Bricca et al (2020)

Benefits and harms of exercise therapy in people with multimorbidity.

Exercise is safe and reduces the risk of serious adverse events in people with multimorbidity.

Younger people with multimorbidity may achieve more improvements in health-related quality of life following exercise therapy.

People with more severe depression might obtain larger reductions in depressive symptoms.


Patients presenting in clinical practice often have multiple health conditions, labeled as multimorbidity. This became increasingly investigated and was defined as a priority for global health research (Anon et al. 2018) Having multiple health conditions is associated with worse physical and psychological health, more drug use, and health care utilization, and apparently, it also increases the risk of premature death and the duration of hospital admissions. Earlier on, healthcare focussed mainly on treating these existing health conditions separately. Nowadays, the importance of individualized therapy for the individual as a whole emerges, meaning that the focus lies more on specific combinations of conditions, linked by physiological factors and risk factors. For osteoarthritis of the knee or hip, hypertension, type 2 diabetes, depression, heart failure, ischemic heart disease, and chronic obstructive pulmonary disease (COPD) alone, exercise was shown to be effective and safe. The assumption that for combinations of these health conditions exercise may be beneficial as well arises from the fact that these conditions share a common risk factor (physical inactivity) and pathogenesis (systemic low-grade inflammation), for which exercise was proven effective. This synopsis summarizes the evidence on exercise therapy for people with multimorbidity from the systematic review with meta-analysis of Bricca et al. which was published in 2020.



The review included RCTs examining exercise therapy interventions with or without other interventions compared to standard care, wait-and-see and placebo treatments. The outcomes assessed were:

  • Health-related quality of life
  • Physical function
  • Symptoms of depression and anxiety



Twenty-three studies were found eligible of which thirteen studies were included in the meta-analysis.

Exercise therapy with an average duration of thirteen weeks was found to cause a small improvement in health-related quality of life, but this finding comes with considerable heterogeneity. Meta-regressions indicated that increasing age was associated with lower effect sizes, meaning that the younger the patient, the more improvements may be expected.

When examining the effect of exercise at one year, a small improvement in health-related quality of life remained, with low heterogeneity.

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From: Bricca et al (2020)


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From: Bricca et al (2020)


Thirteen studies were included measuring the effect of exercise on objectively measured physical function. Exercise of an average duration of twelve weeks showed a small improvement in physical function, although with considerable heterogeneity. However, when considering studies using the 6-minute walk test as an outcome measure, an improvement of nearly forty-three meters of walking distance was observed, with low heterogeneity. This improvement is greater than the 30-meter cut-off generally used in people with chronic conditions. At 1 year, the small effect remained, with considerable heterogeneity. No effect of exercise on self-reported physical function was found, although this was only examined by two studies.

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From: Bricca et al (2020)


Exercise therapy with an average duration of 13 weeks was able to cause a large reduction in depression, but this comes with high heterogeneity. Meta-regression showed that exercise in individuals with higher levels of depression was able to cause a greater reduction of these depressive symptoms. This finding may be partially explained by the regression to the mean phenomenon. At one year, exercise therapy did not exert an effect on depression.

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From: Bricca et al (2020)


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From: Bricca et al (2020)


Exercise therapy with an average duration of thirteen weeks was not able to show reductions in anxiety levels.

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From: Bricca et al (2020)


Overall, exercise caused no more adverse events compared to usual care and on the contrary, exercise therapy was able to reduce the risk of serious adverse events like hospitalisation, death, pneumonia, and cardiac disorders.

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From: Bricca et al (2020)


Talk nerdy to me

A rigorous systematic review and meta-analysis were conducted. Important to note is that no language restrictions were used in the search for papers. Studies from across the globe were included, which makes it likely that the results of this paper are widely generalizable. A date restriction from 1990 was used, but this was properly explained by the increased reporting and the substantial change in treatment of multimorbidity since then. Strengths are the fact that the majority of studies applied proper randomization and assessed the outcomes with validated measures. No evidence of publication bias arose and the authors took bias into account by downgrading the quality of evidence.

Some limitations include that some studies did not include patients with multimorbidity alone. As heterogeneity exists in the definition of multimorbidity and in the interventions, this may imply that the effects seen were not true effects of exercise therapy alone.


Questions and thoughts

Overall, small effects were found for exercise therapy being effective in increasing health-related quality of life, and physical function, and in decreasing depressive symptoms. Importantly, exercise was able to cause an important reduction in the risk of serious adverse events like hospitalization, death, pneumonia, and cardiac disorders. Although these conclusions are based on low-quality evidence, exercise seems safe and beneficial, and should therefore be recommended. The disappearance of the effects at one year may be explained by a decrease in exercise therapy adherence, for which we recommend longer durations of exercise therapy and implementation of exercise in the daily routine of these patients with multimorbidity. It would be interesting to look at the effects of exercise in studies reporting high treatment adherence. But a complete 100% exercise adherence might remain a dream for us as health care providers…


Take home messages

Exercise therapy consisting of aerobic exercise, strengthening, balance and flexibility exercises or a combination of these can be recommended in the treatment of patients with multimorbidity



Bricca, A., Harris, L. K., Jäger, M., Smith, S. M., Juhl, C. B., & Skou, S. T. (2020). Benefits and harms of exercise therapy in people with multimorbidity: a systematic review and meta-analysis of randomised controlled trials. Ageing research reviews63, 101166.

Boast, J., & Lancet. (2018). Making more of multimorbidity: an emerging priority. Lancet391(10131), 1637.



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