Pilocarpine drops for dry mouth in frail patients missed their primary endpoint in an underpowered trial

Design

Multicentre, double-blind, placebo-controlled randomised trial

Population

92 adults with xerostomia and a life-limiting condition or frailty in the Netherlands

Primary outcome

Change in xerostomia severity (NRS 0-10) at 4 weeks

Effect

Adjusted difference −0.37 (95% CI −1.31 to 0.58); not significant

A double-blind trial at two hospitals and three nursing homes in the Netherlands (JAMDA, 25 August 2026) randomised 92 adults with a life-limiting condition or frailty and moderate to severe xerostomia (rating 5 or more out of 10) to four weeks of topical pilocarpine drops or placebo.

There was no significant difference in xerostomia severity at two weeks or four weeks (adjusted difference at four weeks −0.37, 95% CI −1.31 to 0.58). Both groups improved by about 1.5 points by week 2, but only the pilocarpine group continued to improve between weeks 2 and 4. Oral health-related quality of life was better with pilocarpine at two weeks. Adverse effects were limited.

The trial planned 120 participants and recruited 92, so a modest benefit cannot be ruled out. For now, topical pilocarpine is a reasonable, well-tolerated option to try in distressing dry mouth, but without strong evidence behind it.

• Topical pilocarpine drops did not significantly beat placebo for xerostomia in frail or seriously ill adults.
• Consider a time-limited trial if dry mouth is distressing and other measures fail; tolerability was good.
• Expect a large placebo response; both groups improved early.
• Address causes first, including anticholinergic drugs and mouth breathing.

Why it matters

Dry mouth is common and distressing near the end of life, and there are few options with evidence.

Don't overread it

The trial was underpowered, so a negative result does not rule out a modest benefit.

The statistics, in plain English

The CI from −1.31 to 0.58 includes both a small benefit and a small harm. The within-group improvement after week 2 is a secondary observation, not a between-group difference.

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