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British Journal of Clinical Pharmacology Jul 2018To determine the most efficacious and acceptable treatments of agitation in dementia. (Meta-Analysis)
Meta-Analysis
AIMS
To determine the most efficacious and acceptable treatments of agitation in dementia.
METHODS
MEDLINE, EMBASE, PsycINFO, CENTRAL and clinicaltrials.gov were searched up to 7 February 2017. Two independent reviewers selected randomized controlled trials (RCTs) of treatments to alleviate agitation in people with all-types dementia. Data were extracted using standardized forms and study quality was assessed using the revised Cochrane Risk of Bias Tool for RCTs. Data were pooled using meta-analysis. The primary outcome, efficacy, was 8-week response rates defined as a 50% reduction in baseline agitation score. The secondary outcome was treatment acceptability defined as treatment continuation for 8 weeks.
RESULTS
Thirty-six RCTs comprising 5585 participants (30.9% male; mean ± standard deviation age, 81.8 ± 4.9 years) were included. Dextromethorphan/quinidine [odds ratio (OR) 3.04; 95% confidence interval (CI), 1.63-5.66], risperidone (OR 1.96; 95% CI, 1.49-2.59) and selective serotonin reuptake inhibitors as a class (OR 1.61; 95% CI, 1.02-2.53) were found to be significantly more efficacious than placebo. Haloperidol appeared less efficacious than nearly all comparators. Most treatments had noninferior treatment continuation compared to placebo, except oxcarbazepine, which was inferior. Findings were supported by subgroup and sensitivity analyses.
CONCLUSIONS
Risperidone, serotonin reuptake inhibitors as a class and dextromethorphan/quinidine demonstrated evidence of efficacy for agitation in dementia, although findings for dextromethorphan/quinidine were based on a single RCT. Our findings do not support prescribing haloperidol due to lack of efficacy, or oxcarbazepine due to lack of acceptability. The decision to prescribe should be based on comprehensive consideration of the benefits and risks, including those not evaluated in this meta-analysis.
Topics: Antipsychotic Agents; Dementia; Dextromethorphan; Drug Combinations; Humans; Network Meta-Analysis; Psychometrics; Psychomotor Agitation; Quinidine; Randomized Controlled Trials as Topic; Risperidone; Selective Serotonin Reuptake Inhibitors; Severity of Illness Index; Treatment Outcome
PubMed: 29637593
DOI: 10.1111/bcp.13604 -
Optimal nonpharmacological management of agitation in Alzheimer's disease: challenges and solutions.Clinical Interventions in Aging 2016Many patients with Alzheimer's disease will develop agitation at later stages of the disease, which constitutes one of the most challenging and distressing aspects of... (Review)
Review
Many patients with Alzheimer's disease will develop agitation at later stages of the disease, which constitutes one of the most challenging and distressing aspects of dementia. Recently, nonpharmacological therapies have become increasingly popular and have been proven to be effective in managing the behavioral symptoms (including agitation) that are common in the middle or later stages of dementia. These therapies seem to be a good alternative to pharmacological treatment to avoid unpleasant side effects. We present a systematic review of randomized controlled trials (RCTs) focused on the nonpharmacological management of agitation in Alzheimer's disease (AD) patients aged 65 years and above. Of the 754 studies found, eight met the inclusion criteria. This review suggests that music therapy is optimal for the management of agitation in institutionalized patients with moderately severe and severe AD, particularly when the intervention includes individualized and interactive music. Bright light therapy has little and possibly no clinically significant effects with respect to observational ratings of agitation but decreases caregiver ratings of physical and verbal agitation. Therapeutic touch is effective for reducing physical nonaggressive behaviors but is not superior to simulated therapeutic touch or usual care for reducing physically aggressive and verbally agitated behaviors. Melissa oil aromatherapy and behavioral management techniques are not superior to placebo or pharmacological therapies for managing agitation in AD. Further research in clinical trials is required to confirm the effectiveness and long-term effects of nonpharmacological interventions for managing agitation in AD. These types of studies may lead to the development of future intervention protocols to improve the well-being and daily functioning of these patients, thereby avoiding residential care placement.
Topics: Alzheimer Disease; Behavioral Symptoms; Disease Management; Humans; Music Therapy; Phototherapy; Psychiatric Status Rating Scales; Psychomotor Agitation; Randomized Controlled Trials as Topic
PubMed: 26955265
DOI: 10.2147/CIA.S69484 -
Australian Critical Care : Official... May 2023Person-centred nonpharmacological strategies should be used whenever possible to reduce agitation in the intensive care unit due to issues related to an overreliance on... (Review)
Review
BACKGROUND
Person-centred nonpharmacological strategies should be used whenever possible to reduce agitation in the intensive care unit due to issues related to an overreliance on physical restraints and psychoactive drugs. However, the effect of nonpharmacological interventions to reduce agitation is unclear.
OBJECTIVES
The objectives of this study were to systematically review studies that evaluate the effectiveness of nonpharmacological interventions designed to prevent and minimise or manage patient agitation in the adult intensive care unit.
METHODS
This systematic review was conducted following the Joanna Briggs Institute's Systematic Review of Effectiveness method and a priori PROSPERO protocol. Quantitative studies were identified from seven databases, including MEDLINE, EmCare, CINAHL, Web of Science, PsycINFO, Scopus, and Cochrane Library. In addition, grey literature from several repositories and trial registers was searched. The primary outcome of interest was the effect on prevention, minimisation, and management of agitation. The quality of the evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE).
RESULTS
Eleven studies were included (n = 882). Meta-analyses of two studies demonstrated significantly lower levels of agitation (measured with the Richmond Agitation Sedation Scale) in the group receiving a multicomponent nonpharmacological intervention than in those receiving usual care. Individual studies showed a significant effect of nature-based sounds, music, foot reflexology, healing touch, and aromatherapy. The type of the endotracheal suction system did not affect levels of agitation. Overall, the certainty of the findings was rated very low. Harms and adverse effects were not reported in any studies.
CONCLUSIONS
Nonpharmacological interventions have the potential to reduce levels of agitation in the intensive care unit. However, inconsistencies in reporting, low quality of methodological designs, and small sample sizes impact the certainty of the results. Future trials must include larger sample sizes, use rigorous methods to improve knowledge in this field, and consider a range of other outcomes.
Topics: Adult; Humans; Intensive Care Units; Psychomotor Agitation
PubMed: 35513998
DOI: 10.1016/j.aucc.2022.02.005 -
Acta Psychiatrica Scandinavica Nov 2018Evidence-based guidance of clinical decision-making for the management of Autism Spectrum Disorder (ASD) is lacking, particularly for co-occurring psychiatric symptoms....
OBJECTIVE
Evidence-based guidance of clinical decision-making for the management of Autism Spectrum Disorder (ASD) is lacking, particularly for co-occurring psychiatric symptoms. This review evaluates treatment evidence for six common symptom targets in children/adolescents with ASD and provides a resource to facilitate application of the evidence to clinical practice.
METHOD
A systematic search identified randomized controlled trials (RCTs) and high-quality systematic reviews published between 2007 and 2016, focused on: social interaction/communication impairment, stereotypic/repetitive behaviours, irritability/agitation, attention-deficit/hyperactivity disorder symptoms, mood or anxiety symptoms, and sleep difficulties. We then completed qualitative evaluation of high-quality systematic reviews/meta-analyses and quantitative evaluation of recently published RCTs not covered by prior comprehensive systematic reviews.
RESULTS
Recently published RCTs focused on social interaction and communication impairment (trials = 32) using psychosocial interventions. Interventions for irritability/agitation (trials = 16) were mainly pharmacological. Few RCTs focused on other symptom targets (trials = 2-5/target). Integration of these results with our qualitative review indicated that few established treatment modalities exist, and available evidence is limited by small studies with high risk of bias.
CONCLUSION
Given the current evidence-base, treatment targets must be clearly defined, and a systematic approach to intervention trials in children/adolescents with ASD must be undertaken with careful consideration of the limitations of safety/efficacy data.
Topics: Adolescent; Anxiety Disorders; Attention Deficit Disorder with Hyperactivity; Autism Spectrum Disorder; Child; Communication Disorders; Humans; Mood Disorders; Practice Guidelines as Topic; Psychomotor Agitation; Sleep Wake Disorders; Stereotyped Behavior
PubMed: 29904907
DOI: 10.1111/acps.12918 -
Ageing Research Reviews May 2018To provide an up-to-date systematic review of the characteristics, methodology and findings of studies that have investigated the neurochemistry of agitation in...
OBJECTIVE
To provide an up-to-date systematic review of the characteristics, methodology and findings of studies that have investigated the neurochemistry of agitation in Alzheimer's disease (AD).
METHODS
Electronic databases were searched for published peer-reviewed articles which provided data on any neurotransmitter system in relation to agitation in AD. Screening of titles and abstracts and data extraction from full texts were conducted in duplicate.
RESULTS
Forty-five studies were included. Monoamines (serotonin, dopamine and noradrenaline) were most commonly investigated. A variety of methods were used to investigate the neurochemistry underlying agitation in AD and, although there were several conflicting findings, there was evidence of serotonergic deficit, relatively preserved dopaminergic function and compensatory overactivity of postsynaptic noradrenergic neurons in agitation in AD.
CONCLUSIONS
Disruption of the dynamic balance between multiple neurotransmitter systems could impair functional neural networks involved in affective regulation and executive function. Differences in study design and methodology may have contributed to conflicting findings. Future studies that overcome these limitations (e.g. using standardized criteria to define agitation) and employ neuroimaging methods such as MRI/PET to investigate specific neural networks are needed to clarify the role of neurotransmitter alterations in these patients.
Topics: Alzheimer Disease; Brain Chemistry; Dopamine; Humans; Neurochemistry; Neurotransmitter Agents; Psychomotor Agitation
PubMed: 29524596
DOI: 10.1016/j.arr.2018.03.003 -
Journal of Intellectual Disability... Mar 2021The assessment of depression in people with severe to profound intellectual disability (severe-profound ID) is challenging, primarily due to inability to report internal... (Review)
Review
The assessment of depression in people with severe to profound intellectual disability (severe-profound ID) is challenging, primarily due to inability to report internal states such as mood, feelings of worthlessness and suicidal ideation. This group also commonly presents with challenging behaviours (e.g. aggression and self-injury) with debate about whether these behaviours should be considered 'depressive equivalents' or are sensitive for, but not specific to, depression in severe-profound ID. We conducted a systematic review exploring behaviours associated with depression and low mood in individuals with severe-profound ID. The review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (2009) guidelines. Three electronic databases were searched (Embase, PsycINFO and Ovid MEDLINE), and 13 studies were included and rated for quality. Few studies were rated as having high methodological quality. Behaviours captured by standard diagnostic schemes for depression (e.g. Diagnostic and Statistical Manual of Mental Disorders and International Classification of Diseases) showed a relationship with depression in severe-profound ID, including the two core symptoms (depressed affect and anhedonia), as well as irritability, sleep disturbance, psychomotor agitation, reduced appetite and fatigue. Challenging behaviours such as aggression, self-injury, temper tantrums, screaming and disruptive behaviour were associated with depression. Challenging behaviours show a robust relationship with depression. Whilst these behaviours may suggest an underlying depression, study limitations warrant caution in labelling them as 'depressive equivalents'. These limitations include not controlling for potential confounds (autism, other affective disorders and pain) and bias associated with comparing depressed/non-depressed groups on the same behavioural criteria used to initially diagnose and separate these groups. Future studies that use depressive measures designed for ID populations, which control for confounds and which explore low mood irrespective of psychiatric diagnosis, are warranted to better delineate the behaviours associated with depression in this population (PROSPERO 2018: CRD42018103244).
Topics: Aggression; Depression; Humans; Intellectual Disability; Irritable Mood; Self-Injurious Behavior
PubMed: 33426741
DOI: 10.1111/jir.12807 -
Journal of the American Medical... Oct 2014To examine the impact of gardens and outdoor spaces on the mental and physical well-being of people with dementia who are resident in care homes and understand the... (Review)
Review
What is the impact of using outdoor spaces such as gardens on the physical and mental well-being of those with dementia? A systematic review of quantitative and qualitative evidence.
OBJECTIVE
To examine the impact of gardens and outdoor spaces on the mental and physical well-being of people with dementia who are resident in care homes and understand the views of people with dementia, their carers, and care home staff on the value of gardens and outdoor spaces.
DESIGN
Systematic review.
METHODS
Fourteen databases were searched from inception to February 2013. Forward and backward citation chasing of included articles was conducted; 38 relevant organizations were contacted to identify unpublished reports. Titles, abstracts, and full texts were screened independently by 2 reviewers in a 2-stage process and were discussed with a third reviewer where necessary. Results were synthesized narratively.
RESULTS
Seventeen studies were included: 9 quantitative, 7 qualitative, and 1 mixed methods. The quantitative studies were of poor quality but suggested decreased levels of agitation were associated with garden use. The views and experiences of the garden are discussed in relation to themes of how the garden was used, nature of interactions, impact/effect of the gardens, mechanisms/how the garden was thought to have an effect, and negatives (such as perception of the garden as a hazard and the limited staff time).
CONCLUSION
There are promising impacts on levels of agitation in care home residents with dementia who spend time in a garden. Future research would benefit from a focus on key outcomes measured in comparable ways with a separate focus on what lies behind limited accessibility to gardens within the residential care setting.
Topics: Dementia; Horticultural Therapy; Humans; Mental Health; Nursing Homes; Psychomotor Agitation; Quality of Life
PubMed: 25037168
DOI: 10.1016/j.jamda.2014.05.013 -
The Cochrane Database of Systematic... Jun 2018Fluphenazine is one of the first drugs to be classed as an 'antipsychotic' and has been widely available for five decades. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Fluphenazine is one of the first drugs to be classed as an 'antipsychotic' and has been widely available for five decades.
OBJECTIVES
To compare the effects of oral fluphenazine with placebo for the treatment of schizophrenia. To evaluate any available economic studies and value outcome data.
SEARCH METHODS
We searched the Cochrane Schizophrenia Group's Trials Register (23 July 2013, 23 December 2014, 9 November 2016 and 28 December 2017 ) which is based on regular searches of CINAHL, BIOSIS, AMED, EMBASE, PubMed, MEDLINE, PsycINFO, and registries of clinical trials. There is no language, date, document type, or publication status limitations for inclusion of records in the register.
SELECTION CRITERIA
We sought all randomised controlled trials comparing oral fluphenazine with placebo relevant to people with schizophrenia. Primary outcomes of interest were global state and adverse effects.
DATA COLLECTION AND ANALYSIS
For the effects of interventions, a review team inspected citations and abstracts independently, ordered papers and re-inspected and quality assessed trials. We extracted data independently. Dichotomous data were analysed using fixed-effect risk ratio (RR) and the 95% confidence interval (CI). Continuous data were excluded if more than 50% of people were lost to follow-up, but, where possible, mean differences (MD) were calculated. Economic studies were searched and reliably selected by an economic review team to provide an economic summary of available data. Where no relevant economic studies were eligible for inclusion, the economic review team valued the already-included effectiveness outcome data to provide a rudimentary economic summary.
MAIN RESULTS
From over 1200 electronic records of 415 studies identified by our initial search and this updated search, we excluded 48 potentially relevant studies and included seven trials published between 1964 and 1999 that randomised 439 (mostly adult participants). No new included trials were identified for this review update. Compared with placebo, global state outcomes of 'not improved or worsened' were not significantly different in the medium term in one small study (n = 50, 1 RCT, RR 1.12 CI 0.79 to 1.58, very low quality of evidence). The risk of relapse in the long term was greater in two small studies in people receiving placebo (n = 86, 2 RCTs, RR 0.39 CI 0.05 to 3.31, very low quality of evidence), however with high degree of heterogeneity in the results. Only one person allocated fluphenazine was reported in the same small study to have died on long-term follow-up (n = 50, 1 RCT, RR 2.38 CI 0.10 to 55.72, low quality of evidence). Short-term extrapyramidal adverse effects were significantly more frequent with fluphenazine compared to placebo in two other studies for the outcomes of akathisia (n = 227, 2 RCTs, RR 3.43 CI 1.23 to 9.56, moderate quality of evidence) and rigidity (n = 227, 2 RCTs, RR 3.54 CI 1.76 to 7.14, moderate quality of evidence). For economic outcomes, we valued outcomes for relapse and presented them in additional tables.
AUTHORS' CONCLUSIONS
The findings in this review confirm much that clinicians and recipients of care already know, but they provide quantification to support clinical impression. Fluphenazine's global position as an effective treatment for psychoses is not threatened by the outcome of this review. However, fluphenazine is an imperfect treatment and if accessible, other inexpensive drugs less associated with adverse effects may be an equally effective choice for people with schizophrenia.
Topics: Administration, Oral; Akathisia, Drug-Induced; Antipsychotic Agents; Fluphenazine; Humans; Placebos; Randomized Controlled Trials as Topic; Recurrence; Schizophrenia
PubMed: 29893410
DOI: 10.1002/14651858.CD006352.pub3 -
The Cochrane Database of Systematic... Oct 2006Of the many psychiatric symptoms that may result from brain injury, agitation and/or aggression are often the most troublesome. It is therefore important to evaluate the... (Review)
Review
BACKGROUND
Of the many psychiatric symptoms that may result from brain injury, agitation and/or aggression are often the most troublesome. It is therefore important to evaluate the efficacy of psychotropic medication used in its management.
OBJECTIVES
To evaluate the effects of drugs for agitation and/or aggression following acquired brain injury (ABI).
SEARCH STRATEGY
We searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE and other electronic databases. We also searched the reference lists of included studies and recent reviews. In addition we handsearched the journals Brain Injury and the Journal of Head Trauma Rehabilitation. There were no language restrictions. The searches were last updated in June 2006.
SELECTION CRITERIA
Randomised controlled trials (RCTs) that evaluated the efficacy of drugs acting on the central nervous system for agitation and/or aggression, secondary to ABI, in participants over 10 years of age.
DATA COLLECTION AND ANALYSIS
We independently extracted data and assessed trial quality. Studies of patients within six months after brain injury and/or in a confusional state, were distinguished from those of patients more than six months post-injury, or who were not confused.
MAIN RESULTS
Six RCTs were identified and included in this review. Four of theses evaluated the beta-blockers, propranolol and pindolol, one evaluated the central nervous system stimulant, methylphenidate and one evaluated amantadine, a drug normally used in parkinsonism and related disorders. The best evidence of effectiveness in the management of agitation and/or aggression following ABI was for beta-blockers. Two RCTs found propranolol to be effective (one study early and one late after injury). However, these studies used relatively small numbers, have not been replicated, used large doses, and did not use a global outcome measure or long-term follow-up. Comparing early agitation to late aggression, there was no evidence for a differential drug response. Firm evidence that carbamazepine or valproate is effective in the management of agitation and/or aggression following ABI is lacking.
AUTHORS' CONCLUSIONS
Numerous drugs have been tried in the management of aggression in ABI but without firm evidence of their efficacy. It is therefore important to choose drugs with few side effects and to monitor their effect. Beta-blockers have the best evidence for efficacy and deserve more attention. The lack of evidence highlights the need for better evaluations of drugs for this important problem.
Topics: Adrenergic beta-Antagonists; Aggression; Amantadine; Anxiety; Brain Injuries; Humans; Methylphenidate; Neuroprotective Agents; Pindolol; Propranolol; Psychomotor Agitation; Randomized Controlled Trials as Topic
PubMed: 17054165
DOI: 10.1002/14651858.CD003299.pub2 -
European Child & Adolescent Psychiatry May 2015The aim of this study is to estimate the extent to which children and adolescents with hearing impairment (HI) show higher rates of emotional and behavioural... (Meta-Analysis)
Meta-Analysis Review
The aim of this study is to estimate the extent to which children and adolescents with hearing impairment (HI) show higher rates of emotional and behavioural difficulties compared to normally hearing children. Studies of emotional and behavioural difficulties in children and adolescents were traced from computerized systematic searches supplemented, where appropriate, by studies referenced in previous narrative reviews. Effect sizes (Hedges' g) were calculated for all studies. Meta-analyses were conducted on the weighted effect sizes obtained for studies adopting the Strength and Difficulties Questionnaire (SDQ) and on the unweighted effect sizes for non-SDQ studies. 33 non-SDQ studies were identified in which emotional and behavioural difficulties in children with HI could be compared to normally hearing children. The unweighted average g for these studies was 0.36. The meta-analysis of the 12 SDQ studies gave estimated effect sizes of 0.23 (95% CI 0.07, 0.40), 0.34 (95% CI 0.19, 0.49) and -0.01 (95% CI -0.32, 0.13) for Parent, Teacher and Self-ratings of Total Difficulties, respectively. The SDQ sub-scale showing consistent differences across raters between groups with HI and those with normal hearing was Peer Problems. Children and adolescents with HI have scores on emotional and behavioural difficulties measures about a quarter to a third of a standard deviation higher than hearing children. Children and adolescents with HI are in need of support to help their social relationships particularly with their peers.
Topics: Adolescent; Child; Child, Preschool; Emotions; Faculty; Female; Hearing Loss; Humans; Male; Mathematical Computing; Parents; Peer Group; Psychomotor Agitation; Research Report; Risk Factors; Self Report; Social Behavior; Social Behavior Disorders; Surveys and Questionnaires
PubMed: 25758233
DOI: 10.1007/s00787-015-0697-1