# Pharmacological treatment options for cognitive dysfunction induced by multiple sclerosis: a network meta-analysis

**Authors:** Zhuyuan Fan, Dan Liu, Guangwei Zhang, Xinlin Guo

PMC · DOI: 10.3389/fneur.2025.1649429 · Frontiers in Neurology · 2025-10-07

## TL;DR

This study compares drug treatments for cognitive issues in multiple sclerosis patients, finding some drugs improve memory and test performance.

## Contribution

A network meta-analysis comparing pharmacological treatments for cognitive dysfunction in multiple sclerosis.

## Key findings

- L-amphetamine may improve memory in MS-induced cognitive dysfunction compared to placebo.
- Atomoxetine may enhance SDMT and CVLT scores more than other drugs like donepezil and ginkgo biloba.
- Rivastigmine is less likely to cause dyspepsia compared to other treatments.

## Abstract

To compare the effects of various pharmacological treatments on partial test results and adverse effects in patients with cognitive dysfunction (CD) induced by multiple sclerosis (MS) through a network meta-analysis.

PubMed, Embase, Cochrane Library, and Web of Science databases were systematically retrieved for randomized controlled trials (RCTs) evaluating the influence of different pharmacological treatments on CD in MS patients. The search was updated until October 8, 2024. The Risk of Bias tool was used to assess the quality of eligible studies, and R was employed for data analysis.

Twenrt six studies involving 23,839 MS patients were included for our analysis. Network meta-analysis results indicated that compared to placebo, L-amphetamine may improve memory in MS-induced CD. Memantine may enhance performance on the Paced Auditory Serial Addition Test (PASAT). Compared to memantine, fampridine-SR, ginkgo biloba, and melatonin showed inferior effects. Atomoxetine may improve Symbol Digit Modalities Test (SDMT) scores, outperforming donepezil, ginkgo biloba, L-amphetamine, modafinil, and rivastigmine. Additionally, atomoxetine may improve California Verbal Learning Test (CVLT) performance, compared to ginkgo biloba, L-amphetamine, and memantine. In terms of adverse effects, rivastigmine was less likely to cause dyspepsia.

Based on current evidence, L-amphetamine may improve memory in MS-induced CD. Melatonin may enhance PASAT performance, and atomoxetine may improve both SDMT and CVLT scores in these patients. However, rivastigmine was found to have a lower likelihood of causing dyspepsia among the treatments assessed.

https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024623642.

## Linked entities

- **Chemicals:** L-amphetamine (PubChem CID 3007), memantine (PubChem CID 4054), fampridine-SR (PubChem CID 1727), melatonin (PubChem CID 896), atomoxetine (PubChem CID 54841), donepezil (PubChem CID 3152), modafinil (PubChem CID 4236), rivastigmine (PubChem CID 5077)
- **Diseases:** multiple sclerosis (MONDO:0005301)

## Full-text entities

- **Diseases:** dyspepsia (MESH:D004415), MS (MESH:D009103), CD (MESH:D003072)
- **Chemicals:** fampridine (MESH:D015761), Melatonin (MESH:D008550), Memantine (MESH:D008559), Atomoxetine (MESH:D000069445), donepezil (MESH:D000077265), L-amphetamine (MESH:D000661), modafinil (MESH:D000077408), rivastigmine (MESH:D000068836)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

_Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC12537379/full.md

## Figures

9 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12537379/full.md

## References

47 references — full list in the complete paper: https://tomesphere.com/paper/PMC12537379/full.md

---
Source: https://tomesphere.com/paper/PMC12537379