The effects of using the PReDicT Test to guide the antidepressant treatment of depressed patients: study protocol for a randomised controlled trial

Background Antidepressant medication is commonly used to treat depression. However, many patients do not respond to the first medication prescribed and improvements in symptoms are generally only detectable by clinicians 4–6 weeks after the medication has been initiated. As a result, there is often a long delay between the decision to initiate an antidepressant medication and the identification of an effective treatment regimen. Previous work has demonstrated that antidepressant medications alter subtle measures of affective cognition in depressed patients, such as the appraisal of facial expression. Furthermore, these cognitive effects of antidepressants are apparent early in the course of treatment and can also predict later clinical response. This trial will assess whether an electronic test of affective cognition and symptoms (the Predicting Response to Depression Treatment Test; PReDicT Test) can be used to guide antidepressant treatment in depressed patients and, therefore, hasten treatment response compared to a control group of patients treated as usual. Methods/design The study is a randomised, two-arm, multi-centre, open-label, clinical investigation of a medical device, the PReDicT Test. It will be conducted in five European countries (UK, France, Spain, Germany and the Netherlands) in depressed patients who are commencing antidepressant medication. Patients will be randomised to treatment guided by the PReDicT Test (PReDicT arm) or to Treatment as Usual (TaU arm). Patients in the TaU arm will be treated as per current standard guidelines in their particular country. Patients in the PReDicT arm will complete the PReDicT Test after 1 (and if necessary, 2) weeks of treatment. If the test indicates non-response to the treatment, physicians will be advised to immediately alter the patient’s antidepressant therapy by dose escalation or switching to another compound. The primary outcome of the study is the proportion of patients showing a clinical response (defined as 50% or greater decrease in baseline scores of depression measured using the Quick Inventory of Depressive Symptoms – Self-Rated questionnaire) at week 8. Health economic and acceptability data will also be collected and analysed. Discussion This trial will test the clinical efficacy, cost-effectiveness and acceptability of using the novel PReDicT Test to guide antidepressant treatment selection in depressed patients

Clinical Perspectives on Using Remote Measurement Technology in Assessing Epilepsy, Multiple Sclerosis, and Depression: Delphi Study

Background: Multiple sclerosis (MS), epilepsy, and depression are chronic central nervous system conditions in which remote measurement technology (RMT) may offer benefits compared with usual assessment. We previously worked with clinicians, patients, and researchers to develop 13 use cases for RMT: 5 in epilepsy (seizure alert, seizure counting, risk scoring, triage support, and trend analysis), 3 in MS (detecting silent progression, detecting depression in MS, and donating data to a biobank), and 5 in depression (detecting trends, reviewing treatment, self-management, comorbid monitoring, and carer alert). Objective: In this study, we aimed to evaluate the use cases and related implementation issues with an expert panel of clinicians external to our project consortium. Methods: We used a Delphi exercise to validate the use cases and suggest a prioritization among them and to ascertain the importance of a variety of implementation issues related to RMT. The expert panel included clinicians from across Europe who were external to the project consortium. The study had 2 survey rounds (n=23 and n=17) and a follow-up interview round (n=9). Data were analyzed for consensus between participants and for stability between survey rounds. The interviews explored the reasons for answers given in the survey. Results: The findings showed high stability between rounds on questions related to specific use cases but lower stability on questions relating to wider issues around the implementation of RMT. Overall, questions on wider issues also had less consensus. All 5 use cases for epilepsy (seizure alert, seizure counting, risk scoring, triage support, and trend analysis) were considered beneficial, with consensus among participants above the a priori threshold for most questions, although use case 3 (risk scoring) was considered less likely to facilitate or catalyze care. There was very little consensus on the benefits of the use cases in MS, although this may have resulted from a higher dropout rate of MS clinicians (50%). Participants agreed that there would be benefits for all 5 of the depression use cases, although fewer questions on use case 4 (triage support) reached consensus agreement than for depression use cases 1 (detecting trends), 2 (reviewing treatment), 3 (self-management), and 5 (carer alert). The qualitative analysis revealed further insights into each use case and generated 8 themes on practical issues related to implementation. Conclusions: Overall, these findings inform the prioritization of use cases for RMT that could be developed in future work, which may include clinical trials, cost-effectiveness studies, and the commercial development of RMT products and services. Priorities for further development include the use of RMT to provide more accurate records of symptoms and treatment response than is currently possible and to provide data that could help inform patient triage and generate timely alerts for patients and carers

Feasibility of a randomised controlled trial of remotely delivered problem-solving cognitive behaviour therapy versus usual care for young people with depression and repeat self-harm: lessons learnt (e-DASH)

BackgroundSelf-harm and depression are strong risk factors for repeat self-harm and suicide. We aimed to investigate the feasibility of a randomised controlled trial (RCT) of remotely delivered problem-solving cognitive behaviour therapy (PSCBT) plus treatment as usual (TAU) versus TAU in young people with repeat self-harm and depression.MethodsSingle-blind multi-centre RCT with an internal pilot, pre-set stop-go criteria and qualitative semi-structured interviews. Eligible participants (aged 16–30 years) were recruited from 9 adult or child and adolescent self-harm and crisis services; had ≥ 2 lifetime self-harm episodes, one in the preceding 96 h; and Beck Depression Inventory-II (BDI-II) score ≥ 17. Participants were randomised (1:1) to either TAU or TAU and 10–12 sessions of PSCBT delivered by mobile phone or video-calling.ResultsTwenty-two participants were recruited (11 in each arm), 10 (46%) completed follow-up at 6 months, 9 (82%) started the PSCBT and 4 (36%) completed it. The study did not meet three of its four stop-go criteria, reflecting considerable barriers to recruitment and retention. Participants had severe depression symptoms: with mean BDI-II 38.9 in the PSCBT and 37.2 in TAU groups, respectively. Three (14%) unblindings occurred for immediate safety concerns. Barriers to recruitment and retention included lack of agency for participants, severity of depression, recency of crisis with burden for participants and clinicians who diagnosed depression according to pervasiveness.ConclusionsRCTs of PSCBT for young people with depression and self-harm are not feasible using recruitment through mental health services that conduct assessments following self-harm presentations. Clinician assessment following self-harm presentation mainly identifies those with severe rather than mild-moderate depression

Gold-Catalyzed Oxidative Cross-Coupling of Terminal Alkynes: Selective Synthesis of Unsymmetrical 1,3-Diynes

Gold-catalyzed oxidative cross-coupling of alkynes to unsymmetrical diynes has been achieved for the first time. A N,N-ligand (1,10-Phen) and PhI­(OAc)₂ were identified as crucial factors to promote this transformation, giving the desired cross-coupled conjugated diynes in excellent hetero­selectivity (>10:1), in good to excellent yields, and with large substrate tolerability