Dataset Information

Pharmacological treatments for alleviating agitation in dementia: a systematic review and network meta-analysis.

ABSTRACT:

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.

SUBMITTER: Kongpakwattana K

PROVIDER: S-EPMC6005613 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Pharmacological treatments for alleviating agitation in dementia: a systematic review and network meta-analysis.

Kongpakwattana Khachen K Sawangjit Ratree R Tawankanjanachot Itthipol I Bell J Simon JS Hilmer Sarah N SN Chaiyakunapruk Nathorn N Chaiyakunapruk Nathorn N

British journal of clinical pharmacology 20180514 7

<h4>Aims</h4>To determine the most efficacious and acceptable treatments of agitation in dementia.<h4>Methods</h4>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 ...[more]

PMID: 29637593

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Project description:ImportanceIncidence of neonatal abstinence syndrome is rising rapidly, and optimal pharmacotherapy may meaningfully reduce length of treatment.ObjectiveTo compare pharmacological therapies for neonatal abstinence syndrome.Data sourcesSystematic review and network meta-analysis of Medline (1946-June 2018), Embase (1974-June 2018), Cochrane CENTRAL (1966-June 2018), Web of Science (1900-June 2018), and ClinicalTrials.gov (June 2018).Study selectionRandomized clinical trials of pharmacological treatments for neonatal abstinence syndrome alone or in combination with adjuvant treatments. Abstract, title, and full-text screening were conducted independently by 2 reviewers (T.D. and C.G.).Data extraction and synthesisData extraction was conducted independently by 2 reviewers (T.D. and C.G.) according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA)-Network Meta-Analyses guidelines. Quality was assessed with the Cochrane Risk of Bias tool and data were pooled with fixed-effect models as a result of the low number of trials that were included in the analysis.Main outcomes and measuresThe primary outcome was the length of treatment. The length of stay, need for adjuvant therapy, and adverse events were considered as secondary outcomes.ResultsEighteen trials (N = 1072) were eligible for inclusion. The treatments that were included in the length of treatment analysis were buprenorphine, clonidine, diluted tincture of opium and clonidine, diluted tincture of opium, morphine, methadone, and phenobarbital. Sublingual buprenorphine was considered the optimal treatment for a reduction in the length of treatment (days: mean difference vs morphine, -12.75 [95% CI, -17.97 to -7.58]; median rank, 1 [3-1]) and length of stay (days: mean difference vs morphine, -11.43 [95% CI, -16.95 to -5.82]; median rank, 1 [3-1]) but not the need for adjuvant treatment (odds ratio vs morphine, 1.23 [95% CI, 0.46-3.44]; median rank, 3 [5-1]). The results were robust to bias but sensitive to imprecision.Conclusions and relevanceThe current evidence suggests that buprenorphine is the optimal treatment for neonatal abstinence treatment, but limitations are considerable and wide-scale adoption requires a large multisite trial. Morphine, which is considered standard of care in most hospitals, was the lowest-ranked opioid for length of treatment and length of stay.

Project description:BackgroundThere is still no approved medication for the core symptoms of autism spectrum disorder (ASD). This network meta-analysis investigated pharmacological and dietary-supplement treatments for ASD.MethodsWe searched for randomized-controlled-trials (RCTs) with a minimum duration of seven days in ClinicalTrials.gov, EMBASE, MEDLINE, PsycINFO, WHO-ICTRP (from inception up to July 8, 2018), CENTRAL and PubMed (up to November 3, 2021). The co-primary outcomes were core symptoms (social-communication difficulties-SCD, repetitive behaviors-RB, overall core symptoms-OCS) measured by validated scales and standardized-mean-differences (SMDs). Associated symptoms, e.g., irritability/aggression and attention-deficit/hyperactivity disorder (ADHD) symptoms, dropouts and important side-effects, were investigated as secondary outcomes. Studies in children/adolescents and adults were analyzed separately in random-effects pairwise and network meta-analyses.ResultsWe analyzed data for 41 drugs and 17 dietary-supplements, from 125 RCTs (n = 7450 participants) in children/adolescents and 18 RCTs (n = 1104) in adults. The following medications could improve at least one core symptom domain in comparison with placebo: aripiprazole (k = 6 studies in analysis, SCD: SMD = 0.27 95% CI [0.09, 0.44], RB: 0.48 [0.26, 0.70]), atomoxetine (k = 3, RB:0.49 [0.18, 0.80]), bumetanide (k = 4, RB: 0.35 [0.09, 0.62], OCS: 0.61 [0.31, 0.91]), and risperidone (k = 4, SCM: 0.31 [0.06, 0.55], RB: 0.60 [0.29, 0.90]; k = 3, OCS: 1.18 [0.75, 1.61]) in children/adolescents; fluoxetine (k = 1, RB: 1.20 [0.45, 1.96]), fluvoxamine (k = 1, RB: 1.04 [0.27, 1.81]), oxytocin (k = 6, RB:0.41 [0.16, 0.66]) and risperidone (k = 1, RB: 0.97 [0.21,1.74]) in adults. There were some indications of improvement by carnosine, haloperidol, folinic acid, guanfacine, omega-3-fatty-acids, probiotics, sulforaphane, tideglusib and valproate, yet imprecise and not robust. Confidence in these estimates was very low or low, except moderate for oxytocin. Medications differed substantially in improving associated symptoms, and in their side-effect profiles.LimitationsMost of the studies were inadequately powered (sample sizes of 20-80 participants), with short duration (8-13 weeks), and about a third focused on associated symptoms. Networks were mainly star-shaped, and there were indications of reporting bias. There was no optimal rating scale measuring change in core symptoms.ConclusionsSome medications could improve core symptoms, although this could be likely secondary to the improvement of associated symptoms. Evidence on their efficacy and safety is preliminary; therefore, routine prescription of medications for the core symptoms cannot be recommended. Trial registration PROSPERO-ID CRD42019125317.

Project description:BackgroundDementia is a clinical syndrome commonly seen in the elderly individuals. With the prevalence of dementia, the incidence of neuropsychiatric symptoms in dementia patients is increasing annually. Agitation, as one of the neuropsychiatric symptoms, has a serious impact on the quality of life of patients with dementia. Several antidepressant drugs have been shown to be effective for treating agitated behavior symptoms in patients with dementia, but there are no direct comparisons among those drugs. Therefore, we carried out a network meta-analysis (NMA) to examine the efficacy and safety of those antidepressant drugs.MethodsWe searched eight databases (PubMed, Cochrane Library, Web of Science, Embase, Wanfang Database, China National Knowledge Infrastructure, VIP Database and China biomedical literature service) from their inception to 6 November 2022. Randomized controlled trials (RCTs) reporting the efficacy and safety of antidepressant drugs in treating agitated behavior symptoms in patients with dementia were included in our analysis. The quality assessment was carried out by two researchers individually and the analysis was based on the frequency method.ResultsTwelve articles with 1,146 participants were included in our analysis. Based on the outcome of the agitation score, treatment with citalopram (standardized mean difference, SMD = -0.44, 95% confidence interval, 95% CI = -0.72 to -0.16) showed significant benefits over the placebo group. Treatment with trazodone (odds ratio, OR = 4.58, 95% CI = 1.12-18.69) was associated with a higher risk of total adverse events compared with a placebo treatment.ConclusionAmong the antidepressant drugs included in this study, treatment with citalopram was probably the only optimal intervention, when considering the improvement from baseline to the end of the intervention, and there was not a statistically significant difference in safety when compared with a placebo treatment.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/#recordDetails, identifier: PROSPERO, CRD42022320932.

Project description:BackgroundSevere psychomotor agitation and aggression often require immediate pharmacological intervention, but clear evidence-based recommendations for choosing among the multiple options are lacking. To address this gap, we plan a systematic review and individual-participant-data network meta-analysis to investigate their comparative effectiveness in real-world emergency settings with increased precision.MethodsWe will include randomized controlled trials investigating intramuscular or intravenous pharmacological interventions, as monotherapy or in combination, in adults with severe psychomotor agitation irrespective of the underlying diagnosis and requiring rapid tranquilization in general or psychiatric emergency settings. We will exclude studies before 2002, those focusing on specific reasons for agitation and placebo-controlled trials to avoid concerns related to the transitivity assumption and potential selection biases. We will search for eligible studies in BIOSIS, CENTRAL, CINAHL Plus, Embase, LILACS, MEDLINE via Ovid, PubMed, ProQuest, PsycINFO, ClinicalTrials.gov, and WHO-ICTRP. Individual-participant data will be requested from the study authors and harmonized into a uniform format, and aggregated data will also be extracted from the studies. At least two independent reviewers will conduct the study selection, data extraction, risk-of-bias assessment using RoB 2, and applicability evaluation using the RITES tool. The primary outcome will be the number of patients achieving adequate sedation within 30 min after treatment, with secondary outcomes including the need for additional interventions and adverse events, using odds ratios as the effect size. If enough individual-participant data will be collected, we will synthesize them in a network meta-regression model within a Bayesian framework, incorporating study- and participant-level characteristics to explore potential sources of heterogeneity. In cases where individual-participant data are unavailable, potential data availability bias will be explored, and models allowing for the inclusion of studies reporting only aggregated data will be considered. We will assess the confidence in the evidence using the Confidence in Network Meta-Analysis (CINeMA) approach.DiscussionThis individual-participant-data network meta-analysis aims to provide a fine-tuned synthesis of the evidence on the comparative effectiveness of pharmacological interventions for severe psychomotor agitation in real-world emergency settings. The findings from this study can greatly be provided clearer evidence-based guidance on the most effective treatments.Systematic review registrationPROSPERO CRD42023402365.

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Dataset Information

Pharmacological treatments for alleviating agitation in dementia: a systematic review and network meta-analysis.

Aims

Methods

Results

Conclusions

Publications

Pharmacological treatments for alleviating agitation in dementia: a systematic review and network meta-analysis.

Similar Datasets

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