An expert consensus on the most effective components of cognitive behavioural therapy for adults with depression: a modified Delphi study.

Designing new approaches to delivering cognitive behavioural therapy (CBT) requires an understanding of the key components. This study aimed to establish an expert consensus on the effective components of CBT for depressed adults. An international panel of 120 CBT experts was invited to participate in a modified Delphi study. Thirty-two experts participated in round 1; 21 also provided data in round 2. In round 1, experts rated the effectiveness of 35 content and process components. A priori rules identified components carried forward to round 2, in which experts re-rated items and final consensus items were identified. Consensus was achieved for nine content components (ensuring understanding; developing and maintaining a good therapeutic alliance; explaining the rationale for CBT; eliciting feedback; identifying and challenging avoidant behaviour; activity monitoring; undertaking an initial assessment; relapse prevention methods; homework assignments); and three process components (ensuring therapist competence; scheduling sessions flexibly; scheduling sessions for 45-60 mins). Five of the twelve components identified were generic therapeutic competences rather than specific CBT items. There was less agreement about the effectiveness of cognitive components of CBT. This is an important first step in the development of novel approaches to delivering CBT that may increase access to treatment for patients.

The process and delivery of CBT for depression in adults: a systematic review and network meta-analysis.

Cognitive-behavioural therapy (CBT) is an effective treatment for depressed adults. CBT interventions are complex, as they include multiple content components and can be delivered in different ways. We compared the effectiveness of different types of therapy, different components and combinations of components and aspects of delivery used in CBT interventions for adult depression. We conducted a systematic review of randomised controlled trials in adults with a primary diagnosis of depression, which included a CBT intervention. Outcomes were pooled using a component-level network meta-analysis. Our primary analysis classified interventions according to the type of therapy and delivery mode. We also fitted more advanced models to examine the effectiveness of each content component or combination of components. We included 91 studies and found strong evidence that CBT interventions yielded a larger short-term decrease in depression scores compared to treatment-as-usual, with a standardised difference in mean change of -1.11 (95% credible interval -1.62 to -0.60) for face-to-face CBT, -1.06 (-2.05 to -0.08) for hybrid CBT, and -0.59 (-1.20 to 0.02) for multimedia CBT, whereas wait list control showed a detrimental effect of 0.72 (0.09 to 1.35). We found no evidence of specific effects of any content components or combinations of components. Technology is increasingly used in the context of CBT interventions for depression. Multimedia and hybrid CBT might be as effective as face-to-face CBT, although results need to be interpreted cautiously. The effectiveness of specific combinations of content components and delivery formats remain unclear. Wait list controls should be avoided if possible.

Mirtazapine added to SSRIs or SNRIs for treatment resistant depression in primary care: phase III randomised placebo controlled trial (MIR).

OBJECTIVE: To investigate the effectiveness of combining mirtazapine with serotonin-noradrenaline reuptake inhibitor (SNRI) or selective serotonin reuptake inhibitor (SSRI) antidepressants for treatment resistant depression in primary care. DESIGN: Two parallel group multicentre phase III randomised placebo controlled trial. SETTING: 106 general practices in four UK sites; Bristol, Exeter, Hull, and Keele/North Staffs, August 2013 to October 2015. PARTICIPANTS: 480 adults aged 18 or more years who scored 14 or more on the Beck depression inventory, second revision, fulfilled ICD-10 (international classification of diseases, 10th revision) criteria for depression, and had used an SSRI or SNRI for at least six weeks but were still depressed. 241 were randomised to mirtazapine and 239 to placebo, both given in addition to usual SSRI or SNRI treatment. Participants were stratified by centre and minimised by baseline Beck depression inventory score, sex, and current psychological therapy. They were followed up at 12, 24, and 52 weeks. 431 (89.8%) were included in the (primary) 12 week follow-up. MAIN OUTCOME MEASURES: Depressive symptoms at 12 weeks after randomisation, measured using the Beck depression inventory II score as a continuous variable. Secondary outcomes included measures of anxiety, quality of life, and adverse effects at 12, 24, and 52 weeks. RESULTS: Beck depression inventory II scores at 12 weeks were lower in the mirtazapine group after adjustment for baseline scores and minimisation or stratification variables, although the confidence interval included the null (mean (SD) scores at 12 weeks: 18.0 (12.3) in the mirtazapine group, 19.7 (12.4) in the placebo group; adjusted difference between means -1.83 (95% confidence interval -3.92 to 0.27); P=0.09). Adverse effects were more common in the mirtazapine group and were associated with the participants stopping the trial drug. CONCLUSION: This study did not find evidence of a clinically important benefit for mirtazapine in addition to an SSRI or SNRI over placebo in a treatment resistant group of primary care patients with depression. This remains an area of important unmet need where evidence of effective treatment options is limited. TRIAL REGISTRATION: Current Controlled Trials ISRCTN06653773.

Involving patients with depression in research: survey of patients' attitudes to participation.

BACKGROUND: Clinicians report barriers to involving their patients in mental health research and have concerns that participation may have negative effects. AIM: To investigate patients' views on participating in a primary care randomised controlled trial (RCT) comparing two antidepressant drugs. DESIGN OF STUDY: Cross-sectional survey. SETTING: General practices, England. METHOD: Six hundred and one trial participants were surveyed about their reasons for, and experience of, participating. RESULTS: The questionnaire was completed by 252/601 (42%) participants. The most influential factors determining participation were: wanting to help others with depression (94%, 95% confidence interval [CI] = 90 to 97%) of responders rated this as 'important' or 'very important'); friendly researchers (94%, 95% CI = 90 to 96%); and interest in the research (88%, 95% CI = 83 to 91%). Most were glad they took part and would consider participating in future research. Ninety-six per cent (95% CI = 92 to 98%) reported that their confidence in their GP had increased or remained unchanged since referral. Qualitative analysis of free-text responses indicated that patients found participation beneficial and liked: being altruistic, doing something positive, feeling supported by the researchers, and having time to talk. Many gained understanding of their depression and valued feedback on their progress. A minority reported negative views, which commonly related to taking antidepressants, and answering questionnaires. CONCLUSION: GPs have a vital role in facilitating patient involvement in research but report barriers to referring depressed patients to RCTs. However, this data suggests that patients are willing to participate and many find this beneficial. Understanding attitudes to participation in mental health research is a crucial step in designing trials that are more acceptable to patients and GPs. This will strengthen the evidence for therapeutic approaches in primary care.

Bibliographic study showed improving methodology of meta-analyses published in leading journals 1993-2002.

OBJECTIVE: To assess the methodology of meta-analyses published in leading general and specialist medical journals over a 10-year period. STUDY DESIGN AND SETTING: Volumes 1993-2002 of four general medicine journals and four specialist journals were searched by hand for meta-analyses including at least five controlled trials. Characteristics were assessed using a standardized questionnaire. RESULTS: A total of 272 meta-analyses, which included a median of 11 trials (range 5-195), were assessed. Most (81%) were published in general medicine journals. The median (range) number of databases searched increased from 1 (1-9) in 1993/1994 to 3.5 (1-21) in 2001/2002, P<0.0001. The proportion of meta-analyses including searches by hand (10% in 1993/1994, 25% in 2001/2002, P=0.005), searches of the grey literature (29%, 51%, P=0.010 by chi-square test), and of trial registers (10%, 32%, P=0.025) also increased. Assessments of the quality of trials also became more common (45%, 70%, P=0.008), including whether allocation of patients to treatment groups had been concealed (24%, 60%, P=0.001). The methodological and reporting quality was consistently higher in general medicine compared to specialist journals. CONCLUSION: Many meta-analyses published in leading journals have important methodological limitations. The situation has improved in recent years but considerable room for further improvements remains.

Enhancement of antibody responses to influenza vaccination in the elderly following a cognitive-behavioural stress management intervention.

BACKGROUND: Previous research has demonstrated that the psychological morbidity experienced by informal caregivers is associated with increased vulnerability to infectious diseases, in particular influenza. A pragmatic trial was conducted to examine whether a stress management intervention (SMI) could reduce psychological morbidity and enhance the antibody response to influenza vaccination in the elderly, and whether changes in immune response of SMI participants were associated with hypothalamic-pituitary-adrenal (HPA) axis activity. METHODS: Forty-three elderly spousal carers of dementia patients and 27 non-carer controls were recruited. Sixteen carers were allocated to an 8-week SMI or a non-intervention condition (n = 27). The non-carers formed a no treatment, 'normal' comparison group. At the end of the SMI or its equivalent time period, all participants received an influenza vaccination. IgG antibody titres to the vaccine were measured 0, 2, 4 and 6 weeks post-vaccine. RESULTS: There was evidence of elevated distress in both carer groups compared with non-carer controls throughout the SMI period, but no between-group differences in salivary cortisol. Immune responses to the vaccine revealed that 50% of SMI carers, 7% of non-intervention carers and 29% of non-carer controls produced a four-fold increase in antibody titre. CONCLUSIONS: The immune response to influenza vaccination appears amenable to improvement through stress management, although the mechanisms underlying this effect remain unclear.

An investigation into the relationship between salivary cortisol, stress, anxiety and depression.

This study examined the relationship between indices of self-reported emotional distress and absolute versus change in cortisol levels. Fifty-four women attending a diagnostic breast clinic completed scales measuring stress, anxiety and depression and provided five saliva samples over the course of a single day for the measurement of cortisol. No significant relationships were evident between absolute cortisol levels and the distress measures. Analysis of the change in cortisol levels revealed a non-linear interaction effect between stress and anxiety and time of day. There was a non-linear relation between time of day and cortisol levels, but the extent of the non-linearity was dependent upon levels of stress and anxiety, not depression. A relationship was apparent between indices of distress and change in cortisol levels, but not absolute levels of the hormone.

Chronic stress in nonelderly caregivers: psychological, endocrine and immune implications.

OBJECTIVE: This investigation examined whether the immune dysregulation that characterises elderly informal caregivers (e.g., spousal caregivers of dementia patients) extends to a younger caregiver population, specifically spousal carers of patients with multiple sclerosis (MS). METHOD: MS spousal caregivers (n=41, mean age 43 years, 14 women, 27 men) and noncaregiving controls (n=62, mean age 33 years, 44 women, 18 men) were recruited. Psychological morbidity (i.e., self-reported stress, anxiety and depression), endocrine activity (i.e., salivary cortisol and DHEAs) and immunity (i.e., IgG and HAI responses to influenza vaccination and IFN-gamma and IL-4 levels) were assessed. RESULTS AND CONCLUSIONS: MS caregivers and noncaregivers did not differ significantly in their IgG or HAI responses to influenza vaccination or in levels of IFN-gamma and IL-4. However, it remains unclear whether the "preserved" immune response of these younger caregivers was due to (1) an absence of immune senescence, (2) a relative absence of psychological morbidity, or both.