Depression; Psychomotor Agitation; Electroconvulsive Therapy
PubMed: 38907362
DOI: 10.1177/03000605241258473 -
General Hospital Psychiatry Jun 2024Valbenazine is commonly used to treat tardive dyskinesia, and we conducted a pharmacovigilance analysis using the Food and Drug Administration Adverse Event Reporting...
PURPOSE
Valbenazine is commonly used to treat tardive dyskinesia, and we conducted a pharmacovigilance analysis using the Food and Drug Administration Adverse Event Reporting System (FAERS) to evaluate neurological safety signals associated with valbenazine.
METHODS
Data was collected in FAERS from the second quarter of 2017 to the fourth quarter of 2023 for data cleaning. Neurological adverse event (AE) signals of valbenazine were mined by calculating reporting odds ratios (ROR), information component (IC) and empirical Bayesian geometric mean (EBGM). The serious and non-serious cases and signals were prioritized using a rating scale.
RESULTS
The number of neurological AE reports where the primary suspect (PS) drug was 8981 for valbenazine. Significant AE signals were identified by the preferred term (PT) analysis for valbenazine, including somnolence (ROR 19.69), tremor (ROR 15.17), and tardive dyskinesia (ROR 236.91), among which 18 AEs were identified as new signals. Patient age (p < 0.009) and sex (p = 0.197) might be associated with an increased risk of neurological AE severity. Notably, the association between valbenazine and neurological disorders remained when stratified by sex, age, and reporter type. AE timing analysis was performed for the drug and four moderate clinical priority signals [i.e., somnolence, balance disorder, parkinsonism, and akathisia (priorities 7)], showing the same early failure type profiles.
CONCLUSIONS
The increase in neurological safety signals is identified in the post-marketing research of valbenazine. Clinicians need to pay attention to not only common AEs but also be alert to new neurological AE signals when using valbenazine.
PubMed: 38901166
DOI: 10.1016/j.genhosppsych.2024.06.005 -
Pharmacopsychiatry Jun 2024Lurasidone (LUR) was compared with quetiapine extended release (QUE-ER) regarding 1-year discontinuation in patients with bipolar depression (n=317).
INTRODUCTION
Lurasidone (LUR) was compared with quetiapine extended release (QUE-ER) regarding 1-year discontinuation in patients with bipolar depression (n=317).
METHODS
This is a retrospective cohort study.
RESULTS
Although the time to all-cause discontinuation was estimated using the Kaplan-Meier survival curve with log-rank tests to compare treatment groups, no difference was found (p=0.317). The Cox proportional hazard model revealed that only the presence of adverse events (AEs) is associated with increased treatment discontinuation (p<0.0001). The most common AEs were akathisia for LUR (17.7%) and somnolence for QUE-ER (34.7%). In other Cox models divided by LUR or QUE-ER, the presence of akathisia or somnolence was associated with increased LUR (p=0.0205) or QUE-ER (p<0.0001) discontinuation, respectively.
DISCUSSION
The acceptability of both antipsychotics to bipolar depression in clinical practice may be similar. However, specific AEs for each antipsychotic (LUR: akathisia and QUE-ER: somnolence) were associated with high treatment discontinuation.
PubMed: 38897219
DOI: 10.1055/a-2331-2300 -
Schizophrenia Bulletin Jun 2024Antipsychotics are the treatment of choice for schizophrenia, but they often induce akathisia. However, comparative efficacy of treatment strategies for akathisia...
BACKGROUND
Antipsychotics are the treatment of choice for schizophrenia, but they often induce akathisia. However, comparative efficacy of treatment strategies for akathisia remains unclear.
DESIGN
We performed a systematic review and network meta-analyses (PROSPERO CRD42023450720). We searched multiple databases on July 24, 2023. We included randomized clinical trials comparing 1 or more treatment strategies for antipsychotic-induced akathisia against each other or control conditions. We included adults with schizophrenia or other psychiatric disorders treated with antipsychotics. The primary outcome was akathisia severity at posttreatment. Secondary outcomes included akathisia response, all-cause dropout, psychotic symptoms, and long-term akathisia severity. We synthesized data in random effects frequentist network meta-analyses and assessed confidence in the evidence using CINeMA.
RESULTS
We identified 19 trials with 661 randomized participants (mean age 35.9 [standard deviation 12.0]; 36.7% [195 of 532] women). No trials examined dose reduction or switching of antipsychotics. Findings suggested 5-HT2A antagonists (k = 6, n = 108; standardized mean difference [SMD] -1.07 [95% confidence interval, -1.42; -0.71]) and beta-blockers (k = 8, n = 105; SMD -0.46 [-0.85; -0.07]) may improve akathisia severity, but confidence in the evidence was deemed low. We also found that benzodiazepines (k = 2, n = 13; SMD -1.62 [-2.64; -0.59]) and vitamin B6 (k = 3, n = 67; SMD -0.99 [-1.49; -0.50]) might also be beneficial, but confidence in the evidence was very low. Analyses of secondary outcomes did not provide additional insights.
CONCLUSIONS
Our findings suggest that 5-HT2A antagonists, beta-blockers, and with a lesser certainty, benzodiazepines, and vitamin B6 might improve akathisia. Given the low to very low confidence in the evidence of add-on agents and the absence of evidence of their long-term efficacy, careful consideration of side effects is warranted. These recommendations are extremely preliminary and further trials are needed.
PubMed: 38869177
DOI: 10.1093/schbul/sbae098 -
JAMA Network Open Jun 2024
Topics: Humans; Delirium; Emergency Service, Hospital; Male; Female; Aged; Psychomotor Agitation; Middle Aged; Inpatients; Length of Stay; Aged, 80 and over; Hospitalization; Time Factors
PubMed: 38861262
DOI: 10.1001/jamanetworkopen.2024.16343 -
Frontiers in Psychiatry 2024Catatonia is a complex neuropsychiatric syndrome involving a constellation of psychomotor disturbances including catalepsy, waxy flexibility, stupor, mutism, negativism,...
Catatonia is a complex neuropsychiatric syndrome involving a constellation of psychomotor disturbances including catalepsy, waxy flexibility, stupor, mutism, negativism, agitation, posturing, stereotypes, mannerisms, grimacing, echolalia, and echopraxia. Catatonia occurs in several conditions including psychotic, affective and neurodevelopmental disorders such as autism spectrum disorder (ASD). ASD is a neurodevelopmental disorder characterized by persistent deficits in communication, social interaction, restricted interests, repetitive behaviours and sensory sensitivities. Catatonia can occur in response to life stressors such as extreme fear or threat, interpersonal conflict, tragic events or following significant loss. Those with ASD may be particularly vulnerable to the negative impact of stressors and the link between catatonia and ASD is being increasingly recognized. The overlapping features of catatonia and ASD make it difficult to differentiate often resulting in delayed or missed diagnosis. Catatonia in ASD remains a significant clinical challenge; it is difficult to diagnose and can pose debilitating difficulties for those affected. Catatonia is a treatable condition and prompt recognition is vital in securing the best possible outcome. We report a complex and unique case of a 15-year-old boy who presented with severe cognitive and functional decline with a background history of significant bullying and deterioration in his mental state. This case posed a diagnostic conundrum leading to a diagnosis of underlying ASD, anxiety and trauma.
PubMed: 38859882
DOI: 10.3389/fpsyt.2024.1386949 -
The Mental Health Clinician Jun 2024Catatonia is a syndrome characterized by psychomotor and behavioral disturbances and is associated with a substantially increased mortality risk in adolescent patients....
INTRODUCTION
Catatonia is a syndrome characterized by psychomotor and behavioral disturbances and is associated with a substantially increased mortality risk in adolescent patients. There is a dearth of published literature describing treatment strategies for pediatric patients with catatonia. This dual-case series will describe the treatment course of 2 adolescent patients with catatonia at our pediatric inpatient psychiatric facility.
CASE SERIES
This case series presents 2 adolescent patients (a 17-year-old male and a 16-year-old female) who initially presented with worsening agitation and paranoia, later developing catatonia. Both patients required long durations of hospitalization and were treated with high-dose lorazepam before requiring the addition of electroconvulsive therapy (ECT).
DISCUSSION
Treatment of pediatric patients with catatonia creates a significant burden on patients, families, and the healthcare system. Treatment with high-dose benzodiazepines is high risk, while ECT is both difficult to access and comes with its own risks. Both patients discussed are transitional age, meaning they will soon be young adults who will continue to require high-level psychiatric care. Psychiatric pharmacists have a large role to play in ensuring safe medication management for these complex patients.
CONCLUSIONS
This case series of 2 adolescent patients with catatonia demonstrates marginal reduction in symptoms with high-dose lorazepam in conjunction with ECT, with minimal side effects. This case series adds to the limited available literature regarding treatment of catatonia in pediatric patients and highlights the need for further study into effective treatment alternatives.
PubMed: 38835818
DOI: 10.9740/mhc.2024.06.215