Moderate exercise improves depression parameters in treatment-resistant patients with major depressive disorder

Abstract

Background

Treatment-resistant major depressive disorder (MDD) is a complex condition, with very low remission rates. Physical exercise has been used, with some encouraging results, as an alternative therapy in other depressive disorders. This study assessed the impact on depression and functioning parameters of a moderate intensity exercise program, as an adjuvant to pharmacotherapy, in treatment-resistant MDD patients.

Methods

150 individuals with treatment-resistant MDD, defined as taking combined therapy in doses considered adequate for 9–15 months, without showing clinical remission, were initially screened. 33 were randomized to one of two groups: usual pharmacotherapy (N = 11) and usual pharmacotherapy plus aerobic exercise (N = 22). The exercise program consisted of home-based 30–45 min/day walks, 5 days/week, for 12 weeks, being 1 walk per week supervised.

Results

The exercise group showed improvement of all depression and functioning parameters, as indicated by lower HAMD17, BDI and CGI-S and higher GAF (p < 0.05) at last observation compared both to baseline values and to control group. At the end of the study none of the participants in the control group showed response or remission, whilst in the exercise group 21% of participants showed response and 26% remission, although these differences were not statistically significant.

Conclusion

A 12 week, home-based exercise program of 30–45 min/day walks, 5 days/week, improved depression and functioning parameters in treatment-resistant MDD patients, and contributed to remission of 26% of these patients. Moderate intensity exercise may be a helpful and effective adjuvant therapy for treatment-resistant MDD.

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.