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.

Dog visits in nursing homes - increase complexity or keep it simple? A randomised controlled study.

OBJECTIVE: To compare the immediate response of nursing home residents to dog visits with or without an activity, and the impact of cognitive ability. METHODS: In a randomly controlled trial, 174 nursing home residents were allocated to 12 bi-weekly 10-minute visits: either ordinary dog visits (D, n = 57, 49 analysed), dog visits with an activity (DA, n = 56, 48 analysed), or visits with activity but no dog (A, n = 61, 54 analysed). We recorded frequency and duration of residents' verbal and physical interactions with the dog and persons. Data were analysed in three periods of four visits (period 1-3) as binomial variables (generalised linear models) or durations (non-parametric statistics). RESULTS: Both visit type and impairment level affected the likelihood of interacting with the dog (D and DA). In some periods increased cognitive impairment lowered odds of touching the dog in DA visits (period 1: F1,85 = 5.17, P < 0.05) and talking to it directly (period 1: F1,90 = 4.60, P < 0.05; period 3: F1,87 = 5.34, P < 0.05). Throughout, residents talked less to persons during DA visits compared to D and A (P = 0.01-0.05), and level of cognitive impairment correlated negatively with talk duration (P < 0.001). Generally, high cognitive impairment level lowered odds of interacting with (period 1: F1,89 = 7.89, P < 0.01; period 2: F1,97 = 6.76, P = 0.01; period 3: F1,92 = 13.57, P < 0.001) and talking about the activities (period 1: F1,89 = 13.78, P <0.001; period 2: F1,88 = 3.27, P = 0.07; period 3: F1,86 = 3.88, P = 0.05). CONCLUSION: Visits without specific activities stimulated residents to interact with the dog, whereas increasing the complexity of dog visits by adding activities resulted in less interaction with the dog for severely impaired residents. The optimal dog visit for the less cognitively impaired residents could include activities and thereby a possibility to interact with the dog in different ways, whereas for severely impaired residents, just being with the dog seems more appropriate.

Predictors of response to combined wake and light therapy in treatment-resistant inpatients with depression.

There is growing evidence for combined chronotherapeutic interventions as adjunctive treatments for major depression. However, as the treatments can be demanding, we need to identify predictors of response. This study aimed to describe predictors of response, remission and deterioration in the short-term phase, as well as predictors of long-term response. The predictors investigated were gender, type of depression, severity of depression, treatment resistance, quetiapine use, general self-efficacy, educational level and positive diurnal variation. Follow-up data from 27 inpatients with moderate-to-severe depression participating in a chronotherapeutic intervention were analysed. As a supplement to standard treatment, they completed 3 wake therapy sessions in the first week, 30 min daily light treatment and sleep-time stabilisation in the entire 9-week study period. Patients had a significant decrease of depressive symptoms during the first 6 days measured by HAM-D6. At Day 6, 41% of the patients responded to the treatment and 19% fulfilled the criteria of remission. Deterioration by the end of wake therapy sessions was however not uncommon. In the short-term phase, mild degree of treatment resistance was associated with remission and low educational level associated with deterioration. Positive diurnal variation (mood best in the evening) was a predictor of both short-term and long-term response to combined wake and light therapy. Furthermore, patients with evening chronotypes (measured with morningness-eveningness score) were more responsive. Our results suggest that targeting the combined chronotherapeutic intervention at patients with positive diurnal variation and evening types is a viable option.

Experiences of wake and light therapy in patients with depression: A qualitative study.

Wake therapy can reduce depressive symptoms within days, and response rates are high. To sustain the effect, it is often combined with light therapy. Few studies have focussed on factors related to patients' adherence to the regime, and none has used qualitative methods to examine their experience of these combined interventions. Therefore, the aim of the present study was to illuminate patients' experiences with wake and light therapy and factors related to adherence. Thirteen inpatients with depression were included. They participated in an intervention consisting of three wake therapies during the first week, 30 min of daily light treatment for the entire 9 weeks, and ongoing psychoeducation regarding good sleep hygiene. Patients kept a diary, and individual semistructured interviews were conducted. Data were analysed using qualitative content analysis. The participants' overall experience with the treatment was positive. Some experienced a remarkable and rapid antidepressant effect, whereas others described more long-term benefits (e.g. improved sleep and diurnal rhythm). Yet recovery was fragile, and patients were only cautiously optimistic. Social support was important for maintaining the motivation to stay awake and receive daily light therapy. Overall, participants found the treatment worthwhile and would recommend it to others with depression. The study revealed a lack of knowledge among participants about the connection between regular sleep patterns and depression. In conclusion, this study provides insight into patients' experiences, and knowledge that can contribute to guidelines for future adherence-promoting organization of wake and light therapy.

[Wake therapy for major depression]. / Vågenterapi mod depression

Patients admitted with depression are highly tormented and many are suicidal. Standard treatment does not offer full effect until after several weeks. Wake therapy is a method that may reduce depressive symptoms within days. In this paper, the literature regarding wake therapy is reviewed. The response rates in wake therapy are high, but the effect is often transitory. However, recent studies indicate that wake therapy in combination with other chronotherapeutic interventions, e.g. light therapy, can produce a rapid and sustained antidepressant effect.

The Danish PET/depression project: performance on Stroop's test linked to white matter lesions in the brain.

The Stroop test (ST) assesses the integrity of prefrontal and cingulate functioning. Patients with major depression perform poorly on the ST, pointing to disturbed function in these areas. We therefore used positron emission tomography to study 41 in-patients with major depression and 46 age- and gender-matched controls during neuropsychological activation with the ST. Magnetic resonance imaging was used for coregistration and for description of the localization of white matter lesions (WML). The cerebral blood flow (CBF) changes during ST were mapped for each of the two study groups, and inter-group differences were calculated on a voxel-by-voxel basis. The patients were followed for 3 to 5 years to ensure diagnostic stability. The control group activated anterior cingulate regions, prefrontal cortices, insula, thalamus and cerebellum. Despite the patients' slower performance with more errors, no significant differences were found comparing the activations in the two groups. The performance was, however, correlated to the number of WML in frontal lobes, insula and adjacent to the basal ganglia, whereas WML in other locations was not related to performance. We thus partly explain the poorer performance by increased frequency of WML in frontostriatal pathways in the depressed patients, impairing neurotransmission.

The Danish PET/depression project: poor verbal fluency performance despite normal prefrontal activation in patients with major depression.

The verbal fluency (VF) test is associated with prefrontal and cingulate functioning. We used positron emission tomography (PET) to test the hypothesis that inactivity in these regions can explain why patients with depression often perform poorly on this test. Forty-one patients with major depression and 46 controls were scanned during rest and during activation with the VF test. The differences between the two conditions were mapped for each of the two groups, and between-group differences in the activation pattern were calculated on a voxel-by-voxel basis. As predicted, the patients performed significantly more poorly on the test. In both groups activations were seen in the left anterior cingulate region, the left dorsolateral prefrontal cortex, the left medial prefrontal cortex, and the right cerebellum. Performance was correlated to the cerebral perfusion in to the left occipitotemporal gyrus and the left cerebellum. However, no difference in activation between the two groups was significant. The present study had sufficient power to detect potential differences between the two groups, and the subtraction tasks were appropriate. Therefore, the result supports the notion that abnormalities in the prefrontal cortex in depression are qualitative in nature rather than quantitative; this suggests depression involves dys-coordination of neural activity in the frontal lobes rather than a simple reduction in activity.