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.
Summary
Definition
History and exam
Key diagnostic factors
- auditory hallucinations
- delusions
- avolition
- anhedonia
- asocial behavior
- affective blunting
- alogia
- cognitive deficits
- somatization
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
Risk factors
- family history of schizophrenia
- increasing paternal age
- obstetric complications
- cannabis use
- low IQ
- motor dysfunction
- psychological stress
- childhood abuse
- migrant status
Diagnostic tests
1st tests to order
- clinical diagnosis
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
Treatment algorithm
at risk of developing psychosis
acute psychotic episode
chronic symptoms
treatment-resistant schizophrenia
Contributors
Authors
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.
Differentials
- Schizoaffective disorder
- Schizophreniform disorder and brief psychotic disorder
- Substance-induced psychotic disorder
More DifferentialsGuidelines
- Diagnostic and statistical manual of mental disorders, fifth edition (DSM-5-TR)
- Evidence-based guidelines for the pharmacological treatment of schizophrenia
More GuidelinesPatient information
Schizophrenia: what is it?
Schizophrenia: what treatments work?
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