Clinical Pearls · 2026

Gastrointestinal Adverse Events After 5 and 52 Weeks of Xanomeline-Trospium in Inpatients and Outpatients

The question:When do gastrointestinal side effects appear in the 5-week and 52-week trials, which enrolled different populations?

The Two Cohorts Side by Side

Safety populations; xanomeline-trospium arm unless placebo is shown

Pooled EMERGENT-1, -2 and -3n=340 vs n=343 placebo5-Week

EMERGENT-5n=56652-Week

Design

Randomized, placebo-controlled; inpatients

Open-label, single-arm; stable outpatients

Treatment

5 weeks

Mean 228.1 days

Adverse events

Any event

67.9%vs 51.3% with placebo

82.3%over 52 weeks

Stopped

5.9%vs 4.4% with placebo

17.7%over 52 weeks

Serious

0.3%treatment-related, vs 0% with placebo

1.6%treatment-related; 7.2% any serious event

Heart rate

+10.4at week 5 vs +4.5 with placebo

+7.6at week 2, the peak; +2.4 at week 52

Gastrointestinal events, share of participants

Nausea

18.5% vs 3.8% with placebo

23.1%

Vomiting

13.5% vs 1.7% with placebo

20.3%

Constipation

17.1% vs 6.1% with placebo

18.0%

Dyspepsia

15.9% vs 4.7% with placebo

7.2%

Dry mouth

5.0% vs 1.5% with placebo

9.4%

Led to stopping

Nausea 1.5%, vomiting 0.9%, reflux 0.6%

Nausea 5.1%, vomiting 4.1%, dyspepsia 0.7%, diarrhea 0.5%

The most common events were mild or moderate in both cohorts. Heart rate in beats per minute, measured near peak drug levels. At 52 weeks, events were not assessed at baseline, so some may reflect the prior antipsychotic. Selected events only, not the full safety profile or the labeled adverse reactions.

When Events Began

Timing reported differently in each analysis

5-WeekCholinergic events, any day

28.8%on day 7, the peak

16.8%on the last day

Most began within the first 2 weeks and lasted on average 4 days for vomiting to 20 days for dry mouth.

52-WeekNew onset by week, % of participants; darker = more

New onset

Wk 1

Wk 2

Wk 3

Wk 4

Wk 5

Wk 6

Wk 7

Wk 8

Nausea

9.9

4.2

1.8

0.2

0.4

0.5

Vomiting

6.5

3.4

1.6

1.2

0.5

0.9

0.4

Constipation

5.5

1.9

1.2

1.4

0.9

0.5

0.4

0.7

Weekly values from a conference poster that has not been peer reviewed.

5-Week

Take-home: gastrointestinal events began early and were mostly transient in acutely ill inpatients

52-Week

Take-home: new gastrointestinal events decreased over 8 weeks in stable outpatients

Efficacy

Details in the companion efficacy pearl

Efficacy

PANSS total −19.4 vs −9.6 with placebo at week 5

PANSS total −5.5 from baseline at week 52

Pearl

Gastrointestinal events appeared early in both cohorts and declined over the following weeks, though rates differed between groups. The results are not directly comparable given differences in duration, design, and patient status.

Based on

Kaul I, Claxton A, Sawchak S, et al. J Clin Psychiatry. 2025;86(1):24m15497.

Kaul I, Sawchak S, Claxton A, et al. Schizophrenia. 2024;10:102.

Chepke C, Kempf B, Appio J, et al. Poster PS01-1222. ECNP Congress; October 2026; Munich, Germany.

Kaul I, Claxton A, Chaturvedi S, et al. Schizophr Res. 2026;288:86–94.

Sponsor

Financial support was provided by Bristol Myers Squibb. Psychiatrist.com independently developed the content and maintained final editorial control. The authors include employees and consultants of the manufacturer; their disclosures appear in the full publications. The approved labeling does not address switching from another antipsychotic. This summary does not replace prescribing information.