93% say they would recommend it to a friend

STUDY: Weiden P et al, Schizophrenia Bulletin Open 2026;7(1)

STUDY TYPE: Qualitative study (part of an open-label trial)

FUNDING: Karuna Therapeutics, a Bristol Myers Squibb company

Background

Xanomeline/trospium (Cobenfy) is the first antipsychotic that brings a new mechanism to the table. Lacking dopamine blockade, it targets muscarinic M1/M4 receptors. That means more nausea at first, but less weight gain, emotional blunting, and no movement problems over the long-term. Here’s a look from the patient’s view.

The Study
  • 70 adults with stable schizophrenia, switched from standard antipsychotics to open-label xanomeline/trospium
  • Semi-structured interviews at 6 weeks and 6 months, conducted by independent interviewers
  • All made it to 6 weeks, but 32% dropped out by 6 months

Satisfaction was high at both time points, rated 8/10 (compared to 6/10 for old antipsychotic).

Before switching, most had problems with physical functioning (96%), social functioning (86%), role functioning (80%), and emotional well-being (74%). Six weeks after switching, more than half improved in most of those areas. By 6 months, improvement rates ranged from 68% to 95% across specific domains.

Energy and daily functioning showed the largest gains. Depression and sadness were the slowest to respond; only 45% improved at 6 weeks, though that rose to 79% by 6 months.

At 6 months, 93% said they’d recommend xanomeline/trospium to a friend, and 77% wanted to continue it after the trial ended. Common side effects included nausea, constipation, and dry mouth.

Limitations

Strong positive bias from drop-outs, as well as high expectancy effects and social desirability bias in ratings. Open-label design with no placebo comparator. Industry funding.

Practice Implications
  1. Encouraging, but take with skepticism.
  2. Xanomeline/trospium is not a miracle drug. It failed to improve cognition (except in those with severe impairment), has a similar effect size as other antipsychotcs and failed to augment other antipsychotics.
  3. Its long-term tolerability is a plus, but the short term drop-out rates are high (from GI side effects.
  4. Learn more in our Carlat xanomeline/trospium podcast.

— Chris Aiken, MD
Director, Psych Partners
Editor in Chief, Carlat Psychiatry Report

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