Using central gut–brain neuromodulators to manage disorders of gut–brain interaction: a practical guide for gastroenterologists

Disorders of gut–brain interaction (DGBI) are common clinical presentations in gastroenterology. Central gut–brain neuromodulator medications have an increasingly important role in the management of DGBI. However, gastroenterologists often lack confidence in prescribing central neuromodulators and typically lack access to specialist psychiatric support. This review aims to provide a practical guide to the prescribing of key central neuromodulator medications. We first suggest a positive dialogue for discussing DGBI, covering concepts such as visceral hypersensitivity, central sensitisation and psychological maintaining mechanisms, providing the context for prescribing central neuromodulators. We then outline general points about antidepressants, such as response time, medication switches, mitigating discontinuation symptoms and nocebo effects in DGBI. Next, we review key central gut–brain acting neuromodulators for their target gastrointestinal symptoms, mechanisms, usual dosing and titration, common side effects and other key prescribing issues. Respectively, we review tricyclics, serotonin and norepinephrine reuptake inhibitors (SNRIs) (eg, duloxetine), mirtazapine, selective serotonin reuptake inhibitors (SSRIs) and antipsychotics (eg, olanzapine and haloperidol). We also provide practical guidance on combining different central neuromodulators. We suggest that mirtazapine can be combined safely and effectively with SSRIs or SNRIs. While amitriptyline should be combined cautiously with other serotonergic antidepressants, nortriptyline combines more rationally and effectively with SSRIs. Overall, by applying positive psychoeducation about DGBI and using even a modest repertoire of central gut–brain acting neuromodulators, gastroenterology clinicians can support recovery from DGBI symptoms and enable patients to apply non-pharmacological techniques, such as graded food re-exposure. Further clinical trials of central neuromodulator medications across the range of DGBI are now needed.