ArticleBMJ neurology open2020
Safety and acceptability of clozapine and risperidone in progressive multiple sclerosis: a phase I, randomised, blinded, placebo-controlled trial.
Article in BMJ neurology open, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
What it found
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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.
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.
Who cites it
8 citing papers in PubMed, 13 citations in OpenAlex.
- Psychosis in multiple sclerosis-a narrative review of an underestimated, but clinically significant problem.Journal of neural transmission (Vienna, Austria : 1996) · 2026Review
- Neuroimmune, clinical and treatment challenges in multiple sclerosis-related psychoses.World journal of psychiatry · 2023Review
- Opportunities for Molecular Imaging in Multiple Sclerosis Management: Linking Probe to Treatment.Radiology · 2022Review
- Current Insights Into Oligodendrocyte Metabolism and Its Power to Sculpt the Myelin Landscape.Frontiers in cellular neuroscience · 2022Review
- Dopaminergic Receptors as Neuroimmune Mediators in Experimental Autoimmune Encephalomyelitis.Molecular neurobiology · 2021Article
- Antipsychotics, versatility in action.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Effects of Venlafaxine, Risperidone and Febuxostat on Cuprizone-Induced Demyelination, Behavioral Deficits and Oxidative Stress.International journal of molecular sciences · 2021Article
- Localisation of clozapine during experimental autoimmune encephalomyelitis and its impact on dopamine and its receptors.Scientific reports · 2021Article
Corrections and comments
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Authors and funding
13 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveBecause clozapine and risperidone have been shown to reduce neuroinflammation in humans and mice, the Clozapine and Risperidone in Progressive Multiple Sclerosis (CRISP) trial was conducted to determine whether clozapine and risperidone are suitable for progressive multiple sclerosis (pMS).
methodsThe CRISP trial (ACTRN12616000178448) was a blinded, randomised, placebo-controlled trial with three parallel arms (n=12/arm). Participants with pMS were randomised to clozapine (100-150 mg/day), risperidone (2.0-3.5 mg/day) or placebo for 6 months. The primary outcome measures were safety (adverse events (AEs)/serious adverse events (SAE)) and acceptability (Treatment Satisfaction Questionnaire for Medication-9).
resultsAn interim analysis (n=9) revealed significant differences in the time-on-trial between treatment groups and placebo (p=0.030 and 0.025, clozapine and risperidone, respectively) with all participants receiving clozapine being withdrawn during the titration period (mean dose=35±15 mg/day). Participants receiving clozapine or risperidone reported a significantly higher rate of AEs than placebo (p=0.00001) but not SAEs. Specifically, low doses of clozapine appeared to cause an acute and dose-related intoxicant effect in patients with pMS who had fairly severe chronic spastic ataxic gait and worsening over all mobility, which resolved on drug cessation.
interpretationThe CRISP trial results suggest that patients with pMS may experience increased sensitivity to clozapine and risperidone and indicate that the dose and/or titration schedule developed for schizophrenia may not be suitable for pMS. While these findings do not negate the potential of these drugs to reduce multiple sclerosis-associated neuroinflammation, they highlight the need for further research to understand the pharmacodynamic profile and effect of clozapine and risperidone in patients with pMS. TRIAL REGISTRATION NUMBER: ACTRN12616000178448.
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