Internet-delivered cognitive behavioural therapy programme to reduce depressive symptoms in patients with multiple sclerosis: a multicentre, randomised, controlled, phase 3 trial.

BACKGROUND: Depression is three to four times more prevalent in patients with neurological and inflammatory disorders than in the general population. For example, in patients with multiple sclerosis, the 12-month prevalence of major depressive disorder is around 25% and it is associated with a lower quality of life, faster disease progression, and higher morbidity and mortality. Despite its clinical relevance, there are few treatment options for depression associated with multiple sclerosis and confirmatory trials are scarce. We aimed to evaluate the safety and efficacy of a multiple sclerosis-specific, internet-based cognitive behavioural therapy (iCBT) programme for the treatment of depressive symptoms associated with the disease. METHODS: This parallel-group, randomised, controlled, phase 3 trial of an iCBT programme to reduce depressive symptoms in patients with multiple sclerosis was carried out at five academic centres with large outpatient care units in Germany and the USA. Patients with a neurologist-confirmed diagnosis of multiple sclerosis and depressive symptoms were randomly assigned (1:1:1; automated assignment, concealed allocation, no stratification, no blocking) to receive treatment as usual plus one of two versions of the iCBT programme Amiria (stand-alone or therapist-guided) or to a control condition, in which participants received treatment as usual and were offered access to the iCBT programme after 6 months. Masking of participants to group assignment between active treatment and control was not possible, although raters were masked to group assignment. The predefined primary endpoint, which was analysed in the intention-to-treat population, was severity of depressive symptoms as measured by the Beck Depression Inventory-II (BDI-II) at week 12 after randomisation. This trial is registered at ClinicalTrials.gov, NCT02740361, and is complete. FINDINGS: Between May 3, 2017, and Nov 4, 2020, we screened 485 patients for eligibility. 279 participants were enrolled, of whom 101 were allocated to receive stand-alone iCBT, 85 to receive guided iCBT, and 93 to the control condition. The dropout rate at week 12 was 18% (50 participants). Both versions of the iCBT programme significantly reduced depressive symptoms compared with the control group (BDI-II between-group mean differences: control vs stand-alone iCBT 6·32 points [95% CI 3·37-9·27], p<0·0001, effect size d=0·97 [95% CI 0·64-1·30]; control vs guided iCBT 5·80 points [2·71-8·88], p<0·0001, effect size d=0·96 [0·62-1·30]). Clinically relevant worsening of depressive symptoms was observed in three participants in the control group, one in the stand-alone iCBT group, and none in the guided iCBT group. No occurrences of suicidality were observed during the trial and there were no deaths. INTERPRETATION: This trial provides evidence for the safety and efficacy of a multiple sclerosis-specific iCBT tool to reduce depressive symptoms in patients with the disease. This remote-access, scalable intervention increases the therapeutic options in this patient group and could help to overcome treatment barriers. FUNDING: National Multiple Sclerosis Society (USA).

Screening versus multidimensional assessment of symptoms and psychosocial distress in cancer patients from the time of incurability.

Objective: Previous symptom prevalence studies show a diverse spectrum of symptoms and a large diversity in symptom intensities in patients being just diagnosed as having incurable cancer. It is unclear, how physical symptoms and psychosocial burden should be recorded in order to determine the variable need for palliative care and further support. Therefore, we compared two different strategies for detecting physical symptoms and psychosocial burden of patients with newly diagnosed incurable cancer and their effects on the further course of the disease. Methods: SCREBEL is a controlled, randomized, non-blinded, longitudinal study of the research network of the Palliative Medicine Working Group (APM) of the German Cancer Society (DKG). We compared: a less complex repeated brief screening for symptoms and burden in patients using the NCCN Distress Thermometer and IPOS questionnaire versus a multidimensional comprehensive assessment using the FACT-G and their entity-specific questionnaires, the PHQ4 scales, SCNS-34-SF, IPOS and NCCN Distress Thermometer. The primary study endpoint was quality of life (QoL), measured using FACT-G, after six months. Secondary study endpoints were QoL by using evaluation of secondary scores (NCCN DT, IPOS, PHQ4, SCNS-SF-34G) at time 6 months, the number of hospital days, the utilization of palliative care, emergency services, and psychosocial care structures. To assess effects and differences, multiple linear regression models were fitted and survival analyses were conducted. Results: 504 patients were included in the study. 262 patients were lost to follow-up, including 155 fatalities. There were no significant differences between the low-threshold screening approach and a comprehensive assessment with respect to symptoms and other aspects of QoL. Using the IPOS, we were able to measure an improvement in the quality of life in the low-threshold screening arm by a decrease of 0.67 points (95%-CI: 0.34 to 0.99) every 30 days. (p<0.001). Data on the involvement of emergency facilities and on supportive services were insufficient for analysis. Conclusion: A comprehensive, multidimensional assessment did not significantly differ from brief screening in preserving several dimensions of quality of life. These findings may positively influence the implementation of structured low-threshold screening programs for supportive and palliative needs in DKG certified cancer centers.DRKS -No. DRKS00017774 https://drks.de/search/de/trial/DRKS00017774.