Exercise, psychotherapy help boost effectiveness of antidepressants post-CAD

Antidepressants remain the most understood treatment modality for depression after coronary artery disease (CAD), though emerging evidence suggests that combining them with psychotherapy and exercise seems to improve effectiveness, according to a recent network meta-analysis.

Nevertheless, literature surrounding this subject remains limited and biased, “with mostly low evidence ratings for all treatment comparisons because of the sparsity of eligible trials,” the researchers said.

The network meta-analysis included 33 randomized controlled trials, corresponding to 72 trial arms and 7,240 participants. Interventions eligible for inclusions were pharmacotherapy, psychotherapy, a combination of the two, exercise, and collaborative care. The primary outcomes were efficacy response, defined as the between-group difference in depressive symptoms, and acceptability, as determined by discontinuations.

None of the different pairwise comparisons between treatment modalities were more acceptable than others, and a statistically meaningful treatment ranking could not be conducted. The network model for acceptability showed potential evidence of incoherence, suggesting that direct and indirect evidence for two comparisons were inconsistent. An inconsistency model, however, found no such issues. [Psychosom Med 2021;83:423-431]

In terms of 8-week treatment effects, the model again showed strong incoherence for three comparisons, and inconsistency analysis flagged two outliers. After removing these, though, the final model showed that combination therapies and exercise had the strongest effect against depressive scores, though both modalities only had a single study supporting them.

Meanwhile, the use of antidepressants yielded significantly better results compared to placebo and usual care and led to marginal improvements than treatment controls. Psychotherapy, on the other hand, proved to be superior to usual care.

The researchers then generated a rankogram, comparing treatment approaches according to their 8-week efficacies. Combination therapy emerged as the probable best treatment modality, followed by exercise and antidepressant use. Other effective modalities were treatment control, placebo, psychotherapy, collaborative care, and usual care, but scores were largely on the low end.

For both primary endpoints, heterogeneity of evidence was substantial, though modal direct comparisons usually had a low risk of bias.

“[T]he current evidence suggests that, although all treatments for post-CAD depression are equally acceptable, the most robust evidence base is for antidepressants, which should be the first treatment option,” the researchers said.

“Combinations of antidepressants and psychotherapy, along with exercise, could be even more effective than antidepressants alone but require further research before this can be established. Researchers should consider the comparator groups carefully and report them in detail for future evidence synthesis,” they added.