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Psychological Medicine Jul 2022The dissociative subtype of post-traumatic stress disorder (PTSD-DS) was introduced in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders... (Meta-Analysis)
Meta-Analysis Review
The dissociative subtype of post-traumatic stress disorder (PTSD-DS) was introduced in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), and is characterised by symptoms of either depersonalisation or derealisation, in addition to a diagnosis of post-traumatic stress disorder (PTSD). This systematic review and meta-analysis sought to estimate the point prevalence of current PTSD-DS, and the extent to which method of assessment, demographic and trauma variables moderate this estimate, across different methods of prevalence estimation. Studies included were identified by searching MEDLINE (EBSCO), PsycInfo, CINAHL, Academic Search Complete and PTSDpubs, yielding 49 studies that met the inclusion criteria ( = 8214 participants). A random-effects meta-analysis estimated the prevalence of PTSD-DS as 38.1% (95% CI 31.5-45.0%) across all samples, 45.5% (95% CI 37.7-53.4%) across all diagnosis-based and clinical cut-off samples, 22.8% (95% CI 14.8-32.0%) across all latent class analysis (LCA) and latent profile analysis (LPA) samples and 48.1% (95% CI 35.0-61.3%) across samples which strictly used the DSM-5 PTSD criteria; all as a proportion of those already with a diagnosis of PTSD. All results were characterised by high levels of heterogeneity, limiting generalisability. Moderator analyses mostly failed to identify sources of heterogeneity. PTSD-DS was more prevalent in children compared to adults, and in diagnosis-based and clinical cut-off samples compared to LCA and LPA samples. Risk of bias was not significantly related to prevalence estimates. The implications of these results are discussed further.
Topics: Adult; Child; Diagnostic and Statistical Manual of Mental Disorders; Dissociative Disorders; Humans; Prevalence; Stress Disorders, Post-Traumatic
PubMed: 35734787
DOI: 10.1017/S0033291722001647 -
Journal of Trauma & Dissociation : the... 2023Depersonalization-Derealization disorder (DDD) is a psychiatric condition characterized by persistent feelings of detachment from one's self and of unreality about the... (Review)
Review
Depersonalization-Derealization disorder (DDD) is a psychiatric condition characterized by persistent feelings of detachment from one's self and of unreality about the outside world. This review aims to examine the prevalence of DDD amongst different populations. A systematic review protocol was developed before literature searching. Original articles were drawn from three electronic databases and included only studies where prevalence rates of DDD were assessed by standardized diagnostic tools. A narrative synthesis was conducted. Twenty-three papers were identified and categorized into three groups of participants: general population, mixed in/outpatient samples, and patients with specific disorders. The prevalence rates ranged from 0% to 1.9% amongst the general population, 5-20% in outpatients and 17.5-41.9% in inpatients. In studies of patients with specific disorders, prevalence rates varied: 1.8-5.9% (substance abuse), 3.3-20.2% (anxiety), 3.7-20.4% (other dissociative disorders), 16.3% (schizophrenia), 17% (borderline personality disorder), ~50% (depression). The highest rates were found in people who experienced interpersonal abuse (25-53.8%). The prevalence rate of DDD is around 1% in the general population, consistent with previous findings. DDD is more prevalent amongst adolescents and young adults as well as in patients with mental disorders. There is also a possible relationship between interpersonal abuse and DDD, which merits further research.
Topics: Adolescent; Young Adult; Humans; Depersonalization; Prevalence; Dissociative Disorders; Substance-Related Disorders
PubMed: 35699456
DOI: 10.1080/15299732.2022.2079796 -
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 -
Frontiers in Psychiatry 2022Post-traumatic stress disorder (PTSD) is a serious stress-related disorder caused by traumatic experiences. However, identifying a key therapy that can be used for PTSD...
BACKGROUND
Post-traumatic stress disorder (PTSD) is a serious stress-related disorder caused by traumatic experiences. However, identifying a key therapy that can be used for PTSD treatment remains difficult. Ketamine, a well-known dissociative anesthetic, is considered safe to be used in anesthesia, pain management, and antidepressant actions since 1970. At present, it is still controversial whether PTSD can be treated with ketamine. The authors performed a meta-analysis to determine whether the use of perioperative ketamine lowers the incidence of PTSD.
METHODS
Cochrane Central Register of Controlled Trials, Embase, PubMed, and Web of Science were searched to examine the use of ketamine for the treatment of PTSD among soldiers with combating experience. Studies were included if they were randomized placebo-controlled, case-control, and cohort studies. The primary outcome was the incidence of PTSD in the later stage of the wounded or burn soldiers. The secondary outcome was the influence of ketamine on PTSD-scale scores for early and chronic PTSD, respectively.
RESULTS
Our search yielded a total of three studies ( = 503 patients) comparing the use of ketamine ( = 349) to control ( = 154). The available evidence showed no significant difference in the incidence of PTSD between combatant soldiers on the battlefield with or without ketamine treatment (risk ratio = 0.81, 95% CI, 0.63-1.04; = 0.10). In 65 patients from three trials, ketamine was not only ineffective in treating early PTSD but also lead to exacerbation of the disease (risk ratio = 2.45, 95% CI, 1.33-3.58; < 0.001). However, in 91 patients from the other three trials, ketamine is effective in treating chronic PTSD (risk ratio = -3.66, 95% CI, -7.05 to -0.27; = 0.03).
CONCLUSION
Ketamine was not effective on lower the PTSD incidence for soldiers on the battlefield, nor on the PTSD-scale scores in early PTSD patients. However, it may improve the PTSD-scale scores for chronic conditions.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021255516, PROSPERO, identifier: CRD42021255516.
PubMed: 35356723
DOI: 10.3389/fpsyt.2022.813103 -
Cells Feb 2022Ketamine is a rapid-acting antidepressant with proven efficacy as an add-on agent in unipolar and bipolar treatment-resistant depression. Although many studies have been... (Review)
Review
BACKGROUND AND OBJECTIVES
Ketamine is a rapid-acting antidepressant with proven efficacy as an add-on agent in unipolar and bipolar treatment-resistant depression. Although many studies have been published, there is still not enough data on the effect of ketamine in combination with other medications. Particularly interesting is the combination of ketamine and lamotrigine, and its potential role in bipolar depression. The aim of this review was to identify animal and human studies in which ketamine and lamotrigine were used together in order to find out if there is scientific ground for combining ketamine and lamotrigine in the treatment of mood disorders. Directions for future studies are presented.
MATERIALS AND METHODS
PubMed and Web of Science were searched. Preferred Reporting Items for Systematic Reviews and Meta-Analyses PRISMA 2020 methodology was applied.
RESULTS
Seventeen studies were included for review. Animal studies using models of depression suggested a synergistic effect of ketamine and lamotrigine in combination. Studies on healthy humans showed a reduction in ketamine-induced dissociative symptoms with lamotrigine pretreatment. In a study on patients with depression, ketamine and lamotrigine did not have a stronger antidepressant effect than ketamine alone, but in this study only one ketamine infusion was administered. One case series described the antidepressant and anti-suicidal effect of the combination in two bipolar patients. Available clinical studies on patients with mood disorders did not support the hypothesis that lamotrigine reduces ketamine-induced dissociative symptoms.
CONCLUSIONS
The results of the analyzed studies were not sufficient to answer any of the stated questions; however, they allowed us to delineate future research directions. The identified animal studies suggested a possible synergistic antidepressant effect of ketamine and lamotrigine. The available clinical studies were not conclusive. No controlled studies on large groups of bipolar patients with multiple ketamine infusions combined with lamotrigine treatment have been published so far. There is some evidence for the reduction of ketamine's side effects by lamotrigine, and there are reports suggesting that lamotrigine can reduce ketamine craving. More studies with follow-up are needed in order to investigate the ketamine-lamotrigine combination in bipolar patients.
Topics: Animals; Antidepressive Agents; Depression; Humans; Ketamine; Lamotrigine; Psychopharmacology
PubMed: 35203296
DOI: 10.3390/cells11040645 -
The Australian and New Zealand Journal... Oct 2022Borderline Personality Disorder (BPD) is frequently complicated by the presence of dissociative symptoms. Pathological dissociation is linked with earlier and more... (Review)
Review
BACKGROUND
Borderline Personality Disorder (BPD) is frequently complicated by the presence of dissociative symptoms. Pathological dissociation is linked with earlier and more severe trauma exposure, emotional dysregulation and worse treatment outcomes in Posttraumatic Stress Disorder and Dissociative Disorders, with implications for BPD.
OBJECTIVE
A systematic scoping review was conducted to assess the extent of current literature regarding the impact of dissociation on BPD and to identify knowledge gaps.
METHODS
Four electronic databases (MEDLINE, APA PsycINFO, EMBASE, CINAHL Plus) were searched, and English peer-reviewed studies with adults with BPD were included, following Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) extension for scoping reviews (PRISMA-ScR) 2018 guidelines.
RESULTS
Most of the 70 included studies were observational (98%) with first authors from Germany (59%). Overall, dissociation was associated with increased BPD symptom severity, self-harm and reduced psychotherapy treatment response; findings regarding suicide risk were mixed. Dissociation was associated with working memory and cognitive deficits, decreased pain perception, altered body ownership, no substance abuse or the abuse of sedative substances, increased fantasy proneness, personality fragmentation, fearful attachment, dream anxiety, perceived stress and altered stress responses, increased cumulative body mass index, decreased water consumption, several neurological correlates and changes in gene expression.
CONCLUSION
BPD with significant dissociative symptoms may constitute a more severe and at-risk subgroup of BPD patients. However, there are significant research gaps and methodological issues in the area, including the possibility of unrecognized Dissociative Disorders in BPD study populations confounding results. Further studies are needed to better understand the impact of dissociation on BPD course and treatment, and to clarify the most appropriate assessment tools for clinical practice. In addition, interventional studies are needed to develop dissociation-specific BPD treatments to determine whether targeting dissociation in BPD can improve treatment outcomes.
Topics: Adult; Borderline Personality Disorder; Dissociative Disorders; Humans; Hypnotics and Sedatives; Psychotherapy; Self-Injurious Behavior
PubMed: 35152771
DOI: 10.1177/00048674221077029 -
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 -
Psychological Medicine Feb 2022Adverse life events precede the onset of functional neurological disorder (FND, also known as conversion disorder) more commonly than other neuropsychiatric conditions,... (Meta-Analysis)
Meta-Analysis Review
Adverse life events precede the onset of functional neurological disorder (FND, also known as conversion disorder) more commonly than other neuropsychiatric conditions, but their aetiological role is unclear. We conducted a systematic review and quantitative analysis of the type, timing and number of life events preceding the onset of FND in adults, and a meta-analysis of the proportions of types of events in controlled studies. Fifty-one studies of different designs, covering 4247 patients, were eligible for inclusion. There was no clear majority of any type of preceding event. Family problems were the most common category of events, followed by relationship problems. Females were more likely to experience preceding family/relationship problems than males, who reported more work problems. Family problems were the commonest type of preceding event in studies in developing countries, whereas family and health problems were equally common in developed countries. Abuse was associated with early symptom onset, while patients with later onset were more likely to report family problems. The median number of events was one, and the events occurred closer to onset than in controls. Meta-analysis found that family, relationship and work events were all relatively more common in patients than pathological controls, as were events where symptoms might provide a solution to the stressor. In conclusion, although a range of events precede the onset of FND, they do not appear to do so uniformly. This may support a different aetiological role for stressors than in other disorders, although the support is indirect and the quality generally low.
Topics: Adult; Conversion Disorder; Dissociative Disorders; Female; Humans; Male
PubMed: 34819179
DOI: 10.1017/S0033291721004669 -
Neuroscience and Biobehavioral Reviews Jan 2022Dissociative disorders (DD) and conversion disorders (CD) are frequent in general and psychiatric populations. Some evidence suggest that the hypothalamic-pituitary axis... (Review)
Review
Dissociative disorders (DD) and conversion disorders (CD) are frequent in general and psychiatric populations. Some evidence suggest that the hypothalamic-pituitary axis (HPA) and autonomic nervous system (ANS) are dysregulated in both disorders. We carried out a systematic review of the literature to summarize the existing knowledge on the stress response, via HPA and/or ANS, in patients with DD, CD, or dissociative symptoms. We systematically searched Medline and Web of Science using the Medical Subject Headings related to stress axis, CD, DD, and dissociative symptoms following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Results suggest that in participants without psychiatric history, high cortisol secretion is related to high dissociation scores. Conversely the stress system might be blunted in patients with post-traumatic stress disorder who develop dissociative symptoms. Stress response changes seem to be associated with the emergence and persistence of dissociative and conversion disorders. Hence, monitoring the stress response and examining closely the history of stress exposure in DD and CD should be encouraged in future larger studies.
Topics: Autonomic Nervous System; Conversion Disorder; Dissociative Disorders; Humans; Hypothalamo-Hypophyseal System; Pituitary-Adrenal System; Stress Disorders, Post-Traumatic
PubMed: 34740754
DOI: 10.1016/j.neubiorev.2021.10.049 -
Expert Opinion on Drug Safety Jan 2022Ketamine is a dissociative anesthetic that is currently considered for several new indications. (Comparative Study)
Comparative Study
BACKGROUNDS
Ketamine is a dissociative anesthetic that is currently considered for several new indications.
AIM
To deduce the safety of long-term ketamine treatment using the harm of heavy recreational (non-medical) ketamine use as a proxy for maximal possible harm of ketamine treatment.
METHODS
Systematic literature review according to PRISMA guidelines to identify controlled studies on ketamine-related harm in heavy recreational ketamine users. Results were compared with serious adverse events (SAEs) in patients treated with ketamine according to three systematic reviews considering dosing regimen and cumulative dose.
RESULTS
The systematic search yielded 25 studies. Heavy recreational ketamine use can escalate to ketamine dependency and was often dose-dependently associated with other SAEs, including cognitive and mental disorders, and gastrointestinal and urinary tract symptoms, which disappeared upon marked reduction of ketamine use. Heavy ketamine users have a much higher cumulative exposure to ketamine than ketamine treated patients (>90 times), which may explain why SAEs in the clinical context are mostly mild and reversible and why ketamine dependence was not reported in these patients.
CONCLUSION
Treatment of patients with ketamine is not associated with ketamine dependency or SAEs. However, caution is needed since data on long-term clinical ketamine use with a long-term follow-up is lacking.
Topics: Anesthetics, Dissociative; Dose-Response Relationship, Drug; Humans; Ketamine; Substance-Related Disorders; Time Factors
PubMed: 34176409
DOI: 10.1080/14740338.2021.1949454