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Imipramine, a tricyclic antidepressant, represents one of the earliest pharmacologic options for NCCP. This was demonstrated in a randomized, double‐blind, placebo‐controlled three‐week trial of 60 patients assigned to clonidine 0.05–0.1 mg twice daily (included in the study as it had previously been used to treat chronic pain syndromes), imipramine 25–50 mg nightly, or placebo. Only patients in the imipramine group had a significant improvement in their pain (p = 0.03) [95]. More robust data regarding the use of tricyclic antidepressants is lacking; however, there was one retrospective long‐term follow up of 21 outpatients over 2.7 years treated with tricyclic antidepressants (amitriptyline, nortriptyline, imipramine, desipramine; doses ranging from 20–75 mg daily with median 50 mg) after incomplete response to anti‐reflux medications, which found 7 patients (41.2%) were successfully treated continuously or for symptom relapses and 5 patients (29.4%) discontinued therapy after 6 months with sustained benefits [96].