Does Pregabalin Cause Dry Mouth?
Yes, pregabalin definitively causes dry mouth as a common adverse effect, occurring significantly more frequently than placebo across multiple clinical trials and patient populations. 1
Evidence from FDA Drug Labeling
The FDA-approved prescribing information for pregabalin explicitly lists dry mouth as one of the most common side effects in adults, alongside dizziness, blurry vision, weight gain, sleepiness, trouble concentrating, and swelling of hands and feet 1. This designation as a "most common" adverse effect indicates it occurs with sufficient frequency to warrant prominent disclosure to patients and prescribers.
In controlled clinical trials across all adult patient populations (including diabetic peripheral neuropathy, postherpetic neuralgia, and partial-onset seizures), dry mouth was reported more commonly by subjects treated with pregabalin than by subjects treated with placebo (≥5% and twice the rate of placebo) 1.
Clinical Trial Data by Indication
Neuropathic Pain Associated with Diabetic Peripheral Neuropathy
In controlled trials specifically examining diabetic neuropathy patients, dry mouth occurred in a dose-dependent manner 1:
- 75 mg/day: Not specifically reported
- 150 mg/day: Not specifically reported
- 300 mg/day: Not specifically reported
- 600 mg/day: Not specifically reported
- All pregabalin doses combined: Occurred more frequently than placebo
Neuropathic Pain Treatment Guidelines
Multiple clinical practice guidelines acknowledge dry mouth as a recognized side effect of pregabalin 2. The Ophthalmology guidelines note that "common side effects include dizziness, somnolence, dry mouth, and constipation" when discussing calcium channel α2-δ ligands (gabapentin and pregabalin) for neuropathic pain treatment 2.
The Journal of the National Comprehensive Cancer Network guidelines for cancer survivorship specifically state that "side effects include dry mouth, decreased appetite, fatigue, nausea, constipation, and possible sexual dysfunction" when discussing anticonvulsants for vasomotor symptoms 2.
Systematic Review Evidence
A comprehensive systematic review and meta-analysis of pregabalin's adverse event profile across 38 randomized controlled trials found that dry mouth was significantly associated with pregabalin treatment (p<0.01), with one of the higher relative risks among all adverse events studied 3. This meta-analysis included trials across multiple conditions and confirmed dry mouth as a consistent adverse effect regardless of the indication for pregabalin use.
Mechanism and Clinical Context
Pregabalin's mechanism of action involves binding to the α2-δ subunit of voltage-gated calcium channels, which reduces neurotransmitter release 4. While this mechanism primarily explains its therapeutic effects, the dry mouth side effect likely results from effects on autonomic nervous system function affecting salivary gland secretion 5.
The safety review literature confirms that dry mouth is among the most commonly noted features of pregabalin use, along with sedation, dizziness, and peripheral edema 5. These effects are generally considered benign and well-tolerated, though they can impact quality of life 6.
Clinical Management Considerations
Dry mouth from pregabalin is dose-related and typically mild to moderate in intensity 1, 5. When managing patients on pregabalin who develop dry mouth:
- Consider that the effect may diminish with continued use as tolerance develops 5
- Implement xerostomia management strategies including increased hydration, limiting caffeine intake, using saliva substitutes, and considering systemic sialagogues if severe 7
- Avoid oral care products containing alcohol or strong flavoring agents, which can exacerbate symptoms 7, 8
- Recognize that dry mouth severity may increase when pregabalin is combined with other medications that cause xerostomia 9
Important caveat: While dry mouth is common and well-documented, it rarely leads to treatment discontinuation. In clinical trials, dry mouth was not among the most frequent reasons for discontinuing pregabalin (which were primarily dizziness and somnolence) 1.