By Ellen Feldman, MD
Altru Health System, Grand Forks, ND
Summary Points
- Adult patients with depression or anxiety were randomized or self-selected into either running therapy (96 participants) or antidepressant therapy (45 participants).
- Assessments were given periodically and at treatment conclusion (week 16). They measured depression, anxiety, and several measures of physical health in all participants.
- By week 16, depression and anxiety showed equal remission rates in both arms, but only the running program arm showed improvement in multiple health parameters (including weight loss and decrease in systolic blood pressure) while the antidepressant arm showed deterioration in those same measures (including weight gain, decreased heart rate variability, and increased C-reactive protein).
SYNOPSIS: This prospective study blending randomization with preference compared a running program with antidepressant therapy in adults with depression or anxiety and showed an improvement in mental health in both arms. However, physical health parameters increased only in the running group.
SOURCE: Verhoeven JE, Han LKM, Lever-van Milligen BA, et al. Antidepressants or running therapy: Comparing effects on mental and physical health in patients with depression and anxiety disorders. J Affect Disord 2023;329:19-29.
Mental disorders, including depression and anxiety, frequently are linked to a shortened lifespan.1 This likely is caused by multiple interconnected factors, including a reciprocal relationship between physical and mental health impairments as well as the potential adverse effects of some psychiatric medications on overall health and well-being.1-3
The standard first-line treatment for depressive disorders and anxiety includes psychotherapy and/or antidepressant medication. Studies show moderate effectiveness and tolerability for both interventions. However, not all patients respond to those treatments, and other barriers may remain, including limited access to therapy, unaffordability of medication, and intolerance to side effects.4
Several meta-analyses underscore the effectiveness of supervised aerobic exercise as an initial treatment for mild to moderate depression and as a supplementary treatment for severe depression.
While research on exercise as a treatment for anxiety disorders is less extensive, the existing studies show encouraging outcomes. However, despite a seemingly apparent connection, the direct effects of these interventions on physical health are not well studied.5,6
To address this gap, Verhoeven et al designed a study to investigate the effects on depression or anxiety and parameters of physical health when comparing a structured running program (“running therapy”) with antidepressant therapy in adults with anxiety or depression.
The MOod Treatment with Antidepressant or Running (MOTAR) study, based in the Netherlands, was a 16-week partially randomized intervention. This study had two treatment arms — antidepressant therapy and running therapy. Adult patients meeting Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) criteria for a depressive or anxiety disorder were recruited from local clinics to participate.
Participants without a strong preference were randomly assigned to one of the treatment arms, whereas those with a clear preference were sorted to their group of choice. Psychotherapy outside the study was permitted to continue for any patient wanting to do so.
Patients in the antidepressant arm received a standard selective serotonin reuptake inhibitor (SSRI) — escitalopram (beginning at 10 mg with titration to 20 mg if necessary). If this was not well tolerated or appeared ineffective, a different SSRI (sertraline, 50 mg to 150 mg) was prescribed. All participants periodically met with a psychiatrist, and adherence was evaluated by both patient report and psychiatrist record.
Running therapy consisted of a supervised 45-minute outdoor session two to three times a week with monitoring by a running therapist and staff members. All patients wore heart rate monitors, and optimal heart rate range was calculated after a baseline assessment. Data could be uploaded after each session to assure compliance. Patients were able to participate from home for a portion of sessions.
Mental health outcomes were described as full remission or response (severity reduction of at least 50%) at week 16 on either a depression or anxiety inventory administered as part of a structured psychiatric interview.
Physical health measures included serum measures of inflammation, including C-reactive protein (CRP), blood pressure, weight, waist circumference, and heart rate variability.
This study enrolled 141 eligible patients. However, only 22 agreed to random assignment. This led to 96 participants in the running therapy arm and 45 in the antidepressant arm.
To ensure a robust analysis, the study accounted for the differing selection processes by demonstrating that there were no significant differences in outcomes between the randomized participants and those who self-selected their group.
The following results are worth noting:
- Baseline characteristics, such as age, lifestyle, and marital status of both groups were statistically equivalent. However, the mean depression severity of the antidepressant group was significantly higher than the running therapy group (P = 0.028); this was considered in subsequent calculations.
- Treatment compliance was significantly higher in the antidepressant group (P < 0.001).
- Mental health outcomes were similar for the two groups (P = 0.20-0.88). The Inventory of Depressive Symptomatology-Self-Report (IDS-SR) was used to measure depression severity, whereas the Beck Anxiety Inventory was used to evaluate anxiety severity. These questionnaires were accompanied by psychiatric interviews.
- Physical health outcomes differed significantly between the groups and, in general, were more favorable in the running therapy group.
Table 1 shows more details regarding the between-group comparisons for the treatment arms.
Table 1. Between-Group Comparisons of Antidepressant vs. Running Therapy |
|||
| Antidepressant Group (n = 45) |
Running Therapy Group (n = 96) |
P Value | |
Remission rate for depression (no longer meets diagnostic criteria) at week 16 |
44.8% |
43.3% |
0.881 |
Response rate for depression (at least 50% symptom reduction with remaining symptoms) at week 16 |
34.2% |
30.3% |
0.730 |
Treatment compliance |
82.2% |
52.1% |
< 0.001* |
Response rate for anxiety (at least 50% symptom reduction with remaining symptoms) at week 16 |
47.2% |
32.4% |
0.196 |
Mean weight change at week 16 |
-0.6 kg |
3.3 kg |
0.001* |
Waist circumference at week 16 |
1.5 |
-1.6 |
0.011* |
Diastolic blood pressure change at week 16 |
1.9 |
-2.9 |
0.002* |
Heart rate variability change at week 16 |
-14.4 |
1.2 |
0.006* |
*Statistically significant values |
|||
Within the antidepressant group, there was a significant decline in measures of physical health, including heart rate variability (mean = 17.0; P < 0.001), an increase in mean weight (+ 3.2 kg; P = 0.22), and an increase in CRP (mean = 1.59; P < 0.001).
Commentary
Depression and anxiety affect more than 4% of the global population, significantly contributing to the morbidity and mortality of other chronic illnesses as well as overall disability rates. Despite the evolution of antidepressant and talk therapies over the last several decades, there remains an urgent need for treatments that are more universally effective and safe.6,7
Verhoeven et al highlight a crucial gap in treatment efficacy and tolerability, suggesting the potential benefits of incorporating physical activity, specifically structured running therapy, into depression treatment plans. Their research not only explores the overall effectiveness of this approach, but it also compares the physical health changes that accompany running therapy with those from conventional antidepressant treatments. The findings reveal not only the expected improved physical health outcomes with running therapy, but also a less expected and concerning decline in those treated with antidepressants.
Among the notable findings from this study are the similar rates of remission and response for depression and for anxiety in both groups. However, it is striking that a significant portion of participants remained symptomatic at week 16, indicating the need for further research to identify patient characteristics that predict treatment response. Investigating whether individuals who do not respond well to one treatment might benefit more from the other, or from a combination of both, could provide valuable insights.
It is notable that this study allowed patients previously involved with psychotherapy to continue but did not evaluate the role of this treatment in addressing either anxiety or depression. Exploring a combination of psychotherapy with running therapy and/or antidepressant medication might uncover more effective individualized treatment strategies. Additionally, it is important to acknowledge the distinct difference in treatment adherence between the two groups. The running therapy group exhibited a significantly lower adherence rate (52.1%) than the antidepressant group (82.2%). Investigating motivational factors could shed light on this discrepancy and inform tailored treatment strategies. Moreover, the reduced adherence in the running therapy group might indicate challenges faced by participants in meeting the required levels of physical activity and exertion required for this intervention.
For now, integrative providers are well-positioned to consider the implications of this study when working with patients with either depression or anxiety. Monitoring both symptom response and physical health, and proactively addressing any decline, is optimal. Recognizing the interconnectedness of the body and mind is essential for a holistic, comprehensive approach to health and wellness.
References
- Plana-Ripoll O, Pedersen CB, Agerbo E, et al. A comprehensive analysis of mortality-related health metrics associated with mental disorders: A nationwide, register-based cohort study. Lancet 2019;394:1827-1835.
- Walker ER, McGee RE, Druss BG. Mortality in mental disorders and global disease burden implications: A systematic review and meta-analysis. JAMA Psychiatry 2015;72:334-41.
- Stegenga BT, Nazareth I, Torres-González, Xavier M, et al. Depression, anxiety and physical function: Exploring the strength of causality. J Epidemiol Community Health 2012;66:e25.
- Schuch FB, Vancampfort D. Physical activity, exercise, and mental disorders: It is time to move on. Trends Psychiatry Psychother 2021;43:177-184.
- McKeon G, Curtis J, Rosenbaum S. Promoting physical activity for mental health: An updated evidence review and practical guide. Curr Opin Psychiatry 2022;35:270-276.
- World Health Organization. Depressive disorder (depression). Published March 31, 2023. https://www.who.int/news-room/fact-sheets/detail/depression
- American Psychological Association. APA clinical practice guideline for the treatment of depression across three age cohorts. Published February 2019. https://www.apa.org/depression-guideline/guideline.pdf
This prospective study blending randomization with preference compared a running program with antidepressant therapy in adults with depression or anxiety and showed an improvement in mental health in both arms. However, physical health parameters increased only in the running group.
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