Schizophrenia

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Last reviewed: 4 Apr 2025
Last updated: 21 Mar 2025
13 Nov 2024

US FDA approves new treatment for schizophrenia, the first drug with a novel target in decades

A new class of treatment for schizophrenia has been approved by the US Food and Drug Administration (FDA), which is the first new pharmacological approach to be approved for schizophrenia in decades.

Xanomeline/trospium is the first antipsychotic drug to be approved that targets muscarinic cholinergic receptors as opposed to dopamine receptors, which has long been the standard of care.

In two phase 3 trials in patients with acute psychosis, xanomeline/trospium:[240][241]

  • Reduced symptoms from baseline to week 5 as measured by the PANSS total score, a measure of schizophrenia severity, compared to the placebo group

  • Appeared to be generally well tolerated

  • Showed similar discontinuation rates due to adverse events compared to placebo

  • Had similar measures of extrapyramidal symptoms, weight gain, and somnolence relative to placebo.

Long-term efficacy is uncertain; the results of two 52-week, open-label trials are awaited.

Xanomeline/trospium is expected to be commercially available in the US in late 2024. It is not approved in Europe as yet.

See Management: emerging

Original source of update

Summary

Definition

History and exam

Key diagnostic factors

  • auditory hallucinations
  • delusions
  • avolition
  • anhedonia
  • asocial behavior
  • affective blunting
  • alogia
  • cognitive deficits
  • somatization
Full details

Other diagnostic factors

  • lack of insight (anosognosia)
  • bizarre or disorganized behavior
  • tangentiality and looseness of association (derailment)
  • circumstantiality
  • pressured speech
  • distractible speech
  • depression
  • suicidality
  • anxiety
  • elation
  • incongruent affect
  • verbigeration
  • perseveration
  • word salad
  • derealization
  • nonauditory hallucinations
  • déjà-vu
  • stilted goal-directed behaviors
  • catatonic symptoms
  • "soft" neurologic deficits
Full details

Risk factors

  • family history of schizophrenia
  • increasing paternal age
  • obstetric complications
  • cannabis use
  • low IQ
  • motor dysfunction
  • psychological stress
  • childhood abuse
  • migrant status
Full details

Diagnostic tests

1st tests to order

  • clinical diagnosis
Full details

Tests to consider

  • MRI/CT head
  • serum HIV enzyme-linked immunosorbent assay
  • serum rapid plasma reagin (RPR) test
  • CBC including absolute neutrophil count (ANC)
  • drug toxicology screen
  • BUN and electrolytes
  • liver function tests
  • thyroid-stimulating hormone
  • pregnancy test
  • genetic testing
Full details

Treatment algorithm

INITIAL

at risk of developing psychosis

ACUTE

acute psychotic episode

ONGOING

chronic symptoms

treatment-resistant schizophrenia

Contributors

Expert advisers

Xiaoduo Fan, MD, MPH, MSc

Professor of Psychiatry

Director, UMass MIND

UMass Memorial Health/UMass Chan Medical School

Worcester

MA

Disclosures

XF has received research support from Otsuka, Roche, Intra-Cellular Therapies, Avanir, and Janssen. XF holds a patent on "combination treatment for neuropsychiatric disorders" (USPTO patent # 11,331,319).

Acknowledgements

Dr Xiaoduo Fan would like to gratefully acknowledge Dr Adrian Preda and Dr Robert G. Bota, previous contributors to this topic.

Disclosures

AP and RGB declare that they have no competing interests.

Peer reviewers

David Taylor, PhD

Chief Pharmacist

South London and Maudsley NHS Foundation Trust

London

UK

Disclosures

DT declares that he has no competing interests.

Joel Yager, MD

Professor

Department of Psychiatry

University of New Mexico School of Medicine

Albuquerque

NM

Disclosures

JY declares that he has no competing interests.

Kemal Sagduyu, MD

Professor of Psychiatry

University of Missouri Kansas City

Kansas City

MO

Disclosures

KS declares that he has no competing interests.

References

Our in-house evidence and editorial teams collaborate with international expert contributors and peer reviewers to ensure that we provide access to the most clinically relevant information possible.

Key articles

American Psychiatric Association. Diagnostic and statistical manual of mental disorders, 5th ed., text revision (DSM-5-TR). Washington, DC: American Psychiatric Publishing; 2022.Full text

American Psychiatric Association. ​The American Psychiatric Association practice guideline for the treatment of patients with schizophrenia. Washington, DC: American Psychiatric Association; 2021.Full text

Hasan A, Falkai P, Wobrock T, et al. World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for biological treatment of schizophrenia, part 1: update 2012 on the acute treatment of schizophrenia and the management of treatment resistance. World J Biol Psychiatry. 2012 Jul;13(5):318-78. Abstract

Reference articles

A full list of sources referenced in this topic is available to users with access to all of BMJ Best Practice.
  • Differentials

    • Schizoaffective disorder
    • Schizophreniform disorder and brief psychotic disorder
    • Substance-induced psychotic disorder
    More Differentials
  • Guidelines

    • Diagnostic and statistical manual of mental disorders, fifth edition (DSM-5-TR)
    • Evidence-based guidelines for the pharmacological treatment of schizophrenia
    More Guidelines
  • Patient information

    Schizophrenia: what is it?

    Schizophrenia: questions to ask your doctor

    More Patient information
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