Systematic review: the treatment of noncardiac chest pain with antidepressants

Background: Noncardiac chest pain (NCCP) is a common condition, affecting approximately 25% of the general population. The cause of NCCP can be classified as gastro-oesophageal reflux disease (GERD)-related NCCP, where antireflux therapy is the main treatment modality or alternatively as non-GERD-related NCCP, where pain modulators, including antidepressants, are utilised.

Aim: To provide a systematic review evaluating the evidence for the use of antidepressants in the treatment of non-GERD-related NCCP.

Methods: A computerised literature and manual search was conducted to identify relevant randomised, placebo-controlled studies, published in any language for the evaluation of the effectiveness of antidepressant as a therapeutic intervention for NCCP.

Results: Six randomised placebo-controlled trials of antidepressant treatment for NCCP were identified. The medications included were selective serotonin reuptake inhibitors [paroxetine (n = 2), sertraline (n = 1)], tricyclic antidepressant [impramine (n = 1)], serotonin-norepinephrine reuptake inhibitor [venlafaxine (n = 1)] and a triazolopyridine [trazodone (n = 1)]. The percentage reduction in chest pain was statistically significant with venlafaxine (50% vs. 10%; P < 0.001), sertraline (63% vs. 15%; P = 0.02) and imipramine (52% vs. 1%; P = 0.03). The improvement in chest pain symptoms was independent of improvement in depression scores. Clinical global improvement also significantly improved in patients on venlafaxine, sertraline, paroxetine and trazodone. The percentage of patients in treatment groups reporting adverse effects were relatively high compared with those in placebo groups, although majority were statistically insignificant or significance was not reported. Nonetheless, adverse events were the reported reason for discontinuation of trials in 53% of patients from the antidepressant groups compared with 29% from the placebo group.

Conclusions: There is modest evidence for the benefit of antidepressants in reducing NCCP and improving patients' general health. However, there is significant heterogeneity amongst the studies with several study limitations to warrant more rigorous trials and to assess the usefulness of low-dose antidepressants in non-GERD NCCP.