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Frontiers in Psychology 2021There is growing interest in glutamatergic agents as a treatment for depression, especially intranasal ketamine, which has become a hot topic in recent years. We aim to... (Review)
Review
BACKGROUND
There is growing interest in glutamatergic agents as a treatment for depression, especially intranasal ketamine, which has become a hot topic in recent years. We aim to assess the efficacy and safety of intranasal ketamine in the treatment of major depressive disorder (MDD), especially treatment-resistant depression (TRD).
METHODS
We searched Medline, EMBASE, and the Cochrane Library until April 1, 2020 to identify double-blind, randomized controlled trials with allocation concealment evaluating intranasal ketamine in major depressive episodes. Clinical remission, response, and depressive symptoms were extracted by two independent raters. The outcome measures were Montgomery-Asberg Depression Rating Scale (MADRS) score improved from baseline, clinical response and remission, dissociative symptoms, and common adverse events. The analyses employed a random-effects model.
RESULTS
Data were synthesized from five randomized controlled trials (RCTs) employing an intranasal esketamine and one RCT employing intranasal ketamine, representing 840 subjects in parallel arms, and 18 subjects in cross-over designs ( = 858 with MDD, = 792 with TRD). The weighted mean difference of MADRS score was observed to decrease by 6.16 (95% CI 4.44-7.88) in 2-4 h, 9.96 (95% CI 8.97-10.95) in 24 h, and 4.09 (95% CI 2.18-6.00) in 28 day. The pooled relative risk (RR) was 3.55 (95% CI 1.5-8.38, = 2.89, and < 0.001) for clinical remission and 3.22 (95% CI 1.85-5.61, = 4.14, and < 0.001) for clinical response at 24 h, while the pooled RR was 1.7 (95% CI 1.28-2.24, = 3.72, and < 0.001) for clinical remission and 1.48 (95% CI 1.17-1.86, = 3.28, and < 0.001) for clinical response at 28 day. Intranasal ketamine was associated with the occurrence of transient dissociative symptoms and common adverse events, but no persistent psychoses or affective switches.
CONCLUSION
Our meta-analysis suggests that repeated intranasal ketamine conducted a fast-onset antidepression effect in unipolar depression, while the mild and transient adverse effects were acceptable.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO, CRD42020196856.
PubMed: 34140915
DOI: 10.3389/fpsyg.2021.648691 -
Epilepsy & Behavior : E&B Aug 2021Psychogenic nonepileptic attacks (PNEA) are events of altered behavior that resemble epileptic seizures (ES) but are not caused by abnormal electrical cortical activity.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Psychogenic nonepileptic attacks (PNEA) are events of altered behavior that resemble epileptic seizures (ES) but are not caused by abnormal electrical cortical activity. Understanding which clinical signs and symptoms are associated with PNEA may allow better triaging for video-electroencephalogram monitoring (VEM) and for a more accurate prediction when such testing is unavailable.
METHODS
We performed a systematic review searching Medline, Embase, and Cochrane Central from inception to March 29, 2019. We included original research that reported at least one clinical sign or symptom, included distinct groups of adult ES and PNEA with no overlap, and used VEM for the reference standard. Two authors independently assessed quality of the studies using the Quality Assessment of Diagnostic Accuracy Studies tool. Pooled estimates of sensitivity and specificity of studies were evaluated using a bivariate random effects model.
RESULTS
We identified 4028 articles, of which 33 were included. There was a female sex predominance in the PNEA population (n = 22). From our meta-analysis, pooled sensitivities (0.27-0.72) and specificities (0.51-0.89) for PNEA were modest for individual signs. History of sexual abuse had the highest pooled specificity (89%), while the most sensitive feature was female sex (72%). Individual studies (n = 4) reported high levels of accuracy for ictal eye closure (sensitivity 64-73.7% and specificity 76.9-100%) and post-traumatic stress disorder (no reported sensitivity or specificity). Assuming the pre-test probability for PNEA in a tertiary care epilepsy center is 14%, even the strongest meta-analyzed features only exert modest diagnostic value, increasing post-test probabilities to a maximum of 33%.
CONCLUSIONS
This review reflects the limited certainty afforded by individual clinical features to distinguish between PNEA and ES. Specific demographic and comorbid features, even despite moderately high specificities, impart minimal impact on diagnostic decision making. This emphasizes the need for the development of multisource predictive tools to optimize diagnostic likelihood ratios.
Topics: Adult; Electroencephalography; Epilepsy; Female; Humans; Seizures; Sensitivity and Specificity
PubMed: 34029996
DOI: 10.1016/j.yebeh.2021.108030 -
The International Journal of... Jul 2021Ketamine appears to have a therapeutic role in certain mental disorders, most notably unipolar major depressive disorder. However, its efficacy in bipolar depression is...
BACKGROUND
Ketamine appears to have a therapeutic role in certain mental disorders, most notably unipolar major depressive disorder. However, its efficacy in bipolar depression is less clear. This study aimed to assess the efficacy and tolerability of ketamine for bipolar depression.
METHODS
We conducted a systematic review of experimental studies using ketamine for the treatment of bipolar depression. We searched PubMed, MEDLINE, Embase, PsycINFO, and the Cochrane Central Register for relevant studies published since each database's inception. We synthesized evidence regarding efficacy (improvement in depression rating scores) and tolerability (adverse events, dissociation, dropouts) across studies.
RESULTS
We identified 6 studies, with 135 participants (53% female; 44.7 years; standard deviation, 11.7 years). All studies used 0.5 mg/kg of add-on intravenous racemic ketamine, with the number of doses ranging from 1 to 6; all participants continued a mood-stabilizing agent. The overall proportion achieving a response (defined as those having a reduction in their baseline depression severity of at least 50%) was 61% for those receiving ketamine and 5% for those receiving a placebo. The overall response rates varied from 52% to 80% across studies. Ketamine was reasonably well tolerated; however, 2 participants (1 receiving ketamine and 1 receiving placebo) developed manic symptoms. Some participants developed significant dissociative symptoms at the 40-minute mark following ketamine infusion in 2 trials.
CONCLUSIONS
There is some preliminary evidence supporting use of intravenous racemic ketamine to treat adults with bipolar depression. There is a need for additional studies exploring longer-term outcomes and alterative formulations of ketamine.
Topics: Bipolar Disorder; Excitatory Amino Acid Antagonists; Humans; Ketamine
PubMed: 33929489
DOI: 10.1093/ijnp/pyab023 -
Vertex (Buenos Aires, Argentina) Apr 2020Recent theory has proposed that a dysfunction of the opioid system modulates mood, reward and pain; seems to be unstable in people with Borderline Personality Disorder....
[Treatment of borderline personality disorder with opioid antagonists: buprenorphine, nalmefene, naloxone and naltrexone in the treatment of dissociative symptoms, self-mutilation and suicidal behavior].
OBJECTIVE
Recent theory has proposed that a dysfunction of the opioid system modulates mood, reward and pain; seems to be unstable in people with Borderline Personality Disorder. Our purpose is to analyze the evidence on the efficacy of the use of buprenorphine, nalmefene, naloxone and naltrexone, in the treatment of dissociative symptoms, self-mutilation and suicidal behavior of these patients.
METHOD
We conducted a systematic search of MEDLINE and LILACS databases, to retrieve relevant articles. Included studies were experimental and observational designs of borderline personality samples in which dissociative symptoms, self mutilation or suicidal behavior was reported as an outcome and evaluated with some impact measures.
RESULTS
A total of eight studies were reviewed. These provided interesting expectations about posible treatment lines in Borderline Personality Disorder using opioid antagonists. The subgroup most benefited was the one who has analgesia and highest number of diagnostic criteria.
CONCLUSIONS
Studies of higher methodological quality are needed, in larger population samples and using control of confounding variables that allow us to estimate a value power calculation, and thus be able to support firm conclusions.
Topics: Borderline Personality Disorder; Buprenorphine; Dissociative Disorders; Humans; Naloxone; Naltrexone; Narcotic Antagonists; Observational Studies as Topic; Self Mutilation; Suicidal Ideation
PubMed: 33890928
DOI: 10.53680/vertex.v30i148.122 -
AIMS Neuroscience 2021The temporal-parietal junction (TPJ) is a key structure for the embodiment, term referred to as the sense of being localized within one's physical body and is a... (Review)
Review
Targeting temporal parietal junction for assessing and treating disembodiment phenomena: a systematic review of TMS effect on depersonalization and derealization disorders (DPD) and body illusions.
The temporal-parietal junction (TPJ) is a key structure for the embodiment, term referred to as the sense of being localized within one's physical body and is a fundamental aspect of the self. On the contrary, the sense of disembodiment, an alteration of one's sense of self or the sense of being localized out of one's physical body, is a prominent feature in specific dissociative disorders, namely depersonalization/derealization disorders (DPD). The aims of the study were to provide: 1) a qualitative synthesis of the effect of Transcranial Magnetic Stimulation (TMS), taking into account its use for therapeutic and experimental purposes; 2) a better understanding on whether the use of TMS could support the treatment of DPD and other clinical conditions in which depersonalization and derealization are displayed. To identify suitable publications, an online search of the PubMed, Cochrane Library, Web of science and Scopus databases was performed using relevant search terms. In addition, an in-depth search was performed by screening review articles and the references section of each included articles. Our search yielded a total of 108 records through multiple databases searching and one additional record was identified through other sources. After duplicates removal, title and abstract reading, we retained 16 records for the assessment of eligibility. According to our inclusion criteria, we retained 8 studies. The selected studies showed that TMS targeting the TPJ is a promising technique for treating disembodiment phenomena DPD and for inducing reversible disembodiment states in healthy subjects. These data represent the first step towards a greater understanding of possible treatments to be used in disembodiment disorders. The use of TMS over the TPJ appears to be promising for treating disembodiment phenomena.
PubMed: 33709023
DOI: 10.3934/Neuroscience.2021009 -
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 -
PloS One 2021Dissociative experiences occur across a range of mental health disorders. However, the term 'dissociation' has long been argued to lack conceptual clarity and may...
BACKGROUND
Dissociative experiences occur across a range of mental health disorders. However, the term 'dissociation' has long been argued to lack conceptual clarity and may describe several distinct phenomena. We therefore aimed to conceptualise and empirically establish a discrete subset of dissociative experiences and develop a corresponding assessment measure.
METHODS
First, a systematic review of existing measures was carried out to identify themes across dissociative experiences. A theme of 'Felt Sense of Anomaly' (FSA) emerged. Second, assessment items were generated based on this construct and a measure developed using exploratory (EFA) and confirmatory (CFA) factor analyses of 8861 responses to an online self-report survey. Finally, the resulting measure was validated via CFA with data from 1031 patients with psychosis.
RESULTS
'Felt sense of anomaly' (FSA) was identified as common to many dissociative experiences, affecting several domains (e.g. body) and taking different forms ('types'; e.g. unfamiliarity). Items for a novel measure were therefore systematically generated using a conceptual framework whereby each item represented a type-by-domain interaction (e.g. 'my body feels unfamiliar'). Factor analysis of online responses found that FSA-dissociation manifested in seven ways: anomalous experiences of the self, body, and emotion, and altered senses of familiarity, connection, agency, and reality (Χ2 (553) = 4989.435, p<0.001, CFI = 0.929, TLI = 0.924, RMSEA = 0.052, SRMR = 0.047). Additionally, a single-factor 'global FSA' scale was produced (Χ2 (9) = 312.350, p<0.001, CFI = 0.970, TLI = 0.950, RMSEA = 0.107, SRMR = 0.021). Model fit was adequate in the clinical (psychosis) group (Χ2 (553) = 1623.641, p<0.001, CFI = 0.927, TLI = 0.921, RMSEA = 0.043, SRMR = 0.043). The scale had good convergent validity with a widely used dissociation scale (DES-II) (non-clinical: r = 0.802), excellent internal reliability (non-clinical: Cronbach's alpha = 0.98; clinical: Cronbach's alpha = 0.97), and excellent test-retest reliability (non-clinical: ICC = 0.92). Further, in non-clinical respondents scoring highly on a PTSD measure, CFA confirmed adequate model fit (Χ2 (553) = 4758.673, CFI = 0.913, TLI = 0.906, RMSEA = 0.052, SRMR = 0.054).
CONCLUSIONS
The Černis Felt Sense of Anomaly (ČEFSA) scale is a novel measure of a subset of dissociative experiences that share a core feature of FSA. It is psychometrically robust in both non-clinical and psychosis groups.
Topics: Dissociative Disorders; Factor Analysis, Statistical; Humans; Psychometrics; Self Report
PubMed: 33626089
DOI: 10.1371/journal.pone.0247037 -
Journal of Affective Disorders Mar 2021Meta-analytic reviews concerning predictors of PTSD in children and adolescents have predominantly identified evidence relating to pre- and post-trauma risk factors;... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Meta-analytic reviews concerning predictors of PTSD in children and adolescents have predominantly identified evidence relating to pre- and post-trauma risk factors; however, there is little evidence regarding peritraumatic risk factors. This paper comprised a systematic review and meta-analysis of studies exploring psychological peritraumatic risk factors for PTSD in youth.
METHODS
Thirty-two studies were identified. Random effects meta-analyses were undertaken, with meta-regressions to explore the moderating role of study characteristics (gender, sex, timing of assessment after trauma, study quality, design and trauma type) on the size of effect of predictive factors.
RESULTS
Peritraumatic subjective threat (k = 28; r = 0.37, 95% CI=0.31-0.42) yielded a medium effect size estimate, while dissociation (k = 5; r = 0.17, 95% CI=0.03-0.29) and data-driven processing (feeling muddled or confused during the trauma) (k = 2; r = 0.29, 95% CI=0.14-0.43) yielded smaller population effect size estimates for the relationship with PTSD symptoms. Perceived life threat yielded a medium sized effect (k = 12; r = 0.37, 95% CI=0.32-0.41). The relationship between subjective threat and PTSD symptoms was moderated by the percentage of female participants. Estimates of heterogeneity were high in studies assessing perceived threat and fear (I = 95%), but moderate and low within studies assessing dissociation and data-driven processing (I = 57% and 0%, respectively).
LIMITATIONS
Peritraumatic psychological processes were commonly assessed using single-item measures. Studies primarily concerned single-incident traumas, limiting generalisability.
CONCLUSIONS
Peritraumatic experiences, particularly relating to subjective threat, are important correlates of subsequent PTSD, which implicates timely assessment of these experiences in youth to inform identification of at-risk groups and implementation and design of intervention.
Topics: Adolescent; Child; Dissociative Disorders; Emotions; Female; Humans; Risk Factors; Stress Disorders, Post-Traumatic
PubMed: 33601676
DOI: 10.1016/j.jad.2021.01.016 -
European Journal of Clinical... May 2021Ketamine has rapid-onset antidepressant effects in patients with treatment-resistant depression. Common side effects include dissociation (a sense of detachment from...
PURPOSE
Ketamine has rapid-onset antidepressant effects in patients with treatment-resistant depression. Common side effects include dissociation (a sense of detachment from reality) and increases in systolic and diastolic blood pressure. The objective of this structured review was to examine the effect of ketamine formulation and route of administration on its pharmacokinetics, safety and tolerability, to identify formulation characteristics and routes of administration that might minimise side effects.
METHODS
This was a structured review of published ketamine pharmacokinetics, safety and tolerability data for any ketamine formulation. The ratio of ketamine:norketamine was calculated from reported C values, as a measure of first pass metabolism. The effect of formulation and route of administration on safety was evaluated by measuring mean changes in systolic blood pressure and tolerability by changes in dissociation ratings. Data were correlated using Spearman's method.
RESULTS
A total of 41 treatment arms were identified from 21 publications, and included formulation development studies in healthy volunteers, and studies in clinical populations (patients undergoing anaesthesia, or being treated for pain or depression). Ketamine:norketamine ratios were strongly positively correlated with change in dissociation ratings (r = 0.89) and change in blood pressure (r = 0.96), and strongly negatively correlated with ketamine T (r = - 0.87; p < 0.00001 for all). Ketamine T strongly positively correlated with a change in dissociation ratings (r = - 0.96) and change in blood pressure (r = - 0.99; p < 0.00001 for all).
CONCLUSION
Ketamine formulations that maximize first pass metabolism and delay T will be better tolerated and safer than formulations which lack those characteristics.
Topics: Antidepressive Agents; Dissociative Disorders; Drug Administration Routes; Drug Delivery Systems; Humans; Hypertension; Ketamine; Metabolic Clearance Rate
PubMed: 33210159
DOI: 10.1007/s00228-020-03047-z -
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