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The Cochrane Database of Systematic... Jul 2020Maternal hypotension is the most frequent complication of spinal anaesthesia for caesarean section. It can be associated with nausea or vomiting and may pose serious... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Maternal hypotension is the most frequent complication of spinal anaesthesia for caesarean section. It can be associated with nausea or vomiting and may pose serious risks to the mother (unconsciousness, pulmonary aspiration) and baby (hypoxia, acidosis, neurological injury).
OBJECTIVES
To assess the effects of prophylactic interventions for hypotension following spinal anaesthesia for caesarean section.
SEARCH METHODS
We searched Cochrane Pregnancy and Childbirth's Trials Register (9 August 2016) and reference lists of retrieved studies.
SELECTION CRITERIA
Randomised controlled trials, including full texts and abstracts, comparing interventions to prevent hypotension with placebo or alternative treatment in women having spinal anaesthesia for caesarean section. We excluded studies if hypotension was not an outcome measure.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed study quality and extracted data from eligible studies. We report 'Summary of findings' tables using GRADE.
MAIN RESULTS
We included 125 studies involving 9469 women. Interventions were to prevent maternal hypotension following spinal anaesthesia only, and we excluded any interventions considered active treatment. All the included studies reported the review's primary outcome. Across 49 comparisons, we identified three intervention groups: intravenous fluids, pharmacological interventions, and physical interventions. Authors reported no serious adverse effects with any of the interventions investigated. Most trials reported hypotension requiring intervention and Apgar score of less than 8 at five minutes as the only outcomes. None of the trials included in the comparisons we describe reported admission to neonatal intensive care unit. Crystalloid versus control (no fluids) Fewer women experienced hypotension in the crystalloid group compared with no fluids (average risk ratio (RR) 0.84, 95% confidence interval (CI) 0.72 to 0.98; 370 women; 5 studies; low-quality evidence). There was no clear difference between groups in numbers of women with nausea and vomiting (average RR 0.19, 95% CI 0.01 to 3.91; 1 study; 69 women; very low-quality evidence). No baby had an Apgar score of less than 8 at five minutes in either group (60 babies, low-quality evidence). Colloid versus crystalloid Fewer women experienced hypotension in the colloid group compared with the crystalloid group (average RR 0.69, 95% CI 0.58 to 0.81; 2009 women; 27 studies; very low-quality evidence). There were no clear differences between groups for maternal hypertension requiring intervention (average RR 0.64, 95% CI 0.09 to 4.46, 3 studies, 327 women; very low-quality evidence), maternal bradycardia requiring intervention (average RR 0.98, 95% CI 0.54 to 1.78, 5 studies, 413 women; very low-quality evidence), nausea and/or vomiting (average RR 0.89, 95% CI 0.66 to 1.19, 14 studies, 1058 women, I² = 29%; very low-quality evidence), neonatal acidosis (average RR 0.83, 95% CI 0.15 to 4.52, 6 studies, 678 babies; very low-quality evidence), or Apgar score of less than 8 at five minutes (average RR 0.24, 95% CI 0.03 to 2.05, 10 studies, 730 babies; very low-quality evidence). Ephedrine versus phenylephrine There were no clear differences between ephedrine and phenylephrine groups for preventing maternal hypotension (average RR 0.92, 95% CI 0.71 to 1.18; 401 women; 8 studies; very low-quality evidence) or hypertension (average RR 1.72, 95% CI 0.71 to 4.16, 2 studies, 118 women, low-quality evidence). Rates of bradycardia were lower in the ephedrine group (average RR 0.37, 95% CI 0.21 to 0.64, 5 studies, 304 women, low-quality evidence). There was no clear difference in the number of women with nausea and/or vomiting (average RR 0.76, 95% CI 0.39 to 1.49, 4 studies, 204 women, I² = 37%, very low-quality evidence), or babies with neonatal acidosis (average RR 0.89, 95% CI 0.07 to 12.00, 3 studies, 175 babies, low-quality evidence). No baby had an Apgar score of less than 8 at five minutes in either group (321 babies; low-quality evidence). Ondansetron versus control Ondansetron administration was more effective than control (placebo saline) for preventing hypotension requiring treatment (average RR 0.67, 95% CI 0.54 to 0.83; 740 women, 8 studies, low-quality evidence), bradycardia requiring treatment (average RR 0.49, 95% CI 0.28 to 0.87; 740 women, 8 studies, low-quality evidence), and nausea and/or vomiting (average RR 0.35, 95% CI 0.24 to 0.51; 653 women, 7 studies, low-quality evidence). There was no clear difference between the groups in rates of neonatal acidosis (average RR 0.48, 95% CI 0.05 to 5.09; 134 babies; 2 studies, low-quality evidence) or Apgar scores of less than 8 at five minutes (284 babies, low-quality evidence). Lower limb compression versus control Lower limb compression was more effective than control for preventing hypotension (average RR 0.61, 95% CI 0.47 to 0.78, 11 studies, 705 women, I² = 65%, very low-quality evidence). There was no clear difference between the groups in rates of bradycardia (RR 0.63, 95% CI 0.11 to 3.56, 1 study, 74 women, very low-quality evidence) or nausea and/or vomiting (average RR 0.42, 95% CI 0.14 to 1.27, 4 studies, 276 women, I² = 32%, very-low quality evidence). No baby had an Apgar score of less than 8 at five minutes in either group (130 babies, very low-quality evidence). Walking versus lying There was no clear difference between the groups for women with hypotension requiring treatment (RR 0.71, 95% CI 0.41 to 1.21, 1 study, 37 women, very low-quality evidence). Many included studies reported little to no information that would allow an assessment of their risk of bias, limiting our ability to draw meaningful conclusions. GRADE assessments of the quality of evidence ranged from very low to low. We downgraded evidence for limitations in study design, imprecision, and indirectness; most studies assessed only women scheduled for elective caesarean sections. External validity also needs consideration. Readers should question the use of colloids in this context given the serious potential side effects such as allergy and renal failure associated with their administration.
AUTHORS' CONCLUSIONS
While interventions such as crystalloids, colloids, ephedrine, phenylephrine, ondansetron, or lower leg compression can reduce the incidence of hypotension, none have been shown to eliminate the need to treat maternal hypotension in some women. We cannot draw any conclusions regarding rare adverse effects associated with use of the interventions (for example colloids) due to the relatively small numbers of women studied.
Topics: Anesthesia, Obstetrical; Anesthesia, Spinal; Antiemetics; Cesarean Section; Colloids; Crystalloid Solutions; Ephedrine; Female; Humans; Hypotension; Intraoperative Complications; Isotonic Solutions; Ondansetron; Phenylephrine; Postoperative Nausea and Vomiting; Pregnancy; Randomized Controlled Trials as Topic; Vasoconstrictor Agents; Walking
PubMed: 32619039
DOI: 10.1002/14651858.CD002251.pub4 -
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 -
The Cochrane Database of Systematic... Sep 2019Although delirium is typically an acute reversible cognitive impairment, its presence is associated with devastating impact on both short-term and long-term outcomes for...
BACKGROUND
Although delirium is typically an acute reversible cognitive impairment, its presence is associated with devastating impact on both short-term and long-term outcomes for critically ill patients. Advances in our understanding of the negative impact of delirium on patient outcomes have prompted trials evaluating multiple pharmacological interventions. However, considerable uncertainty surrounds the relative benefits and safety of available pharmacological interventions for this population.
OBJECTIVES
Primary objective1. To assess the effects of pharmacological interventions for treatment of delirium on duration of delirium in critically ill adults with confirmed or documented high risk of deliriumSecondary objectivesTo assess the following:1. effects of pharmacological interventions on delirium-free and coma-free days; days with coma; delirium relapse; duration of mechanical ventilation; intensive care unit (ICU) and hospital length of stay; mortality; and long-term outcomes (e.g. cognitive; discharge disposition; health-related quality of life); and2. the safety of such treatments for critically ill adult patients.
SEARCH METHODS
We searched the following databases from their inception date to 21 March 2019: Ovid MEDLINE®, Ovid MEDLINE® In-Process & Other Non-Indexed Citations, Embase Classic+Embase, and PsycINFO using the Ovid platform. We also searched the Cochrane Library on Wiley, the International Prospective Register of Systematic Reviews (PROSPERO) (http://www.crd.york.ac.uk/PROSPERO/), the Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Web of Science. We performed a grey literature search of relevant databases and websites using the resources listed in Grey Matters developed by the Canadian Agency for Drugs and Technologies in Health (CADTH). We also searched trial registries and abstracts from annual scientific critical care and delirium society meetings.
SELECTION CRITERIA
We sought randomized controlled trials (RCTs), including quasi-RCTs, of any pharmacological (drug) for treatment of delirium in critically ill adults. The drug intervention was to be compared to another active drug treatment, placebo, or a non-pharmacological intervention (e.g. mobilization). We did not apply any restrictions in terms of drug class, dose, route of administration, or duration of delirium or drug exposure. We defined critically ill patients as those treated in an ICU of any specialty (e.g. burn, cardiac, medical, surgical, trauma) or high-dependency unit.
DATA COLLECTION AND ANALYSIS
Two review authors independently identified studies from the search results; four review authors (in pairs) performed data extraction and assessed risk of bias independently. We performed data synthesis through pairwise meta-analysis and network meta-analysis (NMA). Our hypothetical network structure was designed to be analysed at the drug class level and illustrated a network diagram of 'nodes' (i.e. drug classes) and 'edges' (i.e. comparisons between different drug classes from existing trials), thus describing a treatment network of all possible comparisons between drug classes. We assessed the quality of the body of evidence according to GRADE, as very low, low, moderate, or high.
MAIN RESULTS
We screened 7674 citations, from which 14 trials with 1844 participants met our inclusion criteria. Ten RCTs were placebo-controlled, and four reported comparisons of different drugs. Drugs examined in these trials were the following: antipsychotics (n = 10), alpha agonists (n = 3; all dexmedetomidine), statins (n = 2), opioids (n = 1; morphine), serotonin antagonists (n = 1; ondansetron), and cholinesterase (CHE) inhibitors (n = 1; rivastigmine). Only one of these trials consistently used non-pharmacological interventions that are known to improve patient outcomes in both intervention and control groups.Eleven studies (n = 1153 participants) contributed to analysis of the primary outcome. Results of the NMA showed that the intervention with the smallest ratio of means (RoM) (i.e. most preferred) compared with placebo was the alpha agonist dexmedetomidine (0.58; 95% credible interval (CrI) 0.26 to 1.27; surface under the cumulative ranking curve (SUCRA) 0.895; moderate-quality evidence). In order of descending SUCRA values (best to worst), the next best interventions were atypical antipsychotics (RoM 0.80, 95% CrI 0.50 to 1.11; SUCRA 0.738; moderate-quality evidence), opioids (RoM 0.88, 95% CrI 0.37 to 2.01; SUCRA 0.578; very-low quality evidence), and typical antipsychotics (RoM 0.96, 95% CrI 0.64 to1.36; SUCRA 0.468; high-quality evidence).The NMAs of multiple secondary outcomes revealed that only the alpha agonist dexmedetomidine was associated with a shorter duration of mechanical ventilation (RoM 0.55, 95% CrI 0.34 to 0.89; moderate-quality evidence), and the CHE inhibitor rivastigmine was associated with a longer ICU stay (RoM 2.19, 95% CrI 1.47 to 3.27; moderate-quality evidence). Adverse events often were not reported in these trials or, when reported, were rare; pair-wise analysis of QTc prolongation in seven studies did not show significant differences between antipsychotics, ondansetron, dexmedetomidine, and placebo.
AUTHORS' CONCLUSIONS
We identified trials of varying quality that examined six different drug classes for treatment of delirium in critically ill adults. We found evidence that the alpha agonist dexmedetomidine may shorten delirium duration, although this small effect (compared with placebo) was seen in pairwise analyses based on a single study and was not seen in the NMA results. Alpha agonists also ranked best for duration of mechanical ventilation and length of ICU stay, whereas the CHE inhibitor rivastigmine was associated with longer ICU stay. We found no evidence of a difference between placebo and any drug in terms of delirium-free and coma-free days, days with coma, physical restraint use, length of stay, long-term cognitive outcomes, or mortality. No studies reported delirium relapse, resolution of symptoms, or quality of life. The ten ongoing studies and the six studies awaiting classification that we identified, once published and assessed, may alter the conclusions of the review.
Topics: Antipsychotic Agents; Critical Illness; Delirium; Humans; Network Meta-Analysis; Randomized Controlled Trials as Topic
PubMed: 31479532
DOI: 10.1002/14651858.CD011749.pub2 -
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 -
Psychiatry Research Feb 2024Second-generation antipsychotics (SGAs) are widely used in treating schizophrenia and related disorders, also other mental disorders. However, the efficacy and safety of... (Meta-Analysis)
Meta-Analysis
Second-generation antipsychotics (SGAs) are widely used in treating schizophrenia and related disorders, also other mental disorders. However, the efficacy and safety of SGAs for treating other mental disorders is unclear. A systematic literature search for randomized, placebo-controlled trials of 11 SGAs for treating 18 mental disorders apart from schizophrenia were carried out from database inception to April 3, 2022. The primary outcome was the mean change in the total score for different mental disorders. The secondary outcome was the odds ratio (OR) of response, remission rates and risk ratio (RR) of adverse events (AEs). A total of 181 studies (N = 65,480) were included. All SGAs showed significant effects in treating other mental disorders compared with placebo, except autistic disorder and dementia. Aripiprazole is the most effective treatment for bipolar mania [effect size = -0.90, 95% CI: -1.59, -0.21] and Tourette's disorder [effect size = -0.80, 95% CI: -1.14, -0.45], olanzapine for bipolar depression [effect size = -0.86, 95% CI: -1.32, -0.39] and post-traumatic stress disorder [effect size = -0.98, 95% CI: -1.55, -0.41], lurasidone for depression [effect size = -0.66, 95% CI: -0.82, -0.50], quetiapine for anxiety [effect size = -1.20, 95% CI: -1.96, -0.43], sleep disorders [effect size = -1.2, 95% CI: -1.97, -0.58], and delirium [effect size = -0.36, 95% CI: -0.70, -0.03], and risperidone for obsessive-compulsive disorder [effect size = -2.37, 95% CI: -3.25, -1.49], respectively. For safety, AE items for each SGAs was different. Interestingly, we found that some AEs of OLZ, QTP, RIS and PALI have significant palliative effects on some symptoms. Significant differences in the efficacy and safety of different SGAs for treatment of other mental disorders should be considered for choosing the drug and for the balance between efficacy and tolerability for the specific patient.
Topics: Humans; Antipsychotic Agents; Olanzapine; Quetiapine Fumarate; Risperidone; Schizophrenia
PubMed: 38150810
DOI: 10.1016/j.psychres.2023.115637 -
Schizophrenia Bulletin Jan 2024Long-acting injectable antipsychotic drugs (LAIs) are mainly used for relapse prevention but could also be advantageous for acutely ill patients with schizophrenia. (Meta-Analysis)
Meta-Analysis
Long-Acting Injectable Second-Generation Antipsychotics vs Placebo and Their Oral Formulations in Acute Schizophrenia: A Systematic Review and Meta-Analysis of Randomized-Controlled-Trials.
BACKGROUND AND HYPOTHESIS
Long-acting injectable antipsychotic drugs (LAIs) are mainly used for relapse prevention but could also be advantageous for acutely ill patients with schizophrenia.
STUDY DESIGN
We conducted a systematic review and meta-analysis of randomized-controlled-trials (RCTs) comparing the second-generation long-acting injectable antipsychotics (SGA-LAIs) olanzapine, risperidone, paliperidone, and aripiprazole with placebo or their oral counterparts in acutely ill patients with schizophrenia. We analyzed 23 efficacy and tolerability outcomes, with the primary outcome being overall symptoms of schizophrenia. The results were obtained through random effects, pairwise meta-analyses, and subgroup tests. The study quality was assessed using the Cochrane-Risk-of-Bias-Tool version-1.
STUDY RESULTS
Sixty-six studies with 16 457 participants were included in the analysis. Eleven studies compared second-generation long-acting injectable antipsychotics (SGA-LAIs) with a placebo, 54 compared second-generation oral antipsychotics (SGA-orals) with a placebo, and one compared an SGA-LAI (aripiprazole) with its oral formulation. All 4 SGA-LAIs reduced overall symptoms more than placebo, with mean standardized differences of -0.66 (95% CI: -0.90; -0.43) for olanzapine, -0.64 (-0.80; -0.48) for aripiprazole, -0.62 (-0.76; -0.48) for risperidone and -0.42 (-0.53; -0.31) for paliperidone. The side-effect profiles of the LAIs corresponded to the patterns known from the oral formulations. In subgroup tests compared to placebo, some side effects were less pronounced under LAIs than under their oral formulations.
CONCLUSIONS
SGA-LAIs effectively treat acute schizophrenia. Some side effects may be less frequent than under oral drugs, but due to the indirect nature of the comparisons, this finding must be confirmed by RCTs comparing LAIs and orals head-to-head.
Topics: Humans; Antipsychotic Agents; Paliperidone Palmitate; Aripiprazole; Olanzapine; Risperidone; Delayed-Action Preparations; Schizophrenia
PubMed: 37350486
DOI: 10.1093/schbul/sbad089 -
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 -
PloS One 2023Second-generation antipsychotics (SGAs) are frequently prescribed for the treatment of resistant anorexia nervosa. However, few clinical trials have been conducted so...
INTRODUCTION
Second-generation antipsychotics (SGAs) are frequently prescribed for the treatment of resistant anorexia nervosa. However, few clinical trials have been conducted so far and no pharmacological treatment has yet been approved by the Food and Drug Administration. The aim of this paper is to conduct a systematic scoping review exploring the effectiveness and safety of atypical antipsychotics in anorexia nervosa (AN).
METHOD
We conducted a systematic scoping review of the effectiveness and tolerability of SGAs in the management of AN. We included articles published from January 1, 2000, through September 12, 2022 from the PubMed and PsycInfo databases and a complementary manual search. We selected articles about adolescents and adults treated for AN by four SGAs (risperidone, quetiapine, aripiprazole or olanzapine). This work complies with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis extension for scoping reviews (PRIMA-ScR) and was registered in the Open Science Framework (OSF) repository.
RESULTS
This review included 55 articles: 48 assessing the effectiveness of SGAs in AN and 7 focusing only on their tolerability and safety. Olanzapine is the treatment most frequently prescribed and studied with 7 randomized double-blind controlled trials. Other atypical antipsychotics have been evaluated much less often, such as aripiprazole (no randomized trials), quetiapine (two randomized controlled trials), and risperidone (one randomized controlled trial). These treatments are well tolerated with mild and transient adverse effects in this population at particular somatic risk.
DISCUSSION
Limitations prevent the studies both from reaching conclusive, reliable, robust, and reproducible results and from concluding whether or not SGAs are effective in anorexia nervosa. Nonetheless, they continue to be regularly prescribed in clinical practice. International guidelines suggest that olanzapine and aripiprazole can be interesting in severe or first-line resistant clinical situations.
Topics: Adult; Adolescent; Humans; Antipsychotic Agents; Olanzapine; Risperidone; Aripiprazole; Quetiapine Fumarate; Anorexia Nervosa; Benzodiazepines; Randomized Controlled Trials as Topic
PubMed: 36928656
DOI: 10.1371/journal.pone.0278189 -
International Clinical... Jan 2023A systematic review was undertaken to identify randomized controlled trials (RCTs) comparing the efficacy and safety of lurasidone, brexpiprazole and cariprazine... (Meta-Analysis)
Meta-Analysis
A systematic review was undertaken to identify randomized controlled trials (RCTs) comparing the efficacy and safety of lurasidone, brexpiprazole and cariprazine (selected because of a shared safety profile) with each other or placebo in adult patients with schizophrenia. Key outcomes included: Positive and Negative Syndrome Scales (PANSS), Clinical Global Impression-Severity (CGI-S) scores and cardiovascular and metabolic parameters. A feasibility assessment evaluated the trials' suitability for inclusion in a Bayesian network meta-analysis (NMA). Random effects models were used. In total, 1138 records were identified and 19 RCTs contributed to the NMA. Lurasidone doses of 160 mg performed best in terms of change in PANSS and CGI-S scores at 6 weeks, with stronger evidence when compared with brexpiprazole than cariprazine. The safety outcomes were variable; for all treatments, the 95% credible intervals usually contained 'no difference'. Active treatments were associated with lower odds of discontinuation due to any cause, and higher odds of experiencing any adverse event. Lurasidone was comparable to brexpiprazole and cariprazine for efficacy and safety outcomes assessed at 6 weeks, with the 160 mg dose being superior for the change in PANSS and CGI-S outcomes. The lurasidone results were relatively consistent across doses compared with brexpiprazole and cariprazine.
Topics: Humans; Lurasidone Hydrochloride; Network Meta-Analysis
PubMed: 35916575
DOI: 10.1097/YIC.0000000000000427 -
The Cochrane Database of Systematic... Jun 2023Autism spectrum disorder (autism) is a neurodevelopmental condition characterised by impairments in social communication and interaction, plus restricted, repetitive... (Review)
Review
BACKGROUND
Autism spectrum disorder (autism) is a neurodevelopmental condition characterised by impairments in social communication and interaction, plus restricted, repetitive patterns of behaviour and interests. Whilst some people embrace autism as part of their identity, others struggle with their difficulties, and some seek treatment. There are no current interventions that result in complete reduction of autism features. Acetylcholine is a neurotransmitter for the cholinergic system and has a role in attention, novelty seeking, and memory. Low levels of acetylcholine have been investigated as a potential contributor to autism symptomatology. Donepezil, galantamine, and rivastigmine (commonly referred to as acetylcholinesterase inhibitors) all inhibit acetylcholinesterase, and have slightly different modes of action and biological availability, so their effectiveness and side-effect profiles may vary. The effect of various acetylcholinesterase inhibitor on core autism features across the lifespan, and possible adverse effects, have not been thoroughly investigated.
OBJECTIVES
To evaluate the efficacy and harms of acetylcholinesterase inhibitors for people with the core features (social interaction, communication, and restrictive and repetitive behaviours) of autism. To assess the effects of acetylcholinesterase inhibitors on non-core features of autism.
SEARCH METHODS
In November 2022, we searched CENTRAL, MEDLINE, Embase, eight other databases, and two trials registers. We also searched the reference lists of included studies and relevant reviews, and contacted authors of relevant studies.
SELECTION CRITERIA
Randomised controlled trials (RCTs), comparing acetylcholinesterase inhibitors (e.g. galantamine, donepezil, or rivastigmine) of varying doses, delivered orally or via transdermal patch, either as monotherapy or adjunct therapy, with placebo. People of any age, with a clinical diagnosis of autism were eligible for inclusion.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. Our primary outcomes were core features of autism and adverse effects. Secondary outcomes were language, irritability, hyperactivity, and general health and function. We used GRADE to assess certainty of evidence.
MAIN RESULTS
We included two RCTs (74 participants). One study was conducted in Iran, the second in the USA, although exact location in the USA is unclear. Galantamine plus risperidone versus placebo plus risperidone One study compared the effects of galantamine plus risperidone to placebo plus risperidone (40 participants, aged 4 years to 12 years). Primary and secondary outcomes of interest were measured postintervention, using subscales of the Aberrant Behavior Checklist (score 0 to 3; higher scores = greater impairment). Very low-certainty evidence showed there was little to no difference between the two groups postintervention for social communication (mean difference (MD) -2.75, 95% confidence interval (CI) -5.88 to 0.38), and restricted and repetitive behaviour (MD -0.55, 95% CI -3.47 to 2.37). Overall autism features were not assessed. Adverse events may be higher in the galantamine plus risperidone group (75%) compared with the placebo plus risperidone group (35%): odds ratio 5.57, 95% CI 1.42 to 21.86, low-certainty evidence. No serious adverse events were reported. Low-certainty evidence showed a small difference in irritability (MD -3.50, 95% CI -6.39 to -0.61), with the galantamine plus risperidone group showing a greater decline on the irritability subscale than the placebo group postintervention. There was no evidence of a difference between the groups in hyperactivity postintervention (MD -5.20, 95% CI -10.51 to 0.11). General health and function were not assessed. Donepezil versus placebo One study compared donepezil to placebo (34 participants aged 8 years to 17 years). Primary outcomes of interest were measured postintervention, using subscales of the Modified Version of The Real Life Rating Scale (scored 0 to 3; higher scores = greater impairment). Very low-certainty evidence showed no evidence of group differences immediately postintervention in overall autism features (MD 0.07, 95% CI -0.19 to 0.33), or in the autism symptom domains of social communication (MD -0.02, 95% CI -0.34 to 0.30), and restricted and repetitive behaviours (MD 0.04, 95% CI -0.27 to 0.35). Significant adverse events leading to study withdrawal in at least one participant was implied in the data analysis section, but not explicitly reported. The evidence is very uncertain about the effect of donepezil, compared to placebo, on the secondary outcomes of interest, including irritability (MD 1.08, 95% CI -0.41 to 2.57), hyperactivity (MD 2.60, 95% CI 0.50 to 4.70), and general health and function (MD 0.03, 95% CI -0.48 to 0.54) postintervention. Across all analyses within this comparison, we judged the evidence to be very low-certainty due to high risk of bias, and very serious imprecision (results based on one small study with wide confidence intervals). The study narratively reported adverse events for the study as a whole, rather than by treatment group.
AUTHORS' CONCLUSIONS
Evidence about the effectiveness of acetylcholinesterase inhibitors as a medication to improve outcomes for autistic adults is lacking, and for autistic children is very uncertain. There is a need for more evidence of improvement in outcomes of relevance to clinical care, autistic people, and their families. There are a number of ongoing studies involving acetylcholinesterase inhibitors, and future updates of this review may add to the current evidence.
Topics: Child; Humans; Acetylcholine; Autism Spectrum Disorder; Cholinesterase Inhibitors; Donepezil; Galantamine; Risperidone; Rivastigmine; Child, Preschool; Adolescent
PubMed: 37267443
DOI: 10.1002/14651858.CD013851.pub2