Mirtazapine for the treatment of irritable bowel syndrome: A systematic review

Table 1 Summary of systematically reviewed clinical cases and studies on the use of Mirtazapine in the treatment of irritable bowel syndrome

Ref.	Patients (n)	Intervention	Comparison	Study design	Outcomes	Results
Akama et al[9], 2018, Japan	Case report: 52-year-old female (1)	Mirtazapine, started 15 mg/day, increased to 30 mg/day after 2 weeks	Not applicable	Case report	IBS–D (diarrhoea–stool frequency, Abdo pain) and adjustment disorder symptoms (anxiety, irritability, depressed mood- Hamilton scale for depression HAM-D and for anxiety HAM-A monitored)	After 2 months of treatment, good response in: Stool frequency reduced from > 10×/day to 3×/day or less, improvement in abdominal pain, diarrhoea, reduction in HAM-D (from 22 points to 5 points) and HAM-A (from 22 points to 11 points)
Khalilian et al[23], 2021, Iran	Randomized, double-blind, placebo-controlled study, included 67 patients meeting Rome IV criteria for IBS-D: 34 randomized to Mirtazapine group, 33 to placebo (67)	Mirtazapine 15 mg/day for the first week, increased from the second week to 30 mg/day for another 7 weeks	Placebo was used for comparison	Randomized, double-blind, placebo controlled	Outcomes included: Changes in the total IBS symptoms severity score, IBS-QoL and changes in the diary-based symptoms–pain, urgency, bloating, stool frequency and consistency; also, the number of days/weeks with pain/urgency/diarrhoea/bloating during first week of treatment and during last week of treatment	Mirtazapine was shown to be more efficacious in reducing the severity of the IBS symptoms (P = 0002) and all diary-derived symptoms except for bloating showed significant improvement in the treatment arm compared to placebo. QoL was improved significantly (P = 004) and so were anxiety symptoms (P = 005) with Mirtazapine
Spiegel and Kolb[21], 2011, United States	Case report: 66 years old female (1)	Mirtazapine	Not applicable	Case report	IBS–mixed type symptoms, worsened by panic attacks	Mirtazapine has resulted in decreasing in diarrhoea and constipation and psychopathological symptoms
Thomas[22], 2000, United States	Case report: 35 years old female (1)	Mirtazapine started at 7.5 mg/day, increased every 2 weeks until a max dose of 30 mg/day	Not applicable	Case report	Abdominal cramping, bloating, constipation and weight loss and repeated hospital visits and work absenteeism	Significant improvement noted at 12 weeks, with normal bowel movement, a marked decrease in all the gastrointestinal symptoms and gained back the lost weight. No missed workdays, no hospital visits
Lu et al[24], 2020, China	Prospective study: Adult patients who met Rome III criteria for IBS-D (using IBS specific symptoms questionnaire) and comorbid depression (using Hamilton Depression rating scale HAM-D: 410 patients recruited)	116 patients were given neuromodulators, 97 patients completed the follow up. 50 patients received Mirtazapine (15-45 mg/day), 52 patients received Paroxetine, 17 received Flupentixol/Melitracen, the rest received Sertraline, Escitalopram, Venlafaxine and Fluoxetine. Mean treatment was 5 months	Not applicable	Prospective study–unable to describe further	Intestinal symptoms assessed using IBS symptoms specific questionnaires and psychological states using HAM-D scale	The baseline sleep disturbances score positively correlated with improvements in abdominal pain/discomfort and diarrhoea after mirtazapine therapy (r = 0.352, P = 0.026; r = 0.356, P = 0.024)

HAM-D: Hamilton Rating Scale for Depression; HAM-A: Hamilton Rating Scale for Anxiety; IBS: Irritable bowel syndrome; IBS-D: Diarrhea-predominant irritable bowel syndrome; QoL: Quality of life.