Evidence map›Paper›PMID 36269510›Full record

SynthesisCNS drugs2022

Clinical Effectiveness of Muscarinic Receptor-Targeted Interventions in Neuropsychiatric Disorders: A Systematic Review.

Shivani Vaidya, Alexandre A Guerin, Leigh C Walker, Andrew J Lawrence

Open access · hybridAbstract readMeta-AnalysisSystematic Review
In one paragraph

Synthesis in CNS drugs, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed, 1 pooled it
1.5field-weighted citation impact, top 18% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed, 1 synthesis or guideline pooled it, 18 citations in OpenAlex.

  1. The effect of scopolamine on memory and attention: a systematic review and meta-analysis.European psychiatry : the journal of the Association of European Psychiatrists · 2025
    Pooled it
  2. Advancing past ketamine: emerging glutamatergic compounds for the treatment of depression.European archives of psychiatry and clinical neuroscience · 2025
    Review
  3. Review
  4. Review
  5. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 2 institutions in 1 country.

Shivani VaidyaFlorey Institute of Neuroscience & Mental Health, Royal Parade, Parkville, VIC, 3010, Australia.
Alexandre A GuerinCentre for Youth Mental Health, University of Melbourne, 35 Poplar Rd, Parkville, VIC, 3052, Australia.
Leigh C WalkerFlorey Institute of Neuroscience & Mental Health, Royal Parade, Parkville, VIC, 3010, Australia.
Andrew J LawrenceFlorey Institute of Neuroscience & Mental Health, Royal Parade, Parkville, VIC, 3010, Australia. Andrew.Lawrence@florey.edu.au.ORCID 0000-0001-6836-727X
The University of Melbourne · AUFlorey Institute of Neuroscience and Mental Health · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundFor decades, treatment of mood disorders, psychoses, anxiety and dementia have been confounded by limited efficacy and high rates of treatment resistance. Preclinical and clinical evidence have highlighted disruption of cholinergic signalling in several neuropsychiatric conditions and examined intervention strategies including acetylcholinesterase inhibitors and nicotinic receptor-targeted intervention. However, the effectiveness of these approaches is often curtailed by on-target side effects. Post mortem studies implicate muscarinic receptor dysregulation in neuropsychiatric pathophysiology; therefore, we conducted a systematic review and meta-analysis to investigate the therapeutic efficacy and safety of muscarinic receptor-targeted interventions in adults with neuropsychiatric disorders.

methodsPubMed, EMBASE, PsycINFO, EBSCO and Web of Science were searched using relevant keywords from database inception to 7 August 2022. Randomised, double-blind, placebo-controlled studies were included if they investigated the effect of muscarinic receptor-targeted intervention in adults with a diagnosis of a neuropsychiatric disorder and were published in English. A narrative synthesis approach was adopted to describe the findings. Wherever three or more studies with a similar intervention were available, effect sizes were calculated, and a meta-analysis was performed. Cochrane risk-of-bias-2 tool was utilised to assess the risk of bias, and sensitivity analyses were performed to identify publication bias. Certainty analysis (high, moderate, low and/or very low) was conducted using GRADE criteria.

resultsOverall, 33 studies met the inclusion criteria and 5 were included in the meta-analysis. Despite a limited pool with several different interventions, we found therapeutic efficacy of xanomeline (M

conclusionWhile the results are not definitive, findings on muscarinic receptor-targeted interventions in several mental disorders are promising in terms of efficacy and safety, specifically in treating schizophrenia, mood disorders, and behavioural and psychiatric symptoms of Alzheimer's disease. However, orthosteric muscarinic receptor-targeted interventions are associated with a range of peripheral adverse effects that are thought to be mediated via M

Indexed as

DementiaMajor Depressive DisorderAcetylcholinesteraseAdultAntidepressive AgentsHumansProspective StudiesRandomized Controlled Trials as TopicReceptors, MuscarinicScopolamine DerivativesTreatment OutcomeAcetylcholinesteraseAntidepressive AgentsReceptors, MuscarinicScopolamine Derivatives

Identifiers

PMID36269510
PMCPMC9653329
OpenAlexW4307032277

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.