Does Pregabalin Cause Constipation?
Yes, pregabalin causes constipation as a recognized adverse effect, occurring in approximately 8.2% of patients compared to 5.7% with placebo according to FDA labeling data. 1
Mechanism and Clinical Significance
Pregabalin affects calcium channels in the enteric nervous system, which may reduce peristaltic activity in a manner similar to opioid effects on the gastrointestinal tract. 2 This mechanism explains why constipation can be a dose-dependent and clinically significant adverse effect in some patients.
Incidence and Severity
- FDA-approved labeling reports constipation in 8.2% of pregabalin-treated patients versus 5.7% on placebo. 1
- Clinical experience from tertiary epilepsy centers demonstrates that severe and disabling constipation can occur in approximately 7.5% of patients, typically developing within 1-2 weeks of initiating pregabalin. 3
- Constipation severity is dose-dependent, with higher doses (300 mg/day) causing more severe symptoms than lower doses (150 mg/day). 4
- In some cases, constipation is severe enough to require drug withdrawal, accounting for 6.3% of pregabalin discontinuations. 3
Risk Factors
Patients with pre-existing gastrointestinal motility disorders are at higher risk for developing pregabalin-induced constipation. 2 Elderly patients appear particularly vulnerable to this adverse effect, especially when combined with other dose-related side effects. 4
Clinical Management Algorithm
First-Line Interventions:
- Ensure adequate hydration and encourage physical activity when appropriate. 2
- Dietary interventions with adequate fiber intake may be helpful for patients with sufficient fluid intake. 2
For Persistent Constipation:
- Osmotic laxatives such as polyethylene glycol (PEG) 17g mixed in 8 ounces of water are recommended as first-line pharmacologic treatment. 2
- Stimulant laxatives like bisacodyl or senna may be needed for more severe cases. 2
For Refractory Cases:
- Dose reduction should be strongly considered, as symptoms typically improve or resolve with lower doses. 3, 4
- Drug discontinuation may be necessary if constipation remains severe despite management, as symptoms are entirely reversible upon pregabalin withdrawal. 3
Important Clinical Pitfalls
Do not overlook this adverse effect. Severe pregabalin-induced constipation can lead to multiple unnecessary investigations and procedures if clinicians are unaware that this is an entirely reversible side effect. 3 The constipation can be marked and disabling, not merely mild or moderate as previously reported in earlier literature.
Postmarketing surveillance has identified life-threatening complications when pregabalin is co-administered with medications that produce constipation (such as opioid analgesics), including intestinal obstruction and paralytic ileus. 1 This represents a critical drug interaction requiring heightened vigilance.
Comparison to Other Medications
Pregabalin and gabapentin share similar constipation profiles, as both are calcium channel α2-δ ligands with common side effects including dizziness, somnolence, dry mouth, and constipation. 5 When pregabalin is discontinued due to constipation, substituting gabapentin may result in similar gastrointestinal adverse effects. 6