Johannes Kruse

The prospective long-term course of adult depression in general practice and the community. A systematic literature review

BACKGROUND Findings about the prospective long-term course of depression are usually derived from clinical populations while knowledge about the course in community and primary care samples is rarer. As depressive disorders are highly prevalent and associated with considerable disability and costs, this information is needed to identify the percentages of subjects with a favorable or unfavorable prognosis. Therefore our aim was to summarize the available evidence on the prospective longitudinal course of depression in both general practice and the community. METHODS We conducted a systematic, computerized search of Medline and PsycINFO. Main selection criteria were (a) adults with observer assessed depressive disorder recruited in the community or in general practice and (b) naturalistic study with follow-up length of at least three years. As primary outcome the percentages of stable recovery, recovery during or at follow-up, recurrence and chronic course were used. RESULTS We identified 12 cohorts, with 4009 followed-up individuals. Follow-up intervals ranged between three and 49 years. Between 35% and 60% of participants experienced a stable recovery with no (further) recurrences, while 70-85% recovered at least once during follow-up. A consistent percentage of 10-17% had a chronic course. Recurrence rates varied considerably ranging between 7% and 65%. Significant predictors of an unfavorable course appear to be mainly those variables that lie within the course of depression itself, i.e. history of depression, baseline severity, and comorbidity. LIMITATIONS Use of broad inclusion criteria heightened study heterogeneity and hampered comparability. CONCLUSION Regarding stable recovery, the long-term course within general practice and community samples seems more favorable than within clinical samples. Further research applying a standardized methodology is required.

Depression as a Risk Factor for Mortality in Individuals with Diabetes: A Meta-Analysis of Prospective Studies

Objective To quantify the impact of depression measured by self-reports and depression measured by clinical interview on all-cause mortality in individuals with diabetes and to analyze the strength of both associations, the influence of covariates, and possible differences between studies assessing self-rated depressive symptoms and those using a clinical interview to measure depression as predictors of mortality. Research Design and Methods PUBMED and PsycINFO were searched up to July 2013 for prospective studies assessing depression, diabetes and mortality. The pooled hazard ratios were calculated using random-effects models. Results Sixteen studies met the inclusion criteria. After adjustment for demographic variables depression measured by self-reports was associated with an increased all-cause mortality risk (pooled HR = 2.56, 95% CI 1.89–3.47), and the mortality risk remained high after additional adjustment for diabetes complications (HR = 1.76, 95% CI 1.45–2.14,). Six studies reporting adjusted HRs for depression measured by clinical interviews supported the results of the other models (HR = 1.49, 95% CI 1.15–1.93). Conclusions Both depression measured by self-report and depression measured by clinical interview have an unfavorable impact on mortality in individuals with diabetes. The results, however, are limited by the heterogeneity of the primary studies. It remains unclear whether self-reports or clinical interviews for depression are the more precise predictor.

Relapse rates after psychotherapy for depression – stable long-term effects? A meta-analysis

BACKGROUND Depression is the most common mental disorder. Effective psychotherapeutic treatments for depression exist; however, data on their long-term effectiveness beyond a time span of two years is still scarce. Our aim was to perform a meta-analysis, investigating (a) overall rates of relapse more than two years after psychotherapy (meta-analysis 1), and (b) if psychotherapy has more enduring effects than non-psychotherapeutic comparison conditions (e.g. pharmacotherapy, treatment as usual), again beyond a time span of two years post-therapy (meta-analysis 2). METHODS We searched electronic databases Medline, PsycINFO and the COCHRANE Library. Main selection criteria were (i) RCT of psychotherapy with follow-up interval of more than 2 years, (ii) primary diagnosis of depression, assessed by observer ratings, (iii) report of relapse at follow-up. RESULTS We identified 11 studies, 6 of which included a non-psychotherapeutic comparison condition. Together they comprised long-term data of 966 patients. Mean follow-up duration was 4.4 years. The overall relapse rate at long-term follow-up was 0.39 (95% CI 0.29, 0.50). Psychotherapy resulted in significantly less relapses (53.1% vs. 71.1%, OR 0.51; 95% CI 0.32, 0.82, p=0.005) than comparison treatments. This finding corresponded to a number needed to treat (NNT) of 5.55. LIMITATIONS Results can only be preliminary as data was sparse and studies differed methodologically. Heterogeneity in the first meta-analysis was high (I(2)=82%). Results indicated publication bias. CONCLUSIONS The relapse rate more than two years after psychotherapy is relatively high, but significantly lower compared to non-psychotherapeutic treatments. Multiannual follow-ups should routinely be included in future psychotherapy RCTs.

What do we know today about the prospective long-term course of social anxiety disorder? A systematic literature review

While we know that social anxiety disorder (SAD) is todays most common anxiety disorder knowledge on its prospective long-term course is sparse. We conducted a systematic literature search using databases Medline and PsycINFO for naturalistic and psychotherapy outcome studies with follow-up durations of at least 24 months. Four naturalistic cohorts and nine psychotherapy trials were included in the review. The naturalistic course in clinical was less favorable than in non-clinical samples (27% vs. 40% recovery rate after 5 years). Psychotherapy trials, all applying (cognitive) behavioral methods, yielded stable outcomes with overall large pre- to follow-up effect sizes on self-report scales. Observer rated remission rates varied considerably (36% to 100%) depending on study design and follow-up length. The results of psychotherapy trials and that of naturalistic studies can hardly be compared due to differences in methodology. More standardized remission and recovery criteria are needed to enhance the understanding of the longitudinal course.

Poor structural social support is associated with an increased risk of Type 2 diabetes mellitus: findings from the MONICA/KORA Augsburg cohort study

Several psychosocial factors have been shown to increase the risk of Type 2 diabetes mellitus. This study investigated the association between structural social support and incidence of Type 2 diabetes mellitus in men and women.

Treating post-traumatic stress disorder by resource activation in Cambodia.

There is a need for effective, low‐threshold psychotherapeutic treatments in post‐conflict settings1. However, systematic outcome research on site is still extremely rare. To address this problem we integrated rigorous research procedures into a humanitarian program, the so called Mekong Project, and conducted a randomized controlled trial for the treatment of post‐traumatic stress disorder (PTSD) in Cambodia. In short, the Mekong Project aims at establishing independent psychotherapeutic services in several Southeast Asian countries via the systematic training of local health professionals and offering free of charge psychological help to traumatized civilians. Cambodia is one of the least developed countries in Asia, facing many challenges (e.g., poor standards of health and education, rural exodus, and political instability). Mental health morbidity in Cambodia is high. It has been found that 53.4% of the Cambodian population suffer from a mental disorder, with anxiety and PTSD being the most frequent (40.0% and 28.4% respectively)2. Thus, although some stability has returned to the country during the past decades, there are urgent mental health care needs, including the need for individualized psychiatric services. Our aim was to test the efficacy of a non‐confrontational psychotherapeutic treatment for PTSD. The therapy includes two main treatment principles described in treatment manuals: resource‐oriented trauma therapy and resource installation with eye movement desensitization and reprocessing (EMDR) (short: ROTATE). ROTATE aims at strengthening resilience and coping capacities by activating positive personal resources, and largely draws on psychodynamic principles of the therapeutic relationship. It includes a variety of imaginative resource‐activating methods3, 4 as well as resource development and installation, an EMDR technique aiming at systematically developing and anchoring resources using alternating bilateral stimulation5. ROTATE has several advantages: a) it can be safely applied even to complex trauma conditions, with no major side effects being observed so far; b) instead of solely focusing on PTSD symptoms, it also considers the mental comorbidities typically found in these clients, notably depression and anxiety; c) it is especially suitable for clients from non‐Western countries, as traditional healing resources like mindfulness strategies can be integrated in an overall framework of resource activation; d) its basic elements can easily be taught, even to paraprofessionals. Our trial was carried out in cooperation with the Royal University of Phnom Penh and was located in Phnom Penh City and the nearby Kandal Province. Help‐seeking outpatients screening positively for PTSD (PTSD Check List ≥ 446) were eligible for inclusion. We allowed for comorbid mental health disorders except for psychosis, organic brain disorder, cognitive impairment, dementia, acute suicidality, and acute need for treatment. Overall, 800 patients were screened for eligibility, of whom 86 (mean age 27 years, 61% female) fulfilled the selection criteria and were randomly assigned to either 5 weekly sessions of ROTATE (N=53) or a 5‐week waiting list control group (N=33). Symptoms were measured before and after the intervention (or waiting period). Assessments were performed via personal interview by an investigator blind to treatment allocation. All patients in the control group were offered treatment after the end of the waiting period. The primary outcome was PTSD symptom change on the Indochinese version of the Harvard Trauma Questionnaire (HTQ)7. The PTSD scale of the HTQ includes 16 items reflecting the DSM‐IV criteria for PTSD. Secondary outcomes included depression, anxiety and social functioning. All applied instruments have been validated for the Cambodian population7. The therapy was provided by six Cambodian psychologists who had completed a 3‐year course in trauma therapy as part of the Mekong Project. Based on previous findings of psychological therapies for PTSD8, we expected ROTATE to be superior to waiting list with a between group effect size of at least d=0.65 on the primary outcome. To detect this difference with a power of 0.80 at α=0.05, 2‐sided test, 2 × 40 patients were required. Unfortunately, the concept of randomization, especially being randomized to a waiting list, was very difficult for some clients. As a consequence, randomization failed in 38 patients, leading to an unbalanced allocation ratio (1.6:1), with an overrepresentation of patients randomized to treatment. The trial stopped when the necessary sample size to achieve a power of 0.80 was reached. Data were analyzed by general linear regression models, controlling for baseline symptom severity. The drop‐out rate during the intervention was very low (N=2, one in each group), thus only completer data were analyzed (N=84). Most frequent types of trauma were traffic accidents (24%), domestic violence (23%) and sexual abuse (16%). Patients receiving ROTATE showed significant reductions in PTSD symptoms compared to the waiting list (baseline adjusted means post‐treatment: 1.39, 95% CI: 1.23‐1.54 for ROTATE, and 2.86, 95% CI: 2.66‐3.06 for waiting list, p<0.00001). The between‐group effect size was large (d=2.59). The within‐group effect size was also large for ROTATE (d=4.43), while it was moderate in the control group (d=0.52). No harms were reported. We conclude that a treatment focusing on stabilization rather than confrontation, by establishing a secure patient‐therapist relationship, applying stabilization techniques, and putting an emphasis on a patients own resources, significantly reduced symptoms of PTSD in comparison to a waiting list. The strengths of our study are the following: a) it was conducted on site by local psychologists, which meant that communication between therapists and patients was natural and no interpreters were needed; b) therapists and patients had similar cultural backgrounds, so that culture specific interpretations of symptoms could be taken into account, a factor that has been identified as vital in the therapeutic work with Cambodian patients9; c) local psychologists were trained in ROTATE, which is expected to facilitate patient access to a psychological treatment in a country struggling with insufficient mental health care. Conducting a randomized controlled trial in a developing country is challenging. Nevertheless, we were able to show that the implementation of such a trial was possible and that this specific form of trauma therapy was well accepted by therapists and patients. Our results are preliminary but promising. Further research is required to corroborate the findings. Christiane Steinert1, Peter J. Bumke2, Rosa L. Hollekamp1, Astrid Larisch1, Falk Leichsenring1, Helga Matthes3, Sek Sisokhom4, Ute Sodemann2, Markus Stingl1, Ret Thearom4, Hana Vojtova5, Wolfgang Woller6, Johannes Kruse1,7 1Clinic for Psychosomatic Medicine and Psychotherapy, University of Giessen, Giessen, Germany; 2Trauma Aid Germany, Berlin, Germany; 3Psychotraumatology Institute Europe, Duisburg, Germany; 4Department of Psychology, Royal University of Phnom Penh, Phnom Penh, Cambodia; 5Slovak Institute for Psychotraumatology and EMDR, Trencin, Slovakia, and Center for Neuropsychiatric Research of Traumatic Stress, Charles University, Prague, Czech Republic; 6Hospital for Psychosomatic Medicine and Psychotherapy, Rhein‐Klinik, Bad Honnef, Germany; 7Clinic for Psychosomatic Medicine and Psychotherapy, University of Marburg, Marburg, Germany

Moderating Effects of Alexithymia on Associations between the Therapeutic Alliance and the Outcome of Brief Psychodynamic-Interpersonal Psychotherapy for Multisomatoform Disorder

This secondary analysis of a trial on brief psychodynamic-interpersonal therapy (PIT) for patients with multisomatoform disorder investigated whether alexithymia moderates the associations between the therapeutic alliance and the outcome of PIT and whether moderating effects of alexithymia remain significant when controlling for depression. Eighty-three patients with multisomatoform disorder receiving PIT were statistically analyzed. Moderation analyses were performed with the SPSS macro PROCESS. The primary outcome (Y), self-reported physical quality of life at 9-month after the end of PIT, was measured with the physical component summary (PCS) of the SF-36 Health Survey. The potential moderator (M) alexithymia was operationalized with the Toronto Alexithymia Scale (TAS-20) at pre-treatment and the predictor (X) the therapeutic alliance was rated by both patients and therapists via the Helping Alliance Questionnaire (HAQ) at the end of PIT. Moreover, the PCS at pre-treatment functioned as covariate in all moderation models. When the patients’ alliance ratings were analyzed, alexithymia did not moderate associations between the alliance and the outcome. When the therapists’ alliance ratings were evaluated, alexithymia moderated the relationship between the alliance and the outcome (p < 0.05): a stronger alliance in the therapists’ perspective was beneficial for the outcome only for patients scoring above 61 on the TAS-20. This moderating effect of alexithymia was, however, not statistically significant anymore when adding the pre-treatment depression scores (PHQ-9) as a covariate to the moderation model. The results underline the importance of a good therapists’ view of the alliance when treating alexithymic patients and highlight the complex interaction between alexithymia and depression. Future studies are needed to extend the scope of research regarding which psychotherapeutic mechanisms of change are beneficial for which patients.

Cumulative effect of depressed mood and obesity on type II diabetes incidence: Findings from the MONICA/KORA cohort study

BACKGROUND Obesity and depression both individually contribute to the risk of Type II Diabetes (T2DM). The extent to which obesity can be set-off by depression is unknown. METHODS In a sample of 9340 participants followed for 15.4 years (79,372 person-years) from the prospective MONICA/KORA population-based cohort conducted in Southern Germany, we investigated the impact of obesity, defined as Body Mass Index (BMI) ≥ 30, and depression on the incidence of T2DM using Cox Proportional Hazards Regression. RESULTS The relative risk of T2DM was over 6 fold higher among obese participants in comparison to normal weight participants (HR 6.05; 95% CI 4.82 to 7.59; p < .0001). Nonetheless, among participants with obesity, comorbidity of depression was associated with an additional 2 fold risk T2DM (HR 8.05, 95% CI 5.90-10.98; p < .0001). This finding corresponded to an increase in the 15.4-year absolute risk of T2DM from 15.9 cases per 1000 person-years (py) in participants with obesity but not depression, to 21.4 cases per 1000 py for participants with obesity and depression. Further analysis of joint effects and Relative Excess Risk due to Interaction disclosed that depressed mood is associated with significantly higher risk of T2DM in participants with obesity, and to a lesser extent in overweight participants, however an association was not found in normal weight participants. CONCLUSIONS The present investigation discloses that despite the overreaching importance of obesity as a risk factor for T2DM, there is room for depressed mood to add measurable risk prediction.