Journal of Psychosocial Nursing and Mental Health Services

Psychopharmacology 

“I Want a New Drug”: Exercise as a Pharmacological Therapy

Robert H. Howland, MD

Abstract

Skeletal muscle can be considered a secretory organ that produces myokines and other humoral factors having autocrine-, paracrine-, and endocrine-like signaling effects throughout the body. Exercise has such profound pharmacological and physiological effects that it should be considered a drug therapy. Exercise has documented benefits for preventing or treating many physical and mental disorders or their sequelae, and it has a potential role in managing adverse effects associated with drug therapies. If exercise were a drug evaluated by the Food and Drug Administration, it might be approved for a large number of therapeutic indications. Exercise can be appropriately prescribed for virtually anyone for primary, secondary, or tertiary prevention of many mental and physical disorders. [Journal of Psychosocial Nursing and Mental Health Services, 53(8), 13–16.]

Dr. Howland is Associate Professor of Psychiatry, University of Pittsburgh School of Medicine, Western Psychiatric Institute and Clinic, Pittsburgh, Pennsylvania.

The author has disclosed no potential conflicts of interest, financial or otherwise.

Address correspondence to Robert H. Howland, MD, Associate Professor of Psychiatry, University of Pittsburgh School of Medicine, Western Psychiatric Institute and Clinic, 3811 O’Hara Street, Pittsburgh, PA 15213; e-mail: HowlandRH@upmc.edu.

Abstract

Skeletal muscle can be considered a secretory organ that produces myokines and other humoral factors having autocrine-, paracrine-, and endocrine-like signaling effects throughout the body. Exercise has such profound pharmacological and physiological effects that it should be considered a drug therapy. Exercise has documented benefits for preventing or treating many physical and mental disorders or their sequelae, and it has a potential role in managing adverse effects associated with drug therapies. If exercise were a drug evaluated by the Food and Drug Administration, it might be approved for a large number of therapeutic indications. Exercise can be appropriately prescribed for virtually anyone for primary, secondary, or tertiary prevention of many mental and physical disorders. [Journal of Psychosocial Nursing and Mental Health Services, 53(8), 13–16.]

Dr. Howland is Associate Professor of Psychiatry, University of Pittsburgh School of Medicine, Western Psychiatric Institute and Clinic, Pittsburgh, Pennsylvania.

The author has disclosed no potential conflicts of interest, financial or otherwise.

Address correspondence to Robert H. Howland, MD, Associate Professor of Psychiatry, University of Pittsburgh School of Medicine, Western Psychiatric Institute and Clinic, 3811 O’Hara Street, Pittsburgh, PA 15213; e-mail: HowlandRH@upmc.edu.

From their album, Sports, the rock musical group Huey Lewis and the News released the popular hit single, “I Want a New Drug” (Hayes & Lewis, 1984), for radio play in January of 1984: I want a new drug—one that won’t make me sick,One that won’t make me crash my car or make me feel three feet thick.I want a new drug—one that won’t hurt my head,One that won’t make my mouth too dry or make my eyes too red.One that won’t make me nervous, wonderin’ what to do….I want a new drug—one that won’t spill.One that don’t cost too much or come in a pill.I want a new drug—one that won’t go away,One that won’t keep me up all night, one that won’t make me sleep all day.One that won’t make me nervous, wonderin’ what to do….I want a new drug—one that does what it should,One that won’t make me feel too bad,One that won’t make me feel too good.I want a new drug—one with no doubt,One that won’t make me nervous, wonderin’ what to do….

It may only be a coincidence, but the U.S. Food and Drug Administration (FDA) approved 18 antidepressant drugs and 11 atypical antipsychotic drugs since this song first hit the airwaves. The most recent new drug is brexpiprazole (Rexulti®), which was approved as a treatment for schizophrenia and as an add-on therapy together with an antidepressant medication to treat major depression. I doubt that the FDA listened to the plea of Huey Lewis and the News, but their song encapsulates rather insightfully what I think we need in a new drug. Does such a drug exist?

Pharmacological Effects of Exercise

The main forms of exercise include (a) aerobic activities, (b) resistance training, and (c) stretching (i.e., flexibility exercises). Skeletal muscle is now characterized as a secretory organ (Pedersen & Febbraio, 2012). Muscle fibers(i.e.,myocytes)producehundreds of secreted factors that include various proteins, growth factors, cytokines, and metallopeptidases (Fiuza-Luces, Garatachea, Berger, & Lucia, 2013). The secretion of these factors increases during muscle contractions, which obviously includes exercise training.

The term myokine was first used by Pedersen et al. (2003) to describe certain cytokines that are produced and released by skeletal muscle and exert their effect elsewhere in the body. Since then, the concept of myokines has been broadened to include various cytokines and other small molecule peptides that are produced, expressed, and released by myocytes, and that have autocrine-signaling (i.e., binding to receptors on the releasing cell), paracrine-signaling (i.e., binding to receptors on nearby cells), or endocrine-signaling (i.e., binding to receptors on distant organs) effects. Examples of myokines that have been investigated in studies of exercise include myostatin, interleukins (e.g., IL-6, IL-15, IL-8), brain-derived neurotrophic factor (BDNF), fibroblast growth factor, leukemia inhibitory factor, irisin, secreted protein acidic and rich in cysteine (SPARC), and myonectin. Although stretching exercises may be considered a more passive form of physical activity compared to aerobic and resistance training, stretching also stimulates the release of myokines. Because receptors for various myokines are found in muscle, fat, liver, pancreas, bone, heart, immune, and brain cells, exercise-induced release of myokines has physiological effects throughout the body (Fiuza-Luces et al., 2013).

Endocannabinoids are modulatory lipid-signaling molecules that bind to cannabinoid receptors. These receptors are located throughout the nervous system as well as peripheral cells and tissue (e.g., skeletal muscle, liver, adipose tissue, the immune system). Endocannabinoid signaling is involved in many physiological processes, including appetite, energy balance and metabolism, stress response, immune function, thermoregulation, memory, and sleep. Physical exercise modulates the endocannabinoid system, and endocannabinoid signaling may mediate some of the effects of exercise on the brain and other end organs (Tantimonaco et al., 2014).

Autophagy refers to the cellular process of degradation and recycling of damaged cellular macromolecules and organelles. Aging has an inhibitory effect on autophagy in muscle and non-muscle tissue, including the brain. Developing evidence from animal studies and preliminary evidence in humans suggests that exercise increases autophagic processes, which may be beneficial for promoting longevity and defending against the development of chronic disease (Fiuza-Luces et al., 2013).

Exercise as a Drug Therapy

Exercise has such profound pharmacological and physiological effects throughout the body that it should be considered a drug therapy (Fiuza-Luces et al., 2013; Vina, Sanchis-Gomar, Martinez-Bello, & Gomez-Cabrera, 2012). Exercise has documented benefits for preventing or treating many cardiovascular, metabolic, neurological, rheumatological, oncologic, and psychiatric conditions or their sequelae. In psychiatry, such benefits have been demonstrated for the treatment of addictions (Linke & Ussher, 2015), attention deficit disorder (Kamp, Sperlich, & Holmberg, 2014), depression (Dinas, Koutedakis, & Flouris, 2011), and anxiety disorders (Asmundson et al., 2013). Exercise is associated with improvements in psychological well-being, sleep, energy, and sexual function (Scully, Kremer, Meade, Graham, & Dudgeon, 1998; Youngstedt, 2005).

Exercise enhances memory and cognitive function, decreases the risk of dementia, and slows the rate of cognitive decline associated with aging (Bherer, Erickson, & Liu-Ambrose, 2013). Some myokines include the neurotrophic factors of BDNF, insulin-like growth factor (i.e., IGF-1), and vascular endothelial growth factor. Neurotrophic factors are important for synaptic plasticity and neurogenesis—processes that may account for increases in the volume (i.e., size) of prefrontal cortical and hippocampal regions that are associated with exercise (Erickson et al., 2011; Erickson, Miller, & Roecklin, 2012; Rottensteiner et al., 2015).

Based on its known physiological effects, exercise has a potential role in addressing adverse effects associated with many drug therapies, including insomnia, sedation, sexual dysfunction, cognitive impairment, weight gain, and metabolic effects. Because exercise improves motor and cognitive symptoms in Parkinson’s disease (Goodwin, Richards, Taylor, Taylor, & Campbell, 2008; Murray, Sacheli, Eng, & Stoessl, 2014), some of the adverse motor and cognitive effects associated with antipsychotic drugs (e.g., in schizophrenia) may be managed through exercise.

Limitations

Exercise has been described as a “miracle drug” (Pimlott, 2010, p. 407), but unfortunately this is not the case. Although exercise “don’t cost too much,” the fact that it takes time and effort and does not “come in a pill” is an inherent limitation. The predisposition to engage in voluntary exercise is complex, involving personal, environmental, and even genetic factors (Kelly & Pomp, 2013). The benefits ascribed to exercise also are not absolute. Not all individuals will benefit from exercise to the same extent. Individual physical limitations may preclude some patients from engaging in certain forms of exercise, but the broad array of aerobic, resistance, or stretching exercises that are potentially available may permit some type of physical activity for almost every patient.

Although exercise has none of the negative effects that Huey Lewis and the News want to avoid in a new drug, harms are still possible (Vina et al., 2012). Jim Fixx (1977), author of The Complete Book of Running, popularized the sport of running for its health benefits. Regrettably, he died of a heart attack while jogging at the young age of 52, only 6 months after “I Want a New Drug” was released. I am a runner and, to this day, some people still mention to me what Fixx was doing when he died. Of course, what they do not say is that he was obese and a heavy smoker when he started running at 36. Through running, he lost weight and quit smoking. By doing so, he outlived his own father, who died of a heart attack at 43. Vigorous exertion can increase the incidence of acute cardiac events in individuals who do not exercise regularly, but habitual physical activity reduces the overall risk of heart attacks and sudden cardiac death by preventing development of heart disease or its progression (Corrado, Migliore, Basso, & Thiene, 2006).

Conclusion

If exercise were a drug evaluated by the FDA, it might be approved for a large number of therapeutic indications. Using the public health concepts of primary, secondary, and tertiary disease prevention (Patterson & Chambers, 1995), exercise could be appropriately prescribed for virtually anyone to prevent or manage many mental and physical disorders.

Within reasonable limits and precautions, exercise should be “prescribed” for all patients (Garber et al., 2011). Nurses and physicians should strive to identify exercises that are amenable for each patient. As front-line providers, nurses have an especially important role in counseling patients about the importance of exercise for their physical and mental health, as well as providing consistent advice and encouragement.

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