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BMJ Open May 2024Although short-term benefits follow parenteral ketamine for treatment-resistant major depressive disorder (TR-MDD), there are challenges that prevent routine use of... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
Although short-term benefits follow parenteral ketamine for treatment-resistant major depressive disorder (TR-MDD), there are challenges that prevent routine use of ketamine by clinicians. These include acute dissociative effects of parenteral ketamine, high relapse rates following ketamine dosing and the uncertain role of psychotherapy. This randomised controlled trial (RCT) seeks to establish the feasibility of evaluating repeated oral doses of ketamine and behavioural activation therapy (BAT), compared with ketamine treatment alone, for TR-MDD. We also aim to compare relapse rates between treatment arms to determine the effect size of adding BAT to oral ketamine.
METHODS AND ANALYSIS
This is a prospectively registered, two-centre, single-blind RCT. We aim to recruit 60 participants with TR-MDD aged between 18 and 65 years. Participants will be randomised to 8 weeks of oral ketamine and BAT, or 8 weeks of oral ketamine alone. Feasibility will be assessed by tracking attendance for ketamine and BAT, acceptability of treatment measures and retention to the study follow-up protocol. The primary efficacy outcome measure is the Montgomery-Asberg Depression Rating Scale (MADRS) measured weekly during treatment and fortnightly during 12 weeks of follow-up. Other outcome measures will assess the tolerability of ketamine and BAT, cognition and activity (using actigraphy). Participants will be categorised as non-responders, responders, remitters and relapsed during follow-up. MADRS scores will be analysed using a linear mixed model. For a definitive follow-up RCT study to be recommended, the recruitment expectations will be met and efficacy outcomes consistent with a >20% reduction in relapse rates favouring the BAT and ketamine arm will be achieved.
ETHICS AND DISSEMINATION
Ethics approval was granted by the New Zealand Central Health and Disability Ethics Committee (reference: 2023 FULL18176). Study findings will be reported to participants, stakeholder groups, conferences and peer-reviewed publications.
TRIAL REGISTRATION NUMBER
UTN: U1111-1294-9310, ACTRN12623000817640p.
Topics: Humans; Ketamine; Depressive Disorder, Treatment-Resistant; Adult; Single-Blind Method; Middle Aged; Depressive Disorder, Major; Male; Female; Randomized Controlled Trials as Topic; Behavior Therapy; Young Adult; Adolescent; Treatment Outcome; Prospective Studies; Aged
PubMed: 38692731
DOI: 10.1136/bmjopen-2024-084844 -
Applying hypnotic associative - dissociative techniques in psychotherapy for psychosomatic symptoms.The American Journal of Clinical... Apr 2024Patients experiencing psychosomatic symptoms frequently have difficulty obtaining correct treatment. They are often reluctant to partially attribute their symptoms to...
Patients experiencing psychosomatic symptoms frequently have difficulty obtaining correct treatment. They are often reluctant to partially attribute their symptoms to psychological factors and, as a result, delay referrals to mental health professionals. Furthermore, the dropout rate from therapy is high and relapses are common. Hypnosis is a complex psycho-physiological phenomenon. Hence, hypnotic psychotherapy may play an important role in managing and treating psychosomatic symptoms and disorders that involve both the mind and body. In the current study, we propose a clinically oriented, four-phase, hypnotic approach, the hypnotic associative-dissociative approach (HADA), which may be useful in encouraging more patients with psychosomatic problems to engage in psychotherapy, thereby achieving effective long-term effects.
PubMed: 38687908
DOI: 10.1080/00029157.2024.2337625 -
The World Journal of Biological... Jun 2024Depersonalisation-derealization disorder (DPD) is a dissociative disorder that impairs cognitive function and occupational performance. Emerging evidence indicate the...
OBJECTIVES
Depersonalisation-derealization disorder (DPD) is a dissociative disorder that impairs cognitive function and occupational performance. Emerging evidence indicate the levels of tumour necrosis factor-α and interleukin associated with the dissociative symptoms. In this study, we aimed to explore the role of the immune system in the pathology of DPD.
METHODS
We screened the protein expression in serum samples of 30 DPD patients and 32 healthy controls. Using a mass spectrometry-based proteomic approach, we identified differential proteins that were verified in another group of 25 DPD patients and 30 healthy controls using immune assays. Finally, we performed a correlation analysis between the expression of differential proteins and clinical symptoms of patients with DPD.
RESULTS
We identified several dysregulated proteins in patients with DPD compared to HCs, including decreased levels of C-reactive protein (CRP), complement C1q subcomponent subunit B, apolipoprotein A-IV, and increased levels of alpha-1-antichymotrypsin (SERPINA3). Moreover, the expression of CRP was positively correlated with visuospatial memory and the ability to inhibit cognitive interference of DPD. The expression of SERPINA3 was positively correlated with the ability to inhibit cognitive interference and negatively correlated with the perceptual alterations of DPD.
CONCLUSIONS
The dysregulation of the immune system may be the underlying biological mechanism in DPD. And the expressions of CRP and SERPINA3 can be the potential predictors for the cognitive performance of DPD.
Topics: Humans; Male; Female; Adult; Depersonalization; C-Reactive Protein; Case-Control Studies; Proteomics; Middle Aged; Immune System; alpha 1-Antichymotrypsin
PubMed: 38679810
DOI: 10.1080/15622975.2024.2346096 -
Frontiers in Pharmacology 2024(, )- and ()-ketamine have made significant progress in the treatment of treatment-resistant depression (TRD) and have become a research focus in recent years. However,... (Review)
Review
(, )- and ()-ketamine have made significant progress in the treatment of treatment-resistant depression (TRD) and have become a research focus in recent years. However, they both have risks of psychomimetic effects, dissociative effects, and abuse liability, which limit their clinical use. Recent preclinical and clinical studies have shown that ()-ketamine has a more efficient and lasting antidepressant effect with fewer side effects compared to (, )- and ()-ketamine. However, a recent small-sample randomized controlled trial found that although ()-ketamine has a lower incidence of adverse reactions in adult TRD treatment, its antidepressant efficacy is not superior to the placebo group, indicating its antidepressant advantage still needs further verification and clarification. Moreover, an increasing body of research suggests that ()-ketamine might also have significant applications in the prevention and treatment of medical fields or diseases such as cognitive disorders, perioperative anesthesia, ischemic stroke, Parkinson's disease, multiple sclerosis, osteoporosis, substance use disorders, inflammatory diseases, COVID-19, and organophosphate poisoning. This article briefly reviews the mechanism of action and research on antidepressants related to ()-ketamine, fully revealing its application potential and development prospects, and providing some references and assistance for subsequent expanded research.
PubMed: 38666026
DOI: 10.3389/fphar.2024.1337749 -
Journal of Affective Disorders Jul 2024Participants who received ketamine at the NIMH were among the first to receive ketamine for depression in controlled clinical trials, providing a unique opportunity to...
BACKGROUND
Participants who received ketamine at the NIMH were among the first to receive ketamine for depression in controlled clinical trials, providing a unique opportunity to assess long-term outcomes. This analysis evaluated the relationship between participating in a ketamine clinical trial and subsequent ketamine/esketamine use after leaving the research setting.
METHODS
Participants seen within the NIMH Experimental Therapeutics and Pathophysiology Branch from 2002 to 2022 (n = 1000) were contacted for follow-up assessment. Participants reported whether they had used ketamine/esketamine, sought non-prescribed ketamine, attempted suicide, or been psychiatrically hospitalized since discharge. Information regarding their recent depressive symptoms, dissociative symptoms, and hallucinations was also collected.
RESULTS
Of the 203 participants in follow-up assessments (55 % female, average time since leaving NIMH = 9.04 years), 52 (25.6 %) had originally received ketamine at the NIMH, and the rest had participated in non-ketamine studies. Individuals who had received ketamine at the NIMH were more likely to have received ketamine/esketamine post-discharge than those who did not receive ketamine at the NIMH (OR = 0.25, p < .001). Participants who reported using ketamine/esketamine post-discharge reported more depressive symptoms than those who had not (p < .001). Receiving ketamine at the NIMH was not associated with differences in suicide attempts, psychiatric hospitalizations, dissociation, hallucinations, or attempt to obtain non-prescribed ketamine.
LIMITATIONS
Low follow-up study participation rate; varying time since discharge.
CONCLUSIONS
Participants who received ketamine in an NIMH clinical trial were more likely to receive ketamine/esketamine post-discharge, but none reported symptoms indicating abuse. Results underscore the critical need for long-term follow-up of individuals receiving these and other rapid-acting antidepressants.
CLINICAL TRIALS IDENTIFIER
NCT04877977.
Topics: Humans; Ketamine; Female; Male; Follow-Up Studies; Adult; Suicide, Attempted; Middle Aged; Mood Disorders; Hallucinations; Antidepressive Agents; Dissociative Disorders
PubMed: 38653350
DOI: 10.1016/j.jad.2024.04.062 -
Journal of Psychiatric Research Jun 2024Dissociative identity disorder (DID) is characterised by, among others, subjectively reported inter-identity amnesia, reflecting compromised information transfer between...
INTRODUCTION
Dissociative identity disorder (DID) is characterised by, among others, subjectively reported inter-identity amnesia, reflecting compromised information transfer between dissociative identity states. Studies have found conflicting results regarding memory transfer between dissociative identity states. Here, we investigated inter-identity amnesia in individuals with DID using self-relevant, subject specific stimuli, and behavioural and neural measures.
METHODS
Data of 46 matched participants were included; 14 individuals with DID in a trauma-avoidant state, 16 trauma-avoiding DID simulators, and 16 healthy controls. Reaction times and neural activation patterns related to three types of subject specific words were acquired and statistically analysed, namely non-self-relevant trauma-related words (NSt), self-relevant trauma-related words from a trauma-avoidant identity state (St), and trauma-related words from a trauma-related identity state (XSt).
RESULTS
We found no differences in reaction times between XSt and St words and faster reaction times for XSt over NSt. Reaction times of the diagnosed DID group were the longest. Increased brain activation to XSt words was found in the frontal and parietal regions, while decreased brain activity was found in the anterior cingulate cortex in the diagnosed DID group.
DISCUSSION
The current study reproduces and amalgamates previous behavioural reports as well as brain activation patterns. Our finding of increased cognitive control over self-relevant trauma-related knowledge processing has important clinical implications and calls for the redefinition of "inter-identity amnesia" to "inter-identity avoidance".
Topics: Humans; Male; Female; Adult; Amnesia; Dissociative Identity Disorder; Young Adult; Magnetic Resonance Imaging; Reaction Time
PubMed: 38653030
DOI: 10.1016/j.jpsychires.2024.04.026 -
Frontiers in Psychology 2024An integrative approach is presented to understand the transmission mechanisms of attachment trauma and the quality of the internal working model through manifestations...
An integrative approach is presented to understand the transmission mechanisms of attachment trauma and the quality of the internal working model through manifestations of bodily symptoms concerning physical and mental health. A case of dissociative symptomatology is described in a woman whose ancestors experienced individual and collective trauma related to the political regime. The approach allows for an analytical view beyond the standard complaints of anxiety, depression, post-traumatic symptoms, eating disorders, etc. A brief description of the transgenerational transmission of trauma is presented.
PubMed: 38650899
DOI: 10.3389/fpsyg.2024.1362561 -
International Journal of General... 2024In clinical work, it has been found that the prevalence of hyperuricemia (HUA) is significantly higher in younger patients with psychiatric disorders, but there are few...
PURPOSE
In clinical work, it has been found that the prevalence of hyperuricemia (HUA) is significantly higher in younger patients with psychiatric disorders, but there are few studies in this area. The present study aims to evaluate the prevalence of HUA and the relationship between the HUA and age in hospitalized patients with psychiatric disorders in the real world, and to provide a theoretical basis for clinical staff to pay attention to the metabolic indicators of younger patients and for future related studies.
METHODS
This is a cross-sectional evaluation of a cohort of 1761 patients with psychiatric disorders of hospitalized. The categories of disorders designed for study included: Depression, Bipolar disorder, Schizophrenia, Anxiety, Obsessive-Compulsive disorder, Acute and transient psychotic disorder, Dissociative(conversion) disorders, Conduct disorders and Tic disorders. In addition, based on age, the participants are stratified into three groups. The authors used Kruskal-Wallis tests, chi-square tests, and multiple linear logistic regression to verify the relationship between HUA and age among hospitalized patients with psychiatric disorders.
RESULTS
Overall, the estimated prevalence of HUA was 35.4%. The prevalence of HUA was significantly higher in individuals with 17 years and under compared to those with 45 years and above (P < 0.001). After adjusting for confounders, the prevalence of HUA remained higher at 17 years and under than at 45 years and above. Bipolar disorder can lead to an increased prevalence of HUA (P<0.05).
CONCLUSION
The prevalence of HUA was higher in hospitalized patients with psychiatric disorders, and the prevalence was inversely proportional to age.
PubMed: 38645402
DOI: 10.2147/IJGM.S454670 -
BMJ Mental Health Apr 2024People with functional/dissociative seizures (FDS) are at elevated suicidality risk.
BACKGROUND
People with functional/dissociative seizures (FDS) are at elevated suicidality risk.
OBJECTIVE
To identify risk factors for suicidality in FDS or epilepsy.
METHODS
Retrospective cohort study from the UK's largest tertiary mental healthcare provider, with linked national admission data from the Hospital Episode Statistics. Participants were 2383 people with a primary or secondary diagnosis of FDS or epilepsy attending between 01 January 2007 and 18 June 2021. Outcomes were a first report of suicidal ideation and a first hospital admission for suicide attempt (International Classification of Diseases, version 10: X60-X84). Demographic and clinical risk factors were assessed using multivariable bias-reduced binomial-response generalised linear models.
FINDINGS
In both groups, ethnic minorities had significantly reduced odds of hospitalisation following suicide attempt (OR: 0.45-0.49). Disorder-specific risk factors were gender, age and comorbidity profile. In FDS, both genders had similar suicidality risk; younger age was a risk factor for both outcomes (OR: 0.16-1.91). A diagnosis of depression or personality disorders was associated with higher odds of suicidal ideation (OR: 1.91-3.01). In epilepsy, females had higher odds of suicide attempt-related hospitalisation (OR: 1.64). Age had a quadratic association with both outcomes (OR: 0.88-1.06). A substance abuse disorder was associated with higher suicidal ideation (OR: 2.67). Developmental disorders lowered the risk (OR: 0.16-0.24).
CONCLUSIONS
This is the first study systematically reporting risk factors for suicidality in people with FDS. Results for the large epilepsy cohort complement previous studies and will be useful in future meta-analyses.
CLINICAL IMPLICATIONS
Risk factors identified will help identify higher-risk groups in clinical settings.
Topics: Humans; Male; Female; Suicide, Attempted; Suicidal Ideation; Cohort Studies; Psychogenic Nonepileptic Seizures; Retrospective Studies; Risk Factors; Epilepsy
PubMed: 38642918
DOI: 10.1136/bmjment-2023-300957 -
Issues in Mental Health Nursing Jun 2024Severe dissociative states involving the experience of being in parts, typically associated with diagnosis such as dissociative identity disorder and other specified...
Severe dissociative states involving the experience of being in parts, typically associated with diagnosis such as dissociative identity disorder and other specified dissociative disorders, continue to be a controversial and rarely studied area of research. However, because persons with severe dissociative states are at risk of being harmed instead of helped within psychiatric care, their experiences of living with such states warrant further examination, while innovative ways to include them in research remain necessary. Against that background, this study aimed to illuminate the meanings of living with severe dissociative states involving the experience of being in parts. This is a phenomenological hermeneutic study with data collected from three social media sources, one personal blog and two Instagram accounts, in February and March 2023. The results were illuminated in light of four themes; Striving to remain in the world, Balancing exposure and trust, Balancing belonging and loneliness and Owning oneselves. The interpretation of the themes suggests that living with severe dissociative states means being a human under inhuman conditions, striving for coherence and meaning in a world that is often unsupportive. This calls for a trauma-informed care to better support recovery for persons with severe dissociative states.
Topics: Humans; Dissociative Disorders; Adult; Female; Male; Hermeneutics; Social Media; Loneliness
PubMed: 38640493
DOI: 10.1080/01612840.2024.2330572