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JAMA Psychiatry Dec 2022Whether ketamine is as effective as electroconvulsive therapy (ECT) among patients with major depressive episode remains unknown. (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Whether ketamine is as effective as electroconvulsive therapy (ECT) among patients with major depressive episode remains unknown.
OBJECTIVE
To systematically review and meta-analyze data about clinical efficacy and safety for ketamine and ECT in patients with major depressive episode.
DATA SOURCES
PubMed, MEDLINE, Cochrane Library, and Embase were systematically searched using Medical Subject Headings (MeSH) terms and text keywords from database inception through April 19, 2022, with no language limits. Two authors also manually and independently searched all relevant studies in US and European clinical trial registries and Google Scholar.
STUDY SELECTION
Included were studies that involved (1) a diagnosis of depression using standardized diagnostic criteria, (2) intervention/comparator groups consisting of ECT and ketamine, and (3) depressive symptoms as an efficacy outcome using standardized measures.
DATA EXTRACTION AND SYNTHESIS
Data extraction was completed independently by 2 extractors and cross-checked for errors. Hedges g standardized mean differences (SMDs) were used for improvement in depressive symptoms. SMDs with corresponding 95% CIs were estimated using fixed- or random-effects models. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline was followed.
MAIN OUTCOMES AND MEASURES
Efficacy outcomes included depression severity, cognition, and memory performance. Safety outcomes included serious adverse events (eg, suicide attempts and deaths) and other adverse events.
RESULTS
Six clinical trials comprising 340 patients (n = 162 for ECT and n = 178 for ketamine) were included in the review. Six of 6 studies enrolled patients who were eligible to receive ECT, 6 studies were conducted in inpatient settings, and 5 studies were randomized clinical trials. The overall pooled SMD for depression symptoms for ECT when compared with ketamine was -0.69 (95% CI, -0.89 to -0.48; Cochran Q, P = .15; I2 = 39%), suggesting an efficacy advantage for ECT compared with ketamine for depression severity. Significant differences were not observed between groups for studies that assessed cognition/memory or serious adverse events. Both ketamine and ECT had unique adverse effect profiles (ie, ketamine: lower risks for headache and muscle pain; ECT: lower risks for blurred vision, vertigo, diplopia/nystagmus, and transient dissociative/depersonalization symptoms). Limitations included low to moderate methodological quality and underpowered study designs.
CONCLUSIONS AND RELEVANCE
Findings from this systematic review and meta-analysis suggest that ECT may be superior to ketamine for improving depression severity in the acute phase, but treatment options should be individualized and patient-centered.
Topics: Humans; Electroconvulsive Therapy; Ketamine; Depressive Disorder, Major; Suicide, Attempted; Randomized Controlled Trials as Topic
PubMed: 36260324
DOI: 10.1001/jamapsychiatry.2022.3352 -
British Journal of Clinical Pharmacology Oct 2022There is a growing interest in the psychiatric properties of the dissociative anaesthetic ketamine, as single doses have been shown to have fast-acting mood-enhancing... (Review)
Review
There is a growing interest in the psychiatric properties of the dissociative anaesthetic ketamine, as single doses have been shown to have fast-acting mood-enhancing and anxiolytic effects, which persist for up to a week after the main psychoactive symptoms have diminished. Therefore, ketamine poses potential beneficial effects in patients with refractory anxiety disorders, where other conventional anxiolytics have been ineffective. Ketamine is a noncompetitive antagonist of the N-methyl-d-aspartate (NMDA) glutamate receptor, which underlies its induction of pain relief and anaesthesia. However, the role of NMDA receptors in anxiety reduction is still relatively unknown. To fill this paucity in the literature, this systematic review assesses the evidence that ketamine significantly reduces refractory anxiety and discusses to what extent this may be mediated by NMDA receptor antagonism and other receptors. We highlight the temporary nature of the anxiolytic effects and discuss the high discrepancy among the study designs regarding many fundamental factors such as administration routes, complementary treatments and other treatments.
Topics: Anti-Anxiety Agents; Anxiety; Anxiety Disorders; Humans; Ketamine; Receptors, N-Methyl-D-Aspartate
PubMed: 35510346
DOI: 10.1111/bcp.15374 -
Neurotoxicology Sep 2019Cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) are the most represented phytocannabinoids in Cannabis sativa plants. However, CBD may present with a different... (Review)
Review
Cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) are the most represented phytocannabinoids in Cannabis sativa plants. However, CBD may present with a different activity compared with the psychotomimetic THC. Most typically, CBD is reported to be used in some medical conditions, including chronic pain. Conversely, the main aim of this systematic review is to assess and summarise the available body of evidence relating to both efficacy and safety of CBD as a treatment for psychiatric disorders, alone and/or in combination with other treatments. Eligible studies included randomized controlled trials (RCT) assessing the effect of CBD in a range of psychopathological conditions, such as substance use; psychosis, anxiety, mood disturbances, and other psychiatric (e.g., cognitive impairment; sleep; personality; eating; obsessive-compulsive; post-traumatic stress/PTSD; dissociative; and somatic) disorders. For data gathering purposes, the PRISMA guidelines were followed. The initial search strategy identified some n = 1301 papers; n = 190 studies were included after the abstract's screening and n = 27 articles met the inclusion criteria. There is currently limited evidence regarding the safety and efficacy of CBD for the treatment of psychiatric disorders. However, available trials reported potential therapeutic effects for specific psychopathological conditions, such as substance use disorders, chronic psychosis, and anxiety. Further large-scale RCTs are required to better evaluate the efficacy of CBD in both acute and chronic illnesses, special categories, as well as to exclude any possible abuse liability.
Topics: Anxiety; Cannabidiol; Humans; Mental Disorders; Randomized Controlled Trials as Topic
PubMed: 31412258
DOI: 10.1016/j.neuro.2019.08.002 -
The American Journal of Drug and... Mar 2023Although the misuse of ketamine constitutes a worldwide issue, ketamine is quickly taking its place as a therapeutic option in the management of several mental...
Although the misuse of ketamine constitutes a worldwide issue, ketamine is quickly taking its place as a therapeutic option in the management of several mental disorders. However, the use of ketamine and/or its analogues, as well as combinations with other drugs, can be fatal. To outline the cases of overdoses and deaths related to the use of ketamine and/or its analogues, as reported in the scientific literature. To investigate if ketamine is safe in a therapeutic context, particularly in its use as an antidepressant. Electronic searches were performed on three medical databases. Articles describing cases of overdose and/or death associated with ketamine and/or its analogues were included. After the removal of duplicates, title analysis and full-text analysis, 34 articles were included in this review. Eighteen articles described fatal cases and sixteen described overdoses. Poly-substance use was mentioned in 53% of the selected articles. Most cases were males and the ages varied from two to 65 years old. A total of 312 overdose cases and 138 deaths were reported. In both death reports and overdose cases, ketamine was preponderant: 89.1% and 79%, respectively. No cases of overdose or death related to the use of ketamine as an antidepressant in a therapeutic setting were found; most of the deaths occurred in the circumstances of polydrug use and overdoses left no sequelae. There is legitimate concern about the risks involving the use of ketamine and its analogues, especially in recreational settings. On the other hand, ketamine as medicine is considered safe and it is listed as an essential medicine by the World Health Organization. Although clinicians must remain vigilant, this should not deter appropriate prescription.
Topics: Male; Humans; Child, Preschool; Child; Adolescent; Young Adult; Adult; Middle Aged; Aged; Female; Ketamine; Drug Overdose; Substance-Related Disorders; Analgesics, Opioid
PubMed: 36410032
DOI: 10.1080/00952990.2022.2132506 -
Journal of Affective Disorders Jun 2023ECT is considered the fastest and most effective treatment for TRD. Ketamine seems to be an attractive alternative due to its rapid-onset antidepressant effects and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
ECT is considered the fastest and most effective treatment for TRD. Ketamine seems to be an attractive alternative due to its rapid-onset antidepressant effects and impact on suicidal thoughts. This study aimed to compare efficacy and tolerability of ECT and ketamine for different depression outcomes (PROSPERO/CRD42022349220).
METHODS
We searched MEDLINE, Web of Science, Embase, PsycINFO, Google Scholar, Cochrane Library and trial registries, which were the ClinicalTrials.gov and the World Health Organization's International Clinical Trials Registry Platform, without restrictions on publication date.
SELECTION CRITERIA
randomized controlled trials or cohorts comparing ketamine versus ECT in patients with TRD.
RESULTS
Eight studies met the inclusion criteria (of 2875 retrieved). Random-effects models comparing ketamine and ECT regarding the following outcomes were conducted: a) reduction of depressive symptoms severity through scales, g = -0.12, p = 0.68; b) response to therapy, RR = 0.89, p = 0.51; c) reported side-effects: dissociative symptoms, RR = 5.41, p = 0.06; nausea, RR = 0.73, p = 0.47; muscle pain, RR = 0.25, p = 0.02; and headache, RR = 0.39, p = 0.08. Influential & subgroup analyses were performed.
LIMITATIONS
Methodological issues with high risk of bias in some of the source material, reduced number of eligible studies with high in-between heterogeneity and small sample sizes.
CONCLUSION
Our study showed no evidence to support the superiority of ketamine over ECT for severity of depressive symptoms and response to therapy. Regarding side effects, there was a statistically significant decreased risk of muscle pain in patients treated with ketamine compared to ECT.
Topics: Humans; Ketamine; Depressive Disorder, Major; Electroconvulsive Therapy; Myalgia; Antidepressive Agents
PubMed: 36907464
DOI: 10.1016/j.jad.2023.02.152 -
The Lancet. Psychiatry Jan 2018This is the first systematic review of the safety of ketamine in the treatment of depression after single and repeated doses. We searched MEDLINE, PubMed, PsycINFO, and...
This is the first systematic review of the safety of ketamine in the treatment of depression after single and repeated doses. We searched MEDLINE, PubMed, PsycINFO, and Cochrane Databases and identified 288 articles, 60 of which met the inclusion criteria. After acute dosing, psychiatric, psychotomimetic, cardiovascular, neurological, and other side-effects were more frequently reported after ketamine treatment than after placebo in patients with depresssion. Our findings suggest a selective reporting bias with limited assessment of long-term use and safety and after repeated dosing, despite these being reported in other patient groups exposed to ketamine (eg, those with chronic pain) and in recreational users. We recommend large-scale clinical trials that include multiple doses of ketamine and long-term follow up to assess the safety of long-term regular use.
Topics: Anesthetics, Dissociative; Antidepressive Agents; Depressive Disorder, Treatment-Resistant; Dose-Response Relationship, Drug; Drug Administration Schedule; Humans; Ketamine; Long Term Adverse Effects; Treatment Outcome
PubMed: 28757132
DOI: 10.1016/S2215-0366(17)30272-9 -
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 -
Psychology of Addictive Behaviors :... May 2021Multilevel consequences related to gambling disorder (GD) are glaring enough to make gambling a worldwide public health issue. Dissociation has been pointed out in... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Multilevel consequences related to gambling disorder (GD) are glaring enough to make gambling a worldwide public health issue. Dissociation has been pointed out in clinical, empirical, and theoretical contributions as a key variable accounting for the development and maintenance of GD. However, we still lack a systematization of available empirical data that may facilitate further accurate conclusions.
METHOD
A systematic review and meta-analysis were performed with the goal to answer to open questions. We followed the PRISMA guidelines conducting a systematic search of 5 scientific databases (PsycINFO, PsycARTICLES, MEDLINE, Scopus, Web of Science, and PubMed) including grey literature.
RESULTS
A total of 843 records were screened, and 20 studies were included in the qualitative and quantitative analyses. A systematic review of selected studies outlines the high heterogeneity in the operationalization of the dissociation construct as well as the absence of studies examining the role played by the specific dimensions of the pathological dissociative feature in GD. A significant, positive, and moderate effect size (r = .37) was found linking GD to dissociation. Moreover, this effect appears to not be moderated by the quality of studies, age, and gender of participants nor measures used to evaluate dissociation.
CONCLUSIONS
Despite empirical evidences supporting the theoretical assertions toward the relationship between GD and dissociation, few studies have reached an articulated understanding of this topic, mostly failing to identify specific dissociative features involved in GD. Furthermore, the existence of the current gap in the literature are discussed to delineate future lines of research. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
Topics: Dissociative Disorders; Gambling; Humans
PubMed: 33646797
DOI: 10.1037/adb0000693 -
Journal of Psychiatric Research Nov 2021Ketamine is a dissociative anesthetic used worldwide for anesthesia, pain management, treatment resistant depression (TRD) and suicidality. Predictors of antidepressant... (Review)
Review
Ketamine is a dissociative anesthetic used worldwide for anesthesia, pain management, treatment resistant depression (TRD) and suicidality. Predictors of antidepressant response and adverse effects to ketamine remain poorly understood due to contradictory results. The objective of the systematic review herein is to identify and evaluate the extant literature assessing pharmacogenomic predictors of ketamine clinical benefits and adverse effects. Electronic databases were searched from inception to July 2021 to identify relevant articles. Twelve articles involving 1,219 participants with TRD, 75 who underwent elective surgeries and received ketamine as an anesthetic, 49 with pain, and 68 healthy participants met the inclusion criteria and enrolled to this review. While identified articles reported mixed results, three predictors emerged: 1) Val66Met (rs6265) brain derived neurotrophic factor (BDNF; Met allele) was associated with reduced antidepressant and anti-suicidal effects, 2) CYP2B6*6 (e.g., CYB2B6 metabolizer) was associated with more severe dissociative effects and 3) NET allelic (rs28386840) variant were associated with greater cardiovascular complications (e.g., moderate to severe treatment emergent hypertension). Several important limitations were identified, most notably the small sample sizes and heterogeneity of study design and results. Taken together, preliminary evidence suggests the potential for pharmacogenomic testing to inform clinical practices; however, further research is needed to better determine genetic variants of greatest importance and the clinical validity of pharmacogenomics to help guide ketamine treatment planning.
PubMed: 34844049
DOI: 10.1016/j.jpsychires.2021.11.036 -
Therapeutic Advances in... 2023More than 2% of the general population experience suicidal ideas each year and a large number of them will attempt suicide. Evidence-based therapeutic options to manage... (Review)
Review
BACKGROUND
More than 2% of the general population experience suicidal ideas each year and a large number of them will attempt suicide. Evidence-based therapeutic options to manage suicidal crisis are currently limited.
OBJECTIVES
The aim of this study was to overview the findings on the use of ketamine and esketamine for the treatment of suicidal ideas and acts.
DESIGN
Systematic review.
DATA SOURCES AND METHODS
PubMed, article references, and Clinicaltrials.gov up to June 30, 2022. Meta-analyses published within the last 2 years were also reviewed.
RESULTS
We identified 12 randomized controlled trials with reduction of suicidal ideation as the primary objective and 14 trials as secondary objectives. Intravenous racemic ketamine was superior to control drugs (placebo or midazolam) within the first 72 h, in spite of large placebo effects. Adverse events were minor and transient. In contrast, intranasal esketamine did not differ from placebo in large-scale studies. Limitations, clinical considerations, and opportunities for future research include the following points: large placebo effects when studying suicidal ideation reduction; small concerns about blinding quality due to dissociative effects; no studies on the risk/prevention of suicidal acts and mortality; lack of studies beyond affective disorders; no studies in adolescents and older people; lack of knowledge of long-term side effects, notably liability for abuse; no robust predictive markers; limited understanding of the mechanisms of ketamine on suicidal ideas; need for improved assessment of suicidal ideation in clinical trials; need for studies in outpatient settings, emergency room, and liaison consultation; need for research on ketamine administration; limited knowledge on the positive and negative effects of concomitant treatments.
CONCLUSION
Overall, there is compelling evidence for a favorable short-term benefit-risk balance with intravenous racemic ketamine but not intranasal esketamine. The place of ketamine will have to be defined within a multimodal care strategy for suicidal patients. Caution remains necessary for clinical use, and pharmacovigilance will be essential.
PubMed: 36776623
DOI: 10.1177/20451253231151327