depression in heart failure: best treatments

A recent systematic review and network meta-analysis found exercise and cognitive behavioral therapy were superior to meds in treating depression in patients with heart failure (see depression in heart failure CBT jpsychres2019 in dropbox, or doi.org/10.1016/j.jpsychires.2018.10.007

Details: 

-- 21 RCTs were identified with 4563 heart failure patients assessing depression treatment with exercise therapy (ET), cognitive behavioral therapy (CBT), or antidepressant medications (AD) 

  -- 1989 patients received an active intervention versus 1826 controls 

        -- 15 RCTs with 3309 patients compared ET with usual care 

        -- 4 RCTs with 390 patients compared CBT with usual care 

        -- 3 RCTs with 878 patients compared AD with placebo 

-- mean age 63 years, 61% men. 47% from North America/43% Europe/5% from South America and Australia 

-- median follow-up duration 3.5 months, with minimum of 1.5 months; median sample size 208 patients (studies ranging from 24 to 2322) 

-- given that these studies measured somewhat different outcomes (depression scores, changes in cognitive behavior, health-related quality of life, functional status, psychological states), they assessed the standardized mean difference (SMD) of the different interventions 

Results: 

-- in comparison to placebo or usual standard of care: 

    -- exercise therapy: SMD -0.38 (-0.54 to -0.22) 

    -- cognitive behavioral therapy: SMD -0.29 (-0.58 to -0.01) 

    -- antidepressant drugs: SMD -0.16 (-0.44 to 0.11), not statistically significant 

-- results of network meta-analysis: 

    -- comparing ET versus CBT: no difference, SMD 0.08 (-0.23 to 0.40) 

    -- comparing ET versus AD: no difference, SMD 0.21 (-0.10 to 0.53) 

    -- comparing CBT versus AD: no difference, SMD 0.13 (-0.26 to 0.53) 

-- subgroup analysis: 

    -- ET had better therapeutic effect for depression in patients <65 yo versus >65 yo: SMD -0.37 (-0.55 to -0.20), p <0.0001 

    -- no difference in depression symptoms with duration of follow-up being >3 months, vs <3 mo; or with LVEF >50%, vs <50% 

Commentary: 

-- patients with heart failure have a significantly higher risk of depression, up to almost 3 times that of the general population 

-- and, depression has been shown to be an independent risk factor for poor prognosis in those post-MI or with acute coronary syndromes, as reinforced in the 2014 American Heart Association guidelines. Notably, there seems to be increased mortality, morbidity, and 30-day rehospitalization rates 

-- although studies have suggested that there may be some benefit for antidepressant medications, exercise training, and cognitive behavioral therapy for depression in patients with heart failure, there have been no head-to-head comparisons. Therefore, a network meta-analysis:

    --a network meta-analysis is a mathematical technique used to compare and combine outcomes from different studies using different therapies: e.g. comparing the relative effects of intervention A vs intervention B, though actual studies were only with either intervention A or B vs placebo; and then making a complex mapping comparing the likely benefit of intervention A vs intervention B, etc. Though helpful, it should be stressed that these results are much less rigorous than a direct comparison of interventions in a randomized controlled trial of a single group of patients

--so, the basic findings of the study were: 

    -- both ET and CBT had significant reductions in depressive symptoms in patients with heart failure 

    -- antidepressant meds did not have clear therapeutic benefit over placebo or usual care 

-- more studies and many more patients were involved in patients getting exercise therapy. There are accumulating data showing that exercise also significantly improves cardiovascular outcomes, e.g. functional capacity, improving cardiovascular risk factors, and improving clinical outcomes (e.g. for a review of the benefits of vigorous exercise in those with heart failure with reduced ejection fraction, see http://gmodestmedblogs.blogspot.com/2016/09/vigorous-exercise-helps-those-with.html ). Other studies have found benefit of exercise therapy in treating patients with depression and ischemic heart disease

-- studies have also suggested that combining exercise therapy and CBT may be better than either therapy alone 

-- not only do drugs appear to be ineffective, many are quite cardiotoxic: QTc prolongation, arrhythmias, orthostatic hypotension etc. 

-- limitations of this study include: inherent heterogeneity between the studies in terms of heart failure (different stages, etiologies, follow-up duration, cardiovascular outcomes) as well as depression characteristics (10 of the 21 studies did not assess changes in depression score as a primary outcome, many evaluating different quality of life measures), comorbidities (including meds used to treat cardiovascular risk factors, sleep), general demographics (e.g. socioeconomic factors), and other study characteristics such as variable duration of follow-up (studies with shorter duration of follow-up are less likely to show a benefit from meds). These types of heterogeneity are common in network meta-analyses. 

-- And, the relatively small changes in the SMD would best be evaluated further with RCTs to assess the real clinical significance

So, this study adds to the long list of benefits of exercise, this time in treating depression in patients with heart failure. and for these patients, this is in addition to the well-established cardiovascular benefits of exercise. 

a recent blog on exercise reviewed a long-term study suggesting that even 5-10 minutes of light-to-moderate exercise had significant mortality benefit: see https://gmodestmedblogs.blogspot.com/2019/03/5-10-min-of-exercise-may-improve-health.html , which also includes many blogs on the effects of exercise on a myriad of different health outcomes.

geoff​

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geoff