Resistance Exercise for Depression

(RESIST Trial)

Overseen By Jeni Lansing

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Wisconsin, Madison

Disqualifiers: Pregnancy, Obesity, Psychosis, Substance use, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 26

Duration: 16 weeks

200 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how varying levels of resistance exercise might help treat Major Depressive Disorder (MDD). Participants will be divided into two groups: one engaging in low-intensity workouts and the other in moderate-intensity workouts, both lasting 16 weeks. The trial targets adults diagnosed with MDD who have mild to moderate symptoms and are either not on mental health medication or have a stable regimen. Participants should be able to exercise safely and possess a smartphone.

As an unphased trial, this study offers a unique opportunity to contribute to understanding how exercise can benefit mental health.

Will I have to stop taking my current medications?

You don't have to stop taking your current medications if you have been on a stable mental health medication regimen for the past 8 weeks and are willing to continue it during the study.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that resistance exercise, such as lifting weights or using resistance machines, is generally safe for people. Studies have found that it can reduce symptoms of depression and lower the risk of death and heart disease, regardless of the amount of exercise performed.

Resistance training is well-tolerated by adults and linked to mental health benefits, regardless of exercise intensity. The reviewed studies did not report any major negative effects. Therefore, whether engaging in a lot or a little resistance exercise, current research indicates it is safe. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Resistance exercise is unique in treating depression because it provides both physical and mental health benefits, which are not typically the focus of traditional treatments like antidepressants or talk therapy. Most treatments for depression work by altering brain chemistry or addressing psychological factors, but resistance exercise offers a different approach by boosting endorphins and enhancing overall physical fitness, which can improve mood and self-esteem. Researchers are particularly excited about high-dose resistance training because it starts at a moderate intensity, potentially offering more significant mental health benefits faster than lower intensity options, which could lead to quicker improvements in mood and motivation. This approach may offer a holistic alternative or complement to existing therapies, with the added benefit of improving physical health.

What evidence suggests that this trial's resistance exercise treatments could be effective for Major Depressive Disorder?

This trial will compare High Dose Resistance Exercise Training with Low Dose Resistance Exercise Training for their effects on depression. Studies have shown that strength training can significantly reduce symptoms of depression. High-dose strength training, involving more intense workouts, has been linked to moderate improvements in depressive symptoms. Even low-dose strength training, which is less intense, can still moderately reduce these symptoms. Research indicates that both types of strength training can help treat major depressive disorder. Strength training, whether intense or not, often proves more effective than exercises like walking or jogging for improving mood and reducing depression. ^{2 5 6 7 8}

Who Is on the Research Team?

Jacob Meyer, PhD

Principal Investigator

University of Wisconsin, Madison

Are You a Good Fit for This Trial?

Adults aged 18-65 with Major Depressive Disorder as confirmed by a clinical interview, who have mild to severe depressive symptoms. Participants should either not be on mental health treatments or be on a stable regimen for at least 8 weeks and willing to maintain it. They must be safe to exercise per doctor's approval and cannot currently meet the resistance exercise recommendations, be pregnant, or have certain other mental health disorders.

Inclusion Criteria

I am not on mental health meds or I've been stable on my current mental health treatment for 8 weeks.

I am currently experiencing mild or more severe depression.

I have been diagnosed with major depression.

Exclusion Criteria

Currently pregnant, nursing, or planning to become pregnant during the trial

Currently meets resistance exercise recommendations (2 days per week) for the last 8 weeks

I have not had a concussion or brain injury in the last 3 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo a 16-week resistance exercise training program, with high vs low dose progressive RET in adults with DSM-5 diagnosed MDD.

16 weeks

Twice per week sessions

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments of cerebral blood flow, physical activity, and depression symptoms.

36 weeks

Assessments at weeks 26 and 52

What Are the Treatments Tested in This Trial?

Interventions

• High Dose Resistance Exercise Training
• Low Dose Resistance Exercise Training Group

Trial Overview The trial is testing how effective two different doses of resistance exercise training are in treating depression over a period of 16 weeks. It will compare the outcomes between a group doing low dose exercises against another doing high dose exercises.

How Is the Trial Designed?

Group I: High Dose Resistance Exercise Training Experimental Treatment 1 Intervention

Participants will complete a 16-week, twice/week progressive program beginning at a moderate intensity. Each session will last \~60 minutes and begin and end with a 5-minute warm-up/cool-down. Training will begin with standard familiarization sessions to introduce participants to the machines, teach correct lifting techniques, and ensure participant safety and comfort with each exercise machine. Participants will perform 3 sets of 8-12 repetitions on 9 different machines (i.e., leg press, hamstring curl, quadriceps extension, chest press, lat pulldown, shoulder press, biceps curl, triceps extension) and one body weight/free-weight abdominal exercise. Workload will begin at 60% of estimated 1-RM and will systematically and progressively increase during the intervention.

Group II: Low Dose Resistance Exercise Training Active Control 1 Intervention

Participants will complete a 16-week, twice/week progressive program beginning at a low intensity. Each session will last \~60 minutes and begin and end with a 5-minute warm-up/cool-down. Training will begin with standard familiarization sessions to introduce participants to the machines, teach correct lifting techniques, and ensure participant safety and comfort with each exercise machine. Participants will perform 3 sets of 8-12 repetitions on 9 different machines (i.e., leg press, hamstring curl, quadriceps extension, chest press, lat pulldown, shoulder press, biceps curl, triceps extension) and one body weight/free-weight abdominal exercise. Workload will begin at 30% of estimated 1-RM and will systematically and progressively increase during the intervention.

Who Is Running the Clinical Trial?

University of Wisconsin, Madison

Lead Sponsor

Trials

1,249

Recruited

3,255,000+

University of Minnesota

Collaborator

Trials

1,459

Recruited

1,623,000+

University of Limerick

Collaborator

Trials

71

Recruited

23,800+

National Institute of Mental Health (NIMH)

Collaborator

Trials

3,007

Recruited

2,852,000+

Iowa State University

Collaborator

Trials

63

Recruited

145,000+

Published Research Related to This Trial

Resistance training has significant health benefits as we age, including improved muscular strength and reduced risk of all-cause mortality, making it comparable to medicine.

Even minimal doses of resistance training (as little as 60 minutes per week, twice a week) can yield substantial physiological and psychological benefits, encouraging more people to participate despite time constraints or perceived difficulty.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A minimal dose approach to resistance training for the older adult; the prophylactic for aging. Fisher, JP., Steele, J., Gentil, P., et al.[2022]

Depressed patients often have low physical fitness due to inactivity, suggesting that incorporating physical fitness training into treatment for depression could be beneficial.

Exercise, including both aerobic and nonaerobic forms, has been shown to have antidepressant effects in patients with mild to moderate depression, and many patients continue exercising after treatment, leading to lower depression scores.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Benefits of exercise for the treatment of depression. Martinsen, EW.[2022]

In a study of 165 adults with unipolar depression, strength training significantly improved work capacity, reducing absenteeism by 12.1% compared to relaxation training, while aerobic training showed no significant effect on work absence.

Despite improvements in physical strength and aerobic capacity, neither strength nor aerobic training led to significant reductions in depression severity as measured by the Hamilton Rating Scale for Depression (HAM-D(17)) at 4 or 12 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The DEMO trial: a randomized, parallel-group, observer-blinded clinical trial of strength versus aerobic versus relaxation training for patients with mild to moderate depression. Krogh, J., Saltin, B., Gluud, C., et al.[2019]

Resistance training (RT) significantly reduces all-cause mortality and the incidence of cardiovascular disease while improving physical functioning in adults, based on an analysis of 11 systematic reviews involving over 382,000 participants.

Although adverse events were not consistently reported, serious adverse events related to RT were uncommon, suggesting that the benefits of resistance training outweigh the potential harms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Resistance training and health in adults: an overview of systematic reviews. El-Kotob, R., Ponzano, M., Chaput, JP., et al.[2021]

In a review of 121 trials involving 6700 older adults, most adverse events related to progressive resistance strength training were musculoskeletal issues like muscle strains and joint pain, particularly in participants with pre-existing health conditions or those engaging in high-intensity training.

Adverse events were often underreported, highlighting the need for clearer definitions and consistent reporting in future studies to better inform practitioners about the risks and benefits of strength training in older adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events reported in progressive resistance strength training trials in older adults: 2 sides of a coin. Liu, CJ., Latham, N.[2010]

In a randomized controlled trial with 55 young adults, eight weeks of resistance exercise training (RET) led to significant reductions in depressive symptoms, with a large effect size of 1.01 overall, indicating its effectiveness as a treatment for mild depression.

The study found even larger reductions in depressive symptoms among participants with Major Depressive Disorder (effect size of 1.71) and Generalized Anxiety Disorder (effect size of 1.39), suggesting that RET can be particularly beneficial for those at risk for elevated depressive symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of resistance exercise training on depressive symptoms among young adults: A randomized controlled trial. O'Sullivan, D., Gordon, BR., Lyons, M., et al.[2023]

A systematic review of supervised resistance training (RT) programs for individuals with depression identified four eligible studies, with mixed results; half showed positive effects on depressive symptoms while the other half did not.

Meta-analysis of the studies indicated significant benefits of RT in improving depressive symptoms in two out of four combinations, with moderate to small effect sizes, but high heterogeneity suggests that more well-designed randomized controlled trials are needed to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effects of Exclusively Resistance Training-Based Supervised Programs in People with Depression: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Carneiro, L., Afonso, J., Ramirez-Campillo, R., et al.[2020]

In a study of 55 middle-aged volunteers, resistance training significantly reduced depressed mood in individuals with high metabolic risk factors (HiMF), as shown by a decrease of 14.8 points on the Cardiac Depression Scale after 10 weeks of training.

The improvement in mood was correlated with increased muscle strength in the HiMF group, suggesting that resistance training not only enhances physical strength but also has a positive impact on mental health in those at risk for metabolic syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Resistance training improves depressive symptoms in individuals at high risk for type 2 diabetes. Levinger, I., Selig, S., Goodman, C., et al.[2017]

In a 15-year inpatient treatment program for depression, patients who participated in physical fitness training three times a week for six to nine weeks showed significant improvements in fitness levels and reductions in depression scores.

More than half of the patients continued to exercise regularly one year after discharge, and they ranked physical fitness training as one of the most valuable components of their treatment, indicating its long-term benefits and safety with no serious complications reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Physical training as a therapeutic method in depression]. Martinsen, EW.[2008]

A study involving 67 participants showed that online home-based resistance training significantly improved depressive symptoms, as measured by the CES-D scale, after eight weeks of training.

The training also enhanced fitness parameters, indicating that low-load resistance exercises can be an effective way to improve mental health and physical fitness, even when conducted online.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Online Home-Based Resistance Exercise Training on Physical Fitness, Depression, Stress, and Well-Being in Middle-Aged Persons: A Pilot Study. Kikuchi, N., Ohta, T., Hashimoto, Y., et al.[2023]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38355154/

Effect of exercise for depression: systematic review and ... Conclusions: Exercise is an effective treatment for depression, with walking or jogging, yoga, and strength training more effective than other ...

2. bmj.com bmj.com/content/384/bmj-2023-075847

Effect of exercise for depression: systematic review and ... In this systematic review and meta-analysis of randomised controlled trials, exercise showed moderate effects on depression compared with active ...

3. jamanetwork.com jamanetwork.com/journals/jamapsychiatry/fullarticle/2680311

Association of Efficacy of Resistance Exercise Training ... Resistance exercise training was associated with a significant reduction in depressive symptoms, with a moderate-sized mean effect.

4. frontiersin.org frontiersin.org/journals/public-health/articles/10.3389/fpubh.2025.1616925/full

The impact of high-intensity exercise on patients with ... The findings suggest that high-intensity interval training has a beneficial effect on depressive symptoms. However, most of these studies ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1471491423002782

Resistance exercise for anxiety and depression: efficacy ... RET is shown to produce significant anxiolytic and antidepressant effects in healthy and clinical populations (ie, GAD and major depressive disorder)

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6137526/

Association of Efficacy of Resistance Exercise Training ... Resistance exercise training significantly reduced depressive symptoms among adults regardless of health status, total prescribed volume of RET, or significant ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12380541/

The impact of high-intensity exercise on patients with ... The findings suggest that high-intensity interval training has a beneficial effect on depressive symptoms. However, most of these studies ...

8. ahajournals.org ahajournals.org/doi/10.1161/CIR.0000000000001189

Resistance Exercise Training in Individuals With and ... Adults who participate in RT have ≈15% lower risk of all-cause mortality and 17% lower risk of CVD, compared with adults who report no RT.