Best Antidepressant for IBS with Constipation
For a patient with IBS-C, selective serotonin reuptake inhibitors (SSRIs) are preferred over tricyclic antidepressants (TCAs) because TCAs worsen constipation through their anticholinergic effects, while SSRIs may improve bowel motility. 1
Rationale for SSRIs in IBS-C
SSRIs increase gastric and intestinal motility, making them theoretically better suited for constipation-predominant IBS compared to TCAs which cause constipation as a common side effect. 1 However, the evidence base has important limitations:
The 2022 AGA guidelines suggest against using SSRIs in general IBS populations due to inconsistent evidence (conditional recommendation, low certainty), with studies showing possible but not definitive improvement (RR 0.74; 95% CI 0.52-1.06). 1
The 2021 British Society of Gastroenterology guidelines give SSRIs a weak recommendation with low-quality evidence for global IBS symptoms. 1
Why Not TCAs in IBS-C
TCAs should be avoided in IBS-C because constipation is their most significant side effect. 1 The guidelines explicitly state:
Secondary amine TCAs (desipramine and nortriptyline) may be better tolerated in IBS-C patients due to their lower anticholinergic effects compared to tertiary amines like amitriptyline. 1
If a TCA must be used in IBS-C (for severe pain refractory to other treatments), choose desipramine or nortriptyline over amitriptyline. 1
Practical Prescribing Approach
When prescribing an SSRI for IBS-C:
Start with citalopram 20 mg daily, which can be increased to 40 mg after 2-4 weeks if needed. 1
Alternative SSRIs include paroxetine 10 mg daily (can be increased) or fluoxetine 20 mg daily. 1
Counsel patients that benefits may take 3-4 weeks to appear, and early side effects like anxiety or disturbed sleep may occur in the first 10 days. 2
Explain that these medications are being used as "gut-brain neuromodulators" rather than for depression, which improves patient acceptance. 1
Important Caveats
If the patient has concurrent moderate-to-severe depression or anxiety, an SSRI at standard antidepressant doses is clearly preferred because low-dose TCAs (10-30 mg) used for IBS are unlikely to address psychological symptoms adequately. 1
The evidence for SSRIs in IBS remains weak overall - they did not significantly improve global symptoms or abdominal pain in pooled analyses, though individual patients may benefit. 1, 3 A 2019 meta-analysis showed antidepressants as a class reduced the risk of persistent IBS symptoms (RR 0.66), but this included both TCAs and SSRIs without subtype-specific analysis for IBS-C. 4
Alternative Consideration
For IBS-C specifically, secretagogues like linaclotide are more effective than antidepressants for constipation and pain (strong recommendation, high-quality evidence), and should be considered as second-line pharmacotherapy before or alongside antidepressants. 1