Evidence map›Paper›PMID 33479273›Full record

ArticleScientific reports2021

Associations between plasma clozapine/N-desmethylclozapine ratio, insulin resistance and cognitive performance in patients with co-morbid obesity and ultra-treatment resistant schizophrenia.

Kenya A Costa-Dookhan, Tarek K Rajji, Veronica N Tran, Sylvie Bowden, Daniel J Mueller, Gary J Remington, Sri Mahavir Agarwal, Margaret K Hahn

Abstract read
In one paragraph

Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
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

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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

3 citing papers in PubMed.

  1. Review
  2. Review
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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

8 authors.

Kenya A Costa-DookhanInstitute of Medical Science, University of Toronto, Toronto, Canada.
Tarek K RajjiInstitute of Medical Science, University of Toronto, Toronto, Canada.
Veronica N TranDepartment of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Canada.
Sylvie BowdenDepartment of Medicine, University of Toronto, Toronto, Canada.
Daniel J MuellerInstitute of Medical Science, University of Toronto, Toronto, Canada.
Gary J RemingtonInstitute of Medical Science, University of Toronto, Toronto, Canada.
Sri Mahavir AgarwalInstitute of Medical Science, University of Toronto, Toronto, Canada.
Margaret K HahnInstitute of Medical Science, University of Toronto, Toronto, Canada. Margaret.Hahn@camh.ca.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Clozapine (CLZ), the sole antipsychotic with superior efficacy for ultra-treatment resistant schizophrenia (TRS), is limited by adverse effects, including metabolic dysregulation. Clozapine's main metabolite, N-desmethylclozapine (NDMC), has potent 5-HT2C antagonist properties which may explain this metabolic dysfunction, thus the CLZ:NDMC ratio is of particular interest. High insulin resistance states could be associated with CYP1A2 induction and lower CLZ:NDMC ratios. Additionally, lower CLZ:NDMC ratios have been associated with better cognitive, but worse metabolic functioning. This study investigated associations between metabolic and cognitive parameters with the CLZ/NDMC ratio. Primary outcomes included relationships between the CLZ:NDMC ratio to the homeostatic model assessment for insulin resistance (HOMA-IR) and Brief Assessment of Cognition in Schizophrenia (BACS) composite z-scores. Secondary outcomes assessed relationships between CLZ:NDMC ratios to fasting insulin, BMI, weight, fasting glucose, and BACS digit sequencing z-scores. 38 patients who were overweight or obese with schizophrenia or schizoaffective disorder completed fasting bloodwork, anthropometric, psychopathological, and cognitive assessments. Multivariate regressions found a statistically significant inverse association between the CLZ/NDMC ratio and HOMA-IR (B = - 1.028, SE B = .473, β = - 0.348 p = 0.037), which may have been driven by fasting insulin levels (B = - 27.124, SE B = 12.081, β = - 0.351 p = 0.031). The CLZ/NDMC ratio may predict insulin resistance/metabolic comorbidity among patients with TRS receiving clozapine.

Indexed as

AdolescentAdultAntipsychotic AgentsClozapineCognitionFemaleHumansInsulin ResistanceMaleMiddle AgedObesityObesity, MorbidPsychotic DisordersSchizophreniaYoung AdultAntipsychotic AgentsClozapinenorclozapine

Identifiers

PMID33479273
PMCPMC7820218

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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.