Treatment of difficult-to-treat depression - clinical guideline for selected interventions.

BACKGROUND: Difficult-to-treat-depression (DTD) is a clinical challenge. The interventions that are well-established for DTD are not suitable or effective for all the patients. Therefore, more treatment options are highly warranted. We formulated an evidence-based guideline concerning six interventions not well-established for DTD in Denmark. METHODS: Selected review questions were formulated according to the PICO principle with specific definitions of the patient population (P), the intervention (I), the comparison (C), and the outcomes of interest (O), and systematic literature searches were performed stepwise for each review question to identify relevant systematic reviews/meta-analyses, and randomized controlled trials. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was used to assess the methodological quality of the included studies. Clinical recommendations were formulated based on the evidence, the risk-benefit ratio, and perceived patient preferences. RESULTS: We found sufficient evidence for a weak recommendation of repetitive transcranial magnetic stimulation (rTMS) and cognitive behavioural analysis system of psychotherapy (CBASP). The use of bright light therapy in DTD was not sufficiently supported by the evidence, but should be considered as good clinical practice. The interventions should be considered in addition to ongoing antidepressant treatment. We did not find sufficient evidence to recommend intravenous ketamine/esketamine, rumination-focused psychotherapy, or cognitive remediation to patients with DTD. CONCLUSION: The evidence supported two of the six reviewed interventions, however it was generally weak which emphasizes the need for more good quality studies. This guideline does not cover all treatment options and should be regarded as a supplement to relevant DTD-guidelines.

A randomized, controlled trial assessing the acute efficacy of triple chronotherapy in unipolar depression.

BACKGROUND: Triple chronotherapy (wake night [one night without sleep], sleep phase advance, and early morning bright light exposure) demonstrated rapid efficacy primarily in bipolar depression, but has not been as well studied in unipolar depression. Our primary hypothesis is that triple chronotherapy is associated with a significantly greater Week 1 remission rate compared to the alternative protocol. METHODS: Unipolar depressed, nonpsychotic adult outpatients were randomized to triple chronotherapy or an alternative protocol (assigned sleep times without wake night, bright light exposure with blue-green wavelengths filtered out). Symptoms were assessed with Structured Interview Guide for Hamilton Depression Rating Scale with Atypical Supplement (SIGH-ADS) at each visit and a modified form (m-SIGH) daily for the first week. Response was defined as a 50% decrease in m-SIGH score, and remission as m-SIGH≤7, modified Clinical Global Impression-Improvement (m-CGI-I)≤2, and no depressed mood on m-SIGH. RESULTS: 44 patients (84.1% major depressive disorder, 75.0% persistent depressive disorder; 54.5% female; age mean±SD 38.3 ±â€¯15.2 years) were randomized to triple chronotherapy (N = 22) or an alternative protocol (N = 22). Week 1 remission rate was numerically higher but not statistically significant in the triple chronotherapy versus alternative protocol group (25.0% vs. 6.7%, Chi-square=1.76, df=1, p = 0.294). m-SIGH scores and response and remission rates on Days 2-7 were numerically improved without reaching statistical significance in the triple chronotherapy versus alternative protocol group. LIMITATIONS: Predominantly white, educated sample. CONCLUSIONS: This small pilot study demonstrated triple chronotherapy's feasibility and tolerability in unipolar depressed outpatients. Larger randomized trials are warranted to further characterize acute and long-term efficacy.

Metta-based group meditation and individual cognitive behavioral therapy (MeCBT) for chronic depression: study protocol for a randomized controlled trial.

BACKGROUND: Depression is a widespread disorder with severe impacts for individuals and society, especially in its chronic form. Current treatment approaches for persistent depression have focused primarily on reducing negative affect and have paid little attention to promoting positive affect. Previous studies have shown that metta meditation increases positive affect in chronically depressed patients. Results from previous trials provide evidence for the efficacy of a stand-alone metta meditation group treatment in combination with mindfulness-based approaches. Further research is needed to better understand the implementation of meditation practice into everyday life. Therefore, mindfulness and metta meditation in a group setting are combined with individual cognitive behavioral therapy (CBT) into a new, low-intensity, cost-effective treatment ("MeCBT") for chronic depression. METHODS/DESIGN: In this single-center, randomized, observer-blinded, parallel-group clinical trial we will test the efficacy of MeCBT in reducing depression compared to a wait-list control condition. Forty-eight participants in a balanced design will be allocated randomly to a treatment group or a wait-list control group. Metta-based group meditation will be offered in eight weekly sessions and one additional half-day retreat. Subsequent individual CBT will be conducted in eight fortnightly sessions. Outcome measures will be assessed at four time points: before intervention (T0); after group meditation (T1); after individual CBT (T2); and, in the treated group only, at 6-month follow-up (T3). Changes in depressive symptoms (clinician rating), assessed with the Quick Inventory of Depressive Symptoms (QIDS-C) are the primary outcome. We expect a significant decline of depressive symptoms at T2 compared to the wait-list control group. Secondary outcome measures include self-rated depression, mindfulness, benevolence, rumination, emotion regulation, social connectedness, social functioning, as well as behavioral and cognitive avoidance. We will explore changes at T1 and T2 in all these secondary outcome variables. DISCUSSION: To our knowledge this is the first study to combine a group program focusing on Metta meditation with state-of-the art individual CBT specifically tailored to chronic depression. Implications for further refinement and examination of the treatment program are discussed. TRIAL REGISTRATION: ISRCTN, ISRCTN97264476. Registered 29 March 2018 (applied on 14 December 2017)-retrospectively registered.