Moderate exercise improves depression parameters in treatment-resistant patients with major depressive disorder
Introduction
Major Depressive Disorder (MDD) is a complex, multifactorial, multigenic condition, which, as all psychiatric disorders at present, is of unknown pathophysiology (Cichon et al., 2009). Due to the paucity of information regarding the underlying mechanisms, therapeutic approaches to MDD are mainly symptomatical, but aim at achieving full remission (Kurian et al., 2009). However, and despite the combined use of psychotherapy, a variety of antidepressants with optimized dose and duration of treatment, and combined strategies of therapeutic enhancement, remission rates remain modest (Koenig and Thase, 2009, Kurian et al., 2009), with over 60% of patients meeting the criteria for treatment-resistant depression (Trivedi and Daly, 2008). MDD is the leading cause of years of life lived with disability (YLDs) worldwide, accounting for 11.9% of total YLDs, and it is estimated that by the year 2020 it will be second only to ischemic heart disease for disability-adjusted life years (DALYs) lost for both sexes (World Health Organization, 2001). Given this dismal scenario, several non-pharmacological strategies have been considered as possible complementary therapies to help improve MDD prognosis and remission rates, namely exercise, light therapy and sleep deprivation (Howland, 2010).
It has been recognized for several years that performing regular exercise is cardioprotective, decreasing the incidence of cardiovascular diseases such as hypertension, coronary artery disease, type 2 diabetes and atherosclerosis (Powers et al., 2002), and the practice of moderate intensity exercise for at least 30 min on most days of the week has been recommended by NIH since 1996 (NIH Consensus Development Panel on Physical Activity and Cardiovascular Health, 1996). Moreover, besides provenly cardioprotective, exercise has shown a positive association with psychological well-being (Hassmen et al., 2000), and therapeutic benefits in older people with depressive disorder (Mather et al., 2002), depression symptoms in patients with Alzheimer’s disease (Teri et al., 2003) and MDD (Dimeo et al., 2001, Babyak et al., 2000, Pilu et al., 2007). Although there is still some controversy concerning exercise intensity and frequency, and duration of exercise program, current recommendations are the adoption of a moderate intensity exercise program of at least 30 min on most days of the week, for 10–12 weeks (aan het et al., 2009).
The possible advantages of exercise as an effective therapeutic adjuvant to MDD are, in many ways, attractive: exercise is an inexpensive therapy that brings several health benefits, improves general well-being, and may fill the time lag of 3–4 weeks that antidepressants require before showing therapeutic effects (Fornaro and Giosue, 2010).
However, before adopting this clearly advantageous therapy, there is still a need for more information on how different clinical populations, in diverse settings will respond to different exercise programs. In fact, in their meta-analysis, Lawlor and Hopker concluded that the effects of exercise on depression could not be determined due to the lack of good quality studies, with proper controls, adequate follow-up and undertaken in clinical populations (Lawlor and Hopker, 2001).
In the present randomized, two-arm, parallel assignment study, non-remitted MDD patients undergoing combined pharmacological therapy for 9–15 months with no adjuvant exercise therapy were compared to patients with the same diagnosis that enrolled a 12 week moderate intensity aerobic exercise program.
Section snippets
Study design
Prospective, randomized, investigator blinded, two-arm, parallel assignment.
Participants
Between September 2009 and March 2010, 150 individuals attending the out-patient psychiatry clinic at Hospital de Magalhães Lemos, Porto, Portugal, diagnosed with major depressive disorder for more than 9 months and less than 15 months, were screened through an interview with a psychiatrist. Of the 45 individuals diagnosed with MDD according to DSM-IV criteria, taking combined therapy in doses considered adequate (
Study population and baseline values
Of the 33 participants included in the study, 1 from the control group and 1 from the exercise group only attended the first appointment and were excluded from analysis. 2 participants from the exercise group were excluded due to non-compliance with the exercise program, assessed based on accelerometer data. There was a 6% overall drop-out rate and a 91% compliance to the exercise program. Baseline demographics and psychiatric profile are shown in Table 1. Participants included in the exercise
Discussion
Although exercise has been recognized for years as important for the general well-being, the effects of exercise on specific populations of diverse psychological conditions has been subject to debate, and although the majority of studies have shown positive results (Babyak et al., 2000) (Blumenthal et al., 2007, Dimeo et al., 2001, Mather et al., 2002, Pilu et al., 2007, Trivedi et al., 2006)others have been less encouraging (Kerse et al., 2010, Sims et al., 2006). This may be due to the
Limitations of the study
This was a prospective, randomized, investigator blinded, two-arm, parallel assignment study, which controlled for the social interaction component often attributed to physical exercise practice, as well as for the patients’ expectation that it would be better for them to be included in the exercise group. One limitation of the study was that there was no assessment of compliance to medication, although there is no indication that patients did not comply. Another variable that was not
Conclusions
Our results suggest that physical exercise can be used as an effective therapy, adjuvant to pharmacological therapy, in treatment-resistant MDD. A 12 week exercise program of 30–45 min walks 5 times a week resulted in improvement of all studied parameters of depression and functioning: HAMD17, BDI, CGI-S and GAF, and this improvement was not due to social interaction. Moreover, patients in the exercise group showed a 26% remission rate, compared to 0% in the control group. Remitted patients
Funding source
This work was partially funded by a research grant from Servier Portugal.
Author contributions
Author Jorge Mota Pereira designed the study, wrote the protocol, compiled the data, undertook the statistical analysis and wrote the first draft of the manuscript. Authors Jorge Silverio and Jose Carlos Ribeiro supervised the study and reviewed the protocol. Author Serafim Carvalho conducted the clinical evaluation of screened patients and managed the literature searches and analyses. Author Joaquim Ramos supervised the study and conducted the clinical evaluation of screened patients. Author
Conflict of interest
None declared.
Acknowledgments
None.
References (41)
- et al.
Physical exercise and psychological well-being: a population study in Finland
Preventive Medicine
(2000) ANCOVA versus change from baseline: more power in randomized studies, more bias in nonrandomized studies [corrected]
Journal of Clinical Epidemiology
(2006)- et al.
Physical exercise and depression
Mount Sinai Journal of Medicine
(2009) - et al.
Short-term exercise approaches on menopausal symptoms, psychological health, and quality of life in postmenopausal women
Obstet. Gynecol. Int
(2010) Practice guideline for the treatment of patients with major depressive disorder
(2000)Guideline watch: practice guideline for the treatment of patients with major depressive disorder
(2005)- et al.
Exercise treatment for major depression: maintenance of therapeutic benefit at 10 months
Psychosomatic Medicine
(2000) - et al.
Current and residual functional disability associated with psychopathology: findings from the Netherlands Mental Health Survey and Incidence Study (NEMESIS)
Psychological Medicine
(2000) - et al.
Exercise and pharmacotherapy in the treatment of major depressive disorder
Psychosomatic Medicine
(2007) - et al.
Genomewide association studies: history, rationale, and prospects for psychiatric disorders
American Journal of Psychiatry
(2009)
Benefits from aerobic exercise in patients with major depression: a pilot study
British Journal of Sports Medicine
The validity of the computer science and applications activity monitor for use in coronary artery disease patients during level walking
Clinical Physiology and Functional Imaging
Current nosology of treatment resistant depression: a controversy resistant to revision
Clinical Practice and Epidemiology in Mental Health
Calibration of the computer science and applications, Inc. accelerometer
Medicine and Science in Sports and Exercise
Recomendations for human blood pressure determination by sphygmomanometers: report of a special task force appointed by the steering committee. American Heart Association
Circulation
Using the GAF as a national mental health outcome measure in the Department of Veterans Affairs
Psychiatric Services
ECDEU assessment manual for psychopharmacology
A rating scale for depression
Journal of Neurology, Neurosurgery and Psychiatry
Physical activity and public health: updated recommendation for adults from the American College of Sports Medicine and the American Heart Association
Medicine and Science in Sports and Exercise
Therapeutic armamentarium for treating depression
Postgraduate Medicine
Cited by (175)
Physical activity, suicidal ideation, suicide attempt and death among individuals with mental or other medical disorders: A systematic review of observational studies
2024, Neuroscience and Biobehavioral ReviewsThe effect of exercise on suicidal ideation and behaviors: A systematic review and meta-analysis of randomized controlled trials
2023, Journal of Affective DisordersProject MOVE: A randomized controlled trial of interventions for initiating and maintaining physical activity in depressed individuals
2023, Mental Health and Physical ActivityLong-term efficacy of exercise across diagnostically heterogenous mental disorders and the mediating role of affect regulation skills
2023, Psychology of Sport and Exercise