Impact of opioid and cannabis use on low‐dose amitriptyline efficacy in cyclical vomiting syndrome: a real‐world study in the United Kingdom

Background

Central neuromodulators, specifically tricyclic antidepressants (TCAs), are prescribed as prophylactic treatment for cyclical vomiting syndrome (CVS). It is unclear whether opioids and/or cannabis affect the treatment response to neuromodulators. The aims of this study were to assess: (i) the prevalence of opioid and cannabis use among outpatients with CVS, (ii) clinical characteristics associated with opioid/cannabis use and response to a three-tiered neuromodulator treatment algorithm, and (iii) the effect of opioid/cannabis cessation on response to the treatment algorithm.

Methodology

Data from consecutive patients newly diagnosed with Rome IV CVS at a single tertiary care neurogastroenterology outpatient clinic (January 2016–June 2024) were retrospectively collected. Patients were advised to stop consuming opioids and/or cannabis and commenced a low-dose TCA.

Results

Sixty-one (46/75) percent of outpatients with CVS responded to the three-tiered treatment algorithm. Among responders, 42 (91%) patients responded to TCA alone (1st line therapy), 3 (7%) patients responded to TCA and selective serotonin reuptake inhibitor or serotonin norepinephrine reuptake inhibitor (2nd line therapy), and 1 (2%) patient required topiramate (3rd line therapy). The mean [SD] dosage of TCA among responders was 26.5 [18.3] mg. Twenty-five (33%) patients consumed opioids, 14 (19%) took cannabis, and five (7%) consumed both opioids and cannabis. While opioid cessation was associated with clinical response to the treatment algorithm (p = 0.03), opioid intake at the initial consultation was not (p = 0.2). Irritable bowel syndrome was independently associated with significantly greater odds (OR [95% CI]) of opioid consumption at baseline (6.59 [1.49–29.24], p = 0.01). Heartburn was independently associated with lower odds of response to the treatment algorithm (0.2 [0.05–0.65], p = 0.006).

Conclusion

Low-dose neuromodulators, along with opioid and cannabis cessation, may be important strategies in the management of CVS.