Pharmacotherapy: non-serotonergic mechanisms

Abstract

Antidepressants rapidly relieve pain in irritable bowel syndrome (IBS) and are effective at low doses. Noradrenaline reuptake inhibitors appear to be more effective than selective serotonergic reuptake inhibitors, suggesting that pathways other than those modulated by serotonin may be involved in visceral sensation. Visceral sensitivity is reduced by both centrally and peripherally acting opioids, suggesting the possible existence of an endogenous opioid deficiency in patients with IBS. The alpha(2) adrenoceptor antagonist clonidine, as well as somatostatin, oxytocin, and possibly amitriptyline have also been shown to act as visceral analgesics. As knowledge increases, there are undoubtedly many other possible targets, and new drugs currently undergoing development may provide future benefit in patients with IBS.

Figure 1

Results of a three month clinical trial of loperamide compared with placebo. The dose was titrated to best effect and ranged from 2 to 8 mg per day. *p<0.05, **p<0.01. Reproduced with permission from Lavo and colleagues.¹⁴

Figure 2

Octreotide 100 µg subcutaneously increased rectal compliance in eight patients with symptoms of diarrhoea compared with placebo. Reproduced with permission from Hasler and colleagues.²³