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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 Journal of Head Trauma...To systematically review the available literature on the pharmacological management of agitation and/or aggression in patients with traumatic brain injury (TBI),...
OBJECTIVE
To systematically review the available literature on the pharmacological management of agitation and/or aggression in patients with traumatic brain injury (TBI), synthesize the available data, and provide guidelines.
DESIGN
Systematic review of systematic reviews.
MAIN MEASURES
A literature review of the following websites was performed looking for systematic reviews on the treatment of agitation and/or aggression among patients with TBI: PubMed, CINAHL, DynaMed, Health Business Elite, and EBSCO (Psychology and behavioral sciences collection). Two researchers independently assessed articles for meeting inclusion/exclusion criteria. Data were extracted on year of publication, reviewed databases, dates of coverage, search limitations, pharmacological agents of interest, and a list of all controlled studies included. The included controlled studies were then examined to determine potential reasons for any difference in recommendations.
RESULTS
The literature review led to 187 citations and 67 unique publications after removing the duplicates. Following review of the title/abstracts and full texts, a total of 11 systematic reviews were included. The systematic reviews evaluated the evidence for safety and efficacy of the following medications: amantadine, amphetamines, methylphenidate, antiepileptics, atypical and typical antipsychotics, benzodiazepines, β-blockers, and sertraline.
CONCLUSIONS
On the basis of the results of this literature review, the authors recommend avoiding benzodiazepines and haloperidol for treating agitation and/or aggression in the context of TBI. Atypical antipsychotics (olanzapine in particular) can be considered as practical alternatives for the as-needed management of agitation and/or aggression in lieu of benzodiazepines and haloperidol. Amantadine, β-blockers (propranolol and pindolol), antiepileptics, and methylphenidate can be considered for scheduled treatment of agitation and/or aggression in patients with TBI.
Topics: Aggression; Antipsychotic Agents; Brain Injuries, Traumatic; Humans; Psychomotor Agitation; Systematic Reviews as Topic
PubMed: 33656478
DOI: 10.1097/HTR.0000000000000656 -
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 -
The Australian and New Zealand Journal... Aug 2021Withdrawal from psychoactive medication such as quetiapine is a well-documented phenomenon. Despite the extensive use of quetiapine, there have been few studies into the...
OBJECTIVE
Withdrawal from psychoactive medication such as quetiapine is a well-documented phenomenon. Despite the extensive use of quetiapine, there have been few studies into the presence of discontinuation symptoms. We therefore performed a systematic review of published literature for evidence of quetiapine withdrawal or symptoms associated with discontinuation.
METHODS
We searched PubMed, Embase, CINAHL, Medline, Web of Science, PsycINFO for articles containing the terms 'Quetiapine' AND 'withdraw' OR 'discontinue'. We included all study types that reported on somatic withdrawal symptoms and had no language restrictions. We excluded studies where there was withdrawal from multiple medications or any other psychoactive substance, or where the only symptoms were psychological such as rebound psychosis or craving.
RESULTS
We included 13 papers, all of which were individual case reports. The quality of the individual case reports was sub-optimal, as assessed by the CARE Case Report Guidelines. There was an association between rapid cessation of quetiapine and onset of somatic symptoms such as nausea, vomiting, agitation, restlessness, diaphoresis, irritability, anxiety, dysphoria, sleep disturbance, insomnia, tachycardia, hypertension and dizziness. Three studies also reported the onset of a withdrawal dyskinesia characterised by abnormal choreiform movements as well as confusion and speech disturbance in some cases. However, these findings were limited by the number and quality of case reports identified.
CONCLUSION
Discontinuation symptoms are an uncommon side effect of quetiapine cessation, which may have clinical implications. Clinicians should therefore be alert to the possibility of quetiapine withdrawal in individuals who present with somatic symptoms or choreiform movements. However, large prospective studies are required to clarify this association.
Topics: Anxiety Disorders; Humans; Psychomotor Agitation; Psychotic Disorders; Quetiapine Fumarate; Substance Withdrawal Syndrome
PubMed: 33059460
DOI: 10.1177/0004867420965693 -
Annals of Internal Medicine Nov 2019Both pharmacologic and nonpharmacologic interventions are used to treat neuropsychiatric symptoms in persons with dementia. (Comparative Study)
Comparative Study Meta-Analysis
BACKGROUND
Both pharmacologic and nonpharmacologic interventions are used to treat neuropsychiatric symptoms in persons with dementia.
PURPOSE
To summarize the comparative efficacy of pharmacologic and nonpharmacologic interventions for treating aggression and agitation in adults with dementia.
DATA SOURCES
MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, CINAHL, and PsycINFO between inception and 28 May 2019 without language restrictions; gray literature; and reference lists scanned from selected studies and systematic reviews.
STUDY SELECTION
Randomized controlled trials comparing interventions for treating aggression and agitation in adults with dementia.
DATA EXTRACTION
Pairs of reviewers independently screened studies, abstracted data, and appraised risk of bias.
DATA SYNTHESIS
After screening of 19 684 citations, 163 studies (23 143 patients) were included in network meta-analyses. Analysis of interventions targeting aggression and agitation (148 studies [21 686 patients]) showed that multidisciplinary care (standardized mean difference [SMD], -0.5 [95% credible interval {CrI}, -0.99 to -0.01]), massage and touch therapy (SMD, -0.75 [CrI, -1.12 to -0.38]), and music combined with massage and touch therapy (SMD, -0.91 [CrI, -1.75 to -0.07]) were clinically more efficacious than usual care. Recreation therapy (SMD, -0.29 [CrI, -0.57 to -0.01]) was statistically but not clinically more efficacious than usual care.
LIMITATIONS
Forty-six percent of studies were at high risk of bias because of missing outcome data. Harms and costs of therapies were not evaluated.
CONCLUSION
Nonpharmacologic interventions seemed to be more efficacious than pharmacologic interventions for reducing aggression and agitation in adults with dementia.
PRIMARY FUNDING SOURCE
Alberta Health Services Critical Care Strategic Clinical Network. (PROSPERO: CRD42017050130).
Topics: Aggression; Dementia; Humans; Network Meta-Analysis; Psychomotor Agitation
PubMed: 31610547
DOI: 10.7326/M19-0993 -
BMJ Open Jul 2019The aim of this systematic review was to assess the efficacy and safety of pharmacological agents in the management of agitated behaviours following traumatic brain...
OBJECTIVE
The aim of this systematic review was to assess the efficacy and safety of pharmacological agents in the management of agitated behaviours following traumatic brain injury (TBI).
METHODS
We performed a search strategy in PubMed, OvidMEDLINE, Embase, CINAHL, PsycINFO, Cochrane Library, Google Scholar, Directory of Open Access Journals, LILACS, Web of Science and Prospero (up to 10 December 2018) for published and unpublished evidence on the risks and benefits of 9 prespecified medications classes used to control agitated behaviours following TBI. We included all randomised controlled trials, quasi-experimental and observational studies examining the effects of medications administered to control agitated behaviours in TBI patients. Included studies were classified into three mutually exclusive categories: (1) agitated behaviour was the presenting symptom; (2) agitated behaviour was not the presenting symptom, but was measured as an outcome variable; and (3) safety of pharmacological interventions administered to control agitated behaviours was measured.
RESULTS
Among the 181 articles assessed for eligibility, 21 studies were included. Of the studies suggesting possible benefits, propranolol reduced maximum intensities of agitation per week and physical restraint use, methylphenidate improved anger measures following 6 weeks of treatment, valproic acid reduced weekly agitated behaviour scale ratings and olanzapine reduced irritability, aggressiveness and insomnia between weeks 1 and 3 of treatment. Amantadine showed variable effects and may increase the risk of agitation in the critically ill. In three studies evaluating safety outcomes, antipsychotics were associated with an increased duration of post-traumatic amnesia (PTA) in unadjusted analyses. Small sample sizes, heterogeneity and an unclear risk of bias were limits.
CONCLUSIONS
Propranolol, methylphenidate, valproic acid and olanzapine may offer some benefit; however, they need to be further studied. Antipsychotics may increase the length of PTA. More studies on tailored interventions and continuous evaluation of safety and efficacy throughout acute, rehabilitation and outpatient settings are needed.
PROSPERO REGISTRATION NUMBER
CRD42016033140.
Topics: Antipsychotic Agents; Brain Injuries, Traumatic; Humans; Psychomotor Agitation; Psychoses, Substance-Induced; Randomized Controlled Trials as Topic
PubMed: 31289093
DOI: 10.1136/bmjopen-2019-029604 -
The American Journal of Emergency... Jan 2022Safe and effective tranquilization of the acutely agitated patient is challenging, and head-to-head comparisons of medications are limited. We aimed to identify the most... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Safe and effective tranquilization of the acutely agitated patient is challenging, and head-to-head comparisons of medications are limited. We aimed to identify the most optimal agent(s) for rapid tranquilization of the severely agitated patient in the emergency department (ED).
METHODS
The protocol for systematic review was registered (PROSPERO; CRD42020212534). We searched MEDLINE, Embase, PsycINFO, and Cochrane Database/CENTRAL from inception to June 2, 2021. We limited studies to randomized controlled trials that enrolled adult ED patients with severe agitation and compared drugs for rapid tranquilization. Predetermined outcomes were: 1) Adequate sedation within 30 min (effectiveness), 2) Immediate, serious adverse event - cardiac arrest, ventricular tachydysrhythmia, endotracheal intubation, laryngospasm, hypoxemia, hypotension (safety), and 3) Time to adequate sedation (effect onset). We extracted data according to PRISMA-NMA and appraised trials using Cochrane RoB 2 tool. We performed Bayesian network meta-analysis (NMA) using a Markov Chain Monte Carlo method with random-effects model and vague prior distribution to calculate odds ratios with 95% credible intervals for dichotomous outcomes and frequentist NMA to calculate mean differences with 95% confidence intervals for continuous outcomes. We assessed confidence in results using CINeMA. We used surface under the cumulative ranking (SUCRA) curves to rank agent(s) for each outcome.
RESULTS
Eleven studies provided data for effectiveness (1142 patients) and safety (1147 patients). Data was insufficient for effect onset. The NMA found that ketamine (SUCRA = 93.0%) is most likely to have superior effectiveness; droperidol-midazolam (SUCRA = 78.8%) is most likely to be safest. There are concerns with study quality and imprecision. Quality of the point estimates varied for effectiveness but mostly rated "very low" for safety.
CONCLUSIONS
Available evidence suggests that ketamine and droperidol have intermediate effectiveness for rapid tranquilization of the severely agitated patient in the ED. There is insufficient evidence to definitively determine which agent(s) may be safest or fastest-acting. Further, direct-comparison study of ketamine and droperidol is recommended.
Topics: Adult; Droperidol; Emergence Delirium; Emergency Service, Hospital; Humans; Ketamine; Network Meta-Analysis; Psychomotor Agitation; Randomized Controlled Trials as Topic; Severity of Illness Index; Treatment Outcome
PubMed: 34823192
DOI: 10.1016/j.ajem.2021.11.011 -
European Neuropsychopharmacology : the... Jul 2023Antipsychotic-induced akathisia is severely distressing. We aimed to investigate relationships between antipsychotic doses and akathisia risk. We searched for randomised... (Meta-Analysis)
Meta-Analysis
Antipsychotic-induced akathisia is severely distressing. We aimed to investigate relationships between antipsychotic doses and akathisia risk. We searched for randomised controlled trials that investigated monotherapy of 17 antipsychotics in adults with acute schizophrenia until 06 March 2022. The primary outcome was the number of participants with akathisia, which was analysed with odds ratios (ORs). We applied one-stage random-effects dose-response meta-analyses using restricted cubic splines to model the dose-response relationships. We included 98 studies (343 dose arms, 34,225 participants), most of which were short-term and had low-to-moderate risk of bias. We obtained data on all antipsychotics except clozapine and zotepine. In patients with acute exacerbations of chronic schizophrenia, from moderate to high certainty of evidence, our analysis showed that sertindole and quetiapine carried negligible risks for akathisia across examined doses (flat curves), while most of the other antipsychotics had their risks increase initially with increasing doses and then either plateaued (hyperbolic curves) or continued to rise (monotonic curves), with maximum ORs ranging from 1.76 with 95% Confidence Intervals [1.24, 2.52] for risperidone at 5.4 mg/day to OR 11.92 [5.18, 27.43] for lurasidone at 240 mg/day. We found limited or no data on akathisia risk in patients with predominant negative symptoms, first-episode schizophrenia, or elderly patients. In conclusion, liability of akathisia varies between antipsychotics and is dose-related. The dose-response curves for akathisia in most antipsychotics are either monotonic or hyperbolic, indicating that higher doses carry a greater or equal risk compared to lower doses.
Topics: Humans; Adult; Aged; Antipsychotic Agents; Schizophrenia; Psychomotor Agitation; Risperidone; Quetiapine Fumarate
PubMed: 37075639
DOI: 10.1016/j.euroneuro.2023.03.015 -
JAMA Network Open Mar 2024Antipsychotic-induced akathisia (AIA) occurs in 14% to 35% of patients treated with antipsychotics and is associated with increased suicide and decreased adherence in... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Antipsychotic-induced akathisia (AIA) occurs in 14% to 35% of patients treated with antipsychotics and is associated with increased suicide and decreased adherence in patients with schizophrenia. However, no comprehensive review and network meta-analysis has been conducted to compare the efficacy of treatments for AIA.
OBJECTIVE
To compare the efficacy associated with AIA treatments.
DATA SOURCES
Three databases (MEDLINE, Web of Science, and Google Scholar) were systematically searched by multiple researchers for double-blind randomized clinical trials (RCTs) comparing active drugs for the treatment of AIA with placebo or another treatment between May 30 and June 18, 2023.
STUDY SELECTION
Selected studies were RCTs that compared adjunctive drugs for AIA vs placebo or adjunctive treatment in patients treated with antipsychotics fulfilling the criteria for akathisia, RCTs with sample size of 10 patients or more, only trials in which no additional drugs were administered during the study, and RCTs that used a validated akathisia score. Trials with missing data for the main outcome (akathisia score at the end points) were excluded.
DATA EXTRACTION AND SYNTHESIS
Data extraction and synthesis were performed, estimating standardized mean differences (SMDs) through pairwise and network meta-analysis with a random-effects model. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline was followed.
MAIN OUTCOMES AND MEASURES
The primary outcome was the severity of akathisia measured by a validated scale at the last available end point.
RESULTS
Fifteen trials involving 492 participants compared 10 treatments with placebo. Mirtazapine (15 mg/d for ≥5 days; SMD, -1.20; 95% CI, -1.83 to -0.58), biperiden (6 mg/d for ≥14 days; SMD, -1.01; 95% CI, -1.69 to -0.34), vitamin B6 (600-1200 mg/d for ≥5 days; SMD, -0.92; 95% CI, -1.57 to -0.26), trazodone (50 mg/d for ≥5 days; SMD, -0.84; 95% CI, -1.54 to -0.14), mianserin (15 mg/d for ≥5 days; SMD, -0.81; 95% CI, -1.44 to -0.19), and propranolol (20 mg/d for ≥6 days; SMD, -0.78; 95% CI, -1.35 to -0.22) were associated with greater efficacy than placebo, with low to moderate heterogeneity (I2 = 34.6%; 95% CI, 0.0%-71.1%). Cyproheptadine, clonazepam, zolmitriptan, and valproate did not yield significant effects. Eight trials were rated as having low risk of bias; 2, moderate risk; and 5, high risk. Sensitivity analyses generally confirmed the results for all drugs except for cyproheptadine and propranolol. No association between effect sizes and psychotic severity was found.
CONCLUSIONS AND RELEVANCE
In this systematic review and network meta-analysis, mirtazapine, biperiden, and vitamin B6 were associated with the greatest efficacy for AIA, with vitamin B6 having the best efficacy and tolerance profile. Trazodone, mianserin, and propranolol appeared as effective alternatives with slightly less favorable efficacy and tolerance profiles. These findings should assist prescribers in selecting an appropriate medication for treating AIA.
Topics: Humans; Antipsychotic Agents; Biperiden; Cyproheptadine; Gallopamil; Mianserin; Mirtazapine; Network Meta-Analysis; Propranolol; Randomized Controlled Trials as Topic; Trazodone; Vitamin B 6; Akathisia, Drug-Induced
PubMed: 38451521
DOI: 10.1001/jamanetworkopen.2024.1527 -
International Clinical... Jul 2023The whole picture of psychotropics for bipolar depression (BPD) remains unclear. This review compares the differences in efficacy and safety profiles among common...
The whole picture of psychotropics for bipolar depression (BPD) remains unclear. This review compares the differences in efficacy and safety profiles among common psychotropics for BPD. MEDLINE, EMBASE, and PsycINFO were searched for proper studies. The changes in the depressive rating scale, remission/response rates, nervous system adverse events (NSAEs), gastrointestinal adverse events (GIAEs), metabolic parameters, and prolactin were compared between medication and placebo or among medications with the Cohen's d or number needed to treat/harm. The search provided 10 psychotropics for comparison. Atypical antipsychotics (AAPs) were superior to lithium and lamotrigine at alleviating acute depressive symptoms. Lithium was more likely to induce dry mouth and nausea. Cariprazine and aripiprazole seemed to be associated with an increased risk of akathisia and upper GIAEs. Lurasidone was associated with an increased risk of developing akathisia and hyperprolactinemia. Olanzapine, olanzapine-fluoxetine combination (OFC), and quetiapine were associated with an increased risk of NSAEs, metabolic risk, dry mouth, and constipation. Cariprazine, lurasidone, OFC, or quetiapine was optimal monotherapy for BPD. Further studies are needed to assess the efficacy and safety of lamotrigine for treating BPD. Adverse events varied widely across different drug types due to variations in psychopharmacological mechanisms, dosages, titration, and ethnicities.
Topics: Humans; Antipsychotic Agents; Bipolar Disorder; Lurasidone Hydrochloride; Quetiapine Fumarate; Lamotrigine; Lithium; Psychomotor Agitation; Antimanic Agents
PubMed: 36947416
DOI: 10.1097/YIC.0000000000000449