Antidepressants for irritable bowel syndrome

Clinical question

Do antidepressant medications improve irritable bowel syndrome (IBS) symptoms?

Bottom line

Both tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs) might improve overall IBS symptoms. About 55% of patients treated with TCAs or SSRIs will benefit compared with about 35% with placebo. Only TCAs improved abdominal pain for about 60% of patients compared with about 30% with placebo. Studies of TCAs reported more side effects (drowsiness and dry mouth) than studies of SSRIs did.

Evidence

• The most recent systematic review included 18 RCTs of 1127 adult patients (42% to 100% women); the IBS subtype was usually not specified. Patient-reported outcomes are presented where available.¹

  • - Twelve RCTs of TCAs (787 patients) studied amitriptyline, imipramine, desipramine, trimipramine, doxepin, and nortriptyline versus placebo over 6 to 12 weeks.

    • — Global IBS symptom improvement was 57% for TCAs versus 36% for placebo (number needed to treat [NNT] of 5).

    • — Abdominal pain improvement was 59% for TCAs versus 28% for placebo (NNT = 4).

    • — Adverse events (mostly drowsiness and dry mouth) were 36% for TCAs versus 20% for placebo (number needed to harm of 7).

  • - Seven RCTs of SSRIs (356 patients) studied fluoxetine, paroxetine, and citalopram over 6 to 12 weeks.

    • — Global IBS symptom improvement was 55% for SSRIs versus 33% for placebo (NNT = 5).

    • — Abdominal pain improvement was 45% for SSRIs versus 26% for placebo (not statistically different).

    • — Adverse events were 37% for SSRIs versus 27% for placebo (not statistically different).

  • - Evidence was limited by small sample sizes, short study duration, and likely publication bias. Adverse events were not reported in all studies.

• Older systematic reviews show similar results.^2,3

Context

• Up to 5 million Canadian adults might have symptoms compatible with IBS.⁴

• Canadian guidelines recommend TCAs or SSRIs irrespective of whether patients have depression or anxiety.⁵

• Evidence for antidepressants appears stronger than for antispasmodics,⁶ fibre,⁴ low FODMAP diet,⁷ or probiotics.⁴

• Newer treatments are limited by cost (linaclotide costs $560 for 90 days⁸ and rifaximin $330 for 14 days⁹) and lack of long-term safety data.¹⁰

Implementation

The fecal calprotectin test might help differentiate inflammatory bowel disease from IBS¹¹ and appears cost effective at a 100 µg/g cutoff.¹²

The choice of antidepressant and dosing can be based on potential side effects. Consider TCAs for diarrhea-predominant IBS and give at night (owing to constipating and sedation effects). Consider SSRIs for constipation-predominant IBS and give during the day. Doses varied in the studies; starting low and increasing slowly based on response seems reasonable.