The limited efficacy of psychological interventions for depression in people with Type 1 or Type 2 diabetes: An Individual Participant Data Meta-Analysis (IPD-MA).

BACKGROUND: People with either Type 1/Type 2 diabetes experiencing anxiety or depression experience worse clinical and social outcomes. Efficacy of available psychological and pharmacological treatments for anxiety and depression is unclear. Aggregate data meta-analyses (AD-MAs) have failed to consider the clinical relevance of any change these treatments elicit. Thus, we sought to complete an individual participant data meta-analysis (IPD-MA) to evaluate this. METHODS: Eligible RCTs of psychological treatments (PTs) and pharmacological treatments (PhTs) were systematically identified and assessed using the Cochrane Risk of Bias Tool-2. IPD was requested and Jacobson's methodology was used to determine the clinical relevance of symptom-change. Traditional effect sizes were calculated to permit comparison of trials providing and not providing IPD and to compare with AD-MAs. RESULTS: Sufficient data was obtained to conduct an IPD-MA for PTs (12/25) but not PhTs (1/5). Across PT trials, rates of 'recovery' for depression post-intervention were low. Whilst significantly more treated patients did recover (17% [95% CI 0.10, 0.25]) than controls (9% [95% CI 0.03, 0.17]), the difference was small (6% [95% CI 0.02, 0.10]). LIMITATIONS: Only 50% of eligible trials provided IPD; we were also only able to examine outcomes immediately following the end of an intervention. CONCLUSION: Current psychological interventions offer limited benefit in treating anxiety and depression in people with Type 1 or Type 2 diabetes (83% remain depressed). More efficacious interventions are urgently needed.

Early Palliative Care Consultation in the Burn Unit: A Quality Improvement Initiative to Increase Utilization.

Despite significant morbidity and mortality for major burns, palliative care consultation (PCC) is underutilized in this population. The purpose of this study is to examine the impact of a protocol using recommended "triggers" for PCC at a single academic burn center. This is a retrospective review of patient deaths over a 4-year period. The use of life-sustaining treatments, comfort care (de-escalation of one or more life-sustaining treatments), and do not attempt resuscitation (DNAR) orders were determined. The use of PCC was compared during periods before and after a protocol establishing recommended triggers for early (<72 hours of admission) PCC was instituted in 2019. A total of 33 patient deaths were reviewed. Most patients were male (n = 28, 85%) and median age was 62 years [IQR: 42-72]. Median-revised Baux score was 112 [IQR: 81-133]. Many patients had life-sustaining interventions such as intubation, dialysis, or cardiopulmonary resuscitation, often prior to admission. Amongst patients who survived >24 hours, 67% (n = 14/21) had PCC. Frequency of PCC increased after protocol development, with 100% vs 36% of these patients having PCC before death (P = .004). However, even during the later period, less than half of patients had early PCC despite meeting criteria at admission. In conclusion, initiation of life-sustaining measures in severely injured burn patients occurs prior to or early during hospitalization. Thus, value-based early goals of care discussions are valuable to prevent interventions that do not align with patient values and assist with de-escalation of life-sustaining treatment. In this small sample, we found that while there was increasing use of PCC overall after developing a protocol of recommended triggers for consultation, many patients who met criteria at admission did not receive early PCC. Further research is needed to elucidate reasons why providers may be resistant to PCC.

Pharmacological Augmentation in Unipolar Depression: A Guide to the Guidelines.

BACKGROUND: Pharmacological augmentation is a recommended strategy for patients with treatment-resistant depression. A range of guidelines provide advice on treatment selection, prescription, monitoring and discontinuation, but variation in the content and quality of guidelines may limit the provision of objective, evidence-based care. This is of importance given the side effect burden and poorer long-term outcomes associated with polypharmacy and treatment-resistant depression. This review provides a definitive overview of pharmacological augmentation recommendations by assessing the quality of guidelines for depression and comparing the recommendations made. METHODS: A systematic literature search identified current treatment guidelines for depression published in English. Guidelines were quality assessed using the Appraisal of Guidelines for Research and Evaluation II tool. Data relating to the prescription of pharmacological augmenters were extracted from those developed with sufficient rigor, and the included recommendations compared. RESULTS: Total of 1696 records were identified, 19 guidelines were assessed for quality, and 10 were included. Guidelines differed in their quality, the stage at which augmentation was recommended, the agents included, and the evidence base cited. Lithium and atypical antipsychotics were recommended by all 10, though the specific advice was not consistent. Of the 15 augmenters identified, no others were universally recommended. CONCLUSIONS: This review provides a comprehensive overview of current pharmacological augmentation recommendations for major depression and will support clinicians in selecting appropriate treatment guidance. Although some variation can be accounted for by date of guideline publication, and limited evidence from clinical trials, there is a clear need for greater consistency across guidelines to ensure patients receive consistent evidence-based care.

Side effect profile and comparative tolerability of 21 antidepressants in the acute treatment of major depression in adults: protocol for a network meta-analysis.

INTRODUCTION: We have recently compared all second-generation as well as selected first-generation antidepressants in terms of efficacy and acceptability in the acute treatment of major depression. Here we present a protocol for a network meta-analysis aimed at extending these results, updating the evidence base and comparing all second-generation as well as selected first-generation antidepressants in terms of specific adverse events and tolerability in the acute treatment of major depression in adults. METHODS AND ANALYSIS: We will include all double-blind randomised controlled trials comparing one active drug with another or with placebo in the acute treatment major depression in adults. We will compare the following active agents: agomelatine, amitriptyline, bupropion, citalopram, clomipramine, desvenlafaxine, duloxetine, escitalopram, fluoxetine, fluvoxamine, levomilnacipran, milnacipran, mirtazapine, nefazodone, paroxetine, reboxetine, sertraline, trazodone, venlafaxine, vilazodone and vortioxetine. The main outcomes will include the total number of patients experiencing specific adverse events; experiencing serious adverse events; and experiencing at least one adverse event. Published and unpublished studies will be retrieved through relevant database searches, trial registries and websites; reference selection and data extraction will be completed by at least two independent reviewers. For each outcome we will undertake a network meta-analysis to synthesise all evidence. We will use local and global methods to evaluate consistency. We will perform all analyses in R. We will assess the quality of evidence contributing to network estimates with the Confidence in Network Meta-Analysis web application. DISCUSSION: This work will provide an in- depth analysis and an insight into the specific adverse events of individual antidepressants. ETHICS AND DISSEMINATION: This review does not require ethical approval. PROSPERO REGISTRATION NUMBER: CRD42019128141.