Ray E. Clouse

Objectives: To identify factors responsible for premature antidepressant discontinuation that would assist in designing management strategies for patients with functional gastrointestinal disorders. Antidepressants are being used increasingly to manage patients with functional gastrointestinal disorders; poor patient adherence to treatment regimens, particularly in the period shortly after antidepressant initiation, is common and interferes with success. Methods: Clinical records were reviewed from 172 outpatients who attended a university-based practice and who had been prescribed antidepressants to manage their functional gastrointestinal symptoms. Survival analysis methods were used to determine independent predictors of premature antidepressant discontinuation (within 6 months of initiation). Logistic regression analyses were used to see if the same predictors were responsible for side effects or poor treatment response. Results: Premature antidepressant discontinuation occurred in 41 (23.8%) subjects. Somatization features (state or trait) and history of depression or an anxiety disorder were the most significant predictors of premature discontinuation (p ≤ .01 for each). Advancing age and female sex also were independent predictors (p < .05 for each). Somatization features and psychiatric illness were each linked to poor treatment response, whereas somatization features most consistently were associated with antidepressant side effects. Conclusions: Failure to maintain treatment occurs in nearly a quarter of outpatients given antidepressants for functional gastrointestinal disorders. Somatization features and history of depression or anxiety most significantly interfered with treatment by predicting side effects, poor treatment response, and premature antidepressant discontinuation. Management algorithms should include specific strategies targeted at patients with these risk factors for poor treatment adherence. IBS = irritable bowel syndrome; HR = hazard ratio; OR = odds ratio; CI = confidence interval.

Chronic vomiting in diabetic patients often is unresponsive to prokinetic agents and poorly explained by delayed gastric emptying or neuropathy. This retrospective study examines clinical response to tricyclic antidepressants, a treatment of reported benefit in nondiabetic patients with unexplained vomiting syndromes. Outcomes were studied in 24 diabetic outpatients who had been treated with tricyclic antidepressants specifically for nausea and vomiting after an unsatisfactory response to prokinetic therapy. Symptom patterns and treatment response were determined from chart review and telephone interview. Ten patients (42%) had recurrent, stereotypical vomiting episodes with symptom-free intervals suggesting cyclic vomiting syndrome; 14 (58%) had persistent symptoms. By chart review, at least moderate symptom response to tricyclic antidepressant treatment (median dosage, 50 mg/day) occurred in 88% of subjects, with complete or nearly complete resolution of symptoms in one-third. At follow-up interview, 77% self-reported at least moderate symptom improvement during therapy and 68% rated tricyclic antidepressants the most effective treatment received. Duration of diabetes, presence of neuropathy, and psychiatric status were not predictive of treatment outcome in multivariate analysis, but a cyclical symptom pattern attenuated antidepressant response (P< 0.05). In this retrospective review, the majority of diabetic patients with chronic vomiting and incomplete response to prokinetic therapy benefited from tricyclic antidepressants in low-dose, open-label regimens and rated them the most effective treatment received. This therapeutic option should be further studied in diabetic patients considering the morbidity of chronic vomiting in this population.

Enhanced appreciation for the relative importance of central mechanisms (for example, signal processing alterations) in many if not most patients with IBS and other painful functional gastrointestinal disorders is an important factor responsible for prescribing shifts among gastroenterologists—more so than a new or improved understanding of the relationship of symptoms to anxiety or depression.⁸ The composite body of investigation over the past 15 years involving visceral stimulation, brain imaging, multidimensional clinical studies, and treatment trials designed to answer mechanistic questions has led us closer to understanding the pathways by which psychopharmacological agents may interrupt the symptomatic process in these common gastrointestinal disorders. Complemented by clinical observations, improved recommendations for their use have evolved.^{6, 12} This review describes the types of psychopharmacological agents used in functional gastrointestinal disorders, new models for their potential benefits, a summary of the reported efficacy, and practical aspects surrounding treatment. The majority of the available information has been accrued in patients with IBS, although findings are similar when other pain or discomfort based functional gastrointestinal disorders have been studied.