Pimavanserin

Blocks the serotonin 5-HT2A receptor. Tested for negative symptoms of schizophrenia; its phase 3 trial found no benefit, and its maker stopped trials in 2024.

At a glance

Type
Medicine: serotonin 5-HT2A receptor inverse agonist
Used for
Tested as an add-on for negative symptoms of schizophrenia
Status
Development stopped, for negative symptoms, after its phase 3 trial found no benefit in 2024
Administration
Capsules, once a day, added to an antipsychotic
Clinical summaryFor health professionals

What it is

Pimavanserin blocks the serotonin 5-HT2A receptor and dampens its baseline activity. It was tested for negative symptoms, such as low motivation and blunted emotion, added to the antipsychotic people already took.1

How well it works

In a phase 2 trial at 83 sites, 65 of them in Europe, 403 people with mainly negative symptoms took pimavanserin or a placebo for 26 weeks, and negative symptoms improved slightly more on pimavanserin.1 A phase 3 trial in 454 people did not confirm this: negative symptoms improved by 11.8 points on pimavanserin and 11.1 on placebo.2 Its maker, Acadia, said it would conduct no further trials.2

Side effects

In the phase 3 trial, side effects were less common on pimavanserin than on placebo: 30 in 100 people against 40 in 100.2

Alternatives

Roluperidone (opens in a new tab), which also blocks 5-HT2A, is in a phase 3 trial for negative symptoms.

What we don’t know yet

  • Why the benefit seen in the first trial did not recur.

Sources

  1. Bugarski-Kirola D, Arango C, Fava M, et al. Pimavanserin for negative symptoms of schizophrenia: results from the ADVANCE phase 2 randomised, placebo-controlled trial in North America and Europe. The Lancet Psychiatry. 2022;9(1):46–58.
    DOI (opens in a new tab)PubMed (opens in a new tab)
  2. Acadia Pharmaceuticals. Acadia Pharmaceuticals announces top-line results from Phase 3 ADVANCE-2 trial of pimavanserin in negative symptoms of schizophrenia. 11 March 2024.
    biospace.com (opens in a new tab)

Not medical advice. Talk to a doctor before starting or changing any treatment. Disclaimer

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Page last reviewed: 5 November 2026Next review due: May 2027

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