How does Lyrica (pregabalin) cause constipation?

Mechanism of Lyrica (Pregabalin) Induced Constipation

Lyrica (pregabalin) causes constipation primarily through its effects on the enteric nervous system, slowing intestinal transit and reducing gastrointestinal secretions. While not as well understood as opioid-induced constipation, pregabalin's constipation mechanism appears to be dose-dependent and affects approximately 8.2% of patients taking the medication 1.

Physiological Mechanisms

• Pregabalin affects calcium channels in the enteric nervous system, which may reduce peristaltic activity similar to how opioids affect the gastrointestinal tract 2
• The drug can cause reduced intestinal motility, leading to slower transit time of stool through the colon 1
• There are postmarketing reports of events related to reduced lower gastrointestinal tract function when pregabalin is co-administered with other medications that have constipating effects, suggesting a potential synergistic mechanism 1
• The severity of constipation symptoms appears to be dose-dependent, with higher doses of pregabalin associated with more severe constipation 3, 4

Clinical Significance and Prevalence

• FDA data shows constipation occurs in 8.2% of pregabalin users compared to 5.7% in placebo groups 1
• Constipation can be severe and disabling in some patients, with reports indicating it may be the most frequent adverse effect requiring pregabalin discontinuation (6.3% of patients in one study) 3
• Symptoms typically develop within 1-2 weeks of starting pregabalin therapy 3
• Elderly patients appear to be more susceptible to pregabalin-induced constipation, likely due to age-related changes in drug metabolism and gastrointestinal function 4

Risk Factors for Pregabalin-Induced Constipation

• Advanced age increases risk of constipation with pregabalin use 4
• Higher doses of pregabalin (300mg/day and above) are associated with greater risk of constipation 1, 4
• Concomitant use of other medications with constipating effects, particularly opioid analgesics 1
• Pre-existing gastrointestinal motility disorders 2
• Female gender may be associated with higher risk of medication-induced constipation in general 5

Management Approaches

• Dose reduction of pregabalin may alleviate constipation symptoms while maintaining some therapeutic effect 4
• For persistent constipation, osmotic laxatives such as polyethylene glycol (PEG) are recommended as first-line treatment 2
• Stimulant laxatives like bisacodyl or senna may be needed for more severe cases 2
• Ensuring adequate hydration and physical activity when appropriate 6
• Dietary interventions with adequate fiber intake may be helpful for patients with sufficient fluid intake 6

Clinical Pearls and Pitfalls

• Constipation symptoms are reversible upon pregabalin discontinuation or dose reduction 3, 4
• Failure to recognize pregabalin as the cause of constipation may lead to unnecessary diagnostic procedures 3
• When treating neuropathic pain, consider adding acetaminophen to allow for lower pregabalin dosing if constipation is problematic 4
• Sleep disorders may exacerbate medication-induced constipation, so addressing any concurrent insomnia may be beneficial 5
• Older patients should be prescribed a lower initial dose of pregabalin with careful titration to avoid constipation and other adverse effects 4