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Cannabinoids for the Neuropsychiatric Symptoms of Dementia: A Systematic Review and Meta-Analysis.

ABSTRACT: BACKGROUND:In 2016, the global number of individuals living with dementia was 43.8 million, representing a 117% increase from 1990-mainly due to increases in aging and population growth. Up to 90% of individuals with dementia experience neuropsychiatric symptoms (NPS). However, the limitations of current treatments for NPS have drivent he search for safer pharmacotherapies-including cannabinoids. AIM:To assess the efficacy and acceptability of cannabinoids for the treatment of NPS in individuals with dementia. DESIGN:Systematic review and meta-analysis of clinical trials. SETTING AND PARTICIPANTS:Of 6,902 papers, 9 were eligible (n = 205, 44% female, 78 ± 7 years, 85% Alzheimer disease). Trials were in North America and Europe and explored tetrahydrocannabinol (n = 3), dronabinol (n = 5), or nabilone (n = 1). MEASUREMENT:Titles/abstracts were independently screened by one reviewer and reviewed by a second. Full-text screening was by two reviewers with discrepancies resolved via a third reviewer. We extracted data on the standardized mean difference (SMD) for several NPS instruments, trial completion, and adverse events. Data were pooled using random-effects models. FINDINGS:Cannabinoids led to significant improvements across NPS instruments, including the Cohen Mansfield Agitation Inventory (SMD = -0.80; 95% confidence interval [CI], -1.45 to -0.16), the Neuropsychiatric Inventory (SMD = -0.61; CI, -1.07 to -0.15), and nocturnal actigraphy (SMD = -1.05; CI, -1.56 to -0.54h). Cannabinoids were well-tolerated, with an overall trial completion rate of 93% (193/205) and no serious treatment-related adverse events. Treatment efficacy was associated with baseline dementia severity and dose, but not dementia subtype, age, or sex. The overall study quality was rated as low. CONCLUSIONS:There is preliminary evidence for the efficacy and tolerability of cannabinoids as treatments for NPS. Population-based studies are needed to characterize their real-world effectiveness and acceptability.

SUBMITTER: Bahji A

PROVIDER: S-EPMC7265608 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Cannabinoids for the Neuropsychiatric Symptoms of Dementia: A Systematic Review and Meta-Analysis.

Bahji Anees A Meyyappan Arthi Chinna AC Hawken Emily R ER

Canadian journal of psychiatry. Revue canadienne de psychiatrie 20191213 6

<h4>Background</h4>In 2016, the global number of individuals living with dementia was 43.8 million, representing a 117% increase from 1990-mainly due to increases in aging and population growth. Up to 90% of individuals with dementia experience neuropsychiatric symptoms (NPS). However, the limitations of current treatments for NPS have drivent he search for safer pharmacotherapies-including cannabinoids.<h4>Aim</h4>To assess the efficacy and acceptability of cannabinoids for the treatment of NPS ...[more]

PMID: 31835954

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Project description:BackgroundPrescribing trends suggest that pharmacologic alternatives to antipsychotics are gaining in popularity, but randomized trial (RCT) data of their comparative safety is scarce. Our objective was to describe the comparative safety of pharmacologic interventions for treating neuropsychiatric symptoms in dementia.MethodsWe searched MEDLINE, EMBASE, CENTRAL, CINAHL, and PsycINFO, from inception to May 28, 2019, for studies of pharmacologic interventions used to treat neuropsychiatric symptoms in dementia. Dementia care partners selected fracture risk as our primary outcome. Pairs of reviewers, working independently, conducted all study screening, data abstraction, and risk of bias appraisal. We conducted Bayesian random-effects network meta-analyses (NMAs) using data from RCTs to derive odds ratios (ORs). In secondary analyses, we conducted frequentist random-effects NMAs using data from RCTs and Bayesian three-level hierarchical random-effects NMAs incorporating data from RCTs and non-randomized studies.ResultsOur systematic review included 209 randomized and non-randomized studies (889,378 persons with dementia). In NMAs of data from randomized trials, there were no increased odds of fracture associated with any intervention in primary analyses; however, data were sparse. We found increased odds of cerebrovascular events associated with antipsychotics (odds ratio [OR] 2.12, 95% credible interval [CrI] 1.29 to 3.62; number needed to harm [NNH] = 99) and increased odds of falls associated with dextromethorphan-quinidine (OR 4.16, 95% CrI 1.47 to 14.22; NNH = 55) compared to placebo in persons with dementia. In a subgroup of persons with Alzheimer disease, antipsychotics were associated with increased odds of fracture compared to anticonvulsants (OR 54.1, 95% CrI 1.15 to 38,300; NNH = 18). In older persons (mean age ≥ 80 years) with dementia, anticonvulsants were associated with increased odds of death compared to placebo (OR 8.36, 95% CrI 1.17 to 203.4; NNH = 35) and antipsychotics were associated with increased odds of death compared to antidepressants (OR 5.28, 95% CrI 1.06 to 3.51; NNH = 47).ConclusionAlthough antipsychotics were associated with greater harm than antidepressants and anticonvulsants in subgroups of persons with dementia, medications used in lieu of antipsychotics for treating neuropsychiatric symptoms in dementia, such as anticonvulsants and dextromethorphan-quinidine, were also associated with harm. Decision-making concerning treatments prescribed in lieu of antipsychotics should include potential harms.Prospero registrationCRD42017050130.

Project description:The nature and extent of persistent neuropsychiatric symptoms after COVID-19 are not established. To help inform mental health service planning in the pandemic recovery phase, we systematically determined the prevalence of neuropsychiatric symptoms in survivors of COVID-19. For this pre-registered systematic review and meta-analysis (PROSPERO ID CRD42021239750), we searched MEDLINE, EMBASE, CINAHL and PsycINFO to 20 February 2021, plus our own curated database. We included peer-reviewed studies reporting neuropsychiatric symptoms at post-acute or later time-points after COVID-19 infection and in control groups where available. For each study, a minimum of two authors extracted summary data. For each symptom, we calculated a pooled prevalence using generalized linear mixed models. Heterogeneity was measured with I 2. Subgroup analyses were conducted for COVID-19 hospitalization, severity and duration of follow-up. From 2844 unique titles, we included 51 studies (n = 18 917 patients). The mean duration of follow-up after COVID-19 was 77 days (range 14-182 days). Study quality was most commonly moderate. The most prevalent neuropsychiatric symptom was sleep disturbance [pooled prevalence = 27.4% (95% confidence interval 21.4-34.4%)], followed by fatigue [24.4% (17.5-32.9%)], objective cognitive impairment [20.2% (10.3-35.7%)], anxiety [19.1% (13.3-26.8%)] and post-traumatic stress [15.7% (9.9-24.1%)]. Only two studies reported symptoms in control groups, both reporting higher frequencies in COVID-19 survivors versus controls. Between-study heterogeneity was high (I 2 = 79.6-98.6%). There was little or no evidence of differential symptom prevalence based on hospitalization status, severity or follow-up duration. Neuropsychiatric symptoms are common and persistent after recovery from COVID-19. The literature on longer-term consequences is still maturing but indicates a particularly high prevalence of insomnia, fatigue, cognitive impairment and anxiety disorders in the first 6 months after infection.

Project description:BackgroundThere are currently no systematic reviews or meta-analyses of Chinese calligraphy therapy (CCT) to reduce neuropsychiatric symptoms. The aim of this systematic review and meta-analysis was to explore the efficacy of CCT for people with neuropsychiatric symptoms.MethodsWe searched Chinese and English databases, including the Cochrane Central Register of Controlled Trials and Wanfang Data for relevant articles published between the earliest year available and December 2016. The search was limited to randomized controlled trials and controlled clinical studies and the associated keywords were "handwriting," "Chinese calligraphy," "Chinese calligraphy therapy," "Calligraphy exercise," and "Calligraphy training." The 21 articles that met these criteria were used in the analysis. The Joanna Briggs Institute critical appraisal checklist was used to assess methodological quality.ResultsCCT significantly reduced psychosis (10 studies, 965 subjects, standardized mean difference [SMD]?=?-?0.17, 95% confidence intervals [CI] [-?0.30, -?0.40], Z?=?2.60, p?<?0.01), anxiety symptoms (9 studies, 579 subjects, SMD?=?-?0.78, 95% CI [-?0.95, -?0.61], Z?=?8.98, p?<?0.001), and depressive symptoms (7 studies, 456 subjects, SMD?=?-?0.69, 95% CI [-?0.88, -?0.50], Z?=?7.11, p?<?0.001). CCT also significantly improved cognitive function (2 studies, 55 subjects, MD?=?2.17, 95% CI [-?0.03, 4.38], Z?=?1.93, p?=?0.05) and neurofeedback (3 studies, 148 subjects, SMD?=?-?1.09, 95% CI [-?1.44, -?0.73], Z?=?6.01, p?<?0.001). The therapy also significantly reduced the positive psychopathological expression of schizophrenia symptoms (4 studies, 287 subjects, SMD?=?-?0.35, 95% CI [-?0.59, -?0.12], Z?=?2.96, p?=?0.003) and reduced the negative symptoms of schizophrenia (4 studies, 276 subjects, SMD?=?-?1.39, 95% CI [-?1.65, -?1.12], Z?=?10.23, p?<?0.001).ConclusionsCCT exerts a curative effect on neuropsychiatric symptoms, but the evidence remains insufficient. A large number of RCTs are needed to facilitate additional systematic reviews of evidence for CCT.

Project description:BackgroundNeuropsychiatric symptoms (NPS) are common in individuals with Alzheimer's disease (AD) dementia, but substantial heterogeneity exists in the manifestation of NPS. Sex differences may explain this clinical variability. We aimed to investigate the sex differences in the prevalence and severity of NPS in AD dementia.MethodsLiterature searches were conducted in Embase, MEDLINE/PubMed, Web of Science Core Collection, Cochrane Central Register of Controlled Trials, PsycINFO, and Google Scholar from inception to February 2021. Study selection, data extraction, and quality assessment were conducted in duplicate. Effect sizes were calculated as odds ratios (OR) for NPS prevalence and Hedges' g for NPS severity. Data were pooled using random-effects models. Sources of heterogeneity were examined using meta-regression analyses.ResultsSixty-two studies were eligible representing 21,554 patients (61.2% females). The majority of the included studies had an overall rating of fair quality (71.0%), with ten studies of good quality (16.1%) and eight studies of poor quality (12.9%). There was no sex difference in the presence of any NPS (k = 4, OR = 1.35 [95% confidence interval 0.78, 2.35]) and overall NPS severity (k = 13, g = 0.04 [- 0.04, 0.12]). Regarding specific symptoms, female sex was associated with more prevalent depressive symptoms (k = 20, OR = 1.60 [1.28, 1.98]), psychotic symptoms (general psychosis k = 4, OR = 1.62 [1.12, 2.33]; delusions k = 12, OR = 1.56 [1.28, 1.89]), and aberrant motor behavior (k = 6, OR = 1.47 [1.09, 1.98]). In addition, female sex was related to more severe depressive symptoms (k = 16, g = 0.24 [0.14, 0.34]), delusions (k = 10, g = 0.19 [0.04, 0.34]), and aberrant motor behavior (k = 9, g = 0.17 [0.08, 0.26]), while apathy was more severe among males compared to females (k = 11, g = - 0.10 [- 0.18, - 0.01]). There was no association between sex and the prevalence and severity of agitation, anxiety, disinhibition, eating behavior, euphoria, hallucinations, irritability, and sleep disturbances. Meta-regression analyses revealed no consistent association between the effect sizes across studies and method of NPS assessment and demographic and clinical characteristics.DiscussionFemale sex was associated with a higher prevalence and greater severity of several specific NPS, while male sex was associated with more severe apathy. While more research is needed into factors underlying these sex differences, our findings may guide tailored treatment approaches of NPS in AD dementia.

Project description:We provide a systematic review and meta-analysis on the efficacy, tolerability, and safety of cannabinoids in palliative medicine. The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, PsycINFO, PubMed, Scopus, and http://clinicaltrials.gov, and a selection of cancer journals were searched up until 15th of March 2017. Of the 108 screened studies, nine studies with a total of 1561 participants were included. Overall, the nine studies were at moderate risk of bias. The quality of evidence comparing cannabinoids with placebo was rated according to Grading of Recommendations Assessment, Development, and Evaluation as low or very low because of indirectness, imprecision, and potential reporting bias. In cancer patients, there were no significant differences between cannabinoids and placebo for improving caloric intake (standardized mean differences [SMD]: 0.2 95% confidence interval [CI]: [-0.66, 1.06] P = 0.65), appetite (SMD: 0.81 95% CI: [-1.14, 2.75]; P = 0.42), nausea/vomiting (SMD: 0.21 [-0.10, 0.52] P = 0.19), >30% decrease in pain (risk differences [RD]: 0.07 95% CI: [-0.01, 0.16]; P = 0.07), or sleep problems (SMD: -0.09 95% CI: [-0.62, 0.43] P = 0.72). In human immunodeficiency virus (HIV) patients, cannabinoids were superior to placebo for weight gain (SMD: 0.57 [0.22; 0.92]; P = 0.001) and appetite (SMD: 0.57 [0.11; 1.03]; P = 0.02) but not for nausea/vomiting (SMD: 0.20 [-0.15, 0.54]; P = 0.26). Regarding side effects in cancer patients, there were no differences between cannabinoids and placebo in symptoms of dizziness (RD: 0.03 [-0.02; 0.08]; P = 0.23) or poor mental health (RD: -0.01 [-0.04; 0.03]; P = 0.69), whereas in HIV patients, there was a significant increase in mental health symptoms (RD: 0.05 [0.00; 0.11]; P = 0.05). Tolerability (measured by the number of withdrawals because of adverse events) did not differ significantly in cancer (RD: 1.15 [0.80; 1.66]; P = 0.46) and HIV patients (RD: 1.87 [0.60; 5.84]; P = 0.28). Safety did not differ in cancer (RD: 1.12 [0.86; 1.46]; P = 0.39) or HIV patients (4.51 [0.54; 37.45]; P = 0.32) although there was large uncertainty about the latter reflected in the width of the CI. In one moderate quality study of 469 cancer patients with cancer-associated anorexia, megestrol was superior to cannabinoids in improving appetite, producing >10% weight gain and tolerability. In another study comparing megestrol to dronabinol in HIV patients, megestrol treatment led to higher weight gain without any differences in tolerability and safety. We found no convincing, unbiased, high quality evidence suggesting that cannabinoids are of value for anorexia or cachexia in cancer or HIV patients.

Dataset Information

Cannabinoids for the Neuropsychiatric Symptoms of Dementia: A Systematic Review and Meta-Analysis.

Publications

Cannabinoids for the Neuropsychiatric Symptoms of Dementia: A Systematic Review and Meta-Analysis.

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