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Trends in Psychiatry and Psychotherapy Jun 2022Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by persistent deficits in social communication and social interaction, associated with the... (Review)
Review
INTRODUCTION
Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by persistent deficits in social communication and social interaction, associated with the presence of restricted and repetitive patterns of behavior, interests, or activities. Cannabis has been used to alleviate symptoms associated with ASD.
METHOD
We carried out a systematic review of studies that investigated the clinical effects of cannabis and cannabinoid use on ASD, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA checklist). The search was carried out in four databases: MEDLINE/PubMed, Scientific Electronic Library Online (SciELO), Scopus, and Web of Science. No limits were established for language during the selection process. Nine studies were selected and analyzed.
RESULTS
Some studies showed that cannabis products reduced the number and/or intensity of different symptoms, including hyperactivity, attacks of self-mutilation and anger, sleep problems, anxiety, restlessness, psychomotor agitation, irritability, aggressiveness perseverance, and depression. Moreover, they found an improvement in cognition, sensory sensitivity, attention, social interaction, and language. The most common adverse effects were sleep disorders, restlessness, nervousness and change in appetite.
CONCLUSION
Cannabis and cannabinoids may have promising effects in the treatment of symptoms related to ASD, and can be used as a therapeutic alternative in the relief of those symptoms. However, randomized, blind, placebo-controlled clinical trials are necessary to clarify findings on the effects of cannabis and its cannabinoids in individuals with ASD.
SYSTEMATIC REVIEW REGISTRATION
International Prospective Register of Systematic Reviews (PROSPERO), code 164161.
Topics: Anxiety; Anxiety Disorders; Autism Spectrum Disorder; Cannabinoids; Cannabis; Humans; Psychomotor Agitation
PubMed: 34043900
DOI: 10.47626/2237-6089-2020-0149 -
The American Journal of Geriatric... Apr 2020To assess the efficacy, safety, and tolerability of brexpiprazole in patients with agitation in Alzheimer's dementia (AAD). (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
To assess the efficacy, safety, and tolerability of brexpiprazole in patients with agitation in Alzheimer's dementia (AAD).
DESIGN
Two 12-week, randomized, double-blind, placebo-controlled, parallel-arm studies (NCT01862640; NCT01922258).
SETTING
Study 1: 81 sites in 7 countries. Study 2: 62 sites in 9 countries.
PARTICIPANTS
Patients with AAD (Study 1: 433 randomized; Study 2: 270 randomized) in a care facility or community-based setting. Stable Alzheimer disease medications were permitted.
INTERVENTION
Study 1 (fixed dose): brexpiprazole 2 mg/day, brexpiprazole 1 mg/day, or placebo (1:1:1) for 12 weeks. Study 2 (flexible dose): brexpiprazole 0.5-2 mg/day or placebo (1:1) for 12 weeks.
MEASUREMENTS
Cohen-Mansfield Agitation Inventory (CMAI) (Total score range: 29-203; higher scores indicate more frequent agitated behaviors), and Clinical Global Impression - Severity of illness (CGI-S) as related to agitation. Safety was also assessed.
RESULTS
In Study 1, brexpiprazole 2 mg/day demonstrated statistically significantly greater improvement in CMAI Total score from baseline to Week 12 than placebo (adjusted mean difference, -3.77; confidence limits, -7.38, -0.17; t = -2.06; p = 0.040; MMRM). Brexpiprazole 1 mg/day did not show meaningful separation from placebo (0.23; -3.40, 3.86; t = 0.12; p = 0.90; MMRM). In Study 2, brexpiprazole 0.5-2 mg/day did not achieve statistical superiority over placebo (-2.34; -5.49, 0.82; t = -1.46; p = 0.15; MMRM). However, a benefit was observed in post hoc analyses among patients titrated to the maximum brexpiprazole dose of 2 mg/day compared with similarly titrated placebo patients (-5.06; -8.99, -1.13; t = -2.54; p = 0.012; MMRM). On the CGI-S, a greater numerical improvement than placebo was demonstrated for brexpiprazole 2 mg/day in Study 1 (-0.16; -0.39, 0.06; t = -1.42; nominal p = 0.16; MMRM), and a greater improvement for brexpiprazole 0.5-2 mg/day in Study 2 (-0.31; -0.55, -0.06; t = -2.42; nominal p = 0.016; MMRM). In Study 1, treatment-emergent adverse events (TEAEs) with incidence ≥5% among patients receiving brexpiprazole 2 mg/day were headache (9.3% versus 8.1% with placebo), insomnia (5.7% versus 4.4%), dizziness (5.7% versus 3.0%), and urinary tract infection (5.0% versus 1.5%). In Study 2, TEAEs with incidence ≥5% among patients receiving brexpiprazole 0.5-2 mg/day were headache (7.6% versus 12.4% with placebo) and somnolence (6.1% versus 3.6%). In both studies, the majority of TEAEs were mild or moderate in severity.
CONCLUSIONS
Brexpiprazole 2 mg/day has the potential to be efficacious, safe, and well tolerated in the treatment of AAD.
Topics: Aged; Aged, 80 and over; Alzheimer Disease; Female; Headache; Humans; Internationality; Male; Middle Aged; Psychiatric Status Rating Scales; Psychomotor Agitation; Quinolones; Sleep Initiation and Maintenance Disorders; Thiophenes; Treatment Outcome
PubMed: 31708380
DOI: 10.1016/j.jagp.2019.09.009 -
International Journal of Environmental... Apr 2021The early and correct assessment of psychomotor agitation (PMA) is essential to ensure prompt intervention by healthcare professionals to improve the patient's... (Review)
Review
The early and correct assessment of psychomotor agitation (PMA) is essential to ensure prompt intervention by healthcare professionals to improve the patient's condition, protect healthcare staff, and facilitate future management. Proper training for recognizing and managing agitation in all care settings is desirable to improve patient outcomes. The best approach is one that is ethical, non-invasive, and respectful of the patient's dignity. When deemed necessary, pharmacological interventions must be administered rapidly and avoid producing an excessive state of sedation, except in cases of severe and imminent danger to the patient or others. The purpose of this brief review is to raise awareness about best practices for the management of PMA in emergency care situations and consider the role of new pharmacological interventions in patients with agitation associated with bipolar disorder or schizophrenia.
Topics: Antipsychotic Agents; Bipolar Disorder; Humans; Loxapine; Psychomotor Agitation; Schizophrenia
PubMed: 33924111
DOI: 10.3390/ijerph18084368 -
Annals of Emergency Medicine Feb 2020Agitation and delirium are common reasons for older adults to seek care in the emergency department (ED). Providing care for this population in the ED setting can be... (Review)
Review
Agitation and delirium are common reasons for older adults to seek care in the emergency department (ED). Providing care for this population in the ED setting can be challenging for emergency physicians. There are several knowledge translation gaps in how to best screen older adults for these conditions and how to manage them. A working group of subject-matter experts convened to develop an easy-to-use, point-of-care tool to assist emergency physicians in the care of these patients. The tool is designed to serve as a resource to address the knowledge translation and implementation gaps that exist in the field. The purpose of this article is present and explain the Assess, Diagnose, Evaluate, Prevent, and Treat tool. Participants were identified with expertise in emergency medicine, geriatric emergency medicine, geriatrics, and psychiatry. Background literature reviews were performed before the in-person meeting in key areas: delirium, dementia, and agitation in older adults. Participants worked electronically before and after an in-person meeting to finalize development of the tool in 2017. Subsequent work was performed electronically in the following months and additional expert review sought. EDs are an important point of care for older adults. Behavioral changes in older adults can be a manifestation of underlying medical problems, mental health concerns, medication adverse effects, substance abuse, or dementia. Five core principles were identified by the group that can help ensure adequate and thorough care for older adults with agitation or delirium: assess, diagnose, evaluate, prevent, and treat. This article provides background for and explains the importance of these principles related to the care of older adults with agitation. It is important for emergency physicians to recognize the spectrum of underlying causes of behavioral changes and have the tools to screen older adults for those causes, and methods to treat the underlying causes and ameliorate their symptoms.
Topics: Aged; Aged, 80 and over; Delirium; Delivery of Health Care; Dementia; Diagnostic and Statistical Manual of Mental Disorders; Emergency Service, Hospital; Geriatric Assessment; Guidelines as Topic; Humans; Psychomotor Agitation
PubMed: 31563402
DOI: 10.1016/j.annemergmed.2019.07.023 -
Korean Journal of Anesthesiology Dec 2020Emergence agitation (EA), also referred to as emergence delirium, can have clinically significant consequences. The mechanism of EA remains unclear. The proposed risk... (Review)
Review
Emergence agitation (EA), also referred to as emergence delirium, can have clinically significant consequences. The mechanism of EA remains unclear. The proposed risk factors of EA include age, male sex, type of surgery, emergency operation, use of inhalational anesthetics with low blood-gas partition coefficients, long duration of surgery, anticholinergics, premedication with benzodiazepines, voiding urgency, postoperative pain, and the presence of invasive devices. If preoperative or intraoperative objective monitoring could predict the occurrence of agitation during emergence, this would help to reduce its adverse consequences. Several tools are available for assessing EA. However, there are no standardized clinical research practice guidelines and its incidence varies considerably with the assessment tool or definition used. Total intravenous anesthesia, propofol, μ-opioid agonists, N-methyl-D-aspartate receptor antagonists, nefopam, α2-adrenoreceptor agonists, regional analgesia, multimodal analgesia, parent-present induction, and preoperative education for surgery may help in preventing of EA. However, it is difficult to identify patients at high risk and apply preventive measures in various clinical situations. The risk factors and outcomes of preventive strategies vary with the methodologies of studies and patients assessed.This review discusses important outcomes of research on EA and directions for future research.
Topics: Adult; Anesthesia Recovery Period; Anesthetics, Inhalation; Child; Child, Preschool; Emergence Delirium; Humans; Male; Psychomotor Agitation; Sevoflurane
PubMed: 32209961
DOI: 10.4097/kja.20097 -
The Cochrane Database of Systematic... Aug 2020Medications licensed for the treatment of dementia have limited efficacy against cognitive impairment or against the distressed behaviours (behavioural and psychological... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Medications licensed for the treatment of dementia have limited efficacy against cognitive impairment or against the distressed behaviours (behavioural and psychological symptoms, or behaviour that challenges) which are also often the most distressing aspect of the disorder for caregivers. Complementary therapies, including aromatherapy, are attractive to patients, practitioners and families, because they are perceived as being unlikely to cause adverse effects. Therefore there is interest in whether aromatherapy might offer a safe means of alleviating distressed behaviours in dementia.
OBJECTIVES
To assess the efficacy and safety of aromatherapy for people with dementia.
SEARCH METHODS
We searched ALOIS, the Cochrane Dementia and Cognitive Improvement Group Specialized Register, on 5 May 2020 using the terms: aromatherapy, lemon, lavender, rose, aroma, alternative therapies, complementary therapies, essential oils. In addition, we searched MEDLINE, Embase, PsycINFO (all via Ovid SP), Web of Science Core Collection (via Thompson Web of Science), LILACS (via BIREME), CENTRAL (via the Cochrane Library), ClinicalTrials.gov and the World Health Organization (WHO) trials portal (ICTRP) on 5 May 2020.
SELECTION CRITERIA
We included randomised controlled trials which compared fragrance from plants in an intervention defined as aromatherapy for people with dementia with placebo aromatherapy or with treatment as usual. All doses, frequencies and fragrances of aromatherapy were considered. Participants in the included studies had a diagnosis of dementia of any subtype and severity.
DATA COLLECTION AND ANALYSIS
Two reviewers independently selected studies for inclusion, extracted data and assessed risk of bias in included studies, involving other authors to reach consensus decisions where necessary. We did not perform any meta-analyses because of heterogeneity between studies, but presented a narrative synthesis of results from the included trials. Because of the heterogeneity of analysis methods and inadequate or absent reporting of data from some trials, we used statistical significance (P ≤ or > 0.5) as a summary metric when synthesising results across studies. As far as possible, we used GRADE methods to assess our confidence in the results of the trials, downgrading for risk of bias and imprecision.
MAIN RESULTS
We included 13 studies with 708 participants. All participants had dementia and in the 12 trials which described the setting, all were resident in institutional care facilities. Nine trials recruited participants because they had significant agitation or other behavioural and psychological symptoms in dementia (BPSD) at baseline. The fragrances used were lavender (eight studies); lemon balm (four studies); lavender and lemon balm, lavender and orange, and cedar extracts (one study each). For six trials, assessment of risk of bias and extraction of results was hampered by poor reporting. Four of the other seven trials were at low risk of bias in all domains, but all were small (range 18 to 186 participants; median 66), reducing our confidence in the results. Our primary outcomes were agitation, overall behavioural and psychological symptoms, and adverse effects. Ten trials assessed agitation using various scales. Among the five trials for which our confidence in the results was moderate or low, four trials reported no significant effect on agitation and one trial reported a significant benefit of aromatherapy. The other five trials either reported no useable data or our confidence in the results was very low. Eight trials assessed overall BPSD using the Neuropsychiatric Inventory and we had moderate or low confidence in the results of five of them. Of these, four reported significant benefit from aromatherapy and one reported no significant effect. Adverse events were poorly reported or not reported at all in most trials. No more than two trials assessed each of our secondary outcomes of quality of life, mood, sleep, activities of daily living, caregiver burden. We did not find evidence of benefit on these outcomes. Three trials assessed cognition: one did not report any data and the other two trials reported no significant effect of aromatherapy on cognition. Our confidence in the results of these studies was low.
AUTHORS' CONCLUSIONS
We have not found any convincing evidence that aromatherapy (or exposure to fragrant plant oils) is beneficial for people with dementia although there are many limitations to the data. Conduct or reporting problems in half of the included studies meant that they could not contribute to the conclusions. Results from the other studies were inconsistent. Harms were very poorly reported in the included studies. In order for clear conclusions to be drawn, better design and reporting and consistency of outcome measurement in future trials would be needed.
Topics: Aromatherapy; Behavioral Symptoms; Bias; Dementia; Humans; Oils, Volatile; Psychomotor Agitation; Randomized Controlled Trials as Topic
PubMed: 32813272
DOI: 10.1002/14651858.CD003150.pub3 -
Psychotherapy and Psychosomatics 2022Benzodiazepines and medications acting on benzodiazepine receptors that do not have a benzodiazepine structure (z-drugs) have been viewed by some experts and regulatory... (Review)
Review
Benzodiazepines and medications acting on benzodiazepine receptors that do not have a benzodiazepine structure (z-drugs) have been viewed by some experts and regulatory bodies as having limited benefit and significant risks. Data presented in this article support the use of these medications as treatments of choice for acute situational anxiety, chronic anxiety disorders, insomnia, alcohol withdrawal syndromes, and catatonia. They may also be useful adjuncts in the treatment of anxious depression and mania, and for medically ill patients. Tolerance develops to sedation and possibly psychomotor impairment, but not to the anxiolytic effect of benzodiazepines. Sedation can impair cognitive function in some patients, but assertions that benzodiazepines increase the risk of dementia are not supported by recent data. Contrary to popular opinion, benzodiazepines are not frequently misused or conduits to misuse of other substances in patients without substance use disorders who are prescribed these medications for appropriate indications; most benzodiazepine misuse involves medications that are obtained from other people. Benzodiazepines are usually not lethal in overdose except when ingested with other substances, especially alcohol and opioids. Benzodiazepines comprise one of the few classes of psychotropic medication the mechanisms of action of which are clearly delineated, allowing for greater precision in their clinical use. These medications, therefore, belong in the therapeutic armamentarium of the knowledgeable clinician.
Topics: Alcoholism; Anxiety; Benzodiazepines; Humans; Substance Withdrawal Syndrome; Substance-Related Disorders
PubMed: 35504267
DOI: 10.1159/000524400 -
JAMA Feb 2022Acute agitation is common in patients with bipolar disorder and requires urgent management to relieve distress and to prevent escalation to aggressive behavior. (Comparative Study)
Comparative Study Randomized Controlled Trial
IMPORTANCE
Acute agitation is common in patients with bipolar disorder and requires urgent management to relieve distress and to prevent escalation to aggressive behavior.
OBJECTIVE
To evaluate the effect of orally absorbed, sublingual dexmedetomidine, a selective α2A-adrenergic receptor agonist on symptoms of acute agitation in patients with bipolar disorder.
DESIGN, SETTING, AND PARTICIPANTS
Phase 3, randomized, double-blind, placebo-controlled trial conducted in 15 sites in the US with enrollment between February 24, 2020, and April 27, 2020, and final follow-up on May 21, 2020. A total of 380 adults with bipolar I or II disorder were randomized and 362 completed the study.
INTERVENTIONS
Participants were randomized to 3 groups: sublingual dexmedetomidine 180 μg (n = 127), sublingual dexmedetomidine 120 μg (n = 127), or placebo (n = 126).
MAIN OUTCOMES AND MEASURES
The primary efficacy end point was the mean change from baseline at 2 hours for the Positive and Negative Syndrome Scale-Excited Component (PEC) total score. The range of possible total scores is 5 (absence of agitation) to 35 (extremely severe). The secondary end point was the earliest time of a statistically significant change in PEC total score from baseline for the drug vs placebo. On the primary efficacy end point, to account for multiplicity associated with comparing 2 sublingual dexmedetomidine doses with placebo, the 2-sided significance level for each dose vs placebo was set at .025.
RESULTS
Of 380 patients randomized (mean age, 45.6 years; 54.8% women; and 56.1% Black individuals), 378 (99.5%) self-administered the study medication and completed the study. Baseline agitation was mild to moderate, with an overall mean PEC total score of 18.0. Two hours after taking the medication, the mean changes from baseline in PEC total score were -10.4 for sublingual dexmedetomidine 180 μg, -9.0 for sublingual dexmedetomidine 120 μg, and -4.9 for placebo. Least-square mean differences from placebo in the sublingual dexmedetomidine groups at 2 hours were -5.4 (97.5% CI, -6.6 to -4.2) for 180 μg and -4.1 (97.5% CI, -5.3 to -2.9) for 120 μg (both doses P < .001 vs placebo). Treatment effects began 20 minutes after taking the medication among patients in the sublingual dexmedetomidine groups (least-square mean difference for 180 μg, -1.1 [97.5% CI, -2.0 to -0.2]; P = .007; for 120 μg, -1.0 [97.5% CI, -1.9 to -0.1]; P = .009). Adverse events occurred in 35.7% of patients taking 180 μg of dexmedetomidine, 34.9% taking 120 μg, and 17.5% taking placebo. The most common adverse events (≥5%) in the respective 180 μg, 120 μg, and placebo groups were somnolence (21.4% and 20.6% vs 4.8%); dry mouth (4.8% and 7.1% vs 0.8%); hypotension (6.3% and 4.8% vs 0%); and dizziness (5.6% and 5.6% vs 0.8%).
CONCLUSIONS AND RELEVANCE
Among patients with mild to moderate agitation associated with bipolar disorder, treatment with a sublingual film formulation of dexmedetomidine 120 μg or 180 μg, compared with placebo, resulted in significantly greater reduction in the agitation score at 2 hours. Further research is needed to understand the spectrum of patients for whom this treatment would be effective and feasible and to better understand the clinical importance of the observed effect size.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT04276883.
Topics: Administration, Sublingual; Adolescent; Adrenergic alpha-2 Receptor Agonists; Adult; Aged; Bipolar Disorder; Dexmedetomidine; Double-Blind Method; Female; Humans; Hypnotics and Sedatives; Male; Middle Aged; Psychomotor Agitation
PubMed: 35191924
DOI: 10.1001/jama.2022.0799 -
CNS Spectrums Apr 2022Accurate diagnosis and appropriate treatment of tardive dyskinesia (TD) are imperative, as its symptoms can be highly disruptive to both patients and their caregivers.... (Review)
Review
Accurate diagnosis and appropriate treatment of tardive dyskinesia (TD) are imperative, as its symptoms can be highly disruptive to both patients and their caregivers. Misdiagnosis can lead to incorrect interventions with suboptimal or even deleterious results. To aid in the identification and differentiation of TD in the psychiatric practice setting, we review its clinical features and movement phenomenology, as well as those of other antipsychotic-induced movement disorders, with accompanying links to illustrative videos. Exposure to dopamine receptor blocking agents (DRBAs) such as antipsychotics or antiemetics is associated with a spectrum of movement disorders including TD. The differential diagnosis of TD is based on history of DRBA exposure, recent discontinuation or dose reduction of a DRBA, and movement phenomenology. Common diagnostic challenges are the abnormal behaviors and dyskinesias associated with advanced age or chronic mental illness, and other movement disorders associated with DRBA therapy, such as akathisia, parkinsonian tremor, and tremor related to use of mood stabilizing agents (eg, lithium, divalproex). Duration of exposure may help rule out acute drug-induced syndromes such as acute dystonia or acute/subacute akathisia. Another important consideration is the potential for TD to present together with other drug-induced movement disorders (eg, parkinsonism, parkinsonian tremor, and postural tremor from mood stabilizers) in the same patient, which can complicate both diagnosis and management. After documentation of the phenomenology, severity, and distribution of TD movements, treatment options should be reviewed with the patient and caregivers.
Topics: Antipsychotic Agents; Humans; Movement Disorders; Psychomotor Agitation; Tardive Dyskinesia; Tremor
PubMed: 33213556
DOI: 10.1017/S109285292000200X