Efficacy of immersive PTSD treatments: A systematic review of virtual and augmented reality exposure therapy and a meta-analysis of virtual reality exposure therapy.

BACKGROUND: Virtual reality exposure therapy (VRET) and augmented reality exposure therapy (ARET) are digitally assisted psychotherapies that potentially enhance posttraumatic stress disorder (PTSD) treatment by increasing a patient's sense of presence during exposure therapy. This study aimed to systematically review current evidence regarding the efficacy of VRET and ARET as PTSD treatment. METHODS: A systematic electronic database search, a systematic quality assessment and two meta-analyses were conducted in accordance with PRISMA guidelines. RESULTS: Eleven studies on the efficacy of VRET for PTSD (n = 438) were found, but no studies on the efficacy of ARET. The majority of VRET studies were of a low quality and had heterogeneous results. Meta-analyses showed VRET outperformed waitlist control (standardized mean difference -0.64 (95% CI -1.05 to -0.22)) while no significant difference was found between VRET and active treatment conditions (standardized mean difference -0.25 (95% CI -0.77 to 0.27)). CONCLUSION: VRET was superior to waitlist control groups and as effective as other psychotherapies. However, the results showed considerable heterogeneity due to the low number of studies and variety of VRET methods. VRET may be an effective alternative to current treatments and shows promise for the treatment of PTSD patients that have not responded to previous treatment. Future research should focus on high quality RCTs, including information on side effects and adverse events, with sufficient numbers of participants. This study recognizes a research gap regarding the efficacy of ARET, while it may have potential for PTSD treatment.

[Hypnosis and hypnotic suggestions: applications in medical disorders]. / Hypnose en hypnotisch taalgebruik.

In recent years, there has been an increased interest in the use of hypnosis and hypnotic suggestions in the treatment of complaints such as pain and anxiety during medical procedures, irritable bowel syndrome, and headaches. Traditionally, hypnosis has been used in patients with psychiatric problems like posttraumatic stress, conversion, and dissociative disorders. Misconceptions about the nature of hypnosis, caused by the association with stage or show hypnosis, seems to prevent a wider integration in medicine. In this article, we try to shed more light on the nature of hypnosis and the evidence for its use in several medical disorders. Moreover, we discuss the use of hypnotic suggestions as a way to increase placebo effects.

[Psychedelics in the treatment of depression, anxiety, and obsessive-compulsive disorder]. / Psychedelica bij de behandeling van depressie, angst en obsessieve-compulsieve stoornis.

BACKGROUND: There is a need for new, effective treatments for patients with (treatment-resistant) depressive disorders, anxiety disorders and obsessive-compulsive disorder (ocd). At the same time, there is renewed interest in psychedelics for the treatment of psychiatric disorders.
AIM: To provide an overview of results from past and current research into psychedelics in the treatment of depression, anxiety disorders and ocd.
METHOD: Literature search in Medline and PubMed databases, supplemented with cross-references and results from recent studies.
RESULTS: There is a considerable evidence base for the atypical psychedelic ketamine. Ketamine has a rapid, beneficial effect on depression and suicidality; longer-term effects are less clear. Research into classical psychedelics for the treatment of depression and anxiety disorders is currently limited to a few small (open label) studies, although positive outcomes are reported even after a single administration, with potentially longer lasting benefits. Studies must be repeated in larger and more diverse groups of patients.
CONCLUSION: Further research into efficacy, therapeutic mechanisms and intervention models is very worthwhile; for the benefit of patients, but also to provide a deeper insight into the psychotherapeutic and neurobiological mechanisms that play a role in (the treatment of) common mental disorders.

[Psychedelics in the treatment of PTSD]. / Psychedelica bij de behandeling van PTSS.

BACKGROUND: Posttraumatic stress disorder (PTSD) is often a chronic condition, despite the availability of various evidence-based treatment options. Psychedelics offer new treatment opportunities.
AIM: An overview of the current evidence, therapeutic context, and possible mechanisms of action of different types of psychedelics in the treatment of PTSD.
METHOD: A scoping review of the available literature.
RESULTS: MDMA-assisted psychotherapy has shown to produce lasting reductions in PTSD symptoms in multiple RCTs. Based on a small number of studies, ketamine administration appears to lead to temporary symptom relief. Current studies are investigating whether the use of ketamine in combination with psychotherapy can lead to lasting reductions in PTSD symptoms. Classical psychedelics (such as psilocybin and LSD) induce psychoactive effects (on behavior or experience) that could contribute to the psychotherapeutic treatment of PTSD but have not yet been investigated in controlled studies. Reported positive effects extend beyond PTSD symptoms only.
CONCLUSION: Psychedelics may have potential to serve as a catalyst for the psychotherapeutic treatment of PTSD. Most evidence exists for MDMA-supported psychotherapy; relatively little research is available on ketamine and classical psychedelics. Future research needs to show whether the use of psychedelics can be integrated into available treatment options for PTSD.

[Psychedelics in the treatment of substance use disorders and psychosis]. / Psychedelica bij de behandeling van verslaving en psychose.

BACKGROUND: After psychedelics were banned in 1968, the flourishing research on the use of psychedelics in patients with a mental disorder stopped abruptly. Recently, we see a renaissance of this research.
AIM: To present an overview of what is known about the treatment of addiction and psychosis with psychedelics.
METHOD: Literature study based on Medline en PubMed publications till December 2019.
RESULTS: Studies on the effectiveness of psychedelics in the treatment of addiction and psychosis is still very limited in size and methodological quality. Nevertheless, most studies show positive effects of both classical and atypical psychedelics in a variety of addictions on motivation, craving, reduced consumption, and abstinence often following a single dose and with long-lasting benefits (3-24 months). Use of ketamine in patients with a psychosis stabilized on an antipsychotic might reduce negative symptoms.
CONCLUSION: Before psychedelics can be used in standard clinical practice for the treatment of patients with an addiction or a psychosis, larger and methodologically better studies are needed. The use of psychedelics also creates an opportunity to better understand the shared underlying pathology of many different mental disorders.

Randomized controlled trial of multi-modular motion-assisted memory desensitization and reconsolidation (3MDR) for male military veterans with treatment-resistant post-traumatic stress disorder.

OBJECTIVE: To explore the potential efficacy of multi-modular motion-assisted memory desensitization and reprocessing (3MDR) in British military veterans with treatment-resistant service-related PTSD. METHODS: Exploratory single-blind, randomized, parallel arm, cross-over controlled trial with nested process evaluation to assess fidelity, adherence and factors that influence outcome. RESULTS: A total of 42 participants (all male) were randomized with 83% retention at 12 weeks and 86% at 26 weeks. The difference in mean Clinician-Administered PTSD Scale for DSM-5 scores between the immediate and delayed 3MDR arms was -9.38 (95% CI -17.33 to -1.44, P = 0.021) at 12 weeks and -3.59 (-14.39 to 7.20, P = 0.513) at 26 weeks when both groups had received 3MDR. The likely effect size of 3MDR was found to be 0.65. Improvements were maintained at 26-week follow-up. 3MDR was found to be acceptable to most, but not all, participants. Several factors that may impact efficacy and acceptability of 3MDR were identified. CONCLUSION: 3MDR is a promising new intervention for treatment-resistant PTSD with emerging evidence of effect.

POST-TRAUMATIC STRESS DISORDER AND COMORBIDITY: THE ROLE OF MEDIATION AND RELATION BETWEEN PTSD AND SOMATIC COMPLAINTS IN MENTAL HEALTH MANAGEMENT.

Several studies have demonstrated the relationship between PTSD, somatic symptoms, and the role of co-morbid depression and anxiety. A study was conducted to test whether symptoms of PTSD influence somatic complaints indirectly through underlying symptoms of depression and anxiety. The participants included 69 veterans following a 6-month deployment and who showed criteria for probable PTSD diagnosis. Data were collected in 2014 and 2015. Measures included the PTSD checklist (PCL-5) and subscales of the Patient Health Questionnaire (PHQ), including anxiety disorder, depression, and somatic complaints. Depressive symptoms, as well as anxiety symptoms, had significantly mediated the relationship between PTSD and somatic complaints and positively related to somatic symptom severity. Otherwise, depression is a more robust factor than anxiety. Both severities of anxiety and severity of depression were more strongly associated with somatic complaints than PTSD itself. These new findings may have implications for the management of PTSD treatment in Military mental health services as well as in public health management since it recognizes the importance of Comorbid depression and anxiety when somatic complaints are present.

Longitudinal analyses of the DNA methylome in deployed military servicemen identify susceptibility loci for post-traumatic stress disorder.

In order to determine the impact of the epigenetic response to traumatic stress on post-traumatic stress disorder (PTSD), this study examined longitudinal changes of genome-wide blood DNA methylation profiles in relation to the development of PTSD symptoms in two prospective military cohorts (one discovery and one replication data set). In the first cohort consisting of male Dutch military servicemen (n=93), the emergence of PTSD symptoms over a deployment period to a combat zone was significantly associated with alterations in DNA methylation levels at 17 genomic positions and 12 genomic regions. Evidence for mediation of the relation between combat trauma and PTSD symptoms by longitudinal changes in DNA methylation was observed at several positions and regions. Bioinformatic analyses of the reported associations identified significant enrichment in several pathways relevant for symptoms of PTSD. Targeted analyses of the significant findings from the discovery sample in an independent prospective cohort of male US marines (n=98) replicated the observed relation between decreases in DNA methylation levels and PTSD symptoms at genomic regions in ZFP57, RNF39 and HIST1H2APS2. Together, our study pinpoints three novel genomic regions where longitudinal decreases in DNA methylation across the period of exposure to combat trauma marks susceptibility for PTSD.

Longitudinal changes in glucocorticoid receptor exon 1F methylation and psychopathology after military deployment.

Several cross-sectional studies have demonstrated the relevance of DNA methylation of the glucocorticoid receptor exon 1F region (GR-1F) for trauma-related psychopathology. We conducted a longitudinal study to examine GR-1F methylation changes over time in relation to trauma exposure and the development of post-deployment psychopathology. GR-1F methylation (52 loci) was quantified using pyrosequencing in whole blood of 92 military men 1 month before and 6 months after a 4-month deployment period to Afghanistan. GR-1F methylation overall (mean methylation and the number of methylated loci) and functional methylation (methylation at loci associated with GR exon 1F expression) measures were examined. We first investigated the effect of exposure to potentially traumatic events during deployment on these measures. Subsequently, changes in GR-1F methylation were related to changes in mental health problems (total Symptom Checklist-90 score) and posttraumatic stress disorder (PTSD) symptoms (Self-Report Inventory for PTSD). Trauma exposure during deployment was associated with an increase in all methylation measures, but development of mental health problems 6 months after deployment was only significantly associated with an increased functional methylation. Emergence of post-deployment PTSD symptoms was not related to increased functional methylation over time. Pre-deployment methylation levels did not predict post-deployment psychopathology. To our knowledge, this is the first study to prospectively demonstrate trauma-related increases in GR-1F methylation, and it shows that only increases at specific functionally relevant sites predispose for post-deployment psychopathology.

Prevalence of use of erectile dysfunction medication by Dutch military personnel between 2003 and 2012.

Use of ED medication can be seen as a marker for ED. ED is associated with increasing age, exposure to traumatic events and physical injuries in military veterans. The objective of this study was to assess the prevalence of use of ED medication in Dutch military personnel in the period 2003-2012 and to assess its association with age and psychotropic medication use. Data on dispensing of ED medication, age and co-medication with psychotropic medication of all Dutch military personnel between 2003 and 2012 were collected. The prevalence of ED medication use in each year was estimated, stratified for age and use of psychotropic medication. The number of ED medication users increased a hundredfold from 0.09 to 9.29 per 1000 per year between 2003 and 2012. ED medication was more often used by men over 40 than under 40 (prevalence in 2012: 2.4% vs 0.2%, OR (2003-2012, adjusted for calendar year) 15.6, 95% CI 13.5-17.9) and by men using psychotropic medication (prevalence in 2012: 3.8% vs 0.9%, OR (2003-2012, adjusted for calendar year) 3.13, 95% CI 2.66-3.67). This study shows a strong increase between 2003 and 2012 in a number of ED medication users in male Dutch military personnel. ED medication use increases with age and with psychotropic medication use.

[Efficacy of HRV-biofeedback as additional treatment of depression and PTSD]. / Effectiviteit van hartritmevariabiliteitbiofeedback als aanvulling bij behandeling van depressie en posttraumatische stressstoornis.

BACKGROUND: Heartrate variability biofeedback (HRVB) is a non-invasive treatment in which patients are assumed to self-regulate a physiological dysregulated vagal nerve. Although the therapeutic approach of HRVB is promising in various stress-related disorders, it has only been offered on a regular basis in a few mental health treatment settings. AIM: To analyse the efficacy of HRV biofeedback as an additional psychophysiological treatment for depression and PTSD. METHOD: Systematic review with search terms HRV, biofeedback, PTSD, depression, panic disorder and anxiety disorder. RESULTS: Our search of the literature yielded 789 studies. After critical appraisal using the GRADE method, we selected 6 randomised controlled trials (RCTs) and 4 relevant studies. The RCTs with control groups 'treatment as usual' and muscle relaxation training revealed significant clinical efficacy and better results than control conditions after 4 to 8 weeks training. CONCLUSION: Although this systematic review shows the popularity of HRV in literature, it does not indicate that HRVB really has been reviewed systematically. Significant outcomes of this limited number of randomised studies indicate there may be a clinical improvement when HRVB training is integrated into treatment of PTSD and depression, particularly when this integration procedure is combined with psychotherapy. More research needs to be done with larger groups and further efforts are needed to integrate HRVB into treatment of stress-related disorders in psychiatry. Future research also needs to focus on the psychophysiological mechanisms involved.

Blended care; development of a day treatment program for medically unexplained physical symptoms (MUPS) in the Dutch Armed Forces.

BACKGROUND: A subgroup of servicemen can be identified that seek a disproportionally amount of health care in comparison to diagnostic and therapeutic perspectives. This group can be identified on the basis of an absence of a structural medical explanation for their symptoms. The symptoms manifest predominantly as fatigue and pain, and are often chronic. Patients with medical unexplained medical symptoms (MUPS) often have multiple and complex problems that would be best treated by a multidisciplinary team of medical specialists and paramedics. The military is characterized by high loyalty towards peers and leadership, leading to neglect for personal care. OBJECTIVE: While consensus on the biological basis for these complaints is lacking, awareness on the need for effective treatments for this patient group is high. METHOD: Based on reviews, expert recommendations and clinical demand, a specialized treatment program for soldiers with MUPS has recently been developed and implemented in the system of health care in the Netherlands Armed Forces. We developed a functional rehabilitation program with blended care elements of cognitive behavioral therapy (CBT), physical therapy, case management, and psychoeducation, embedded in a day treatment setting. RESULTS: The program received high scores on participant as well as team satisfaction. The program is illustrated by two clinical vignettes. CONCLUSION: The blended care program for MUPS that focused on allostatic load awareness offered a more holistic and preventive approach that contributed to a reduction of unnecessary medical consumption, and increased job participation. We recommend that the development of guidelines for diagnoses and treatment of these complaints in military settings will improve the quality of patient care, reduce disability, facilitate reintegration, and encourage scientific research.

Prevalence of mental health symptoms in Dutch military personnel returning from deployment to Afghanistan: a 2-year longitudinal analysis.

OBJECTIVE: Recent studies in troops deployed to Iraq and Afghanistan have shown that combat exposure and exposure to deployment-related stressors increase the risk for the development of mental health symptoms. The aim of this study is to assess the prevalence of mental health symptoms in a cohort of Dutch military personnel prior to and at multiple time-points after deployment. METHODS: Military personnel (n=994) completed various questionnaires at 5 time-points; starting prior to deployment and following the same cohort at 1 and 6 months and 1 and 2 years after their return from Afghanistan. RESULTS: The prevalence of symptoms of fatigue, PTSD, hostility, depression and anxiety was found to significantly increase after deployment compared with pre-deployment rates. As opposed to depressive symptoms and fatigue, the prevalence of PTSD was found to decrease after the 6-month assessment. The prevalence of sleeping problems and hostility remained relatively stable. CONCLUSIONS: The prevalence of mental health symptoms in military personnel increases after deployment, however, symptoms progression over time appears to be specific for various mental health symptoms. Comprehensive screening and monitoring for a wide range of mental health symptoms at multiple time-points after deployment is essential for early detection and to provide opportunities for intervention. DECLARATION OF INTEREST: This project was funded by the Dutch Ministry of Defence.

Perceived threat predicts the neural sequelae of combat stress.

Exposure to severe stressors increases the risk for psychiatric disorders in vulnerable individuals, but can lead to positive outcomes for others. However, it remains unknown how severe stress affects neural functioning in humans and what factors mediate individual differences in the neural sequelae of stress. The amygdala is a key brain region involved in threat detection and fear regulation, and previous animal studies have suggested that stress sensitizes amygdala responsivity and reduces its regulation by the prefrontal cortex. In this study, we used a prospective design to investigate the consequences of severe stress in soldiers before and after deployment to a combat zone. We found that combat stress increased amygdala and insula reactivity to biologically salient stimuli across the group of combat-exposed individuals. In contrast, its influence on amygdala coupling with the insula and dorsal anterior cingulate cortex was dependent on perceived threat, rather than actual exposure, suggesting that threat appraisal affects interoceptive awareness and amygdala regulation. Our results demonstrate that combat stress has sustained consequences on neural responsivity, and suggest a key role for the appraisal of threat on an amygdala-centered neural network in the aftermath of severe stress.