Mild to moderate depression: exercise, antidepressants, and combination therapy?

Medical Pulse Guide

This is the first network meta-analysis comparing exercise, antidepressants, exercise plus antidepressants in adults with non-major
depression.

Network meta-analysis and pairwise meta-analysis showed that all three treatments were significantly better than controls, but there was no significant difference
between the three modalities.
In addition, exercise treatment was less acceptable than antidepressant treatment, reflected in a higher
number of people dropping out of the study early.

Although exercise combined with antidepressants did not show efficacy, a range of physical benefits from exercise are expected to offset the side effects of antidepressants and accelerate the overall recovery process
.

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The World Health Organization (WHO) estimates that there are more than 320 million
people with depression worldwide.
Antidepressants are an effective treatment for depression, saving the lives
of thousands of people with severe depression.
On the other hand, patients with mild to moderate depression need more treatment options, such as lifestyle interventions
.

In recent years, exercise has been recommended by European EPA guidelines, Canadian CANMAT guidelines, British NICE guidelines, and Australian RANZCP guidelines as an alternative treatment
for non-major depression.
However, the American Psychological Association's guidelines for depression take a different view, arguing that use
should only be considered when medications or psychotherapies are ineffective or unacceptable.

Brief introduction to the study

On 16 September, Francesco Recchia of the University of Hong Kong and his collaborators published an online review and online meta-analysis at Br J Sports Med.
(impact factor 18.
473) comparing the efficacy and acceptability
of exercise, antidepressants, and exercise plus antidepressants for non-severe depression.

Briefly, researchers systematically searched for randomised controlled studies
from Embase, MEDLINE, PsycInfo, Cochrane Library, Web of Science, Scopus, and SportDiscus from January 1990 to January 2022 on exercise and/or antidepressants for the treatment of non-major depression in adults.
Thereinto:

▶ "Exercise" is defined by the American College of Sports Medicine guidelines as "planned, structured, repetitive physical movements designed to improve and/or maintain one or more bodily functions.
"
The active ingredients of mind-body sports such as yoga and tai chi are complex and not included
.

▶ "Non-major depression" means mild and moderate depression
as assessed based on formal diagnostic criteria or cut-off values on symptom rating scales.

▶ The target studies had no language restrictions for publication, and participants were all adults-naïve patients
.

The main outcome index of the study was depression severity, which was assessed by depression scale scores.
The secondary outcome measure was acceptability, which was assessed by the number of people who dropped out of the study
.
For specific study design and statistical analysis methods, please refer to the original literature (open source).

Study results

A total of 21 studies involving 25 comparisons and 2551 patients
were included in this analysis.
The number of studies at low, moderate and high risk of bias was five, 15 and one
, respectively.

The study yielded three main findings:

First, for mild to moderate depression, the efficacy of exercise, antidepressants, exercise + antidepressants was significantly better than that of the control
.

Network meta-analysis showed that at the end of the intervention, exercise (SMD, −0.
45; 95% CI −0.
67 to −0.
23), antidepressant (SMD, −0.
33; 95% CI −0.
48 to −0.
19), exercise + antidepressant (SMD, −0.
45; The improvement of depressive symptoms in the 95% CI −0.
76 to −0.
14 group was significantly better than that of the control (e.
g.
, placebo, stretching, etc.
).

Pairwise meta-analyses support these findings
.

Second, for mild to moderate depression, there was no significant difference
in the efficacy of exercise, antidepressants, exercise + antidepressants.

Table 1 Relative efficacy of the three treatment modalities; deep, network meta-analysis; Shallow, pairwise meta-analysis

Network meta-analysis showed no significant difference between exercise and antidepressants (SMD, −0.
12; 95% CI −0.
33 to 0.
10), exercise + antidepressants versus exercise (SMD, 0.
00; 95% CI −0.
33 to 0.
33) and antidepressant efficacy (SMD, −0.
12; 95% CI −0.
40 to 0.
16) was also not significantly different
.

Pairwise meta-analysis showed that neither exercise nor antidepressants were significantly superior to each other (SMD, −0.
08; 95% CI −0.
29 to 0.
12), and combination therapy was not significantly better than exercise alone (SMD, 0.
18; 95% CI −0.
20 to 0.
55) or antidepressant (SMD, −0.
13; 95% CI −0.
63 to 0.
36）
。

Third, for mild to moderate depression, the excretion rate in the exercise group was higher than that in the antidepressant group, indicating worse acceptability
.

Table 2 Relative acceptability of the three treatment modalities; deep, network meta-analysis; Shallow, pairwise meta-analysis

Both network meta-analyses (RR 1.
31; 95% CI 1.
09 to 1.
57), or pairwise meta-analysis (RR 1.
40; 95% CI 1.
13 to 1.
72), and the exercise group had a higher number of patients withdrawing from the study early, suggesting poorer acceptability
.
In addition, the dropout rate in the exercise group was significantly higher than that in the control group (RR 1.
29; 95% CI 1.
03 to 1.
61）
。

The heterogeneity of the network meta-analysis was moderate (τ2=0.
03; I²=46%）
。

conclusion

This is the first network meta-analysis comparing exercise, antidepressants, and combination therapy in adults with non-major
depression.
The results showed that the efficacy of all three treatment modalities was significantly better than that of the control, including antidepressants, which have been more questioned in recent years; However, there was no significant difference
in efficacy between the three treatment modalities.
In addition, exercise was less acceptable than antidepressant treatment
.

In this study, exercise combined with antidepressants was not significantly more effective than exercise or antidepressants alone, which may be related to the small number of relevant studies, and the potential synergistic effect of the two needs to be further clarified
.
However, exercise can confer a range of physical benefits that, when combined with antidepressants, may offset the latter side effects and speed up the overall recovery process
.

More people in the exercise group dropped out of the study early than in the antidepressant group
.
Both interventions had their own challenges with adherence: antidepressants had greater side effects, higher treatment costs, and social stigma; Exercise is physically demanding and more difficult to perform
than medication.
In any case, there is a need to develop new strategies to improve treatment adherence in depressed patients
.

Bibliography: Recchia F, Leung CK, Chin EC, Fong DY, Montero D, Cheng CP, Yau SY, Siu PM.
Comparative effectiveness of exercise, antidepressants and their combination in treating non-severe depression: a systematic review and network meta-analysis of randomised controlled trials.
Br J Sports Med.
2022 Sep 16:bjsports-2022-105964.
doi: 10.
1136/bjsports-2022-105964.
Epub ahead of print.
PMID: 36113975.