Sertraline versus venlafaxine combined with psychotherapy in trauma-affected refugees - a follow-up study on a pragmatic randomised trial.

BACKGROUND: Research on long-term pharmacotherapy for trauma-affected refugees is scarce. The purpose of this follow-up study of a randomised trial was to investigate the effects of sertraline compared to venlafaxine in combination with psychotherapy, 6 and 18 months after end of trial. METHOD: The primary outcome was PTSD symptoms, measured by the Harvard Trauma Questionnaire (HTQ). The secondary outcomes included: Hopkins Symptom Checklist-25 (HSCL-25), somatisation items of the Symptoms Checklist-90 (SCL), pain on a visual analogue scale, well-being on the WHO-5, Sheehan Disability Scale, Hamilton Depression and Anxiety scales and Global Assessment of Functioning. Moreover, the shorter version of the Recent Life Events (IRLE) was adopted to obtain information regarding the patients' treatment and life events between the follow-up periods. RESULTS: Out of 195 patients eligible for intention-to-treat analyses during trial, 116 participated in the 6-month follow-up and 97 participated in the 18-month follow-up. The results of our intention-to-treat analyses revealed no significant long-term differences between the groups on the primary outcome assessing PTSD symptoms (HTQ). For the secondary outcomes significant differences were found at the 18-month follow-up in favour of venlafaxine assessing symptoms of anxiety, depression and somatisation (HSCL-25 and SCL), although only in intention-to-treat and not per-protocol analyses. CONCLUSIONS: No conclusions could be drawn due to conflicting results between our intention-to-treat and per-protocol analyses.

Potential advantages of combining randomized controlled trials with qualitative research in mood and anxiety disorders - A systematic review.

INTRODUCTION: Most randomized controlled trials (RCTs) of mood and anxiety disorders employ solely quantitative methods. Supplementing quantitative data with qualitative methods, a so-called mixed-method approach, would seem useful, however this area has not been rigorously reviewed. We undertook a systematic review of RCTs of mood and anxiety disorders that employed concurrent quantitative data collection and qualitative methods exploring the participants' perspective, with the aim of 1. determining the number of such studies, 2. describing study characteristics, and 3. identifying potential advantages of a mixed-method approach. METHODS: Following PRISMA guidelines, a systematic literature search for RCTs of mood and anxiety disorders, concurrently applying quantitative and qualitative methods, was conducted using EMBASE, PsycINFO and Pubmed, from their inception to February 2021. Categories of potential advantages of this mixed method approach were developed. RESULTS: A total of 45 RCTs were included. The qualitative components typically included 10-40 participants, mostly consisting of interviews after the intervention. The majority of papers did not state a specific rationale for using a mixed method approach. Four categories of advantages emerged: 1. determine acceptability/feasibility, 2. investigate efficacy, 3. inform implementation in clinical practice and 4. generate new hypotheses based on the combination of quantitative and qualitative data. LIMITATIONS: Lack of cross-referencing and consistent terminology challenged identification of relevant publications. CONCLUSION: There are a number of potential advantages of applying mixed method approaches in RCTs within psychiatric research. Intentional consideration of such advantages early in trial design may increase the likelihood of gaining added value.

Evaluating the procedural validity of the multilingual computer assisted self interview (MultiCASI) in a refugee population.

Multimedia-based administration of questionnaires, presenting items both in writing and spoken word, offers numerous potential benefits in transcultural psychiatry, such as improved comprehension of each question, ease of administration, prevention of missing or arbitrary responses, and obviating subsequent data entry. The concept has become known as "Computer-Assisted Self Interviewing" (CASI), and while preliminary results are promising, previous studies have not directly compared CASI to paper-and-pen administration in a large and representative sample of refugees. The aim of this study was to evaluate the procedural validity of multilingual CASI in comparison to paper-based-administration. The Hopkins Symptom Checklist-25 anxiety and depression subscales were administered in both modalities with a total of N = 281 participants from sites in Australia, New Zealand, and Denmark. We evaluated potential deviations in both the raw item and scale scores in each modality, while psychometric properties of each subscale were compared for an Arabic-speaking subsample (n = 125). Results showed no significant differences between raw item- or scale score across the two modalities, nor between the level of construct validity. In conclusion, this study supports a wider adaptation of multilingual CASI in the context of transcultural psychiatry, both for purposes of screening and treatment evaluation.

Stress management versus cognitive restructuring in trauma-affected refugees - A follow-up study on a pragmatic randomised trial.

BACKGROUND: There is a lack of research and consensus with respect to long-term effective treatments for trauma-affected refugees. The purpose of this follow-up study of a randomised clinical trial was to investigate the effectiveness of Stress Management (SM) versus Cognitive Restructuring (CR) in treating trauma-affected refugees, six and 18 months post-treatment, respectively. METHODS: From a total of 126 refugees with PTSD, the intention-to-treat sample in the original trial, 74 patients were present at the six-month follow-up (SM; n = 37, CR; n = 37) and 34 patients at the 18-month follow-up (SM; n = 14, CR; n = 20). During the trial, the patients had been offered a total of 16 psychotherapy sessions and 10 sessions with a medical doctor. RESULTS: Mixed regression analyses at six and 18-month follow-up showed a non-significant small reduction in PTSD symptoms at both follow-up points with no significant between-group differences between the two psychotherapeutic interventions. Statistically significant between-group treatment effects were, however, observed with the patients receiving SM having significantly reduced symptoms of somatisation measured by the Symptom Checklist (ß = 0.40), depression (ß = 0.29) and anxiety (ß = 0.37) (measured by the Hamilton Depression and Anxiety ratings) at 18 months post-treatment compared to the CR group. LIMITATIONS: Limitations to the present study include the dropout rate at follow-up(s). CONCLUSIONS: The findings suggest that the consolidation of coping strategies including relaxation, attention-diversion and behavioural activation in SM appears to be more beneficial than CR in reducing long-term somatisation, depression and anxiety symptoms for this population.

Investigating the link between subjective sleep quality, symptoms of PTSD, and level of functioning in a sample of trauma-affected refugees.

STUDY OBJECTIVES: To examine whether baseline sleep quality is associated with baseline symptoms of posttraumatic stress disorder (PTSD) and level of functioning and whether baseline sleep quality and improvement of sleep quality are specific predictors of change in PTSD symptoms and level of functioning. METHODS: Data were derived from a four-armed randomized controlled superiority trial (N = 219 trauma-affected refugees). All four groups received treatment as usual consisting of a 10-12 months bio-psycho-social treatment program with an additional differential treatment component added to each arm. We performed bivariate correlation analyses, multiple linear regression analyses, and mediation analyses to examine associations between baseline sleep quality, change in sleep quality, and treatment response for PTSD symptoms and level of functioning. RESULTS: Baseline sleep quality correlated with symptoms of PTSD (r = 0.33) and level of functioning (r = 0.15). Baseline sleep quality, improvement of sleep quality, and improvement of general well-being were predictors of treatment response for symptoms of PTSD and level of functioning when controlling for age, gender, and baseline symptoms of PTSD and depression. CONCLUSIONS: We found that good sleep quality at baseline and improvement of sleep quality were predictors of PTSD treatment response. However, treatment response was more closely associated with improvement in general well-being. The results indicate that the effect of improved sleep quality was partly mediated by a more general mental state improvement. Further research is needed to differentiate if a selected subgroup of patients may profit from sleep-enhancing treatment. CLINICALTRIALS.GOV REGISTRATION: NCT02761161.

The Accuracy of Traumatic Memories in Posttraumatic Stress Disorder: A Review.

ABSTRACT: This review sought to investigate the accuracy of traumatic memories in persons with a diagnosis of posttraumatic stress disorder (PTSD). PubMed, PsycINFO, and Embase were searched for articles, and 11 studies were included. Three different methods of studying memory accuracy were identified in the included articles: coherence, change in recollection of trauma over time, and remembering details of trauma. Three studies found a deficiency in the accuracy of traumatic memory. Despite some inconsistencies, most of the studies concluded that the memory of trauma is as accurate in people with as in those without PTSD. The only recurring difference identified across studies was in recollection of trauma over time. The findings are of importance both clinically and for the legal system.

Predictors of treatment outcomes for trauma-affected refugees - results from two randomised trials.

INTRODUCTION: Treatment effects in trials with trauma-affected refugees vary considerably between studies, but the variability in outcome between individual patients is often overlooked. Consequently, we know little about why some patients benefit more from treatment than others. The aim of the study was therefore to identify predictors of treatment outcome for refugees with Posttraumatic Stress Disorder (PTSD). METHODS: Data was derived from two randomised trials including 321 refugees, who had all participated in a 6-7 months bio-psycho-social treatment programme. Outcome measures were the Harvard Trauma Questionnaire (PTSD, self-rating), Hopkins Symptom Checklist-25 (depression and anxiety, self-rating) and Hamilton Depression and Anxiety rating scales (observer-ratings). Using hierarchical regressions models, associations were analysed between pre- to post treatment score changes (dependent variable) and a range of variables including sociodemographics, pre-migration trauma, post-migratory stressors, baseline symptom scores and level of functioning. RESULTS: A high baseline score (=more symptoms) and a high level of functioning were found to be associated with improvement on all ratings. Additionally, the following variables were associated with symptom improvement on at least one outcome measure: short time in host country, full time occupation, young age and status as family reunified (in contrast to refugee status). Being Muslim was inversely correlated with improvement. LIMITATIONS: Translated self-ratings were used, which could impact reliability. CONCLUSION: These results call for screening and early interventions for arriving refugees. For clinical populations, level of functioning should be included in assessments of refugees, to possibly begin stratifying samples to different interventions based on their likelihood of responding.

Trauma-affected refugees treated with basic body awareness therapy or mixed physical activity as augmentation to treatment as usual-A pragmatic randomised controlled trial.

BACKGROUND: The prevalence of post-traumatic stress disorder (PTSD) is estimated to be as high as 30% among refugees. The coexistence of prevalent chronic pain is believed to maintain symptoms of PTSD and add complexity to the condition. Despite this, little evidence exists on how to treat PTSD and comorbid conditions best in trauma-affected refugees. AIM: The aim of the present study was to investigate if adding either BBAT or mixed physical activity to the treatment as usual (TAU) for trauma-affected refugees with PTSD would increase the treatment effect compared to TAU alone. METHOD: Randomised controlled trial, 3-armed parallel group superiority study, conducted at Competence Centre for Transcultural Psychiatry, Denmark. Participants were adult trauma-affected refugees with PTSD. Allocation ratio was 1:1:1, stratified for PTSD severity and gender. An open-label design was applied due to the nature of the intervention. Participants were randomised to receive either individual basic body awareness therapy (group B) or individual mixed physical activity (group M) one hour/week for 20 weeks plus TAU, or TAU only (group C). The primary outcome was PTSD severity measured by Harvard Trauma Questionnaire (HTQ). Trial registration: ClinicalTrials.gov, NCT01955538. RESULTS: Of the 338 patients included (C/B/M = 110/114/114), 318 patients were eligible for intention-to-treat analysis (C/B/M = 104/105/109). On the primary outcome, intention-to-treat as well as per-protocol analyses showed small but significant improvement on scores from pre- to post-treatment in all three groups but with no significant difference in improvement between groups. CONCLUSIONS: The findings do not provide evidence that either BBAT or mixed physical activity as add-on treatment bring significantly larger improvement on symptoms of PTSD compared to TAU alone for adult, trauma-affected refugees. There is a need for studies on potential subpopulations of trauma-affected refugees who could benefit from physical activity as a part of their treatment.

Prevention of trauma-related mental health problems among refugees: A mixed-methods evaluation of the MindSpring group programme in Denmark.

MindSpring (MS) is a community group intervention for refugees with the purpose of strengthening the participants' ability to cope with psychosocial problems, thereby preventing that premigration trauma and postmigratory stressors evolve into psychiatric disorders. The aim of the present project was to study the acceptability and impacts of MS. The study was a mixed-methods observational study including 92 Arabic speaking refugees. Participants completed a baseline demographic questionnaire, an outcome questionnaire and the World Health Organization (WHO)-5 well-being questionnaire (which is also validated as a depression screening tool) before and after the intervention. The paired t test showed a highly significant prepost difference on 12.84 points on the WHO-5. Participants' satisfaction was very high with a 98% overall satisfaction rate. The focus groups results supported these findings. The MS programme is an acceptable intervention for refugees. The significant improvement on WHO-5 suggests a positive impact on depressive symptoms and well-being.

Stress management versus cognitive restructuring in trauma-affected refugees-A pragmatic randomised study.

The aim of this randomised trial was to compare the effectiveness of stress management (SM) versus cognitive restructuring (CR) in trauma-affected refugees. The intention-to-treat sample comprised 126 refugees with PTSD (SM = 62, CR = 64). The treatment consisted of 16 sessions of psychotherapy with manualised SM or CR in addition to 10 sessions with a medical doctor (psychoeducation and pharmacological treatment). The primary outcome was PTSD symptom severity (Harvard Trauma Questionnaire). Secondary outcomes were symptoms of depression and anxiety (Hopkins Symptom Checklist-25, Hamilton Depression and Anxiety Ratings), quality of life (WHO-5), functioning (Global Assessment of Functioning, Sheehan Disability Scale), pain (Visual Analogue Scale) and somatisation (Symptom Checklist). There was no difference in the primary outcome between groups. A significant group difference was found on the Hamilton Anxiety Rating with the SM group improving more than the CR group (effect size 0.46) indicating that methods in SM could potentially be helpful in this population.

Secondary psychotic features in refugees diagnosed with post-traumatic stress disorder: a retrospective cohort study.

BACKGROUND: A substantial amount of refugees (10-30%) suffer from Post-Traumatic Stress Disorder (PTSD). In Denmark there are different facilities specialised in psychiatric treatment of trauma-affected refugees. A previously published case report from such a facility in Denmark shows that some patients suffer from secondary psychotic symptoms alongside their PTSD. The aim of this study was to illustrate the characteristics and estimate the prevalence of psychotic features in a clinical population of trauma-affected refugees with PTSD. METHODS: Psychiatric records from 220 consecutive patients at Competence Centre for Transcultural Psychiatry (CTP) were examined, and all the PTSD patients were divided into two groups; one group with secondary psychotic features (PTSD-SP group) and one without (PTSD group). A categorisation and description of the secondary psychotic features was undertaken. RESULTS: One hundred eighty-one patients were diagnosed with PTSD among which psychotic symptoms were identified in 74 (40.9, 95% CI 33.7-48.1%). The majority of symptoms identified were auditory hallucinations (66.2%) and persecutory delusions (50.0%). There were significantly more patients diagnosed with enduring personality change after catastrophic experience in the PTSD-SP group than in the PTSD group (P = 0.009). Furthermore the PTSD-SP group included significantly more patients exposed to torture (P = 0.001) and imprisonment (P = 0.005). CONCLUSION: This study provides an estimation of PTSD-SP prevalence in a clinical refugee population with PTSD. The study points to the difficulties distinguishing psychotic features from flashbacks and the authors call for attention to psychotic features in PTSD patients in order to improve documentation and understanding of the disorder.

Pharmacological treatment of refugees with trauma-related disorders: What do we know today?

There is a dearth of evidence on the effectiveness of pharmacological treatment for refugees with trauma-related disorders. The present paper provides an overview of available literature on the subject and discusses the transferability of results from studies on other groups of patients with post traumatic stress disorder (PTSD). We conducted a systematic review of published treatment outcome studies on PTSD and depression among refugees. Fifteen studies were identified and reviewed. Most studies focused on the use of antidepressants. Included studies differed widely in method and quality. The majority were observational studies and case studies. Small sample sizes limited the statistical power. Few studies reported effect sizes, confidence intervals, and statistical significance of findings. No specific pharmacological treatment for PTSD among refugees can be recommended on the basis of the available literature. There is a need for well-designed clinical trials, especially with newer antidepressants and antipsychotics. Until such studies are available, clinical practice and design of trials can be guided by results from studies of other groups of PTSD patients, although differences in pharmacogenetics, compliance, and trauma reactions may affect the direct transferability of results from studies on nonrefugee populations.

Treatment of trauma-affected refugees with venlafaxine versus sertraline combined with psychotherapy - a randomised study.

BACKGROUND: The prevalence of trauma-related psychiatric disorders is high among refugees. Despite this, little is known about the effect of pharmacological treatment for this patient group. The objective of the present study was therefore to examine differences in the effects of venlafaxine and sertraline on Post-Traumatic Stress Disorder (PTSD), depression and functional impairment in trauma-affected refugees. METHODS: The study was a randomised pragmatic trial comparing venlafaxine and sertraline in combination with psychotherapy and social counselling. PTSD symptoms were measured on the Harvard Trauma Questionnaire - part IV, which was the primary outcome measure. Other outcome measures included: Hopkins Symptom Check List-25 (depression and anxiety), Social Adjustment Scale - short version (social functioning), WHO-5 Well-being Index (quality of life), Crisis Support Scale (support from social network), Sheehan Disability Scale (disability in three areas of functioning), Hamilton Depression and Anxiety scale, the somatisation items of the Symptoms Checklist-90, Global Assessment of Functioning scales and the summarised score of pain in four body areas rated on visual analogue scales. RESULTS: Two hundred seven adult refugee patients were included in the trial (98 in the venlafaxine and 109 in the sertraline group). Of these, 195 patients were eligible for intention-to-treat analyses. Small but significant pre-treatment to post-treatment differences were found on the Harvard Trauma Questionnaire and a number of other ratings in both groups. On the primary outcome measure, no difference was found in treatment effect between the sertraline and venlafaxine group. A significant group difference was found in favour of sertraline on the Sheehan Disability Scale. CONCLUSION: Sertraline had a slightly better outcome than venlafaxine on some of the secondary outcome measures, but not on the primary outcome measure. Furthermore, a higher percentage of dropouts was found in the venlafaxine group compared to the sertraline group. Although this could indicate that sertraline was better tolerated, which is supported by other studies, a final conclusion on tolerability cannot be drawn from the current study due to lack of systematic reporting of side effects. TRIAL REGISTRATION: ClinicalTrials.gov NCT01569685 . Registration date: 28/2/12.

Psychosocial predictors of treatment outcome for trauma-affected refugees.

BACKGROUND: The effects of treatment in trials with trauma-affected refugees vary considerably not only between studies but also between patients within a single study. However, we know little about why some patients benefit more from treatment, as few studies have analysed predictors of treatment outcome. OBJECTIVE: The objective of the study was to examine possible psychosocial predictors of treatment outcome for trauma-affected refugees. METHOD: The participants were 195 adult refugees with posttraumatic stress disorder (PTSD) who were enrolled in a 6- to 7-month treatment programme at the Competence Centre for Transcultural Psychiatry (CTP), Denmark. The CTP Predictor Index used in the study included 15 different possible outcome predictors concerning the patients' past, chronicity of mental health problems, pain, treatment motivation, prerequisites for engaging in psychotherapy, and social situation. The primary outcome measure was PTSD symptoms measured on the Harvard Trauma Questionnaire (HTQ). Other outcome measures included the Hopkins Symptom Check List-25, the WHO-5 Well-being Index, Sheehan Disability Scale, Hamilton Depression and Anxiety Scales, the somatisation scale of the Symptoms Checklist-90, Global Assessment of Functioning scales, and pain rated on visual analogue scales. The relations between treatment outcomes and the total score as well as subscores of the CTP Predictor Index were analysed. RESULTS: Overall, the total score of the CTP Predictor Index was significantly correlated to pre- to post treatment score changes on the majority of the ratings mentioned above. While employment status was the only single item significantly correlated to HTQ-score changes, a number of single items from the CTP Predictor Index correlated significantly with changes in depression and anxiety symptoms, but the size of the correlation coefficients were modest. CONCLUSIONS: The total score of the CTP Predictor Index correlated significantly with outcomes on most of the rating scales, but correlations were modest in size, possibly due to the number of different factors influencing treatment outcome.

From pioneers to scientists: challenges in establishing evidence-gathering models in torture and trauma mental health services for refugees.

Outcome studies on treatment of trauma-affected refugees have been published but are limited in design and quality. In this article, we discuss possible impediments to pursuing research aimed at gathering evidence to support the efficacy of treatments in the field and the challenges in carrying out such inquiries. We then present a working model that demonstrates the feasibility of integrating outcome research into clinical settings. The aim of this model is to involve all personnel in generating research of high quality with minimal additional costs and time commitment. We conclude that although challenges remain in carrying out treatment outcome studies, they can be overcome by careful consultation and negotiation in a setting with an established ethos of commitment to the scientific endeavor. Ultimately, identifying the most effective interventions will provide better treatment and quality of life for the large number of traumatized refugees seeking assistance for mental health problems.

Treatment of traumatized refugees with sertraline versus venlafaxine in combination with psychotherapy - study protocol for a randomized clinical trial.

BACKGROUND: Sufficient evidence is lacking to draw final conclusions on the efficiency of medical and psychological treatments of traumatized refugees with PTSD. The pharmacological treatments of choice today for post-traumatic stress disorder are antidepressants from the subgroup selective serotonin reuptake inhibitors, especially sertraline. The evidence for the use of selective serotonin reuptake inhibitors in the treatment of complex post-traumatic stress disorder in traumatized refugees is very limited. Venlafaxine is a dual-action antidepressant that works on several pathways in the brain. It influences areas in the brain which are responsible for the enhanced anxiety and hyper-arousal experienced by traumatized refugees and which some studies have found to be enlarged among patients suffering from post-traumatic stress disorder. DESIGN: This study will include approximately 150 patients, randomized into two different groups treated with either sertraline or venlafaxine. Patients in both groups will receive the same manual-based cognitive behavioral therapy, which has been especially adapted to this group of patients. The treatment period will be 6 to 7 months. The trial endpoints will be post-traumatic stress disorder and depressive symptoms and social functioning, all measured on validated ratings scales. Furthermore the study will examine the relation between a psycho-social resources and treatment outcome based on 15 different possible outcome predictors. DISCUSSION: This study is expected to bring forward new knowledge on treatment and clinical evaluation of traumatized refugees and the results are expected to be used in reference programs and clinical guidelines. TRIAL REGISTRATION: ClinicalTrials.gov NCT01569685.

[Diagnostics and treatment of Wernicke-Korsakoff syndrome patients with an alcohol abuse]. / Diagnostik og behandling af Wernicke-Korsakovs syndrom hos alkoholmisbrugere kan optimeres.

Wernicke-Korsakoff syndrome is a condition with high morbidity and mortality and occurs as a consequence of thiamine deficiency. Clinical symptoms are often ambiguous and post-mortem examinations show that the syndrome is underdiagnosed and probably undertreated. There is sparse clinical evidence concerning optimal dosage and duration of treatment. This article reviews the current literature and concludes that all patients with a history of alcohol abuse should be treated with high dosage IV thiamine for an extended period of time, albeit further research is needed.