Fatigue in patients with systemic lupus erythematosus and neuropsychiatric symptoms is associated with anxiety and depression rather than inflammatory disease activity.

INTRODUCTION: We aimed to investigate risk factors for fatigue in patients with systemic lupus erythematosus (SLE) and neuropsychiatric symptoms in order to identify potential interventional strategies. METHODS: Patients visiting the neuropsychiatric SLE (NPSLE) clinic of the Leiden University Medical Center between 2007-2019 were included. In a multidisciplinary consensus meeting, SLE patients were classified as having neuropsychiatric symptoms of inflammatory origin (inflammatory phenotype) or other origin (non-inflammatory phenotype). Fatigue was assessed with the SF-36 vitality domain (VT) since 2007 and the multidimensional fatigue inventory (MFI) and visual analogue scale (VAS) since 2011. Patients with a score on the SF-36 VT ≥1 standard deviation (SD) away from the mean of age-related controls of the general population were classified as fatigued; patients ≥2 SD away were classified as extremely fatigued. Disease activity was measured using the SLE disease activity index-2000. The influence of the presence of an inflammatory phenotype, disease activity and symptoms of depression and anxiety as measured by the hospital anxiety and depression scale (HADS) was analyzed using multiple regression analyses corrected for age, sex and education. RESULTS: 348 out of 371 eligible patients filled in questionnaires and were included in this study . The majority was female (87%) and the mean age was 43 ± 14 years. 72 patients (21%) had neuropsychiatric symptoms of an inflammatory origin. Fatigue was present in 78% of all patients and extreme fatigue was present in 50% of patients with an inflammatory phenotype vs 46% in the non-inflammatory phenotype. Fatigue was similar in patients with an inflammatory phenotype compared to patients with a non-inflammatory phenotype on the SF-36 VT (ß: 0.8 (95% CI -4.8; 6.1) and there was less fatigue in patients with an inflammatory phenotype on the MFI and VAS (ß: -3.7 (95% CI: -6.9; -0.5) and ß: -1.0 (95% CI -1.6; -0.3)). There was no association between disease activity and fatigue, but symptoms of anxiety and depression (HADS) associated strongly with all fatigue measurements. CONCLUSION: This study suggests that intervention strategies to target fatigue in (NP)SLE patients may need to focus on symptoms of anxiety and depression rather than immunosuppressive treatment.

The generalizability of psychotherapy efficacy trials in major depressive disorder: an analysis of the influence of patient selection in efficacy trials on symptom outcome in daily practice.

BACKGROUND: Treatment guidelines for major depressive disorder (MDD) are based on results from randomized clinical trials, among others in psychotherapy efficacy trials. However, patients in these trials differ from routine practice patients since trials use stringent criteria for patient selection. It is unknown whether the exclusion criteria used in psychotherapy efficacy trials (PETs) influence symptom outcome in clinical practice. We first explored which exclusion criteria are used in PETs. Second, we investigated the influence of commonly used exclusion criteria on symptom outcome in routine clinical practice. METHODS: We performed an extensive literature search in PubMed, PsycInfo and additional databases for PETs for MDD. From these, we identified commonly used exclusion criteria. We investigated the influence of exclusion criteria on symptom outcome by multivariate regression models in a sample of patients suffering from MDD according to the MINIplus from a routine clinical practice setting (n=598). Data on routine clinical practice patients were gathered through Routine Outcome Monitoring. RESULTS: We selected 20 PETs and identified the following commonly used exclusion criteria: 'a baseline severity threshold of HAM-D≤14', 'current or past abuse or dependence of alcohol and/or drugs' and 'previous use of medication or ECT'. In our routine clinical practice sample of patients suffering from MDD (n=598), presence of 'current or past abuse of or dependence on alcohol and/or drugs' had no significant influence on outcome.'Meeting a baseline severity threshold of HAM-D≤14' and 'previous use of medication or ECT' were associated with better outcome, but the explained variance of the models was very small (R2=2-11%). CONCLUSIONS: The most consistently used exclusion criteria are not a major threat to the generalizability of results found in PETs. However, PETs do somewhat improve their results by exclusion of patients with minor depression and patients who used antidepressants prior to psychotherapy.

Preventing mood and anxiety disorders in youth: a multi-centre RCT in the high risk offspring of depressed and anxious patients.

BACKGROUND: Anxiety and mood disorders are highly prevalent and pose a huge burden on patients. Their offspring is at increased risk of developing these disorders as well, indicating a clear need for prevention of psychopathology in this group. Given high comorbidity and non-specificity of intergenerational transmission of disorders, prevention programs should target both anxiety and depression. Further, while the indication for preventive interventions is often elevated symptoms, offspring with other high risk profiles may also benefit from resilience-based prevention programs. METHOD/DESIGN: The current STERK-study (Screening and Training: Enhancing Resilience in Kids) is a randomized controlled clinical trial combining selected and indicated prevention: it is targeted at both high risk individuals without symptoms and at those with subsyndromal symptoms. Individuals without symptoms meet two of three criteria of the High Risk Index (HRI; female gender, both parents affected, history of a parental suicide (attempt). This index was developed in an earlier study and corresponds with elevated risk in offspring of depressed patients. Children aged 8-17 years (n = 204) with subthreshold symptoms or meeting the criteria on the HRI are randomised to one of two treatment conditions, namely (a) 10 weekly individual child CBT sessions and 2 parent sessions or (b) minimal information. Assessments are held at pre-test, post-test and at 12 and 24 months follow-up. Primary outcome is the time to onset of a mood or anxiety disorder in the offspring. Secondary outcome measures include number of days with depression or anxiety, child and parent symptom levels, quality of life, and cost-effectiveness. Based on models of aetiology of mood and anxiety disorders as well as mechanisms of change during interventions, we selected potential mediators and moderators of treatment outcome, namely coping, parent-child interaction, self-associations, optimism/pessimism, temperament, and emotion processing. DISCUSSION: The current intervention trial aims to significantly reduce the risk of intergenerational transmission of mood and anxiety disorders with a short and well targeted intervention that is directed at strengthening the resilience in potentially vulnerable children. We plan to evaluate the effectiveness and cost-effectiveness of such an intervention and to identify mechanisms of change. TRIAL REGISTRATION: NTR2888.