Effects of structured exercise and pharmacotherapy vs. pharmacotherapy for adults with depressive symptoms: A randomized clinical trial
Graphical abstract
Flow diagram for the HAPPY BRAIN trial.
Introduction
Depression affects over 120 million people worldwide (Lepine and Briley, 2011) and is much more common among women than men, with female/male risk ratios roughly 2:1 (Kessler, 2003). Indeed, the increasing burden of depression makes it essential to search for an extended understanding of causes and for development of complementary effective treatments. The American Psychiatric Association has supported the inclusion of physical exercise (PE) treatment in patients with major depressive disorder (MDD) (American Psychiatric Association, 2010), and according to their practice guidelines, new research should include evaluation of benefits of PE in reducing side effects of other therapies and in improving health. Despite the current gold standard for the treatment for MDD including antidepressant medication and psychotherapy, data indicate that only 55% of individuals seek treatment (Lepine and Briley, 2011). Thus, PE has been proposed as a rehabilitation strategy and a complementary treatment to reduce symptoms of depression. Indeed, evidence from other studies including systematic reviews and meta-analysis of the literature (Knapen et al., 2014, Rethorst et al., 2009, Silveira et al., 2013), supports the efficacy of exercise in the treatment of depression. Therefore, several biological and psychological hypotheses have been posited to explain the mechanisms that mediate the impact of exercise on depression. For instance, PE has shown to have anti-inflammatory effects in non depressed subjects (Gleeson et al., 2011), and thus, in the long term, regular aerobic exercise leads to lower levels of several circulating pro-inflammatory biomarkers, including Interleukin-6 (IL-6) and C-reactive protein (CRP) (Kohut et al., 2006), which are increased in depressed patients (Dowlati et al., 2010). Furthermore, PE induces the release of proteins such as brain-derived neurotrophic factor (BDNF) (Heyman et al., 2012), which is a neurotrophin responsible for the stimulation and control of neurogenesis, and altering the hypothalamic–pituitary axis function through decreasing long-term basal levels of cortisol (Sousa e Silva et al., 2010). Additionally, PE increases self-esteem (Callaghan et al., 2011), reduces tendency to ruminate (Craft, 2005), and restores psychosocial function (Mota-Pereira et al., 2011).
Thus, PE remains an area of active investigation and raises questions regarding dose–response and the best type of exercise for various depressed patients. However, researchers investigating this association in women are limited, with most focusing on postnatal depressed women (Teychenne and York, 2013) and others emphasizing observational studies that examined walking, yoga or recreational physical activity (Shahidi et al., 2011). In most of the studies women were not recruited by psychiatrists but by physicians, advertisements placed in local newspapers, posted fliers and university communities (Callaghan et al., 2011, Chu et al., 2009). Regarding the limitations and importance incidences of depression in women, the aim was to evaluate the efficacy of four months of aerobic exercise intervention in a group of women referred by psychiatrists.
Section snippets
Methods
Recruitment for the trial took place from July to December 2013. A total of 26 women (aged 50.16 ± 12.08) were randomized. This research protocol was performed according to the Declaration of Helsinki, and was approved by the Ethics Committee of Centro Hospitalar de São João (March 11, 2013) with ethics reference number 112/13.
Exercise group
Nine individuals were assigned to moderately intense exercise in addition to their usual pharmacology therapy. Exercise consisted of 45–50 min per session, three times a week, for a total of 16 weeks (36 sessions). Sessions took place at the Faculty of Sport at the University of Porto, Portugal, between January and April 2013, in the presence of a physical training teacher. The intensity for each patient was based on the baseline fitness (physical fitness tests). All patients in the aerobic
Assessment procedures
Patients underwent medical screening by a clinical physician before participating in the study. If a patient was found to have any significant medical condition that contraindicated safe participation, they were excluded.
Study population and baseline values
From July to December 2013, 78 potential individuals were referred to the trial by their psychiatrists during routine external consultations at Psychiatry and Mental Health Clinic, Centro Hospitalar São João, Porto, Portugal. Out of these, 52 were excluded and 26 patients were enrolled and randomized; 13 were allocated to the aerobic exercise group versus 13 to the control group. The main reasons for exclusion were declining participation (N = 9), psychiatric comorbidity (N = 11) and age over
Discussion
The HAPPY BRAIN trial (implemented from July 2013 to May 2014), aimed to assess the efficacy of a four-month exercise intervention as complementary therapy in a group of patients referred by psychiatrists. Results suggest that 16 weeks of aerobic exercise improved functional functioning and reduced depressive symptomatology. These results are similar to several previous trials that described positive effects of aerobic exercise as adjuvant treatment for patients with clinical depression (
Conclusion
This study demonstrated that PE is an effective treatment, adjuvant to pharmacological therapy for depressed women. Furthermore, we concluded that 16 weeks of aerobic PE resulted in decreasing the parameters of depression (BDI-II) and physical functioning. Nonetheless, no differences in anthropometric (weight, body mass index and waist circumference) and self-esteem between groups were found. We also observed that a multi-disciplinary team and the defined strategies could effectively enhance
Role of funding source
The authors did not receive financial support for the preparation of the papers.
Author contributions
Author Lara S. F. Carneiro designed the study, wrote the protocol, analyzed the data, undertook the statistical analysis and produced the first draft of the manuscript under the oversight of authors Professor José Vasconcelos-Raposo and Professor Maria Paula Mota. Author Professor Maria Augusta Vieira-Coelho identified potentially eligible patients for the clinical trial, and conducted the clinical evaluation of screened patients. Author Professor António Manuel Fonseca contributed to the
Conflict of interest
All authors report no conflict of interest.
Acknowledgments
Lara S. F. Carneiro is grateful to Fundação para a Ciência e Tecnologia (FCT) for the PhD grant (SFRH/BD/84988/2012), financed by POPH, and subsidized by FSE and MCTES. Our gratitude to the Portuguese Olympic Committee and Millennium BCP Foundation, which awarded this research with the first prize of Psychology and Pedagogy in Sports, 2014. We thank Pedro Tedim (physical training teacher) for his dedication to the HAPPY BRAIN program. Furthermore, we would like to thank Aquaplace Academy for
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