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BMC Medicine Dec 2022Liquid biopsy has been widely researched for early diagnosis, prognostication and disease monitoring in lung cancer, but there is a need to investigate its clinical... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Liquid biopsy has been widely researched for early diagnosis, prognostication and disease monitoring in lung cancer, but there is a need to investigate its clinical utility for early-stage non-small cell lung cancer (NSCLC).
METHODS
We performed a meta-analysis and systematic review to evaluate diagnostic and prognostic values of liquid biopsy for early-stage NSCLC, regarding the common biomarkers, circulating tumor cells, circulating tumor DNA (ctDNA), methylation signatures, and microRNAs. Cochrane Library, PubMed, EMBASE databases, ClinicalTrials.gov, and reference lists were searched for eligible studies since inception to 17 May 2022. Sensitivity, specificity and area under the curve (AUC) were assessed for diagnostic values. Hazard ratio (HR) with a 95% confidence interval (CI) was extracted from the recurrence-free survival (RFS) and overall survival (OS) plots for prognostic analysis. Also, potential predictive values and treatment response evaluation were further investigated.
RESULTS
In this meta-analysis, there were 34 studies eligible for diagnostic assessment and 21 for prognostic analysis. The estimated diagnostic values of biomarkers for early-stage NSCLC with AUCs ranged from 0.84 to 0.87. The factors TNM stage I, T1 stage, N0 stage, adenocarcinoma, young age, and nonsmoking contributed to a lower tumor burden, with a median cell-free DNA concentration of 8.64 ng/ml. For prognostic analysis, the presence of molecular residual disease (MRD) detection was a strong predictor of disease relapse (RFS, HR, 4.95; 95% CI, 3.06-8.02; p < 0.001) and inferior OS (HR, 3.93; 95% CI, 1.97-7.83; p < 0.001), with average lead time of 179 ± 74 days between molecular recurrence and radiographic progression. Predictive values analysis showed adjuvant therapy significantly benefited the RFS of MRD + patients (HR, 0.27; p < 0.001), while an opposite tendency was detected for MRD - patients (HR, 1.51; p = 0.19). For treatment response evaluation, a strong correlation between pathological response and ctDNA clearance was detected, and both were associated with longer survival after neoadjuvant therapy.
CONCLUSIONS
In conclusion, our study indicated liquid biopsy could reliably facilitate more precision and effective management of early-stage NSCLC. Improvement of liquid biopsy techniques and detection approaches and platforms is still needed, and higher-quality trials are required to provide more rigorous evidence prior to their routine clinical application.
Topics: Humans; Biomarkers, Tumor; Carcinoma, Non-Small-Cell Lung; Liquid Biopsy; Lung Neoplasms; Neoplasm Recurrence, Local
PubMed: 36514063
DOI: 10.1186/s12916-022-02681-x -
Systematic Reviews Jan 2023Rett syndrome is a rare, severe neurodevelopmental disorder. Almost all cases occur in girls, in association with spontaneous (non-inherited) mutations involving the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Rett syndrome is a rare, severe neurodevelopmental disorder. Almost all cases occur in girls, in association with spontaneous (non-inherited) mutations involving the methyl-CpG-binding protein 2 gene located on the X chromosome. Diagnostic criteria for typical Rett syndrome require a period of regression, followed by recovery or stabilization, and fulfillment of all four main criteria (loss of purposeful hand skills, loss of spoken language, gait abnormalities, and stereotypic hand movements). Our objective was to estimate the prevalence of Rett syndrome in the general population, stratified by sex.
METHODS
We conducted a search of PubMed, Embase, Web of Science, Cochrane Library, LILACS, and LIVIVO to retrieve studies published in English between Jan. 1, 2000, and June 30, 2021. Pooled prevalence with a 95% confidence interval (CI) was estimated using a random-effects meta-analysis based on a generalized linear mixed model with a logit link.
RESULTS
Ten eligible studies were identified (all in females), with a combined sample size of 9.57 million women and 673 Rett syndrome cases. The pooled prevalence estimate (random effects) was 7.1 per 100,000 females (95% CI: 4.8, 10.5, heterogeneity p < 0.001). Despite greatly variable precision of estimation, all estimates were compatible with a prevalence range of approximately 5 to 10 cases per 100,000 females based on their respective 95% CIs.
CONCLUSION
These findings may facilitate planning of therapeutic trials in this indication in terms of target sample size and accrual times.
Topics: Humans; Female; Rett Syndrome; Methyl-CpG-Binding Protein 2; Prevalence; Mutation
PubMed: 36642718
DOI: 10.1186/s13643-023-02169-6 -
Journal of Personalized Medicine Aug 2021Autism spectrum disorder (ASD) is a common neurodevelopmental disorder affecting 2% of children in the United States. Biochemical abnormalities associated with ASD... (Review)
Review
Autism spectrum disorder (ASD) is a common neurodevelopmental disorder affecting 2% of children in the United States. Biochemical abnormalities associated with ASD include impaired methylation and sulphation capacities along with low glutathione (GSH) redox capacity. Potential treatments for these abnormalities include cobalamin (B12). This systematic review collates the studies using B12 as a treatment in ASD. A total of 17 studies were identified; 4 were double-blind, placebo-controlled studies (2 examined B12 injections alone and 2 used B12 in an oral multivitamin); 1 was a prospective controlled study; 6 were prospective, uncontrolled studies, and 6 were retrospective (case series and reports). Most studies (83%) used oral or injected methylcobalamin (mB12), while the remaining studies did not specify the type of B12 used. Studies using subcutaneous mB12 injections (including 2 placebo-controlled studies) used a 64.5-75 µg/kg/dose. One study reported anemia in 2 ASD children with injected cyanocobalamin that resolved with switching to injected mB12. Two studies reported improvements in markers of mitochondrial metabolism. A meta-analysis of methylation metabolites demonstrated decreased S-adenosylhomocysteine (SAH), and increased methionine, S-adenosylmethionine (SAM), SAM/SAH ratio, and homocysteine (with small effect sizes) with mB12. Meta-analysis of the transsulfuration and redox metabolism metabolites demonstrated significant improvements with mB12 in oxidized glutathione (GSSG), cysteine, total glutathione (GSH), and total GSH/GSSG redox ratio with medium to large effect sizes. Improvements in methylation capacity and GSH redox ratio were significantly associated with clinical improvements (with a mean moderate effect size of 0.59) in core and associated ASD symptoms, including expressive communication, personal and domestic daily living skills, and interpersonal, play-leisure, and coping social skills, suggesting these biomarkers may predict response to B12. Other clinical improvements observed with B12 included sleep, gastrointestinal symptoms, hyperactivity, tantrums, nonverbal intellectual quotient, vision, eye contact, echolalia, stereotypy, anemia, and nocturnal enuresis. Adverse events identified by meta-analysis included hyperactivity (11.9%), irritability (3.4%), trouble sleeping (7.6%), aggression (1.8%), and worsening behaviors (7.7%) but were generally few, mild, not serious, and not significantly different compared to placebo. In one study, 78% of parents desired to continue mB12 injections after the study conclusion. Preliminary clinical evidence suggests that B12, particularly subcutaneously injected mB12, improves metabolic abnormalities in ASD along with clinical symptoms. Further large multicenter placebo-controlled studies are needed to confirm these data. B12 is a promising treatment for ASD.
PubMed: 34442428
DOI: 10.3390/jpm11080784 -
Neurological Sciences : Official... Jul 2022To explore the pathogenetic hypothesis provided to explain the comorbidity of anxious and depressive symptomatology and AD and to assess the association between anxious... (Review)
Review
OBJECTIVES
To explore the pathogenetic hypothesis provided to explain the comorbidity of anxious and depressive symptomatology and AD and to assess the association between anxious and depressive symptoms and the AD-related cognitive impairment.
METHODS
In October 2020 and March 2021, PsycINFO, Embase, Ovid, and CINAHL were searched for peer-reviewed original articles investigating anxiety and/or depression in AD.
RESULTS
A total of 14,760 studies were identified and 34 papers on AD patients were included in the review. Suggested biological causes of depression and anxiety in AD include higher strychnine-sensitive glycine receptor (GlyRS) functioning and selective reduction of N-methyl-D-aspartate (NMDA) receptor NR2A density, cortical and limbic atrophy, lower resting cortical metabolism, lower CSF Aβ42 and higher t-tau and p-tau levels, and neuritic plaques. At the same time, dysthymia arises in the early stages of AD as an emotional reaction to the progressive cognitive decline and can cause it; anxiety can appear as an initial compensating behaviour; and depression might be related to AD awareness and loss of functional abilities. Affective symptoms and the expression of the depressive symptoms tend to reduce as AD progresses.
CONCLUSION
The neurodegeneration of areas and circuits dealing with emotions can elicit anxiety and depression in AD. In the early stages of the disease, anxiety and depression could arise as a psychological reaction to AD and due to coping difficulties. In late AD stages, the cognitive impairment reduces the emotional responses and their expression. Anxiety and depression are more intense in early-onset AD, due to the major impact of AD on the individual.
Topics: Alzheimer Disease; Anxiety; Anxiety Disorders; Biomarkers; Cognitive Dysfunction; Depression; Humans; Receptors, N-Methyl-D-Aspartate
PubMed: 35461471
DOI: 10.1007/s10072-022-06068-x -
Advances in Therapy Nov 2021In the absence of head-to-head trials, we performed an indirect treatment comparison of the β-adrenergic agonists vibegron and mirabegron in the treatment of overactive...
BACKGROUND
In the absence of head-to-head trials, we performed an indirect treatment comparison of the β-adrenergic agonists vibegron and mirabegron in the treatment of overactive bladder (OAB).
METHODS
PubMed, Embase, and Cochrane Library were searched for articles related to phase 3, double-blind, controlled trials of vibegron 75 mg and mirabegron 25/50 mg in patients with OAB. Efficacy outcomes included change from baseline at weeks 4, 12, and 52 in mean daily number of total urinary incontinence episodes and micturitions and mean volume voided/micturition. Effect size was computed as placebo-subtracted change from baseline (weeks 4, 12) or active control (tolterodine)-subtracted change from baseline (week 52) for each treatment group. Adverse events (AEs) are presented descriptively.
RESULTS
After removal of duplicates, 49 records were identified, and after screening 9 met inclusion criteria for analysis. Vibegron showed significantly greater reduction in mean daily number of total incontinence episodes than mirabegron 25 mg at week 4, mirabegron 50 mg (weeks 4, 52), and tolterodine (weeks 4, 12) (P < 0.05, each) and significantly greater improvement in volume voided versus mirabegron 25 mg (week 12), mirabegron 50 mg (weeks 12, 52), and tolterodine (week 4) (P < 0.05, each). Confidence intervals of point estimates overlapped zero for all other comparisons of vibegron and mirabegron (25 or 50 mg) or tolterodine, indicating no significant differences between treatments for these time/endpoints. Urinary tract infection, hypertension, and dry mouth were the most commonly occurring AEs for vibegron, mirabegron, and tolterodine, respectively, in the short-term trials; hypertension was the most commonly occurring AE with all three treatments in the long-term trials.
CONCLUSIONS
Vibegron was associated with significant improvement in total incontinence episodes versus mirabegron at 4 and 52 weeks and volume voided at 12 and 52 weeks. Improvement in micturitions was similar between vibegron and mirabegron or tolterodine. Incidence of AEs was generally comparable between vibegron and mirabegron.
Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Clinical Trials, Phase III as Topic; Double-Blind Method; Humans; Muscarinic Antagonists; Pyrimidinones; Pyrrolidines; Randomized Controlled Trials as Topic; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive
PubMed: 34537953
DOI: 10.1007/s12325-021-01902-8 -
Medicina (Kaunas, Lithuania) Jul 2022: The prevalence of cachexia has increased across all of the cancer types and accounts for up to 20% of cancer-related deaths. This paper is a systematic review of... (Review)
Review
: The prevalence of cachexia has increased across all of the cancer types and accounts for up to 20% of cancer-related deaths. This paper is a systematic review of nutritional interventions aiming to improve cachexia outcomes in cancer, focusing on weight gain. : A search in Medline and Elsevier databases for articles up until the 23 January 2022, was conducted. : Out of 5732 screened records, 26 publications were included in the final analysis. Four randomized clinical trials showed a significant body weight (BW) increase in patients treated with eicosapentaenoic acid (EPA), β-hydroxy-beta-methyl butyrate (β-HMB), arginine, and glutamine or marine phospholipids (MPL). An upward BW trend was observed in patients treated with L-carnitine, an Ethanwell/Ethanzyme (EE) regimen enriched with ω-3 fatty acids, micronutrients, probiotics, fish oil, a leucine-rich supplement, or total parental nutrition (TPN) with a high dose of a branched-chain amino acid (BCAA). : Although clinical trials relating to large numbers of nutritional supplements present promising data, many trials provided negative results. Further studies investigating the underlying mechanisms of action of these nutritional supplements in cancer cachexia are needed. Early screening for cancer cachexia risk and nutritional intervention in cancer patients before aggravating weight loss may stabilize their weight, preventing cachexia syndrome. According to the GRADE methodology, no positive recommendation for these nutritional supplements may be expressed.
Topics: Cachexia; Dietary Supplements; Eicosapentaenoic Acid; Humans; Micronutrients; Neoplasms
PubMed: 35888685
DOI: 10.3390/medicina58070966 -
Journal of Prosthodontic Research Jan 2022This study comprehensively reviewed the current status of the digital workflow of removable partial dentures (RPDs) and summarized information about the fabrication...
PURPOSE
This study comprehensively reviewed the current status of the digital workflow of removable partial dentures (RPDs) and summarized information about the fabrication methods and material properties of the dental framework, artificial teeth, and denture base.
STUDY SELECTION
We performed a systematic review of the literature published in online databases from January 1980 to April 2020 regarding RPD fabrication and materials used in the related digital technology. We selected eligible articles, retrieved information regarding digital RPDs, and conducted qualitative/quantitative analyses. In this paper, the computer-aided design/computer-aided manufacturing (CAD/CAM) framework, artificial teeth, and denture base materials are reported.
RESULTS
A variety of materials, such as cobalt-chromium alloy, titanium, zirconia, and polyether ether ketone, are used for dental CAD/CAM frameworks. The mechanical strength of the metal materials used for the CAD/CAM framework was superior to that of the cast framework. However, the fitness and surface roughness of the framework and clasp fabricated using a selective laser melting (SLM) method were not superior to those obtained via cast fabrication. Most material properties and the surface roughness of poly methyl methacrylate (PMMA) discs used for digital RPDs were superior to those of heat-cured PMMA.
CONCLUSION
The use of a CAD/CAM framework and PMMA disc for digital RPDs offers numerous advantages over conventional RPDs. However, technical challenges regarding the accuracy and durability of adhesion between the framework and denture base remain to be solved. In digital fabrication, human technical factors influence the quality of the framework.
Topics: Computer-Aided Design; Denture Bases; Denture, Partial, Removable; Humans; Tooth, Artificial; Workflow
PubMed: 33504722
DOI: 10.2186/jpr.JPR_D_20_00117 -
Lipids in Health and Disease Oct 2019Chronic illnesses like obesity, type 2 diabetes (T2D) and cardiovascular diseases, are worldwide major causes of morbidity and mortality. These pathological conditions...
BACKGROUND
Chronic illnesses like obesity, type 2 diabetes (T2D) and cardiovascular diseases, are worldwide major causes of morbidity and mortality. These pathological conditions involve interactions between environmental, genetic, and epigenetic factors. Recent advances in nutriepigenomics are contributing to clarify the role of some nutritional factors, including dietary fatty acids in gene expression regulation. This systematic review assesses currently available information concerning the role of the different fatty acids on epigenetic mechanisms that affect the development of chronic diseases or induce protective effects on metabolic alterations.
METHODS
A targeted search was conducted in the PubMed/Medline databases using the keywords "fatty acids and epigenetic". The data were analyzed according to the PRISMA-P guidelines.
RESULTS
Consumption fatty acids like n-3 PUFA: EPA and DHA, and MUFA: oleic and palmitoleic acid was associated with an improvement of metabolic alterations. On the other hand, fatty acids that have been associated with the presence or development of obesity, T2D, pro-inflammatory profile, atherosclerosis and IR were n-6 PUFA, saturated fatty acids (stearic and palmitic), and trans fatty acids (elaidic), have been also linked with epigenetic changes.
CONCLUSIONS
Fatty acids can regulate gene expression by modifying epigenetic mechanisms and consequently result in positive or negative impacts on metabolic outcomes.
Topics: Animals; Cardiovascular Diseases; Chronic Disease; DNA Methylation; Diabetes Mellitus, Type 2; Dietary Fats; Disease Models, Animal; Epigenesis, Genetic; Fatty Acids; Fatty Acids, Omega-3; Fatty Acids, Omega-6; Gene-Environment Interaction; Humans; Insulin Resistance; Lipid Metabolism; Obesity; Trans Fatty Acids
PubMed: 31615571
DOI: 10.1186/s12944-019-1120-6 -
The Cochrane Database of Systematic... Nov 2020Basal cell carcinoma (BCC) is the commonest cancer affecting white-skinned individuals, and worldwide incidence is increasing. Although rarely fatal, BCC is associated... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Basal cell carcinoma (BCC) is the commonest cancer affecting white-skinned individuals, and worldwide incidence is increasing. Although rarely fatal, BCC is associated with significant morbidity and costs. First-line treatment is usually surgical excision, but alternatives are available. New published studies and the development of non-surgical treatments meant an update of our Cochrane Review (first published in 2003, and previously updated in 2007) was timely.
OBJECTIVES
To assess the effects of interventions for BCC in immunocompetent adults.
SEARCH METHODS
We updated our searches of the following databases to November 2019: Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL, and LILACS.
SELECTION CRITERIA
Randomised controlled trials (RCTs) of interventions for BCC in immunocompetent adults with histologically-proven, primary BCC. Eligible comparators were placebo, active treatment, other treatments, or no treatment.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. Primary outcome measures were recurrence at three years and five years (measured clinically) (we included recurrence data outside of these time points if there was no measurement at three or five years) and participant- and observer-rated good/excellent cosmetic outcome. Secondary outcomes included pain during and after treatment, early treatment failure within six months, and adverse effects (AEs). We used GRADE to assess evidence certainty for each outcome.
MAIN RESULTS
We included 52 RCTs (26 new) involving 6690 participants (median 89) in this update. All studies recruited from secondary care outpatient clinics. More males than females were included. Study duration ranged from six weeks to 10 years (average 13 months). Most studies (48/52) included only low-risk BCC (superficial (sBCC) and nodular (nBCC) histological subtypes). The majority of studies were at low or unclear risk of bias for most domains. Twenty-two studies were industry-funded: commercial sponsors conducted most of the studies assessing imiquimod, and just under half of the photodynamic therapy (PDT) studies. Overall, surgical interventions have the lowest recurrence rates. For high-risk facial BCC (high-risk histological subtype or located in the facial 'H-zone' or both), there may be slightly fewer recurrences with Mohs micrographic surgery (MMS) compared to surgical excision (SE) at three years (1.9% versus 2.9%, respectively) (risk ratio (RR) 0.64, 95% confidence interval (CI) 0.16 to 2.64; 1 study, 331 participants; low-certainty evidence) and at five years (3.2% versus 5.2%, respectively) (RR 0.61, 95% CI 0.18 to 2.04; 1 study, 259 participants; low-certainty evidence). However, the 95% CI also includes the possibility of increased risk of recurrence and no difference between treatments. There may be little to no difference regarding improvement of cosmetic outcomes between MMS and SE, judged by participants and observers 18 months post-operatively (one study; low-certainty evidence); however, no raw data were available for this outcome. When comparing imiquimod and SE for nBCC or sBCC at low-risk sites, imiquimod probably results in more recurrences than SE at three years (16.4% versus 1.6%, respectively) (RR 10.30, 95% CI 3.22 to 32.94; 1 study, 401 participants; moderate-certainty evidence) and five years (17.5% versus 2.3%, respectively) (RR 7.73, 95% CI 2.81 to 21.3; 1 study, 383 participants; moderate-certainty evidence). There may be little to no difference in the number of participant-rated good/excellent cosmetic outcomes (RR 1.00, 95% CI 0.94 to 1.06; 1 study, 326 participants; low-certainty evidence). However, imiquimod may result in greater numbers of good/excellent cosmetic outcomes compared to SE when observer-rated (60.6% versus 35.6%, respectively) (RR 1.70, 95% CI 1.35 to 2.15; 1 study, 344 participants; low-certainty evidence). Both cosmetic outcomes were measured at three years. Based on one study of 347 participants with high- and low-risk primary BCC of the face, radiotherapy may result in more recurrences compared to SE under frozen section margin control at three years (5.2% versus 0%, respectively) (RR 19.11, 95% CI 1.12 to 325.78; low-certainty evidence) and at four years (6.4% versus 0.6%, respectively) (RR 11.06, 95% CI 1.44 to 84.77; low-certainty evidence). Radiotherapy probably results in a smaller number of good participant- (RR 0.76, 95% CI 0.63 to 0.91; 50.3% versus 66.1%, respectively) or observer-rated (RR 0.48, 95% CI 0.37 to 0.62; 28.9% versus 60.3%, respectively) good/excellent cosmetic outcomes compared to SE, when measured at four years, where dyspigmentation and telangiectasia can occur (both moderate-certainty evidence). Methyl-aminolevulinate (MAL)-PDT may result in more recurrences compared to SE at three years (36.4% versus 0%, respectively) (RR 26.47, 95% CI 1.63 to 429.92; 1 study; 68 participants with low-risk nBCC in the head and neck area; low-certainty evidence). There were no useable data for measurement at five years. MAL-PDT probably results in greater numbers of participant- (RR 1.18, 95% CI 1.09 to 1.27; 97.3% versus 82.5%) or observer-rated (RR 1.87, 95% CI 1.54 to 2.26; 87.1% versus 46.6%) good/excellent cosmetic outcomes at one year compared to SE (2 studies, 309 participants with low-risk nBCC and sBCC; moderate-certainty evidence). Based on moderate-certainty evidence (single low-risk sBCC), imiquimod probably results in fewer recurrences at three years compared to MAL-PDT (22.8% versus 51.6%, respectively) (RR 0.44, 95% CI 0.32 to 0.62; 277 participants) and five years (28.6% versus 68.6%, respectively) (RR 0.42, 95% CI 0.31 to 0.57; 228 participants). There is probably little to no difference in numbers of observer-rated good/excellent cosmetic outcomes at one year (RR 0.98, 95% CI 0.84 to 1.16; 370 participants). Participant-rated cosmetic outcomes were not measured for this comparison. AEs with surgical interventions include wound infections, graft necrosis and post-operative bleeding. Local AEs such as itching, weeping, pain and redness occur frequently with non-surgical interventions. Treatment-related AEs resulting in study modification or withdrawal occurred with imiquimod and MAL-PDT.
AUTHORS' CONCLUSIONS
Surgical interventions have the lowest recurrence rates, and there may be slightly fewer recurrences with MMS over SE for high-risk facial primary BCC (low-certainty evidence). Non-surgical treatments, when used for low-risk BCC, are less effective than surgical treatments, but recurrence rates are acceptable and cosmetic outcomes are probably superior. Of the non-surgical treatments, imiquimod has the best evidence to support its efficacy. Overall, evidence certainty was low to moderate. Priorities for future research include core outcome measures and studies with longer-term follow-up.
Topics: Adult; Aminolevulinic Acid; Antineoplastic Agents; Carcinoma, Basal Cell; Cryotherapy; Female; Humans; Imiquimod; Immunocompetence; Laser Therapy; Male; Mohs Surgery; Neoplasm Recurrence, Local; Photochemotherapy; Photosensitizing Agents; Radiotherapy; Randomized Controlled Trials as Topic; Skin Neoplasms; Treatment Outcome
PubMed: 33202063
DOI: 10.1002/14651858.CD003412.pub3 -
Canadian Journal of Psychiatry. Revue... Feb 2021Patients with major depressive disorder often have limited response to first-line and second-line medications; hence, novel pharmacological treatments are needed for...
The Canadian Network for Mood and Anxiety Treatments (CANMAT) Task Force Recommendations for the Use of Racemic Ketamine in Adults with Major Depressive Disorder: Recommandations Du Groupe De Travail Du Réseau Canadien Pour Les Traitements De L'humeur Et De L'anxiété (Canmat) Concernant...
OBJECTIVE
Patients with major depressive disorder often have limited response to first-line and second-line medications; hence, novel pharmacological treatments are needed for treatment-resistant depression (TRD). Ketamine, an -methyl-d-aspartate (NMDA) receptor antagonist, has demonstrated rapid antidepressant effects in patients with TRD. The Canadian Network for Mood and Anxiety Treatments (CANMAT) convened a task force to review the evidence for efficacy and safety of racemic ketamine and to provide recommendations for its use in clinical practice.
METHODS
A systematic review was conducted with computerized search of electronic databases up to January 31, 2020 using combinations of search terms, inspection of bibliographies, and review of other ketamine guidelines and consensus statements. The level of evidence and lines of treatment were assigned according to CANMAT criteria. Recommendations were given in question-answer format.
RESULTS
Intravenous (IV) racemic ketamine given as a single infusion has Level 1 evidence for efficacy in adults with TRD. The evidence for multiple infusions, given as an acute series or as ongoing maintenance treatment, is limited to Level 3. Adverse events associated with ketamine infusions include behavioral (e.g., dissociative symptoms) and physiological (e.g., hypertension) events. There is only Level 3 or 4 evidence for non-IV formulations of racemic ketamine. Consensus recommendations are given for clinical administration of IV ketamine including patient selection, facility and personnel issues, monitoring, and maintaining response.
CONCLUSIONS
Single-dose IV racemic ketamine is a third-line recommendation for adults with TRD. The need for repeated and maintenance ketamine infusions should be carefully assessed on a case-by-case basis with consideration of potential risks and benefits. Because of limited evidence for efficacy and risk for misuse and diversion, the use of oral and other formulations of racemic ketamine should be limited to specialists with ketamine-prescribing expertise and affiliations with tertiary or specialized centers.
Topics: Adult; Antidepressive Agents; Anxiety; Canada; Depressive Disorder, Major; Humans; Ketamine
PubMed: 33174760
DOI: 10.1177/0706743720970860