Mirtazapine for symptom control in refractory gastroparesis

Abstract

IntroductionGastroparesis symptoms can be severe and debilitating. Many patients do not respond to currently available treatments. Mirtazapine has been shown in case reports to reduce symptoms in gastroparesis.AimTo assess the efficacy and safety of mirtazapine in gastroparetic patients.MethodsAdults with gastroparesis and poorly controlled symptoms were eligible. Participants were prescribed mirtazapine 15 mg PO qhs. Questionnaires containing the gastrointestinal cardinal symptom index (GCSI) and the clinical patient grading assessment scale (CPGAS) were completed by patients’ pretreatment, at 2 weeks, and at 4 weeks. Primary end point was nausea and vomiting response to mirtazapine using the GCSI. Secondary end point was nausea and vomiting severity assessment using the CPGAS. P-values were calculated using the paired two-tailed Student’s t-test. Intention to treat analysis was used.ResultsA total of 30 patients aged 19–86 years were enrolled. Of those, 24 patients (80%) completed 4 weeks of therapy. There were statistically significant improvements in nausea, vomiting, retching, and perceived loss of appetite at 2 and 4 weeks (all P-values <0.05) compared with pretreatment. There was a statistically significant improvement in the CPGAS score at week 2 (P=0.003) and week 4 (P<0.001). Of the total patients, 14 (46.7%) experienced adverse effects from mirtazapine and due to this, 6 patients stopped therapy.ConclusionMirtazapine significantly improved both nausea and vomiting in gastroparetics after 2 and 4 weeks of treatment. Side effects led to treatment self-cessation in a fifth of patients. From these data, we conclude that mirtazapine improves nausea and vomiting, among other symptoms, in patients with gastroparesis and might be useful in select patients.

Gastroparesis: a turning point in understanding and treatment

“…Nortriptyline also failed to prove superiority compared with placebo in another randomised controlled trial of patients with gastroparesis 135. On the contrary, mirtazapine, an antidepressant with central adrenergic and serotonergic activity, improved nausea, vomiting and loss of appetite in an open-label study of patients with gastroparesis 136. If these results are confirmed, mirtazapine would find an indication in patients with weight and appetite loss.…”

Status of Brain Imaging in Gastroparesis

“…Selective serotonin reuptake inhibitors (SSRIs) and selective noradrenaline reuptake inhibitors (SNRIs) have been shown to be no better than placebo in treating gastrointestinal symptoms in patients with FD in a systematic review and meta-analysis of 13 randomized controlled trials (1241 patients) [76]. In the multicenter Functional Dyspepsia Treatment Trial, 292 patients with FD were randomly assigned to groups to receive either placebo, 50 mg of amitriptyline (TCA), or 10 mg of escitalopram (SSRI) for 10 weeks [77]. The primary end point was defined as adequate relief of functional dyspepsia symptoms for ≥5 weeks of the last 10 weeks.…”

“…Nocturnal TCAs address the "brain-gut" relationship as well as improve sleep which leads to better patient tolerability and resilience. An important observation from the Functional Dyspepsia Treatment Trial [77] was that amitriptyline did not worsen gastric emptying in gastroparesis patients, and hence, this is not a liability. Prokinetics can also be simultaneously administered with TCAs in a documented gastroparesis setting.…”

Psychiatric Issues in Older Adults with Gastrointestinal Disorders

“…Highly anticholinergic TCAs should be avoided for similar reasons as cited in treatment of GERD. Considering its appetite-stimulating and slight antiemetic effects, another antidepressant, mirtazapine, has been used in patients with gastroparesis (Kim et al 2006;Johnstone et al 2009) with beneficial effect likely due to increasing noradrenergic and serotonergic neurotransmission and directly blocking 5HT3 receptors (Malamood et al 2016;Bielefeldt 2012).…”