Walking, Revisited

Redux, RFK Jr. Edition.

The Frontier Psychiatrists is a daily health-themed newsletter. Today is a repost of a classic and my most popular article in one day, in 758 prior posts. In honor of the new “natural cures” enthusiasm in potential political appointees, I present what was, originally, a joke but now might be the sort of thing the new FDA would do…Quoting RFK Jr:

“FDA’s war on public health is about to end. This includes its aggressive suppression of psychedelics, peptides, stem cells, raw milk, hyperbaric therapies, chelating compounds, ivermectin, hydroxychloroquine, vitamins, clean foods, sunshine, exercise, nutraceuticals and anything else that advances human health and can’t be patented by Pharma.”

Here is what I said (when it was still a joke)…

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Today, it’s more health-themed than ever. I’ve been writing a series of articles in the past year—remember 2023? It feels like a lifetime ago!—on drugs¹. They all had just the “name of the drug” as the title. Today’s article gives a neuromodulatory intervention—yes, that is how I think about walking—the same “treatment.” I’m going to address walking in the same way I address drugs. Unfortunately, for the conceit, there is no FDA label to reference.

We begin by addressing the data on walking for major depressive disorder. A large meta-analysis was done! It found:

[in] eight randomised, controlled trials…walking was an effective intervention for depression having an effect size of −0.86 [−1.12, −0.61]. This is comparable to several recent systematic reviews and meta-analyses of physical activity (not restricted to walking) as a treatment for depression².

Holy cow! Honestly, that is huge. Using the Muir-Skee Lo EQE, if walking were medicine for height, it would make you 2.15 inches taller.

Remember that FDA-approved medicines for depression clock in at 0.5, which would be a 1.25-inch difference.

A 2023 Meta-analysis using different methodologies and a large data set found even more robust differences:

Outcomes from the random-effects model indicated a substantial effect size for depression, -1.00 (95% CI=-1.35, -0.65), signifying a significant effect (z=-5.56, p=.0001). ³

This is the forest plot format from the second walking meta-analysis. It compares very favorably to data from drug trials…

Further, It might not be any old “a physical activity” is as effective a treatment…

The most recent of these reviews [physical activity for depression] of which we are aware (Krogh et al., 2011) reported lower effect size, with a pooled standardized mean difference of −0.40.

It may even be the case (in one trial) that there are better kinds of walking than others for treating depression…have you heard of Nordic walking?

I had not!

It’s walking…but also with poles:

Nordic walking (originally Finnish sauvakävely) is fitness walking with specially designed poles. While trekkers, backpackers, and skiers had been using the basic concept for decades, Nordic walking was first formally defined with the publication of "Hiihdon lajiosa" (translation: "A part of cross-country skiing training methodic") by Mauri Repo in 1979.^[1]

And in at least one RCT, it beat regular walking as a depression treatment:

There was a significant difference in depression with a main effect of time in both groups. There was also a significant difference in sleep in over time and interaction. The differences over time between the two groups were significant for depression, sleep, and skeletal muscle mass.⁴

Walking, in large population samples, benefits both those with mild and more severe depression:

[in] 2,084 subjects with complete data, valid information about depressive symptoms, and ability to walk across a small room were divided into two cohort groups at baseline: those with few and those with more depressive symptoms. …both groups benefited from daily walking.

This is the opposite of what we find with antidepressant medications⁵, as

Awais Aftab

reviewed in 2022.

In these articles on drugs, I usually rip on the side effects. I also rip on the problems with the trials. I’m a downer, I know. However, I have also found some important differences in this walking round-up. Antidepressants have been blamed for sexual functioning impairment. Walking, on the other hand, might do the opposite, both in women with co-occurring medical conditions:

Based on our results, an 8-week aerobic walking program is recommended as an effective way to improve sexual function in women with rheumatoid arthritis.⁶

Walking—It also provides robust benefits in men who have had heart attacks when it comes to reducing the risk of erectile dysfunction:

However, the home-based walking group had a significant decrease of 71% in reported Erectile Dysfunction (p <0.0001).⁷

As well as in samples of both—granted, they didn’t break out “walking” from other physical activity. I will also note I giggled when they chose to analyze the data in “sextiles” in a paper about sexual function because, apparently, I’m both a physician author and a 7-year-old child:

3,906 men and 2,264 women (median age 41–45 and 31–35 years, respectively) met the inclusion criteria for the study. Men in sextiles 2–6 had reduced odds of ED compared with the reference sextile⁸ in adjusted analysis (P_trend = .03), with an OR of 0.77 (95% CI = 0.61–0.97) for sextile 4 and 0.78 (95% CI = 0.62–0.99) for sextile 6, both statistically significant. Women in higher sextiles had a reduced adjusted OR of female sexual dysfunction (P_trend = .02), which was significant in sextile 4 (OR = 0.70; 95% CI = 0.51–0.96). A similar pattern held true for orgasm dissatisfaction (P_trend < .01) and arousal difficulty (P_trend < .01) among women, with sextiles 4–6 reaching statistical significance in both.

At this point, it could be argued that I’m in the pocket of “big ambulation” and a shill for Nike (pssst….you are welcome to call me for sponsorship opportunities…)!

There are significant risks to walking. I can’t get over this title of an academic paper:

Falling while walking: A hidden contributor to pedestrian injury

This paper’s authors report from Australia, some older adults take a spill while walking:

Across the Victorian Injury Surveillance Unit, there were at least 17,727 non-admitted presentations to emergency departments (EDs) and 8436 admissions to hospitals for fall-related injuries to pedestrians between July 2009 and June 2014. The number of ED presentations and hospital admissions were found to increase over the five year period from 3382 to 3545 and 1681 to 1788 for ED presentations and hospital admissions respectively.⁹

The authors don't provide population-level data to calculate such data's relative risk or frequency.

The risk of injury while walking increases with the co-administration of “talking on the phone” with a cell phone:

The results confirm risk of injury to pedestrians using mobile phones. Although the national estimated appear small (for example, 1506 pedestrian injuries in 2010), the actual number of injuries are probably much higher. Many people who suffer an injury may not go to the emergency room; they may go to their primary care doctor, not go to a doctor, may not report the cell phone as the cause, or may die.

I didn't see that last phrase coming!

Specific injuries possible from walking include the risk of ankle sprain, which is common in the population:

During the study period, an estimated 3,140,132 ankle sprains occurred among an at-risk population of 1,461,379,599 person-years for an incidence rate of 2.15 per 1000 person-years in the United States.

Although half of the ankle sprain incidence is explained by sports and not plain old walking, and is more common in male, athleticly oriented youth:

Nearly half of all ankle sprains (49.3%) occurred during athletic activity, with basketball (41.1%), football (9.3%), and soccer (7.9%) being associated with the highest percentage of ankle sprains during athletics.¹⁰

Announcing….new Walking

TheFrontierPsychiatrists BioMedicine, Inc.

…is thrilled to present our new treatment for depression, “Walking” to the FDA!

If Walking were submitted to the FDA, it would likely be approved for major depression, but probably include a package insert warning of the significant risk associated with falling down and spraining your god-damn ankle.

I’ve gone ahead and created the package insert for us all:

FDA-Approved Package Insert: Walking as a Treatment for Depression

INDICATIONS:

Walking is indicated as an adjunctive treatment for depression in adults. It may be considered as part of a comprehensive treatment plan, which may include psychotherapy, pharmacotherapy, and other therapeutic interventions. The decision to use walking as a treatment option should be made by a qualified healthcare professional, taking into account the individual patient's needs and preferences.

EFFECTIVENESS:

Walking has been shown to have an effect size ranging from 0.81 to 1 in improving mood and reducing symptoms of depression. It is believed to be effective through various mechanisms, including the release of endorphins and the promotion of cardiovascular health.

WARNINGS AND PRECAUTIONS:

1. Risk of Ankle Sprain: Patients engaging in walking therapy should be aware of the risk of ankle sprains. The estimated risk is 2.5 per 1000 person-years of walking. Patients with a history of ankle sprains or other lower limb issues should exercise caution and consult their healthcare provider before starting a walking regimen.

2. Risk of Serious Falls Leading to Injury or Death: Patients should exercise caution while walking, especially in unfamiliar or hazardous terrain. Serious falls leading to injury or death have been reported in rare cases. Patients with balance or mobility issues, or those taking medications that affect balance, should be particularly cautious.

3. Cell Phone Use: Using cell phones while walking may increase the risk of accidents, including tripping and falling. Patients are advised to refrain from using cell phones, texting, or engaging in distracting activities while walking, especially near roadways or other potentially dangerous areas.

4. Fatigue: Excessive walking can make you really tired. Don’t overdo it.

ADVERSE REACTIONS:

Serious adverse reactions associated with walking therapy for depression are rare. However, patients should be aware of the potential risks, including:

• Ankle sprains

• Serious falls leading to injury or death (rare)

• Getting Really Tired

• Soreness of the Foot, Knee, or Low Back

• Plantar Fasciitis risk is increased with regular use of Walking

DOSAGE AND ADMINISTRATION:

The recommended dosage of walking for the treatment of depression is individualized and should be determined by a qualified healthcare professional. Factors to consider include the patient's physical fitness level, preferences, and any existing medical conditions or contraindications. Although high-dose walking may be the most efficacious, it exhibits a dose dependent relationship with adverse effects as well.

PATIENT COUNSELING INFORMATION:

1. Patients should be informed of the benefits of walking as a treatment for depression and its potential risks, including ankle sprains and falls leading to injury or death.

2. Patients should be advised to wear appropriate footwear and to choose walking routes that are safe and free from potential hazards.

3. Patients should be cautious while walking in adverse weather conditions, uneven terrain, or poorly lit areas.

4. Patients should refrain from using cell phones or engaging in distracting activities while walking.

5. Patients should report any adverse events, injuries, or changes in their physical condition to their healthcare provider.

STORAGE:

Walking does not require specific storage conditions. Patients should store and maintain their walking equipment, such as walking shoes, in a suitable environment. This Package insert does not address storage concerns related to nordic walking—those poles!—and those are covered under a separate FDA label. Please, don’t poke you eye out with nordic walking poles.

DISPENSING:

Walking requires a prescription and can only be initiated by the patient in consultation with their healthcare provider.

MANUFACTURER:

Walking is a non-pharmaceutical therapy option but, similar to other hard-to-enforce IP like the color of the walls in psycedelic therapy, has proprietary IP owned by TheFrontierPsychiatrists BioMedicine, Inc.

This package insert provides essential information about the use of walking as a treatment for depression. Patients are encouraged to discuss their treatment options and any concerns with their healthcare provider. Healthcare professionals should assess the suitability of walking therapy for individual patients and provide appropriate guidance for its safe and effective use.

1. This article is another in my series about one drug or another. Prior installments include Depakote, Geodon, Ambien, Prozac, Xanax, Klonopin, Lurasidone, Olanzapine, Zulranolone, Benzos, Caffeine, Semeglutide, Lamotrigine, Cocaine, Xylazine, Lithium, dextromethorphan/bupropion and Adderall, etc.

2. Roma Robertson, Ann Robertson, Ruth Jepson, Margaret Maxwell, Walking for depression or depressive symptoms: A systematic review and meta-analysis, Mental Health and Physical Activity, Volume 5, Issue 1, 2012, Pages 66-75, ISSN 1755-2966, https://doi.org/10.1016/j.mhpa.2012.03.002.

3. Lee, J., & Kim, Y. (2023). A Meta-Analysis of the Effects of Walking Exercise on Depression. The Asian Journal of Kinesiology, 25(4), 12-19.

4. Park, S. D., & Yu, S. H. (2015). The effects of Nordic and general walking on depression disorder patients’ depression, sleep, and body composition. Journal of physical therapy science, 27(8), 2481-2485.

5. Hegerl, U., Allgaier, A. K., Henkel, V., & Mergl, R. (2012). Can effects of antidepressants in patients with mild depression be considered as clinically significant?. Journal of affective disorders, 138(3), 183-191.

6. Rezaei, S., Mohammadhossini, S., Karimi, Z., Yazdanpanah, P., Zarei Nezhad, M., & Ghafarian Shirazi, H. R. (2020). Effect of 8-week aerobic walking program on sexual function in women with rheumatoid arthritis. International journal of general medicine, 169-176.

7. Begot, I., Peixoto, T. C., Gonzaga, L. R., Bolzan, D. W., Papa, V., Carvalho, A. C., ... & Guizilini, S. (2015). A home-based walking program improves erectile dysfunction in men with an acute myocardial infarction. The American Journal of Cardiology, 115(5), 571-575.

8. Ha! Sorry, that was childish humor.

9. Oxley, J., O’Hern, S., Burtt, D., & Rossiter, B. (2018). Falling while walking: A hidden contributor to pedestrian injury. Accident Analysis & Prevention, 114, 77-82. https://doi.org/10.1016/j.aap.2017.01.010

10. Waterman, Brian R. MD1; Owens, Brett D. MD2; Davey, Shaunette DO1; Zacchilli, Michael A. MD1; Belmont, Philip J. Jr. MD1. The Epidemiology of Ankle Sprains in the United States. The Journal of Bone & Joint Surgery 92(13):p 2279-2284, October 6, 2010. | DOI: 10.2106/JBJS.I.01537